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One ofthe basic themes of life is that

manyorganismsconsume or use other

organismsto survive. For example, ter-

mites feed on wood, deer graze on

grasses, spiderseat termites, and wolves

feed on deer. A parasite liveson or in an-

other organism called the host. The hostpro-

vides the parasite with the conditionsand food

necessary for survival. For example, hookwormscan

live in the sheltered environment of the human intestine, where theyfeed on

blood. Humansare host to many different kindsof organisms, including microor-

ganisms, such asbacteria, viruses, fungi, and protozoans; insects; and worms.

It’soften the case that parasites harm humans, causing disease and sometimes

death. However, our bodieshave ways to resist or destroy harmful microorgan-

isms. Thischapter considers the lymphatic system (772), immunity (779), innate

immunity (780), adaptive immunity (785), immune interactions (800), im-

munotherapy(800),acquired immunity (804), and the effects of aging on the lym-

phaticsystem and immunity (805).

Lymphatic

System and

Immunity

A macrophage (largercell) isabout to

phagocytize a bacterial cell (E. coli).

CHAPTER

Part 4 Regulationsand Maintenance

Seeley−Stephens−Tate:

Anatomy and Physiology,

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IV. Regulations and

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22. Lymphatic System and

Immunity

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LymphaticSystem

Objectives

■ Describe the functionsof the lymphatic system.

■ Explain the anatomyand location of the lymphatic vessels.

■ Describe the structuresand functions of diffuse lymphatic

tissue, lymphaticnodules, tonsils, lymph nodes, spleen,

and thymus.

The lymphatic (lim-fat⬘ik)system includes lymph,lym-

phatic vessels,lymphatic tissue, lymphatic nodules, lymph nodes,

tonsils,the spleen, and the thymus (ﬁgure 22.1).

Functionsof the Lymphatic System

The lymphatic system helps to maintain ﬂuid balance in tissues

and absorb fats from the digestive tract.It’s also part of the body’s

defense system against microorganisms and other harmful sub-

stances.

1. Fluid balance.Approximately 30 L ofﬂuid pass from the

blood capillaries into the interstitial ﬂuid each day,whereas

only 27 L pass from the interstitial ﬂuid back into the blood

capillaries.If the extra 3 L of ﬂuid were to remain in the

interstitial ﬂuid,edema would result, causing tissue damage

and eventual death.Instead, the 3 L of ﬂuid enters the

lymphatic capillaries,where the ﬂuid is called lymph (limf;

clear spring water),and passes through the lymphatic

vessels back to the blood (see chapter 21).In addition to

water,lymph contains solutes derived from two sources:

(1)substances in plasma, such as ions, nutrients, gases, and

some proteins,pass from blood capillaries into the

interstitial ﬂuid and become part ofthe lymph; and

(2)substances derived from cells, such as hormones,

enzymes,and waste products, are also found in the lymph.

Part4 Regulationsand Maintenance772

2. Fat absorption.The lymphatic system absorbs fats and other

substances from the digestive tract (see chapter 24).Special

lymphatic vessels called lacteals(lak⬘te¯-a˘lz) are located in

the lining ofthe small intestine. Fats enter the lacteals and

pass through the lymphatic vessels to the venous

circulation.The lymph passing through these lymphatic

vessels has a milky appearance because ofits fat content and

is called chyle(kı¯l).

3. Defense.Microorganisms and other foreign substances are

ﬁltered from lymph by lymph nodes and from blood by the

spleen.In addition, lymphocytes and other cells are capable

ofdestroying microorganisms and other foreign substances.

LymphaticVessels

The lymphatic vessels are essential for the maintenance of ﬂuid

balance. They begin as small, dead-end tubes called lymphatic

capillaries(ﬁgure 22.2a). Fluids tend to move out of blood capil-

laries into tissue spaces (see “Capillary Exchange and Regulation of

Interstitial Fluid Volume”in chapter 21). Excess ﬂuid passes

through the tissue spaces and enters lymphatic capillaries to be-

come lymph.Lymphatic capillaries are in almost all tissues of the

body,with the exception of the central nervous system, the bone

marrow,and tissues without blood vessels, such as cartilage, epi-

dermis,and the cornea. A superﬁcial group of lymphatic capillar-

ies is in the dermis of the skin and the hypodermis.A deep group

of lymphatic capillaries drains the muscles, joints, viscera, and

other deep structures.

Lymphatic capillaries differ from blood capillaries in that

they lack a basement membrane and the cells of the simple squa-

mous epithelium slightly overlap and are attached loosely to one

another (ﬁgure 22.2b).Two things occur as a result of this struc-

ture.First, the lymphatic capillaries are far more permeable than

blood capillaries, and nothing in the interstitial ﬂuid is excluded

from the lymphatic capillaries.Second, the lymphatic capillary ep-

ithelium functions as a series of one-way valves that allow ﬂuid to

enter the capillary but prevent it from passing back into the inter-

stitial spaces.

The lymphatic capillaries join to form larger lymphatic ves-

sels, which resemble small veins. The inner layer of the lymphatic

vessel consists ofendothelium surrounded by an elastic membrane,

the middle layer consists ofsmooth muscle cells and elastic ﬁbers,

and the outer layer is a thin layer ofﬁbrous connective tissue.

Small lymphatic vessels have a beaded appearance because of

the presence ofone-way valves along their lengths that are similar

to the valves ofveins (see ﬁgure 22.2b). When a lymphatic vessel is

compressed, backward movement of lymph is prevented by the

valves; as a consequence, the lymph moves forward through

the lymphatic vessel. Three factors are responsible for the com-

pression of lymphatic vessels: (1) contraction of surrounding

skeletal muscles during activity, (2) contraction of the smooth

muscles in the lymphatic vessel walls,and (3) pressure changes in

the thorax during respiration.

Lymph nodes are round, oval, or bean-shaped bodies dis-

tributed along the various lymphatic vessels (see “Lymph Nodes”

on p.775). They function to ﬁlter lymph,which enters and exits the

Thymus

Lymphatic

vessel

Tonsils

Cervical

lymph

node

Axillary

lymph

node

Mammary

plexus

Thoracic

duct

Spleen

Inguinal

lymph node

Figure 22.1

LymphaticSystem

The major lymphaticorgans and vessels are shown.

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Chapter 22 LymphaticSystem and Immunity 773

lymph nodes through the lymphatic vessels.The lymph nodes are

connected together in a series, so that lymph leaving one lymph

node is carried to another lymph node,and so on.

After passing through the lymph nodes,the lymphatic vessels

converge to form larger vessels called lymphatic trunks, each of

which drains a major portion ofthe body (ﬁgure 22.3a and b). The

jugular trunks drain the head and neck; the subclavian trunks

drain the upper limbs, superﬁcial thoracic wall, and mammary

glands; the bronchomediastinal (brong⬘ko¯-me¯⬘de¯-as-tı¯⬘na˘l)

trunksdrain thoracic organs and the deep thoracic wall; the intes-

tinal trunks drain abdominal organs such as the intestines,stom-

ach,pancreas, spleen, and liver; and the lumbar trunks drain the

lower limbs,pelvic and abdominal walls, pelvic organs, ovaries or

testes,kidneys, and adrenal glands.

The lymphatic trunks connect to large veins in the thorax or

join to yet larger vessels called lymphatic ducts,which then con-

nect to the large veins.The connections of the lymphatic trunks

and ducts to veins are quite variable.Many connect at the junction

of the internal jugular and subclavian veins, but connections on

the subclavian,jugular, and even brachiocephalic vein exist.

On the right side,the jugular, subclavian, and bronchomedi-

astinal trunks typically join a thoracic vein separately (see ﬁgure

22.3b). About 20% of the time,the three trunks join together to

form a short duct 1 cm in length called the right lymphatic duct

(not shown in ﬁgure 22.3b), which joins a thoracic vein. These

trunks drain the right side of the head,rig ht-upper limb,and right

thorax (ﬁgure 22.3c).

The right side of the body inferior to the thorax and the en-

tire left side ofthe body (see ﬁgure 22.3c) mostly drain through the

thoracic duct (see ﬁgure 22.3b). The thoracic duct is the largest

lymphatic vessel.It is approximately 38–45 cm in length,extending

from the twelfth thoracic vertebra to the base ofthe neck (see ﬁg-

ure 22.3c). The jugular and subclavian trunks join the thoracic

duct. The bronchomediastinal trunk sometimes connects to the

thoracic duct,but typically joins a vein. The intestinal and lumbar

trunks, which drain lymph inferior to the diaphragm, supply the

inferior end of the thoracic duct. They can directly join the tho-

racic duct or merge to form a network that connects to the thoracic

duct.In a small proportion of cases,the lymphatic trunks form a

sac called the cisterna chyli(sis-ter⬘na˘ kı¯⬘lı¯;a cistern or tank that

contains juice).

1. List the parts of the lymphatic system, and describe the

three main functionsof the lymphatic system.

2. How is lymph formed?

3. Describe the structure of a lymphatic capillary. Why is it

easyfor ﬂuid and other substances to enter a lymphatic

capillary?

4. What is the function of the valves in lymphatic vessels?

Name three thingsthat cause lymph to move through the

lymphaticvessels.

5. What are lymphatic trunks and ducts? Name the largest

lymphaticvessel. What is the cisterna chyli?

6. What areas of the body are drained by the right lymphatic

trunks, leftlymphatic trunks, and thoracic duct?

PREDICT

During radicalcancer surgery, malignantlymph nodes are often

removed, and the lymphaticvessels to them are tied off to prevent

metastasis, or spread, ofthe cancer. Predictthe consequences of tying

offthe lymphatic vessels.

Lymph

Fluid entering

lymphatic capillary

Direction of lymph

flow in capillary

Valve closed

(backflow of lymph

is prevented)

Arteriole

(from heart)

Blood

capillary

Fluid entering

lymphatic

capillary

Lymphatic

capillary

To venous system

Tissue cells

Venule

(to heart)

Valve open

(lymph flows

forward)

Overlapping

epithelial

cells

Figure 22.2

Lymph Formation and Movement

(a) Movementof ﬂuid from blood capillaries into tissuesand from tissues into lymphatic capillaries to form lymph. (b) The overlap of epithelial cellsof the lymphatic

capillaryallows easy entry of ﬂuid but prevents movementback into the tissue. Valves, located farther along in lymphatic vessels, also ensure one-wayﬂow of lymph.

(a)

(b)

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Part4 Regulationsand Maintenance774

eign substances,the ly mphocytes divide,increase in number, and

are part ofthe immune response that destroys microorganisms and

foreign substances. Lymphatic tissue also has very ﬁne collagen

ﬁbers, called reticular ﬁbers, which are produced by reticular

cells. Lymphocytes and other cells attach to these ﬁbers. When

lymph or blood ﬁlters through lymphatic organs,the ﬁber network

traps microorganisms and other particles in the ﬂuid.

LymphaticTissue and Organs

Lymphatic organs contain lymphatic tissue, which consists pri-

marily oflymphocy tes;but it also includes macrophages, dendritic

cells,reticular cells, and other cell types. Lymphocytes are a type of

white blood cell (see chapter 19). They originate from red bone

marrow and are carried by the blood to lymphatic organs and

other tissues.When the body is exposed to microorganisms or for-

Area drained by

left lymphatic

trunks and

thoracic duct

Area drained by

right lymphatic

trunks

Right jugular trunk

Right subclavian

trunk

Left jugular trunk

Left subclavian

trunk

Left broncho-

mediastinal trunk

Right broncho-

mediastinal trunk

Thoracic duct

Left internal jugular vein

Left jugular trunk

Thoracic duct

Left subclavian trunk

Left bronchomediastinal trunk

Left subclavian vein

First rib (cut)

Thoracic duct

Thoracic lymph nodes

Hemiazygos vein

Parietal pleura (cut)

Intestinal trunk

Left lumbar trunk

Right lumbar trunk

Inferior vena cava

Cisterna chyli

Diaphragm

Azygos vein

T12

Intercostal muscle

Rib (cut)

Superior vena cava

Right bronchomediastinal trunk

Right subclavian vein

Right subclavian trunk

Right jugular trunk

Right internal jugular vein

Brachiocephalic veins

Figure 22.3

Lymph Drainage Into Veins

(a) Anterior view ofthe major lymphatic vessels in the thoraxand abdomen. (b) Close-up view of the lymphatic vessels from which lymph enters the blood.

(c)Regions of the body drained by the right and left lymphaticvessels.

(a)

(b)

(c)

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There are three groups of tonsils, but the palatine tonsils

usually are referred to as “the tonsils.”They are relatively large,oval

lymphoid masses on each side ofthe junction between the oral cav-

ity and the pharynx. The pharyngeal (fa˘-rin⬘je¯-a˘l) tonsil, or ade-

noid (ad⬘e˘-noyd), is a collection of somewhat closely aggregated

lymphatic nodules near the junction between the nasal cavity and

the pharynx.An enlarged pharyngeal tonsil can interfere with nor-

mal breathing.The lingual tonsil is a loosely associated collection

oflymphatic nodules on the posterior surface of the tongue.

Sometimes the palatine or pharyngeal tonsils become chroni-

cally infected and must be removed.The lingual tonsil becomes in-

fected less often than the other tonsils and is more difﬁcult to remove.

7. What are the functions of lymphocytes and reticular ﬁbers

in lymphatictissue?

8. What is mucosa-associated lymphoid tissue (MALT)? In

whatway is the location of MALT beneﬁcial?

9. Deﬁne diffuse lymphatic tissue, lymphatic nodule, Peyer’s

patches, and lymphaticfollicle.

10. Describe the structure, function, and location of the tonsils.

Lymph Nodes

Lymph nodesare small, round, or bean-shaped structures, ranging

in size from 1–25 mm long,and are distributed along the course of

the lymphatic vessels (see ﬁgures 22.1 and 22.6). They ﬁlter the

lymph, removing bacteria and other materials. In addition, lym-

phocytes congregate,function, and proliferate within lymph nodes.

Lymph nodes are categorized as superﬁcial or deep.Superﬁcial

lymph nodes are in the hypodermis beneath the skin and deep

lymph nodes are everywhere else. Both superﬁcial and deep lymph

nodes typically are located in adipose tissue near or on blood vessels.

Approximately 450 lymph nodes are found throughout the body.Cer-

vical and head nodes (about 70) ﬁlter lymph from the head and neck,

axillary nodes (about 30) ﬁlter lymph from the upper limbs and su-

perﬁcial thorax,thoracic nodes (about 100) ﬁlter lymph from the tho-

racic wall and organs,abdominopelvic nodes (about 230) ﬁlter lymph

from the abdomen and pelvis, and inguinal and popliteal nodes

(about 20) ﬁlter lymph from the lower limbs and superﬁcial pelvis.

Lymphatic tissue surrounded by a connective tissue capsule is

said to be encapsulated,whereas lymphatic tissue without a capsule

is called nonencapsulated.Lymphatic organs with a capsule include

lymph nodes, the spleen, and the thymus. Mucosa-associated

lymphoid tissue (MALT) is aggregates of nonencapsulated lym-

phatic tissue found in and beneath the mucous membranes lining

the digestive,respiratory, urinary,and reproductive tracts. In these

locations,the lymphatic tissue is well located to intercept microor-

ganisms as they enter the body.Examples of MALT include diffuse

lymphatic tissue,lymphatic nodules, and the tonsils.

Diffuse LymphaticTissue and Lymphatic Nodules

Diffuse lymphatic tissue contains dispersed lymphocytes,

macrophages,and other cells; has no clear boundary ; and blends

with surrounding tissues (ﬁgure 22.4).It is located deep to mucous

membranes, around lymphatic nodules, and within the lymph

nodes and spleen.

Lymphatic nodules are denser arrangements of lymphoid

tissue organized into compact, somewhat spherical structures,

ranging in size from a few hundred microns to a few millimeters or

more in diameter (see ﬁgure 22.4).Lymphatic nodules are numer-

ous in the loose connective tissue ofthe digestive, respiratory, uri-

nary,and reproductive systems. Peyer’s patches are aggregations

oflymphatic nodules found in the distal half ofthe small intestine

and the appendix. In addition to MALT,lymphatic nodules are

found within lymph nodes and the spleen,w here they are usually

referred to as lymphatic follicles.

Tonsils

Tonsilsare large groups of lymphatic nodules and diffuse lym-

phatic tissue located deep to the mucous membranes within the

pharynx (throat) (ﬁgure 22.5). The tonsils provide protection

against bacteria and other potentially harmful material entering

the pharynx from the nasal or oral cavities.In adults, the tonsils de-

crease in size and eventually may disappear.

LM 25x

Lymphatic

nodule

Diffuse

lymphatic

tissue

Figure 22.4

Diffuse LymphaticTissue and Lymphatic

Nodule

Diffuse lymphatictissue surrounding a lymphatic nodule in the small intestine

(Peyer’spatch).

Pharyngeal tonsil

Palatine tonsil

Lingual tonsil

Figure 22.5

Location ofthe Tonsils

Anterior view ofthe oral cavity showing the tonsils. Part ofthe palate is

removed (dotted line) to show the pharyngealtonsil.

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FemoralHernia

Lymph from the lower limbsdrains into the inguinal lymph nodes, which

are located in the groin region. The femoralcanal is a passageway

through which lymphaticvessels from the inguinal nodes enter the

abdominalcavity. A femoralhernia occurs when a loop of intestine

pushesinto, or even passes completely through, the femoral canal.

A dense connective tissue capsule surrounds each lymph

node. Extensions of the capsule,called t rabeculae (tra˘-bek⬘u¯-le¯),

form a delicate internal skeleton in the lymph node. Reticular

ﬁbers extend from the capsule and trabeculae to form a ﬁbrous

network throughout the entire node.In some areas of the lymph

node,lymphocytes and macrophages are packed around the retic-

ular ﬁbers to form lymphatic tissue,and in other areas the reticular

Part4 Regulationsand Maintenance776

ﬁbers extend across open spaces to form lymphatic sinuses.The

lymphatic tissue and sinuses within the node are arranged into two

somewhat indistinct layers,an outer cortex and an inner medulla.

The cortex consists ofa subcapsular sinus, beneath the capsule,

and cortical sinuses,which are separated by diffuse lymphatic tis-

sue,trabeculae, and lymphatic nodules. The inner medulla is or-

ganized into branching, irregular strands of diffuse lymphatic

tissue,the medullary cords, separated by medullary sinuses.

Lymph nodes are the only structures to ﬁlter lymph.The y

have afferent lymphatic vessels,which carry lymph to the ly mph

nodes,where it is ﬁltered, and efferent lymphatic vessels, which

carry lymph away from the nodes.Lymph from afferent lymphatic

vessels enters the subcapsular sinus and ﬁlters through the cortex

to the medulla,passing through the cortical sinuses and lymphatic

Diffuse lymphatic tissue

Cortical sinus

Lymphatic nodule

Germinal center

Afferent lymphatic vessel

carrying lymph to the

lymph node

Capsule

Trabecula

Medullary cord

Medullary sinus

Efferent lymphatic vessel

carrying lymph away from

the lymph node

Artery

Vein

Medulla

Cortex

Subcapsular sinus

Lymphatic

nodule

Diffuse

lymphatic

tissue

Trabecula

Medullary

cords

Germinal

center

Capsule

Subcapsular

sinus

Cortex

Medulla

LM 10x

Figure 22.6

Lymph Node

(a)Arrows indicate direction of lymph ﬂow. As lymph moves through the sinuses, phagocytic cellsremove foreign substances. The germinal centers are sites of

lymphocyte production. (b)Histology of a lymph node.

(a)

(b)

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tissue of the cortex. Lymph then passes through the sinuses and

lymphatic tissue of the medulla and exits the lymph node through

efferent lymphatic vessels.The efferent vessels of one lymph node

may become the afferent vessels ofanother node or may converge

to form lymphatic trunks,which carr y lymph to the blood at tho-

racic blood vessels.

Macrophages line the lymphatic sinuses, and they remove

bacteria and other foreign substances from the lymph as it slowly

ﬁlters through the sinuses.Microorganisms or other foreign sub-

stances in the lymph can stimulate lymphocytes throughout the

lymph node to undergo cell division,with proliferation especially

evident in the lymphatic nodules ofthe cortex. These areas of rapid

lymphocyte division are called germinal centers. The newly pro-

duced lymphocytes are released into the lymph and eventually

reach the bloodstream, where they circulate. Subsequently,the

lymphocytes can leave the blood and enter other lymphatic tissues.

Lymph NodesTrap Cancer Cells

Cancer cellscan spread from a tumor site, enter lymphaticcapillaries,

and be carried to lymph nodeswhere they can be trapped and where

theycan proliferate. If the cancer cellsescape from the lymph nodes,

theymay pass through lymphatic vesselsto the blood and eventually

reach other partsof the body. During cancer surgery, malignant

(cancerous) lymph nodesare often removed, and their vessels are tied

offand cut to prevent the spread of the cancer.

Spleen

Thespleen, which is roughly the size ofa clenched ﬁst, is located

on the left side in the extreme,superior part of the abdominal cav-

ity (ﬁgure 22.7).The average weight of the adult spleen is 180 g in

males and 140 g in females.The size and weight of the spleen tends

to decrease in older people,but in certain diseases the spleen can

achieve weights of2000 g or more.

The spleen has an outer capsuleof dense irregular connec-

tive tissue and a small amount ofsmooth muscle. Bundles of con-

nective tissue ﬁbers from the capsule form trabeculae, which

extend into the organ, subdividing it into small,interconnected

compartments. Arteries, veins, and lymphatic vessels extend

through the trabeculae to supply the compartments, which are

ﬁlled with white and red pulp.White pulp is associated with the

arterial supply and red pulpis associated with the veins. Approxi-

mately one-fourth of the volume of the spleen is white pulp and

three-fourths is red pulp.

Branches ofthe splenic (splen⬘ik)artery enter the spleen at

the hilum, and their branches follow the various trabeculae into

the spleen (see ﬁgure 22.7a and b). From the trabeculae, arterial

branches extend into the white pulp,which consists of the periar-

terial lymphatic sheath and lymphatic nodules (see ﬁgure 22.7c).

Theperiarterial ly mphatic sheath is diffuse lymphatic tissue sur-

rounding arteries and arterioles extending to lymphatic nodules.

Arterioles enter lymphatic nodules and give rise to capillaries sup-

plying the red pulp,which consists of the splenic cords and venous

sinuses. The splenic cords are a network of reticular cells which

produce reticular ﬁbers (see chapter 4). The spaces between the

reticular cells are occupied by splenic macrophages and blood cells

that have come from the capillaries.The venous sinuses are en-

larged capillaries between the splenic cords. The venous sinuses

typically connect to trabecular veins, which unite to form vessels

that leave the spleen to form the splenic vein.

Blood ﬂows through the spleen at three different rates.The

fast ﬂow takes a few seconds,intermediate ﬂow a few minutes, and

slow ﬂow an hour or more.Most blood ﬂows through the spleen

rapidly, but about 10% moves at the intermediate rate,and 2%

ﬂows at the slow rate.

The fast ﬂow is typical of ﬂow through organs with a closed

circulation, in which there is a direct capillary connection be-

tween the arterial and venous vessels (see ﬁgure 22.7c). In the

spleen,however, direct connections only occur rarely.Most circu-

lation in the spleen is an open circulation,in which there is no di-

rect capillary connection between the arterial and venous vessels.

Instead,blood empties into the boundary between the white and

red pulp or into the splenic cords.In most cases, blood quickly en-

ters into the open ends ofvenous sinuses, which originate near the

boundary. Otherwise, the blood percolates through the splenic

cords and passes through the walls of the venous sinuses, which

have intercellular slits.The fast ﬂow through the spleen results

from blood moving through the closed circulation or quickly into

the open ends of the venous sinuses in the open circulation.The

intermediate ﬂow is the passage ofblood through the splenic cords

and through the walls ofthe venous sinuses. The slow ﬂow follows

the same pathway as the intermediate ﬂow,but it takes longer be-

cause ofthe temporary adhesion of blood cells to splenic cord cells.

The spleen destroys defective red blood cells,detects and re-

sponds to foreign substances in the blood,and acts as a blood reser-

voir.As red blood cells age, they lose their ability to bend and fold.

Consequently,the cells can rupture as they pass through the mesh-

work of the splenic cords or the intercellular slits ofthe venous si-

nus walls.Splenic macrophages then phagocytize the cellular debris.

Foreign substances in the blood passing through the spleen

can stimulate an immune response because ofthe presence in the

white pulp ofspecialized lymphocytes, described later in this chap-

ter.There are high concentrations of T cells in the periarterial lym-

phatic sheath and B cells in the lymphatic nodules.

The human spleen is a limited reservoir for blood.For exam-

ple, during exercise splenic volume can be reduced by approxi-

mately 40%–50%.The resulting small increase in circulating red

blood cells can promote better oxygen delivery to muscles during

exercise or emergency situations.It’s not presently known if in hu-

mans this reduction results from contraction of smooth muscle

within the capsule, from contraction of smooth muscle (myoﬁ-

broblast) within the trabeculae, or from reduced blood ﬂow

through the spleen caused by constriction ofblood vessels.

Removalof the Injured Spleen

The spleen can be ruptured in traumaticabdominal injuries, even though

itis protected by the ribs. A ruptured spleen can resultin severe

bleeding, shock, and possiblydeath. A splenectomy (sple¯-nek⬘to¯-me¯),

removalof the spleen, can be performed to stop the bleeding. The liver

and other lymphatictissues are able to compensate for lossof the

spleen’sfunctions.

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Thymus

The thymus (thı¯⬘mu˘s) is a bilobed gland (ﬁgure 22.8) located in

the superior mediastinum,the partition dividing the thoracic cav-

ity into left and right parts.It was once thought that the thymus in-

creases in size until puberty,after which it dramatically decreases in

size. It’s now believed that the thymus increases in size until the

ﬁrst year oflife, after which it remains approximately the same size,

even though the size of the individual increases.After 60 years of

age,it decreases in size, and in older adults, the thymus may be so

Part4 Regulationsand Maintenance778

small that it is difﬁcult to ﬁnd during dissection.Although the size

of the thymus is fairly constant throughout much of life, by 40

years ofage much of the thymic lymphatic tissue has been replaced

with adipose tissue.

Each lobe of the thymus is surrounded by a thin connective

tissue capsule. Trabeculae extend from the capsule into the sub-

stance of the gland, dividing it into lobules. Unlike other lym-

phatic tissue, which has a ﬁbrous network of reticular ﬁbers,the

framework of thymic tissue consists of epithelial cells. The

Renal surface

Splenic artery

Splenic vein

Gastric surface

Hilum

Trabecular

artery

Branch of

trabecular

artery

Trabecular

vein

Capsule

Branch of

trabecular artery

Arteriole

Capillaries

Reticular cell

Space

Trabecula

White pulp

Red pulp

Trabeculae

Capsule

Red pulp

White pulp

Artery

1. Branches from the trabecular arteries are

surrounded by periarterial lymphatic sheaths.

2. An arteriole enters a lymphatic nodule and

divides.

3. A few capillaries directly connect to a venous

sinus (closed, fast circulation).

4. The ends of most capillaries are separated from

the beginning of the venous sinuses by a small

gap (open, fast circulation).

5. Some capillaries empty into the splenic cords

(open, intermediate and slow circulations). Blood

percolates through the splenic cords and passes

through the walls of the splenic sinuses.

6. The venous sinuses connect to the trabecular

vein.

White

pulp

Periarterial

sheath

Lymphatic

nodule

Trabecula

Trabecular vein

Venous

sinus

Splenic

cord

Red

pulp

LM 10x

Figure 22.7

Spleen

(a)Inferior view of the spleen. (b) Section showing the arrangement of

arteries, veins, white pulp, and red pulp. White pulp isassociated with

arteries, and red pulp isassociated with veins. (c) Blood ﬂow through white

and red pulp.(d) Histology of spleen.

(a)

(b)

(c)

(d)

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processes ofthe epithelial cells are joined by desmosomes, and the

cells form small,irregularly shaped compartments ﬁlled with lym-

phocytes.Near the capsule and trabeculae, the lymphocytes are nu-

merous and form dark staining areas of the lobules called the

cortex. A lighter staining central portion of the lobules, called the

medulla, has fewer lymphocytes. The medulla also contains

rounded epithelial structures,called thymic corpuscles (Hassall’s

corpuscles),whose function is unknown.

The thymus is the site ofmaturation of certain lymphocytes

called T cells.Large numbers of ly mphocytes are produced in the

thymus, but most degenerate. The lymphocytes that survive the

maturation process are capable of reacting to foreign substances,

but they normally do not react to and destroy healthy body cells

(see the “Origin and Development of Lymphocytes”on p. 786).

These surviving thymic lymphocytes migrate to the medulla,enter

the blood,and travel to other lymphatic tissues.

11. Where are lymph nodes found? Describe the parts of a lymph

node and explain howlymph ﬂows through a lymph node.

12. What are the functions of lymph nodes? How is this

accomplished? Whatis a germinal center?

13. Where is the spleen located? Name the two components of

white pulp. Of red pulp.

14. Explain the fast, intermediate, and slow ﬂow of blood

through the spleen.

15. What are three functions of the spleen?

16. Where is the thymus located? Describe its structure. What is

the blood-thymicbarrier? How is it related to the function

of the thymus?

Immunity

Objective

■ Describe the two majorcategories of immunity.

Immunityis the ability to resist damage from foreign sub-

stances such as microorganisms and harmful chemicals.Immu-

nity is categorized as innate immunity (also called nonspeciﬁc

resistance) or adaptive immunity (also called specific immu-

nity).In innate immunity, the body recognizes and destroys cer-

tain foreign substances, but the response to them is the same

each time the body is exposed to them.In adaptive immunity,

the body recognizes and destroys foreign substances,but the re-

sponse to them improves each time the foreign substance is

encountered.

Trachea

Lymph

nodes

Thymus

gland

Fat

Heart

Capsule

Cortex

Medulla

Trabecula

Blood

vessels

Lobule

Thymic

corpuscle

Trabecula

Cortex

Medulla

Lobule

Thymic

corpuscle

LM 10x

Figure 22.8

Thymus

(a)Location and shape of the thymus.

(b)Section showing a thymic lobule.

(c)Histology of the thymus, showing outer cortex and inner medulla.

(a) (b)

(c)

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Clinical Focus Disordersof the Lymphatic System

It’snot surprising that many infectious dis-

eases produce symptomsassociated with

the lymphaticsystem. The lymphatic system

is involved with the production oflympho-

cytes, which ﬁght infectious diseases, and

the lymphatic system ﬁlters blood and

lymph to remove microorganisms. Lym-

phadenitis(lim-fad⬘e˘-nı¯⬘tis)is an inﬂamma-

tion ofthe lymph nodes, which causes them

to become enlarged and tender. Thisinﬂam-

mation isan indication that microorganisms

are being trapped and destroyed within the

lymph nodes. Somtimesthe lymphatic ves-

selsbecome inﬂamed to produce lymphan-

gitis (lim-fan-jı¯⬘tis). This often results in

visible red streaksin the skin that extend

away from the site of infection. If microor-

ganismspass through the lymphaticvessels

and nodes to reach the blood, septicemia

(sep-ti-se¯⬘me¯-a˘), or blood poisoning, can re-

sult(see chapter 19).

Bubonic plague and elephantiasisare

diseasesof the lymphatic system. Bubonic

(boo-bon⬘ik)

plague is caused by bacteria

(Yersinia pestis), which are transferred to

humansfrom rats by the bite of the rat ﬂea

(Xenopsylla). The bacteria localize in the

lymph nodes, causing them to enlarge. The

termbubonic isderived from a Greek word

referring to the groin because the disease

often causes the inguinal lymph nodes of

the groin to swell. Without treatment, the

bacteria enter the blood, multiply, and in-

fect tissues throughout the body, rapidly

causing death in 70%–90% of those in-

fected. In the sixth, fourteenth, and nine-

teenth centuries, the bubonicplague killed

large numbersof people in Europe. Because

ofimproved sanitation and the advent of an-

tibiotics, fortunatelyrelatively few cases oc-

cur today. Elephantiasis(el-e˘-fan-tı¯⬘a˘-sis) is

caused by long, slender roundworms

(Wuchereria bancrofti). The adult worms

lodge in the lymphatic vessels and block

lymph ﬂow. The resulting accumulation of

ﬂuid in the interstitialspaces and lymphatic

vessels can cause permanentswelling and

enlargement of a limb. The affected limb

supposedly resembles an elephant’s leg,

providing the basisfor the name of the dis-

ease. The offspring ofthe adult worms pass

through the lymphatic system into the

blood, from which theycan be transferred to

another human bymosquitoes.

Alymphoma (lim-fo¯⬘ma˘) isa neoplasm

(tumor) of lymphatic tissue. Lymphomas

are usually divided into two groups: (1)

Hodgkin’s disease and (2) all other lym-

phomas, which are called non-Hodgkin’s

lymphomas. Typically, lymphomasbegin as

an enlarged, painless mass of lymph

nodes. The immune system is depressed,

and the patienthas an increased suscepti-

bility to infections. Enlargement of the

lymph nodescan also compress surround-

ing structuresand produce complications.

Fortunately, treatmentwith drugs and radi-

ation iseffective for many people who suf-

fer from lymphoma.

Speciﬁcity and memory are characteristics of adaptive im-

munity but not innate immunity.Speciﬁcity is the ability of adap-

tive immunity to recognize a particular substance. For example,

innate immunity can act against bacteria in general,whereas adap-

tive immunity can distinguish among different kinds of bacteria.

Memory is the ability of adaptive immunity to remember previous

encounters with a particular substance and,as a result, to respond

to it more rapidly.

In innate immunity,each time the body is exposed to a sub-

stance,the response is the same because speciﬁcity and memory of

previous encounters is not present.For example, each time a bacte-

rial cell is introduced into the body,it is phagocytized with the

same speed and efﬁciency.In adaptive immunity,the response dur-

ing the second exposure is faster and stronger than the response to

the ﬁrst exposure because the immune system remembers the bac-

teria from the ﬁrst exposure.For example, following initial expo-

sure to the bacteria,the body can take many days to destroy them.

During this time, the bacteria damage tissues and produce the

symptoms ofdisease. After the second exposure to the same bacte-

ria,however, the response is very rapid and effective. Bacteria are

destroyed before any symptoms develop,and the person is said to

beimmune.

17. Deﬁne the terms immunity, speciﬁcity, and memory.

18. What are the differences between innate and adaptive

immunity?

Part4 Regulationsand Maintenance780

Innate Immunity

Objectives

■ Describe the cellsand chemicals responsible for innate

immunity.

■ Listthe events that occur during an inﬂammatoryresponse,

and explain theirsigniﬁcance.

The main components of innate immunity include (1) me-

chanical mechanisms that prevent the entry of microbes into the

body or that physically remove them from body surfaces;

(2)chemical mediators that act directly against microorganisms or

that activate other mechanisms,leading to the destruction of the

microorganisms; and (3) cells involved in phagocytosis and the

production ofchemicals that participate in the response of the im-

mune system.

MechanicalMechanisms

Mechanical mechanisms, such as the skin and mucous mem-

branes, form barriers that prevent the entry of microorganisms

and chemicals into the tissues of the body.They also remove mi-

croorganisms and other substances from the surface ofthe body in

several ways. The substances are washed from the eyes by tears,

from the mouth by saliva,and from the urinary tract by urine. In

the respiratory tract,ciliated mucous membranes sweep microbes

trapped in the mucus to the back of the throat, where they are

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swallowed. Coughing and sneezing also remove microorganisms

from the respiratory tract.Microorganisms cannot cause disease if

they cannot get into the body.

ChemicalMediators

Chemical mediators are molecules responsible for many aspects

of innate immunity (table 22.1). Some chemical mediators found

on the surface of cells, such as lysozyme,sebum, and mucus, kill

microorganisms or prevent their entry into the cells.Other chemi-

cal mediators,such as histamine, complement, prostaglandins,and

leukotrienes, promote inﬂammation by causing vasodilation,in-

creasing vascular permeability, attracting white blood cells,and

stimulating phagocytosis. In addition, interferons protect cells

against viral infections.

Complement

Complement is a group of about 20 proteins that make up ap-

proximately 10% ofthe globulin part of serum.They include pro-

teins named C1–C9 and factors B,D,and P (properdin). Normally,

complement proteins circulate in the blood in an inactive,non-

functional form.The y become activated in the complement cas-

cade, a series of reactions in which each component of the series

activates the next component (ﬁgure 22.9).The complement cas-

cade begins through either the alternative pathway or the classical

pathway.The alternative pathway is part of innate immunity and

is initiated when the complement protein C3 becomes sponta-

neously active.Activated C3 normally is quickly inactivated by pro-

teins on the surface of the body’s cells.Activated C3 can combine

with some foreign substances, such as part of a bacterial cell or

virus.It can become stabilized and cause activation of the comple-

ment cascade. The classical pathwayis par t of the adaptive im-

mune system,discussed on p. 796.

Activated complement proteins provide protection in several

ways (see ﬁgure 22.9).Five of the complement proteins come to-

gether to form a membrane attack complex (MAC),which forms

a hole in the membrane.When membrane attack complexes form

in the plasma membrane of a nucleated cell,Na

and water enter

the cell through the hole and cause the cell to lysis.When mem-

brane attack complexes form in the outer membrane of certain

bacteria (Gram negative), an enzyme called lysozyme passes

through the hole and digests the bacterial cell wall.When the wall

breaks apart,the bacterial cell undergoes lysis.

Complement proteins can also attach to the surface ofbacte-

rial cells and stimulate macrophages to phagocytize the bacteria.In

addition,complement proteins attract immune system cells to sites

ofinfection and promote inﬂammation.

Interferons

Interferons (in-ter-fe¯r⬘onz) are proteins that protect the body

against viral infection and perhaps some forms of cancer.After a

virus infects a cell, viral replication can occur.Viral nucleic acids

and proteins,which are produced using the cell’s organelles,are as-

sembled into new viruses. The new viruses are released from the

infected cell to infect other cells.Because infected cells usually stop

their normal functions or die during viral replication, viral infec-

tions are clearly harmful to the body.Fortunately,viruses and other

Table 22.1

Chemical Description

Surface chemicals Lysozymes (in tears, saliva, nasal secretions,

and sweat) lyse cells; acid secretions

(sebum in the skin and hydrochloric acid in

the stomach) prevent microbial growth or

kill microorganisms; mucus on the mucous

membranes traps microorganisms until

they can be destroyed

Histamine An amine released from mast cells, basophils,

and platelets; histamine causes

vasodilation, increases vascular

permeability, stimulates gland secretions

(especially mucus and tear production),

causes smooth muscle contraction of

airway passages (bronchioles) in the lungs,

and attracts eosinophils

Kinins Polypeptides derived from plasma proteins;

kinins cause vasodilation, increase vascular

permeability, stimulate pain receptors, and

attract neutrophils

Interferon A protein, produced by most cells, that

interferes with virus production and

infection

Chemical Description

Complement A group of plasma proteins that increase

vascular permeability, stimulate the release

of histamine, activate kinins, lyse cells,

promote phagocytosis, and attract

neutrophils, monocytes, macrophages,

and eosinophils

Prostaglandins A group of lipids(PGEs, PGFs, thromboxanes,

and prostacyclins), produced by mast cells,

that cause smooth muscle relaxation and

vasodilation, increase vascular

permeability, and stimulate pain receptors

Leukotrienes A group of lipids, produced primarily by mast

cells and basophils, that cause prolonged

smooth muscle contraction (especially in

the lung bronchioles), increase vascular

permeability, and attract neutrophils and

eosinophils

Pyrogens Chemicals, released by neutrophils, monocytes,

and other cells, that stimulate fever

production

Chemicals of Innate Immunity and Their Functions

Abbreviations:PGE ⫽ prostaglandin E; PGF ⫽ prostaglandin F.

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Antigen–

antibody complex

Activated C1

Activated C4

Activated C2

Activated C3

Activated C5

Activated C6

Activated C7

Activated C8

Activated C9

Foreign substances

and factors B, D, and P

Stabilization of

activated C3

Classical pathway

Alternative pathway

Plasma

membrane

Complement

proteins form

a membrane

attack complex

Complement proteins

C3 – C7 promote

phagocytosis,

inflammation, and

chemotaxis (attract

immune system cells).

They can be activated

by either the classical

or alternative pathway.

The alternative pathway is activated

when complement protein C3

becomes spontaneously active and

combines with foreign substances

and factors B, D, and P.

Complement proteins C5 – C9 (yellow)

combine to form a hole in the plasma

membrane of target cells, causing the

cells to lyse.

The classical pathway is activated

at C1 and requires antibodies that

have bound to antigens.

Figure 22.9

ComplementCascade

Inactive complementproteins become active complement proteins (blue ovals) in a cascade reaction: each activated complementprotein activates the next protein

in the sequence.

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substances can stimulate infected cells to produce interferons.In-

terferons neither protect the cell that produces them nor act di-

rectly against viruses. Instead, they bind to the surface of

neighboring cells,where they stimulate them to produce antiviral

proteins. These antiviral proteins stop viral reproduction in the

neighboring cells by preventing the production of viral nucleic

acids and proteins.Interferon viral resistance is innate rather than

adaptive, and the same interferons act against many different

viruses.Infection by one kind of virus actually can produce protec-

tion against infection by other kinds of viruses. Some interferons

also play a role in the activation of immune cells such as

macrophages and natural killer cells.

Treating ViralInfections and Cancer with Interferons

Because some cancersare induced by viruses, interferonsmay play a

role in controlling cancers. Interferonsactivate macrophages and natural

killer cells(a type of lymphocyte), which attacktumor cells. Through

geneticengineering, interferons currently are produced in sufﬁcient

quantitiesfor clinical use and, along with other therapies, have been

effective in treating certain viralinfections and cancers. For example,

interferonsare used to treat hepatitis C, a viral disorder that can cause

cirrhosisand cancer of the liver, and to treatgenital warts, caused by the

herpesvirus. Interferons are also approved for the treatment of Kaposi’s

sarcoma, a cancer thatcan develop in AIDSpatients.

19. List the three main components of innate immunity.

20. Name two mechanical mechanisms that form barriers

preventing the entryof microorganisms. In what ways are

microorganismsremoved from the surfaces of the body?

21. What is complement? In what two ways is it activated? How

doescomplement provide protection?

22. What are interferons? How do they provide protection

againstviruses?

Cells

White blood cells and the cells derived from them (see table 19.2)

are the most important cellular components ofthe immune system

(table 22.2).White blood cells are produced in red bone marrow

and lymphatic tissue and are released into the blood,where they

are transported throughout the body.To be effective, white blood

cells must move into the tissues where they are needed.Chemotac-

tic(ke¯-mo¯-tak⬘tik)factors are parts ofmicrobes or chemicals re-

leased by tissue cells that act as chemical signals to attract white

blood cells. Important chemotactic factors include complement,

leukotrienes, kinins, and histamine. They diffuse from the area

where they are released.White blood cells can detect small differ-

ences in chemotactic factor concentration and move from areas of

lower chemotactic factor concentration to areas ofhigher concen-

tration.Thus, they move toward the source of these substances, an

ability called chemotaxis.White blood cells can move by ameboid

Table 22.2

Cell Primary Function

Innate Immunity

Neutrophil Phagocytosis and inflammation; usually

the first cell to leave the blood and

enter infected tissues

Monocyte Leaves the blood and enters tissues to

become a macrophage

Macrophage Most effective phagocyte; important in

later stages of infection and in tissue

repair; located throughout the body to

"intercept" foreign substances;

processes antigens; involved in the

activation of B and T cells

Basophil Motile cell that leaves the blood, enters

tissues, and releases chemicals that

promote inflammation

Mast cell Nonmotile cell in connective tissues that

promotes inflammation through the

release of chemicals

Eosinophil Enters tissues from the blood and releases

chemicals that inhibit inflammation

Natural killer cell Lyses tumor and virus-infected cells

Cell Primary Function

Adaptive Immunity

B cell After activation, differentiates to become

plasma cell or memory B cell

Plasma cell Produces antibodies that are directly or

indirectly responsible for the

destruction of the antigen

Memory B cell Quick and effective response to an antigen

againstwhich the immune system has

previously reacted; responsible for

immunity

Cytotoxic T cell Responsible for the destruction of cells by

lysisor by the production of cytokines

Delayed hypersensitivity Produces cytokines that promote

T cell inflammation

Helper T cell Activates B and effector T cells

Suppressor T cell Inhibits B and effector T cells

Memory T cell Quick and effective response to an antigen

againstwhich the immune system has

previously reacted; responsible for

adaptive immunity

Dendritic cell Processes antigen and is involved in the

activation of B and T cells

Immune System Cells and Their Primary Functions

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movement over the surface ofcells, can squeeze between cells, and

sometimes pass directly through other cells.

Phagocytosis (fag-o¯-sı¯-to¯⬘sis) is the endocytosis and de-

struction of particles by cells called phagocytes (see ﬁgure 3.21).

The particles can be microorganisms or their parts, foreign sub-

stances,or dead cells from the individual’s body.The most impor-

tant phagocytic cells are neutrophils and macrophages.

Neutrophils

Neutrophilsare small phagocytic cells produced in large numbers

in red bone marrow that are released into the blood,where they

circulate for a few hours. Approximately 126 billion neutrophils

per day leave the blood and pass through the wall ofthe gastroin-

testinal tract,where they provide phagocytic protection. The neu-

trophils are then eliminated as part of the feces. Neutrophils are

usually the ﬁrst cells to enter infected tissues,and they often die af-

ter a single phagocytic event.

Neutrophils also release lysosomal enzymes that kill mi-

croorganisms and also cause tissue damage and inﬂammation.Pus

is an accumulation ofdead neutrophils, dead microorganisms, de-

bris from dead tissue,and ﬂuid.

Macrophages

Macrophagesare monocytes that leave the blood, enter tissues,en-

large about ﬁvefold,and increase their number of lysosomes and

mitochondria. They are large phagocytic cells that outlive neu-

trophils,and they can ingest more and larger phagocytic particles

than neutrophils.Macrophages usually accumulate in tissues after

neutrophils and are responsible for most ofthe phagocytic activity

in the late stages of an infection, including the cleanup of dead

neutrophils and other cellular debris.In addition to their phago-

cytic role,macrophages produce a variety of chemicals, such as in-

terferons, prostaglandins, and complement, that enhance the

immune response.

Macrophages are beneath the free surfaces ofthe body, such

as the skin (dermis),hypodermis, mucous membranes, and serous

membranes,and around blood and lymphatic vessels. In these lo-

cations,macrophages provide protection by trapping and destroy-

ing microorganisms entering the tissues.

Ifmicrobes do gain entr y to the blood or lymphatic system,

macrophages are waiting within enlarged spaces,called sinuses, to

phagocytize them. Blood vessels in the spleen,bone marrow, and

liver have sinuses,as do lymph nodes. Within the sinuses,reticular

cells produce a ﬁne network ofreticular ﬁbers that slows the ﬂow of

blood or lymph and provides a large surface area for the attach-

ment of macrophages. In addition, macrophages are on the en-

dothelial lining ofthe sinuses.

Because macrophages on the reticular ﬁbers and endothelial

lining of the sinuses were among the ﬁrst macrophages studied,

these cells were referred to as the reticuloendothelial system.It’s

now recognized that macrophages are derived from monocytes

and are in locations other than the sinuses.Because monocytes and

macrophages have a single,unlobed nucleus, they are now called

the mononuclear phagocytic system. Sometimes macrophages

are given speciﬁc names,for instance dust cells in the lungs, Kupf-

fer cells in the liver,and microglia in the central nervous system.

Part4 Regulationsand Maintenance784

Basophils, MastCells, and Eosinophils

Basophils, which are derived from red bone marrow, are motile

white blood cells that can leave the blood and enter infected tissues.

Mast cells,which are also derived from red bone marrow,are non-

motile cells in connective tissue, especially near capillaries.Like

macrophages,mast cells are located at potential points of entry of

microorganisms into the body,such as the skin, lungs, gastroin-

testinal tract,and urogenital tract.

Basophils and mast cells can be activated through innate im-

munity (e.g.,by complement) or through adaptive immunity (see

“Antibodies”on p.793).When activated, they release chemicals, for

example,histamine and leukotrienes, that produce an inﬂamma-

tory response or activate other mechanisms,for example, smooth

muscle contraction in the lungs.

Eosinophils are produced in red bone marrow, enter the

blood,and within a few minutes enter tissues. Enzymes released by

eosinophils break down chemicals released by basophils and mast

cells.Thus, at the same time that inﬂammation is initiated, mecha-

nisms are activated that contain and reduce the inﬂammatory re-

sponse. This process is similar to the blood clotting system in

which clot prevention and removal mechanisms are activated while

the clot is being formed (see chapter 19).In patients with parasitic

infections or allergic reactions with much inﬂammation,

eosinophil numbers greatly increase.Eosinophils also secrete en-

zymes that effectively kill some parasites.

Natural KillerCells

Natural killer (NK) cellsare a type of lymphocyte produced in red

bone marrow,and they account for up to 15% of lymphocytes. NK

cells recognize classes ofcells, such as tumor cells or virus-infected

cells in general,rather than speciﬁc tumor cells or cells infected by

a speciﬁc virus.For this reason and because NK cells don’t exhibit

a memory response,they are classiﬁed as part of innate immunity.

NK cells use a variety ofmethods to kill their target cells, including

the release of chemicals that damage plasma membranes, causing

the cells to lyse.

23. Deﬁne the terms chemotactic factor, chemotaxis, and

phagocytosis.

24. What are the functions of neutrophils and macrophages?

Whatis pus?

25. What effects are produced by the chemicals released from

basophils, mastcells, and eosinophils?

26. Describe the function of NK cells.

Inﬂammatory Response

The inﬂammatory response is a complex sequence of events in-

volving many ofthe chemical mediators and cells of innate immu-

nity.Tissue injury, regardless of the type, can cause inﬂammation.

Trauma,burns, chemicals,or infections can damage tissues, result-

ing in inﬂammation.A bacterial infection is used here to illustrate

an inﬂammatory response (ﬁgure 22.10).The bacteria, or damage

to tissues, cause the release or activation of chemical mediators,

such as histamine, prostaglandins, leukotrienes, complement,

kinins,and others. The chemical mediators produce several effects:

(1)vasodilation, which increases blood ﬂow and brings phagocytes

and other white blood cells to the area;(2) chemotactic attraction

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of phagocytes, which leave the blood and enter the tissue; and

(3) increased vascular permeability,which allows ﬁbrinogen and

complement to enter the tissue from the blood.Fibrinogen is con-

verted to ﬁbrin,which prevents the spread of infection by walling

offthe infected area. Complement further enhances the inﬂamma-

tory response and attracts additional phagocytes. The process of

releasing chemical mediators and attracting phagocytes and other

white blood cells continues until the bacteria are destroyed.Phago-

cytes (mainly macrophages) remove microorganisms and dead tis-

sue,and the damaged tissues are repaired.

Inﬂammation can be localized or systemic.Local inﬂamma-

tionis an inﬂammatory response conﬁned to a speciﬁc area of the

body (see chapter 4). Symptoms of local inﬂammation include

redness, heat,swelling, pain, and loss of function. Redness, heat,

and swelling result from increased blood ﬂow and increased vascu-

lar permeability.Pain is caused by swelling and by chemicals acting

on pain receptors.Loss of function results from tissue destruction,

swelling,and pain.

Systemic inﬂammation is an inﬂammatory response that

occurs in many parts of the body.In addition to the local symp-

toms at the sites ofinﬂammation, three additional features can be

present.First, red bone marrow produces and releases large num-

bers ofneutrophils, which promote phagocytosis. Second, pyrogens

(pı¯⬘ro¯-jenz,ﬁre producing),chemicals released by microorganisms,

macrophages, neutrophils,and other cells, stimulate fever produc-

tion. Pyrogens affect the body’s temperature-regulating mecha-

nism in the hypothalamus, heat is conserved, and body

temperature increases. Fever promotes the activities of the im-

mune system, such as phagocytosis, and inhibits the growth of

some microorganisms. Third,in severe cases of systemic inﬂam-

mation,increased vascular permeability is so widespread that large

amounts of ﬂuid are lost from the blood into the tissues.The de-

creased blood volume can cause shock and death.

27. Describe the events that take place during an inﬂammatory

response.

28. What are the symptoms of local and systemic

inﬂammations?

Adaptive Immunity

Objectives

■ Explain the origin, development, activation, and inhibition

of lymphocytes.

■ Describe antibody-mediated immunity, including the

structure, types, and effectsof antibodies.

■ Describe cell-mediated immunityand the functions of T

cells.

Adaptive immunityinvolves the ability to recognize,respond

to,and remember a particular substance. Substances that stimulate

adaptive immunity are called antigens (an⬘ti-jenz). They usually

are large molecules with a molecular weight of 10,000 or more.

Haptens (hap⬘tenz) are small molecules (low molecular weight)

capable of combining with larger molecules like blood proteins to

stimulate an adaptive immune system response.

AllergicReactions to Penicillin

Penicillin isan example of a hapten of clinical importance. It’sa small

molecule thatdoesn’t evoke an immune system response. Penicillin can,

however, breakdown and bind to serum proteins to form a combined

molecule thatcan produce an allergic reaction. Most commonly, the

reaction producesa rash and fever, but rarely a severe reaction can

cause death.

Bacteria

enter tissue

Tissue

damage occurs

Chemical mediators

are released

Chemotaxis

Increased

blood flow

Increased

vascular

permeability

Increased numbers of

white blood cells and

chemical mediators at

site of tissue damage

Bacteria

are contained,

destroyed, and

phagocytized

Bacteria gone

Bacteria remain

Tissue

repair

Additional chemical

mediators activated

Figure 22.10

InﬂammatoryResponse

Flow diagram ofthe inﬂammatory response. Bacteria cause tissue damage

and release ofchemical mediators that initiate inﬂammation, resulting in the

destruction ofthe bacteria.

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Antigens are divided into two groups:foreign antigens and

self-antigens.Foreign antigens are not produced by the body but

are introduced from outside it.Components of bacteria,viruses,

and other microorganisms are examples of foreign antigens that

cause disease. Pollen,animal dander (scaly, dried skin), feces of

house dust mites, foods,and drugs are also foreign antigens and

can trigger an overreaction ofthe immune system in some people,

called an allergic reaction. Transplanted tissues and organs that

contain foreign antigens result in the rejection of the transplant.

Self-antigens are molecules produced by the body that stimulate

an adaptive immune system response. The response to self-

antigens can be beneﬁcial or harmful. For example,the recogni-

tion of tumor antigens can result in tumor destruction, whereas

autoimmune diseasecan result when self-antigens stimulate un-

wanted tissue destruction.

Adaptive immunity historically has been divided into two

types: humoral (hu¯⬘mo¯r-a˘l) and cell-mediated immunity. Early

investigators ofthe immune system found that, when plasma from

an immune animal was injected into the blood of a nonimmune

animal, the nonimmune animal became immune. Because this

process involved body ﬂuids (humors),it was called humoral im-

munity.It was also discovered that blood cells transferred from an

immune animal could be responsible for immunity, and this

process was called cell-mediated immunity.

It’s now known that immunity results from the activities of

lymphocytes called B and T cells (see table 22.2).B cells give rise to

cells that produce proteins called antibodies,which are found in

the plasma.Humoral immunity is now called antibody-mediated

immunity because antibodies are responsible.

Part4 Regulationsand Maintenance786

T cells are responsible for cell-mediated immunity.Several

subpopulations of T cells exist, each of which is responsible for a

particular aspect ofcell-mediated immunity. For example, effector

T cells,such as cy totoxic T cells and delayed hypersensitivity T

cells,are responsible for producing the effects of cell-mediated im-

munity; whereas regulatory T cells, such as helper T cells and

suppressor T cells, can promote or inhibit the activities of both

antibody-mediated immunity and cell-mediated immunity.

Table 22.3 summarizes and contrasts the main features ofin-

nate,antibody-mediated, and cell-mediated immunity.

29. Deﬁne the terms antigen and hapten. Distinguish between

a foreign antigen and a self-antigen.

30. What are allergic reactions and autoimmune diseases?

Origin and Development ofLymphocytes

All blood cells,including lymphocytes, are derived from stem cells

in the red bone marrow (see chapter 19).The process of blood cell

formation begins during embryonic development and continues

throughout life.Some stem cells give rise to pre-T cells that migrate

through the blood to the thymus, where they divide and are

processed into T cells.The thymus produces hormones such as thy-

mosin,which stimulates T-cell maturation. Other stem cells pro-

duce pre-B cells,which are processed in the red bone marrow into

B cells (ﬁgure 22.11).A p ositive selection process results in the

survival ofpre-B and pre-T cells that are capable of an immune re-

sponse.Cells that are incapable of an immune response die.

The B and T cells that can respond to antigens are composed

of small groups of identical lymphocytes called clones. Although

Table 22.3

Antibody-Mediated

Characteristics Innate Immunity Immunity Cell-Mediated Immunity

Primary cells Neutrophils, eosinophils, basophils, mast B cells T cells

cells, monocytes, and macrophages

Origin of cells Red bone marrow Red bone marrow Red bone marrow

Site of maturation Red bone marrow (neutrophils, Red bone marrow Thymus

eosinophils, basophils, monocytes)

and tissues (mast cells and macrophages)

Location of mature Blood, connective tissue, and lymphatic Blood and lymphatic Blood and lymphatic tissue

cells tissue tissue

Primary secretory Histamine, kinins, complement, Antibodies Cytokines

products prostaglandins, leukotrienes, and

interferon

Primary actions Inflammatory response and Protection against Protection against intracellular

phagocytosis extracellular antigens antigens (viruses, intracellular

(bacteria, toxins, bacteria, and intracellular fungi)

parasites, and and tumors: regulates antibody-

viruses outside of mediated immunity and cell-

cells) mediated immunity responses (helper T

and suppressor T cells)

Hypersensitivity None Immediate hypersensitivity Delayed hypersensitivity (allergy

reactions (atopy, anaphylaxis, of infection and contact hypersensitivity)

cytotoxic reactions, and

immune complex disease)

Comparison of Innate Immunity, Antibody-Mediated Immunity, and Cell-Mediated Immunity

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each clone can respond only to a particular antigen,such a large

number of clones exist that the immune system can react to most

molecules.Some of the clones can also respond to self-antigens. A

negative selection process eliminates or suppresses clones acting

against self-antigens, thereby preventing the destruction of self-

cells.Although the negative selection process mostly occurs during

prenatal development,it continues throughout life (see section on

“Inhibition ofLymphocytes” on p. 792).

B cells are released from red bone marrow,T cells are re-

leased from the thymus,and both types of cells move through the

blood to lymphatic tissue.There are approximately ﬁve T cells for

every B cell in the blood.These lymphocytes live for a few months

to many years and continually circulate between the blood and the

lymphatic tissues.Antigens can come into contact with and acti-

vate lymphocytes,resulting in cell divisions that increase the num-

ber of lymphocytes that can recognize the antigen. These

lymphocytes can circulate in blood and lymph to reach antigens in

tissues throughout the body.

Theprimary ly mphatic organs are the sites where lympho-

cytes mature into functional cells.These organs are the red bone

marrow and thymus.The secondar y lymphatic organs and tis-

sues are the sites where lymphocytes interact with each other,

antigen-presenting cells,and antigens to produce an immune re-

sponse. The secondary lymphatic organs and tissues include dif-

fuse lymphatic tissue, lymphatic nodules, tonsils, lymph nodes,

and the spleen.

31. Describe the origin and development of B and T cells.

32. What are lymphocyte clones? Distinguish between positive

and negative lymphocyte selection.

33. What are primary and secondary lymphatic organs and

tissues?

Activation ofLymphocytes

Antigens activate lymphocytes in different ways,depending on the

type of lymphocyte and the type of antigen involved.Despite these

differences,however, two general principles of lymphocyte activa-

tion exist:(1) lymphocy tes must be able to recognize the antigen,

and (2)after recognition, the lymphocytes must increase in num-

ber to effectively destroy the antigen.

AntigenicDeterminants and Antigen Receptors

If an adaptive immune system response is to occur,lymphocytes

must recognize an antigen.Lymphocytes don’t interact with an en-

tire antigen, however.Instead, antigenic determinants, or epi-

topes(ep⬘i-to¯pz),are speciﬁc regions ofa given antigen recognized

by a lymphocyte,and each antigen has many different antigenic de-

terminants (ﬁgure 22.12). All the lymphocytes of a given clone

have on their surfaces identical proteins called antigenreceptors,

which combine with a speciﬁc antigenic determinant.The immune

system response to an antigen with a particular antigenic determi-

nant is similar to the lock-and-key model for enzymes (see chapter

2),and any given antigenic determinant can combine only with a

speciﬁc antigen receptor. The T-cell receptor consists of two

polypeptide chains,which are subdivided into a variable and a con-

stant region (ﬁgure 22.13).The variable region can bind to an anti-

gen. The many different types of T-cell receptors respond to

different antigens because they have different variable regions.The

B-cell receptorconsists of four polypeptide chains with two iden-

tical variable regions.It is a ty pe of antibody and is considered in

greater detail on p.793.

MajorHistocompatibility Complex Molecules

Although some antigens bind to their receptors and directly acti-

vate B cells and some T cells,most lymphocyte activation involves

glycoproteins on the surfaces ofcells called major histocompati-

bility complex (MHC) molecules. MHC molecules are attached

to plasma membranes, and they have a variable region that can

bind to foreign and self-antigens.

Red bone marrow

Circulation

Lymph

node

Circulation

Thymus

Circulation

Stem cell

Pre-T cell

B cell

Pre-B cell

Pre-T cell

T cell

B cell

T cell

Figure 22.11

Origin and Processing ofB and T Cells

Both B and T cellsoriginate in red bone marrow. B cellsare processed in the

red marrow, whereasT cellsa re processed in the thymus. Both celltypes

circulate to other lymphatictissues, where they can divide and increase in

number in response to antigens.

Antigen

Different

antigenic

determinants

Figure 22.12

AntigenicDeterminants

An antigen hasmany antigenic determinants to which lymphocytescan

respond.

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MHC class I molecules are found on nucleated cells and

function to display antigens produced inside the cells on their sur-

faces (ﬁgure 22.14a).This is necessary because the immune system

cannot directly respond to an antigen inside a cell.For example,

viruses reproduce inside cells,forming viral proteins that are for-

eign antigens.Some of these viral proteins are broken down in the

cytoplasm. The protein fragments enter the rough endoplasmic

reticulum and combine with MHC class I molecules to form com-

plexes that move through the Golgi apparatus to be distributed on

the surface ofthe cell (see chapter 3).

MHC class I/antigen complexes on the surface of cells can

bind to T-cell receptors on the surface ofT cells. This combination

is a signal that activates T cells.As described later in this chapter,

activated T cells can destroy infected cells,which effectively stops

viral replication.Thus, the MHC class I/antigen complex functions

as a signal, or “red ﬂag,”that prompts the immune system to de-

stroy the displaying cell.In essence, the cell is displaying a sign that

says,“Kill me!”This process is said to be MHC-restricted, because

both the antigen and the individual organism’s own MHC mole-

cule are required.

PREDICT

In mouse A, T cellscan respond to virus X. If these T cellsare

transferred to mouse B, which isinfected with virusX, will the T cells

respond to the virus? Explain.

The same process that moves foreign protein fragments to

the surface of cells can also inadvertently transport self-protein

fragments (see ﬁgure 22.14a).As part of nor mal protein metabo-

lism,cells continually break down old proteins and synthesize new

ones.Some self-protein fragments that result from protein break-

down can combine with MHC class I molecules and be displayed

Part4 Regulationsand Maintenance788

on the surface of the cell, thus becoming self-antigens.Normally,

the immune system doesn’t respond to self-antigens in combina-

tion with MHC molecules because the lymphocytes that could re-

spond have been eliminated or inactivated (see section on

“Inhibition ofLymphocytes” on p. 792).

MHC class II molecules are found on antigen-presenting

cells, which include B cells, macrophages, monocytes, and den-

dritic cells.Dendritic (den-drit⬘ik) cells are large, motile cells with

long cytoplasmic extensions, and they are scattered throughout

most tissues (except the brain),with their highest concentrations

in lymphatic tissues and the skin.Dendritic cells in the skin are of-

ten calledLangerhans’ cells.

Antigen-presenting cells are specialized to take in foreign

antigens,to process the antigens, and to use MHC class II molecules

to display the foreign antigens to other immune system cells (ﬁgure

22.14b).For example, the MHC class II/antigen complex can bind

with a T-cell receptor.Because both the antigen and the individual’s

own MHC class II molecule are required,this process is said to be

MHC-restricted.Unlike MHC class I molecules, however, this dis-

play does not result in the destruction of the antigen-presenting

cell.Instead the MHC class II/antigen complex is a “rally around the

ﬂag”signal that stimulates other immune system cells to respond to

the antigen.The displaying cell is like Paul Revere, who spread the

alarm for the militia to arm and organize.The militia then went out

and killed the enemy.For example,when the ly mphocytes of the B-

cell clone that can recognize the antigen come into contact with the

MHC class II/antigen complex,they are stimulated to divide. The

activities of these lymphocytes, such as the production of antibod-

ies,then result in the destruction of the antigen.

34. Deﬁne the terms antigenic determinant and antigen

receptor. Howare theyrelated to each other?

35. What type of antigens are displayed by MHC class I and II

molecules?

36. What type of cells display MHC class I and II antigen

complexes, and whathappens as a result?

37. Deﬁne MHC-restricted.

PREDICT

How doeselimination of the antigen stop the production of

antibodies?

Costimulation

The combination of an MHC class II/antigen complex with an

antigen receptor is usually only the ﬁrst signal necessary to produce

a response from a B or T cell.In many cases, costimulation by ad-

ditional signals is also required.Costimulation is accomplished by

molecules released from cells and by molecules attached to the sur-

face ofcells. Cytokines (sı¯⬘to¯-kı¯nz), which are proteins or peptides

secreted by one cell as a regulator of neighboring cells, promote

costimulation(ﬁgure 22.15a). Cytokines produced by lymphocytes

are often called lymphokines (lim⬘fo¯-kı¯nz). Cytokines are in-

volved in the regulation ofimmunity, inﬂammation, tissue repair,

cell growth, and other processes.Table 22.4 lists important cy-

tokines and their functions.

Antigen-binding

site

Variable region

Constant region

Cell exterior

Cell interior

Plasma membrane

Figure 22.13

The T-CellReceptor

The T-cellreceptor consistsof two polypeptide chains. The variable region of

each type ofT-cellreceptor is speciﬁc for a given antigen. The constant region

attachesthe T-cellreceptor to the plasma membrane.

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Certain pairs of surface molecules can also be involved in cos-

timulation (ﬁgure 22.15b).When the surface molecule on one cell

combines with the surface molecule on another,the combination can

act as a signal that stimulates a response from one ofthe cells, or the

combination can hold the cells together.Typically, several different

kinds of surface molecules are necessary to produce a response.For

example, a molecule called B7 on macrophages must bind with a

molecule called CD28 on helper T cells before the helper T cells can

respond to the antigen presented by the macrophage.In addition,

helper T cells have a glycoprotein called CD4,which helps to connect

helper T cells to the macrophage by binding to MHC class II mole-

cules.For this reason,helper T cells are sometimes referred to as CD4,

orT4, cells.In a similar fashion, cytotoxic T cells are sometimes called

CD8,or T8, cells because they have a glycoprotein called CD8,which

helps to connect cytotoxic T cells to cells displaying MHC class I mol-

ecules. The CD designation stands for “cluster ofdifferentiation,”

which is a system used to classify many surface molecules.

Lymphocyte Proliferation

Before exposure to an antigen, the number of lymphocytes in a

clone is too small to produce an effective response against the anti-

gen. Exposure to an antigen results in an increase in lymphocyte

number.First, there is an increase in the number of helper T cells.

This is important because the increased number of helper T cells

MHC class II

molecule

Processed

antigen

Protein

fragments

(antigens)

Protein

Rough

endoplasmic

reticulum

MHC class I

molecule

Membrane Lumen

1. Foreign proteins or self-

proteins within the cytosol

are broken down into

fragments that are antigens.

2. Antigens are transported into

the rough endoplasmic

reticulum.

3. Antigens combine with MHC

class I molecules.

4. The MHC class I/antigen

complex is transported to the

Golgi apparatus, packaged

into a vesicle, and

transported to the plasma

membrane.

5. Foreign antigens combined

with MHC class I molecules

stimulate cell destruction.

6. Self-antigens combined with

MHC class I molecules do

not stimulate cell destruction.

Golgi

apparatus

Foreign antigen

Self-antigen

The unprocessed extracellular

antigen is ingested by

endocytosis and is within a

vesicle.

The antigen is broken down into

fragments to form processed

antigens.

The vesicle containing the

processed antigen fuses with

vesicles produced by the Golgi

apparatus that contain MHC

class II molecules. The

processed antigen and the MHC

class II molecule combine.

The MHC class II/antigen

complex is transported to the

plasma membrane.

The displayed MHC class

II/antigen complex can

stimulate immune cells.

Vesicle

containing

MHC class II

molecules

Vesicle

containing

processed

antigen

Unprocessed

antigen

ProcessFigure 22.14

Antigen Processing

(a)Foreign proteins, such as viral proteins, or self-proteinsin the cytosol, are processed and presented at the cell surface by MHC class I molecules. (b) Extracellular

antigensare taken into an antigen-presenting cell, processed, and presented atthe cell surface by MHC class II molecules.

(a)

(b)

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First signal

MHC

class II

molecule

T-cell

receptor

Processed

antigen

Macrophage

Helper

T cell

Cytokine

receptor

Costimulation by cytokines

MHC class II

molecule

Macrophage

Helper

T cell

CD4

CD28

Costimulation by surface molecules

Table 22.4

Cytokine* Description

Interferon alpha (IFNα) Prevents viral replication and inhibits cellgrowth; secreted by virus-infected cells

Interferon beta (IFNβ) Prevents viral replication, inhibits cell growth, and decreases the expression of major histocompatibility complex (MHC)

class I and II molecules; secreted by virus-infected fibroblasts

Interferon gamma (IFNγ) About 20 different proteins that activate macrophages and natural killer (NK) cells, stimulate adaptive immunity by

increasing the expression of MHC class I and II molecules, and prevent viral replication; secreted by helper T,

cytotoxic T, and NK cells

Interleukin-1 (IL-1) Costimulation of B and T cells, promotes inflammation through prostaglandin production, and induces fever acting

through the hypothalamus (pyrogen); secreted by macrophages, B cells, and fibroblasts

Interleukin-2 (IL-2) Costimulation of B and T cells, activation of macrophages and NK cells; secreted by helper T cells

Interleukin-4 (IL-4) Plays a role in allergic reactions by activation of B cells, resulting in the production of immunoglobulin E (lgE); secreted

byhelper T cells

Interleukin-5 (IL-5) Part of the response against parasites by stimulating eosinophil production; secreted by helper T cells

Interleukin-8 (IL-8) Chemotactic factor that promotes inflammation by attracting neutrophils and basophils; secreted by macrophages

Interleukin-10 (IL-10) Inhibits the secretion of interferon gamma and interleukins; secreted by suppressor T cells

Lymphotoxin Kills target cells; secreted by cytotoxic T cells

Perforin Makes a hole in the membrane of target cells, resulting in lysis of the cell; secreted by cytotoxic T cells

Tumor necrosis Activates macrophages and promotes fever (pyrogen); secreted by macrophages

factor (TNF)

Cytokines and Their Functions

*Some cytokines were named according to the laboratory test first used to identify them; however, these names rarely are a good description of the actual function of the cytokine.

Figure 22.15

Costimulation

The ﬁrstsignal required for activation of a helper T cellis the

binding ofthe MHC class II/antigen complexto the T-cell receptor.

(a)One costimulatory signal is the release bythe macrophage of

a cytokine thatbinds to a receptor on the helper T cell.

(b)Another costimulatory signal is the binding of a B7 molecule

ofthe macrophage with a CD28 molecule of the helper T cell. The

CD4 molecule ofthe helper T cell binds to the macrophage’sMHC

classII molecule and helps to hold the cellstogether.

(a)

(b)

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responding to the antigen can ﬁnd and stimulate B or effector T

cells.Second, the number of B or effector T cells increases. This is

important because it is these cells that are responsible for the im-

mune response that destroys the antigen.

1. Proliferation ofhelper T cells(ﬁgure 22.16). Antigen-presenting

cells use MHC class II molecules to present processed antigens

to helper T cells.Only the helper T cells with the T-cell

receptors that can bind to the antigen respond.These helper T

cells respond to the MHC class II/antigen complex and

costimulation by dividing.As a result, the number of helper T

cells that recognize the antigen increases.

2. Proliferation and activation ofB or effector T cells.Typically,

the proliferation and activation ofB or effector T cells

involves helper T cells.This process is illustrated in ﬁgure

22.17 for B cells,but a similar set of events occurs for effector

T cells.The clone of B cells that can recognize a particular

antigen have B-cell receptors that can bind to that antigen.B

cells use MHC class II/antigen complexes to present antigens

to the helper T cells produced in step 1.These helper T cells

stimulate the B cells to divide and produce antibodies.The

increased number ofcells, each producing antibodies, can

produce an immune response that destroys the antigens (see

“Effects ofAntibodies” on p. 796).

1. Antigen-presenting cells such

as macrophages take in,

process, and display antigens

on the cell’s surface.

2. The antigens are bound to

MHC class II molecules, which

function to present the

processed antigen to the T-cell

receptor of the helper T cell for

recognition.

3. Costimulation occurs by the

CD4 glycoprotein of the helper

T cell or by cytokines. The

macrophage secretes a

cytokine called interleukin-1.

4. Interleukin-1 stimulates the

helper T cell to secrete the

cytokine interleukin-2 and to

produce interleukin-2

receptors.

5. The helper T cell stimulates

itself to divide when

interleukin-2 binds to

interleukin-2 receptors.

6. The “daughter” helper T cells

resulting from this division can

be stimulated to divide again if

they are exposed to the same

antigen that stimulated the

“parent” helper T cell. This

greatly increases the number

of helper T cells.

7. The increased number of

helper T cells can facilitate the

activation of B cells or effector

T cells.

Macrophage

Antigen

processed

MHC class II molecule

Processed antigen

T-cell receptor

Antigen

Helper T cell

can stimulate B cells

or effector T cells

Helper T cell

Daughter

helper T cell

Daughter

helper T cell

Helper T cell

can be stimulated

to divide again

Costimulation

Interleukin-2

Interleukin-1

receptor

CD4

CD28

Interleukin-2

receptor

Interleukin-1

ProcessFigure 22.16

Proliferation ofHelper T Cells

An antigen-presenting cell(macrophage) stimulates helper T cellsto divide.

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38. What is costimulation? State two ways in which it can

happen.

39. Why are helper T cells sometimes called CD4, or T4, cells?

Whyare cytotoxic T cells sometimes called CD8, orT8, cells?

40. Describe how antigen-presenting cells stimulate an

increase in the numberof helper T cells. Why is this

important?

41. Describe how helper T cells stimulate an increase in the

numberof B or T cells. Why is this important?

Inhibition of Lymphocytes

Toleranceis a state of unresponsiveness of lymphocytes to a spe-

ciﬁc antigen.Although foreign antigens can induce tolerance, the

most important function of tolerance is to prevent the immune

system from responding to self-antigens.The need to maintain tol-

Part4 Regulationsand Maintenance792

erance and to avoid the development ofautoimmune disease is ob-

vious.Tolerance can be induced in many ways.

1. Deletion ofself-reactive lymphocytes. During prenatal

development and after birth,stem cells in red bone marrow

and the thymus give rise to immature lymphocytes that

develop into mature lymphocytes capable ofan immune

response.When immature lymphocytes are exposed to

antigens,instead of responding in ways that result in the

elimination ofthe antigen, they respond by dying. Because

immature lymphocytes are exposed to self-antigens,this

process eliminates self-reactive lymphocytes.In addition,

immature lymphocytes that escape deletion during their

development and become mature,self-reacting lympho-

cytes can still be deleted in ways that are not clearly

understood.

Before a B cell can be

activated by a helper T cell, the

B cell must process the same

antigen that activated the

helper T cell. The antigen binds

to a B-cell receptor, and both

the receptor and antigen are

taken into the cell by

endocytosis.

The B cell uses an MHC class

II molecule to present the

processed antigen to the

helper T cell.

The helper T cell responds by

releasing various interleukins

that stimulate the B cell to

divide.

The B cell divides, and the

resulting daughter cells divide,

and so on, eventually

producing many cells (only two

are shown here).

The increased number of cells

produce antibodies, which are

part of the antibody-mediated

immune system response that

eliminates the antigen.

B-cell

receptor

B cell

Helper T cell

Class II

MHC

molecule

Processed

antigen

T-cell

receptor

Unprocessed

antigen

Daughter cells

continue to divide

and produce

antibodies

Interleukins

trigger B cell

division

CD4

Daughter

B cell

Daughter

B cell

ProcessFigure 22.17

Proliferation ofB Cells

A helper T cellstimulates a B cell to divide.

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2. Preventing activation oflymphocytes. For activation of

lymphocytes to take place,two signals are usually required:

(1)the MHC/antigen complex binding with an antigen

receptor and (2)costimulation. Preventing either of these

events stops lymphocyte activation.For example, blocking,

altering,or deleting an antigen receptor prevents activation.

Anergy(an⬘er-je¯),which means “without working,”is a

condition ofinactivity in which a B or T cell does not

respond to an antigen.Anergy develops when an MHC/

antigen complex binds to an antigen receptor,and no

costimulation occurs.For example, if a T cell encounters a

self-antigen on a cell that cannot provide costimulation,the

T cell is turned off.It’s likely that only antigen-presenting

cells can provide costimulation.

Inhibiting and Stimulating Immunity

Decreasing the production or activityof cytokines can suppress the

immune system. For example, cyclosporine, a drug used to preventthe

rejection oftransplanted organs, inhibits the production of interleukin-2.

Conversely, geneticallyengineered interleukinscan be used to stimulate

the immune system. Administering interleukin-2 haspromoted the

destruction ofcancer cells in some casesby increasing the activities of

effector T cells.

3. Activation ofsuppressor T cells.Suppressor T cells are a

poorly understood group ofT cells that are deﬁned by their

ability to suppress immune responses.It’s likely that

suppressor T cells are subpopulations ofhelper T cells and

cytotoxic T cells.The suppressor (helper) T cells release

suppressive cytokines,or the suppressor (cytotoxic) T cells

kill antigen-presenting cells.

42. What is tolerance? List three ways it is accomplished.

Antibody-Mediated Immunity

Exposure ofthe body to an antigen can lead to activation of B cells

and to production of antibodies, which are responsible for de-

struction of the antigen. Because antibodies occur in body ﬂuids,

antibody-mediated immunityis effective against extracellular anti-

gens. These include bacteria, viruses, protozoans,fungi, parasites,

and toxins when they are outside cells.Antibody-mediated immunity

can also cause immediate hypersensitivity reactions (see “Clinical Fo-

cus:Immune System Problems of Clinical Signiﬁcance” on p.794).

Antibodies

Antibodies are proteins produced in response to an antigen.Large

amounts of antibodies occur in plasma,althoug h plasma also con-

tains other proteins. On the basis of protein type and associated

lipids, plasma proteins are separated into albumin and alpha-(␣),

beta-(␤),and gamma-(␥)globulin parts. As a group, antibodies are

sometimes called gamma globulins because they are mostly found

in the ␥-globulin part ofplasma. They are also called immunoglob-

ulins(Ig) because they are globulin proteins involved in immunity.

The ﬁve general classes of immunoglobulins are denoted IgG,

IgM,IgA, IgE, and IgD (table 22.5). All classes of antibodies have a

similar structure,consisting of four polypeptide chains (ﬁgure 22.18):

two identical heavy chains and two identical light chains.Each light

chain is attached to a heavy chain,and the ends of the combined

heavy and light chains form the variable region of the antibody,

which is the part that combines with the antigenic determinant ofthe

antigen.Different antibodies have different variable regions, and they

are speciﬁc for different antigens.The rest of the antibody is the con-

stant region,which is responsible for activities of antibodies like the

ability to activate complement or to attach the antibody to such cells

as macrophages,basophils, mast cells, and eosinophils. All the anti-

bodies ofa particular class have nearly the same constant regions.

Antigen-binding

sites

Heavy chain

Light chain

Complement-binding site

Site of binding to

macrophages, basophils,

and mast cells

Variable regions

of light and

heavy chains

Constant regions

of light and

heavy chains

Figure 22.18

Structure ofan Antibody

Antibodiesconsist of two heavy and two light polypeptide chains. The variable region ofthe antibody binds to the antigen. The constant region of the antibody can

activate the classicalpathway of the complementcascade. The constant region can also attach the antibody to the plasma membrane of cellssuch as

macrophages, basophils, or mastcells.

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Clinical Focus Immune System Problemsof Clinical Signiﬁcance

HypersensitivityReactions

Immune and hypersensitivity(allergy) reac-

tionsinvolve the same mechanisms, but the

differencesbetween them are unclear. Both

require exposure to an antigen and subse-

quentstimulation of antibody-mediated im-

munityor cell-mediated immunity (or both).

If immunity to an antigen is established,

later exposure to the antigen results in an

immune system response that eliminates

the antigen, and no symptoms appear. In

hypersensitivityreactions, the antigen is

called an allergen,and later exposure to the

allergen stimulatesmuch the same process

thatoccurs during the normal immune sys-

tem response. The processesthat eliminate

the allergen, however, also produce unde-

sirable side effects, such asa very strong in-

ﬂammatory reaction. This immune system

response can be more harmfulthan beneﬁ-

cial and can produce many unpleasant

symptoms. Hypersensitivity reactions are

categorized asimmediate or delayed.

Immediate Hypersensitivities

An immediate hypersensitivity reaction

occurswhen antibodies interact with aller-

gensand cause symptoms to appear within

a few minutesof exposure to the allergens.

Immediate hypersensitivity reactions in-

clude atopy, anaphylaxis, cytotoxic reac-

tions, and immune complexdisease.

Atopy (at⬘o¯-pe¯) isa localized IgE-medi-

ated hypersensitivity reaction. For example,

plantpollens can be allergens that cause hay

fever when they are inhaled and absorbed

through the respiratorymucosa. The resulting

localized inﬂammatory response produces

swelling of the mucosa and excessmucus

production. In asthma patients, allergenscan

stimulate the release ofleukotrienes and his-

tamine in the bronchiolesof the lung, caus-

ing constriction ofthe smooth muscles of the

bronchiolesand difﬁculty in breathing. Hives

(urticaria) isan allergicreaction that results in

a skin rash or localized swellingsand is usu-

allycaused by an ingested allergen.

Anaphylaxis (an⬘a˘-fı¯-lak⬘sis) is a sys-

temicIgE-mediated reaction and can be life-

threatening. Introduction ofallergens, such as

drugs(e.g., penicillin) and insectstings, is the

mostcommon cause. The chemicals released

from mastcellsand basophils cause systemic

vasodilation, a drop in blood pressure, and

cardiac failure. Symptoms of hay fever,

asthma, and hivesmay also be observed.

Incytotoxic reactions, IgG or IgM com-

bines with the antigen on the surface ofa

cell, resulting in the activation of comple-

mentand subsequent lysis of the cell. A cy-

totoxic reaction againsta bacterial cell can

be protective, butagainst a human cell itcan

be harmful. Transfusion reactionscaused by

incompatible blood types, hemolytic dis-

ease of the newborn (see chapter 19), and

some types ofautoimmune disease are ex-

amplesof harmful cytotoxic reactions.

Immune complex disease occurs

when too many immune complexes are

formed. Immune complexes are combina-

tions of soluble antigensand IgG or IgM.

When too many immune complexes are

present, too much complement is acti-

vated, and an acute inﬂammatoryresponse

develops. Complementattracts neutrophils

to the area ofinﬂammation and stimulates

the release oflysosomal enzymes. This re-

lease causes tissue damage, especiallyin

small blood vessels, where the immune

complexestend to lodge; and lack of blood

supplycauses tissue necrosis. Arthus reac-

tions, serum sickness, some autoimmune

diseases, and chronicgraft rejection are ex-

amplesof immune complex diseases.

An Arthus reaction isa localized im-

mune complexreaction. For example, sup-

pose an individual hasbeen sensitized to

antigens in the tetanustoxoid vaccine be-

cause ofrepeated vaccinations. If that indi-

vidual were vaccinated again, large

amountsof antigen in the vaccine would be

present at the injection site. Antibodies

could complexwith the antigens, causing a

localized inﬂammatory response, neu-

trophilinﬁltration, and tissue necrosis.

Serum sickness is a systemicArthus

reaction in which the antibody–antigen

complexescirculate and lodge in many dif-

ferenttissues. Serum sickness can develop

from prolonged exposure to an antigen,

which providesenough time for an antibody

response and the formation of many im-

mune complexes. Examplesof antigens in-

clude long-lasting drugsand proteins found

in the serum used for achieving passive ar-

tiﬁcial immunity. Symptomsinclude fever,

swollen lymph nodes and spleen, and

arthritis. Symptomsof anaphylaxis, such as

hives, mayalso be present because IgE in-

volvement is a part of serum sickness. If

large numbersof the circulating antibody–

antigen complexes are removed from the

blood by the kidney, immune complex

glomerulonephritis can develop, in which

kidneyblood vessels are destroyed and the

kidneysfail to function.

Delayed Hypersensitivity

Delayed hypersensitivityis mediated by T

cells, and symptoms usually take several

hours or days to develop. Like immediate

hypersensitivity, delayed hypersensitivityis

an acute extension ofthe normal operation

ofthe immune system. Exposure to the al-

lergen causesactivation of T cells and the

production of cytokines. The cytokinesat-

tract basophils and monocytes, which dif-

ferentiate into macrophages. The activities

of these cells result in progressive tissue

destruction, lossof function, and scarring.

Delayed hypersensitivity can develop

as allergy of infection and contacthyper-

sensitivity. Allergyof infection is a side ef-

fect of cell-mediated efforts to eliminate

intracellular microorganisms, and the

amount of tissue destroyed isdetermined

by the persistence and distribution ofthe

antigen. The minor rash ofmeasles results

from tissue damage ascell-mediated immu-

nitydestroys virus-infected cells.

In patientswith chronic infections with

long-term antigenicstimulation, the allergy-

of-infection response can cause extensive

tissue damage. The destruction oflung tis-

sue in tuberculosisis an example.

Contacthypersensitivity is a delayed

hypersensitivity reaction to allergensthat

contact the skin or mucous membranes.

Poison ivy, poison oak, soaps, cosmetics,

drugs, and a variety of chemicals can

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induce contacthypersensitivity, usually af-

ter prolonged exposure. The allergen isab-

sorbed byepithelial cells, and T cellsinvade

the affected area, causing inﬂammation

and tissue destruction. Although itching

can be intense, scratching isharmful be-

cause itdamages tissues and causes addi-

tionalinﬂammation.

Autoimmune Diseases

Inautoimmune disease, the immune system

fails to differentiate between self-antigens

and foreign antigens. Consequently, an im-

mune system response isproduced against

some self-antigens, resulting in tissue de-

struction. In manyinstances, autoimmunity

probablyresults from a breakdown of toler-

ance, which normallyprevents an immune

system response to self-antigens. In a situ-

ation called molecular mimicry, a foreign

antigen thatis very similar to a self-antigen

stimulatesan immune system response. Af-

ter the foreign antigen iseliminated, the im-

mune system continues to actagainst the

self-antigen. It’shypothesized thattype I di-

abetes (see chapter 18) develops in this

fashion. In susceptible people, a foreign

antigen can stimulate adaptive immunity,

especially cell-mediated immunity, which

destroysthe insulin-producing beta cells of

the pancreas. Other autoimmune diseases

that involve antibodies are rheumatoid

arthritis, rheumatic fever, Graves’ disease,

systemic lupus erythematosus, and myas-

thenia gravis.

Immunodeﬁciencies

Immunodeﬁciencyis a failure of some part

ofthe immune system to function properly.

A deﬁcient immune system isnot uncom-

mon because itcan have many causes. In-

adequate protein in the dietinhibits protein

synthesis, therebyallowing antibody levels

to decrease. Stress can depress the im-

mune system, and ﬁghting an infection can

deplete lymphocyte and granulocyte re-

servesand make a person more susceptible

to further infection. Diseases that cause

proliferation of lymphocytes, such as

mononucleosis, leukemias, and myelomas,

can resultin an abundance of lymphocytes

thatdon’t function properly. Finally, the im-

mune system can purposefully be sup-

pressed bydrugs to prevent graft rejection.

Congenital (present atbir th) immuno-

deﬁciencies can involve inadequate B-cell

formation, inadequate T-cell formation, or

both. Severe combined immunodeﬁciency

disease (SCID)in which both B and T cellsfail

to differentiate, although rare, isprobably the

bestknown. Unless the person suffering from

SCID iskept in a sterile environment or ispro-

vided with a compatible bone marrow trans-

plant, death from infection results.

Tumor Control

Tumor cellshave tumor antigensthat distin-

guish them from normalcells. According to

the concept of immune surveillance,the

immune system detectstumor cells and de-

stroysthem before a tumor can form. T cells,

naturalkiller cells, and macrophagesare in-

volved in the destruction oftumor cells. Im-

mune surveillance mayexist for some forms

of cancer caused byviruses. The immune

response appears to be directed more

againstthe viruses, however, than against

tumors in general. Only a few cancersare

known to be caused byviruses in humans.

For most tumors, the response of the im-

mune system may be ineffective and too

late.

Transplantation

Genesthat code for the production of MHC

moleculesare generally called major histo-

compatibilitycomplex genes. Histocompat-

ibilityrefers to the ability of tissues (Greek,

histo) to getalong (compatibility) when tis-

sues are transplanted from one individual

to another. In humans, the major histocom-

patibility complexgenes are often referred

to as human leukocyte antigen (HLA)

genesbecause they were ﬁrst identiﬁed in

leukocytes. The HLA genescontrol the pro-

duction ofHLAs, also called MHC antigens,

which are inserted onto the surface ofcells.

The immune system can distinguish be-

tween self-cells and foreign cellsbecause

theyare both marked with HLAs. Rejection

ofa transplanted tissue is caused by a nor-

malimmune system response to the foreign

HLAs. Millionsof possible combinations of

the HLA genes exist, and it’s very rare for

two individuals (exceptidentical twins) to

have the same set ofHLA genes. Because

they are genetically determined, however,

the closer the relationship between two in-

dividuals, the greater the likelihood ofshar-

ing the same HLA genes.

Acute rejection of a graftoccurs sev-

eralweeks after transplantation and results

from a delayed hypersensitivity reaction

and cell lysis. Lymphocytes and

macrophagesinﬁltrate the area, a strong in-

ﬂammatory response occurs, and the for-

eign tissue is destroyed. If acute rejection

doesn’tdevelop, chronic rejection may oc-

cur ata later time. In chronic rejection, im-

mune complexes form in the arteries

supplying the graft, blood supplyfails, and

the graftis rejected.

Graftrejection can occur in two different

directions. In host-versus-graftrejection,

the recipient’s immune system recognizes

the donor’stissue as foreign and rejects the

transplant. In a graft-versus-hostrejection,

the donor tissue recognizesthe recipient’s

tissue asforeign, and the transplant rejects

the recipient, causing destruction ofthe re-

cipient’stissues, and death.

To reduce graft rejection, a tissue

match isperformed. Only tissues with HLAs

similar to the recipient’s have a chance of

acceptance. Even when the match isclose,

immunosuppressive drugsmust be admin-

istered throughoutthe person’s life to pre-

vent rejection. Unfortunately, the person

then has a drug-produced immunodeﬁ-

ciencyand is more susceptible to infections.

An exact match ispossible only for a graft

from one part to another part of the same

person’sbody or between identical twins.

HLAsare important in ways in addition

to organ transplants. Because theyare ge-

netically determined, characterization of

HLAs can help resolve paternity suits. In

forensic medicine, the HLAs in blood, se-

men, and other tissues help identify the

person from whom the tissue came.

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Usesof Monoclonal Antibodies

Each type ofmonoclonal antibody is a pure antibody preparation thatis

speciﬁcfor only one antigen. When the antigen is injected into a

laboratoryanimal, it activates a B-cell clone againstthe antigen. The B

cellsare removed from the animal and fused with tumor cells. The

resulting hybridoma cellshave two ideal characteristics: theydivide to

form large numbersof cells, and the cells ofa given clone produce only

one kind ofantibody.

Monoclonalantibodies are used for determining pregnancy and

for diagnosing diseaseslike gonorrhea, syphilis, hepatitis, rabies, and

cancer. These testsare speciﬁc and rapid because the monoclonal

antibodiesbind only to the antigen being tested. Monoclonal antibodies

maysomeday be used to effectively treat cancer by delivering drugsto

cancer cells(see “Immunotherapy” on p. 800).

Effectsof Antibodies

Antibodies can directly affect antigens in two ways.The antibody

can bind to the antigenic determinant and interfere with the ability

of the antigen to function (ﬁgure 22.19a).Alternatively, the anti-

body can combine with an antigenic determinant on two different

antigens, rendering the antigens ineffective (ﬁgure 22.19b).The

ability of antibodies to join antigens together is the basis for many

clinical tests,such as blood typing, because, when enough antigens

are bound together,they become visible as a clump or a precipitate.

Although antibodies can directly affect antigens, most of

their effectiveness results from other mechanisms.When an anti-

body (IgG or IgM) combines with an antigen through the variable

region, the constant region can activate the complement cascade

Part4 Regulationsand Maintenance796

through the classical pathway (ﬁgure 22.9c).Activated complement

stimulates inﬂammation; attracts neutrophils, monocytes,

macrophages,and eosinophils to sites of infection; and kills bacte-

ria by lysis.

Antibodies (IgE) can initiate an inﬂammatory response (ﬁg-

ure 22.9d).The antibodies attach to mast cells or basophils through

their constant region.When antigens combine with the variable re-

gion ofthe antibodies, the mast cells or basophils release chemicals

through exocytosis,and inﬂammation results.

Opsonins(op⬘so˘-ninz) are substances that make an antigen

more susceptible to phagocytosis.An antibody (IgG) acts as an op-

sonin by connecting to an antigen through the variable region of

the antibody and to a macrophage through the constant region of

the antibody. The macrophage then phagocytizes the antigen

andthe antibody (ﬁgure 22.19e).

AntibodyProduction

The production ofantibodies after the ﬁrst exposure to an antigen

is different from that after a second or subsequent exposure.The

primary response results from the ﬁrst exposure of a B cell to an

antigen for which it is speciﬁc and includes a series ofcell divisions,

cell differentiation,and antibody production. The B-cell receptors

on the surface ofB cells are antibodies, usually IgM and IgD.The re-

ceptors have the same variable region as the antibodies that are

eventually produced by the B cell.Before stimulation by an antigen,

B cells are small lymphocytes.After activation, the B cells undergo a

series ofdiv isions to produce large lymphocytes.Some of these en-

larged cells become plasma cells, which produce antibodies, and

others revert back to small lymphocytes and become memory B

Table 22.5

TotalSerum

Antibody Antibody (%) Structure Description

IgG 80–85 Activates complement and functions as an opsonin to increase

phagocytosis; can cross the placenta and provide immune

protection to the fetus and newborn; responsible for Rh

reactions, such as hemolytic disease of the newborn

IgM 5–10 Activates complement and acts as an antigen-binding receptor on

the surface of B cells; responsible for transfusion reactions in

the ABO blood system; often the first antibody produced in

response to an antigen

IgA 15 Secreted into saliva, tears, and onto mucous membranes to

provide protection on body surfaces; found in colostrum and

milk to provide immune protection to the newborn

IgE 0.002 Binds to mast cells and basophils and stimulates the inflammatory

response

IgD 0.2 Functions as antigen-binding receptors on B cells

Classes of Antibodies and Their Functions

IgG

IgA

IgM

Heavy chain

Light chain

IgE

IgD

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(a)Inactivates the antigen. An antibody binds

to an antigen and inactivates it.

(b)Binds antigens together. Antibodies bind

several antigens together.

(c)Activates the complement cascade. An

antigen binds to an antibody. As a result,

the antibody can activate complement

proteins, which can produce inflammation,

chemotaxis, and lysis.

(d)Initiates the release of inflammatory

chemicals. An antibody binds to a mast

cell or basophil. When an antigen binds to

the antibody, it triggers a release of

chemicals that cause inflammation.

(e)Facilitates phagocytosis. An antibody

binds to an antigen and then to a

macrophage, which phagocytizes the

antibody and antigen.

Complement

cascade

activated

Inflammation

Chemotaxis

Lysis

Inflammation

Chemicals

Mast cell or basophil

Macrophage

Antigen

Antibody

Figure 22.19

Actionsof Antibodies

Antibodiescan inactivate antigens, promote phagocytosis(binding antigens together or opsonization), and cause inﬂammation (release of chemicals from mast

cellsor basophils and activation of the complement cascade).

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cells (ﬁgure 22.20). Usually, IgM is the ﬁrst antibody produced in

response to an antigen,but later other classes of antibodies are pro-

duced as well.The primar y response normally takes 3–14 days to

produce enough antibodies to be effective against the antigen.In the

meantime, the individual usually develops disease symptoms be-

cause the antigen has had time to cause tissue damage.

The secondary, or memory,response occurs when the im-

mune system is exposed to an antigen against which it has already

produced a primary response.The secondar y response results from

memory B cells, which rapidly divide to produce plasma cells and

large amounts ofantibody when exposed to the antigen. The second-

ary response provides better protection than the primary response for

two reasons.First, the time required to start producing antibodies is

less (hours to a few days);and second, the amount of antibody pro-

Part4 Regulationsand Maintenance798

duced is much larger.As a consequence, the antigen is quickly de-

stroyed,no disease symptoms develop, and the person is immune.

The memory response also includes the formation of new

memory B cells,which provide protection against additional expo-

sures to the antigen.Memory B cells are the basis for adaptive im-

munity. After destruction of the antigen, plasma cells die,the

antibodies they released are degraded,and antibody levels decline

to the point at which they can no longer provide adequate protec-

tion.Memory B cells may persist for many years and probably for

life in some cases. If memory cell production is not stimulated,

however,or if the memory B cells produced are short-lived,re-

peated infections ofthe same disease are possible. For example, the

same cold virus can cause the common cold more than once in the

same person.

First

exposure

Second

exposure

Shorter

response

time

Longer

response

time

Magnitude

of response

B cell

Fewer

plasma

cells

Memory

B cells

Memory

B cells

plasma

cells

memory

B cells

Secondary

response

antibodies

Primary

response

Fewer

antibodies

Primary response. The primary response occurs

when a B cell is first activated by an antigen. The

B cell proliferates to form plasma cells and

memory cells. The plasma cells produce

antibodies.

Secondary response. The secondary response

occurs when another exposure to the same antigen

causes the memory cells to rapidly form plasma

cells and additional memory cells. The secondary

response is faster and produces more antibodies

than the primary response.

ProcessFigure 22.20

AntibodyProduction

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43. What type of lymphocyte is responsible for antibody-

mediated immunity? Whatare the functions of antibody-

mediated immunity?

44. What are the functions of the constant and variable regions

of an antibody? Listthe ﬁve classes of antibodies, and state

theirfunctions.

45. Describe the different ways that antibodies participate in

the destruction of antigens.

46. What are plasma cells and memory cells, and what are their

functions?

47. What are the primary and secondary antibody responses?

Whydoesn’t the primary response prevent illness but the

secondaryresponse does?

PREDICT

One theoryfor long-lasting immunity assumes that humansare

continuallyexposed to the disease-causing agent. Explain how this

exposure could produce lifelong immunity.

Cell-Mediated Immunity

Cell-mediated immunity is a function ofT cells and is most effective

against intracellular microorganisms,such as viruses, fungi, intracel-

lular bacteria, and parasites.Delayed hypersensitivity reactions and

control oftumors also involve cell-mediated immunity (see “Clinical

Focus:Immune System Problems of Clinical Signiﬁcance”on p. 794).

Activation of T cells to antigens is regulated by antigen-

presenting cells and helper T cells.Once activated, T cells undergo

a series of divisions and produce effector T cells,such as cytotoxic

T cells,and memory T cells (ﬁgure 22.21). Effector T cells are re-

sponsible for the cell-mediated immunity response. Memory T

cells can provide a secondary response and long-lasting immunity

in the same fashion as memory B cells.

CytotoxicT Cells

Cytotoxic T cells have two main effects: they lyse cells and they

produce cytokines. Cytotoxic T cells can come into contact with

other cells and cause them to lyse.Virus-infected cells have viral

antigens, tumor cells have tumor antigens,and tissue transplants

have foreign antigens on their surfaces that can stimulate cytotoxic

T-cell activity.A cytotoxic T cell binds to a target cell and releases

chemicals that cause the target cell to lyse.The major method of ly-

sis involves a protein called perforin,which forms a pore in the

membrane ofthe target cell. The cytotoxic T cell then moves on to

destroy additional target cells.

In addition to lysing cells,cytotoxic T cells release cytokines

that activate additional components ofthe immune system. For ex-

ample,one important function of cytokines is the recruitment of

cells like macrophages.These cells are then responsible for phago-

cytosis and inﬂammation.

PREDICT

In patientswith acquired immunodeﬁciency syndrome (AIDS), helper T

cellsare destroyed by a viral infection. The patientscan die of

pneumonia caused byan intracellular fungus (Pneumocystiscarinii) or

from Kaposi’ssarcoma, which consistsof tumorous growths in the

skin and lymph nodes. Explain whatis happening.

Delayed HypersensitivityT Cells

Delayed hypersensitivity T cellsrespond to antigens by releasing

cytokines. Consequently,they promote phagocytosis and inﬂam-

mation, especially in allergic reactions (see “Clinical Focus:Im-

mune System Problems of Clinical Signiﬁcance”on p. 794). For

example,poison ivy antigens can be processed by Langerhans’ cells

in the skin,which present the antigen to delayed hypersensitivity

Tcells, resulting in an intense inﬂammatory response.

Activation of

T cell by antigen

on the surface of

a cell

T cell

Cytotoxic

T cells

Release

cytokines

Memory T cells

Contact

killing

Inflammation

Phagocytosis

Activate T cells

Lysis of

target cell

Target cell

Cytotoxic T cell

Figure 22.21

Stimulation and Effectsof T Cells

When T cellsare presented with a processed antigen, theycan form memory T and cytotoxic T cells. Memory T cells are responsible for the secondary response, and

cytotoxicT cells cause contactkilling or release cytokines that promote the destruction of the antigen.

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48. What type of lymphocyte is responsible for cell-mediated

immunity? Whatare the functions of cell-mediated

immunity?

49. State the two main responses of cytotoxic T cells.

50. What kind of immune response is produce by delayed

hypersensitivityT cells?

51. How is long-lasting immunity achieved in cell-mediated

immunity?

Immune Interactions

Objective

■ Describe immune interactions.

Although the immune system can be described in terms of

innate, antibody-mediated, and cell-mediated immunity,only

one immune system really exists. These categories are an arti-

ficial division that is used to emphasize particular aspects of

immunity. Actually,immune system responses often involve

components of more than one type of immunity (ﬁgure 22.22).

For example, although adaptive immunity can recognize and

remember specific antigens, once recognition has occurred,

many of the events that lead to the destruction of the antigen

are innate immunity activities, such as inflammation and

phagocytosis.

52. Describe how interactions between innate, antibody-

mediated, and cell-mediated immunitycan eliminate an

antigen.

Immunotherapy

Objective

■ Deﬁne and give examplesof immunotherapy.

Knowledge ofthe basic ways that the immune system oper-

ates has produced two fundamental beneﬁts:(1) an understanding

of the cause and progression of many diseases, and (2) the devel-

opment or proposed development ofeffective methods to prevent,

stop,or even reverse diseases.

Immunotherapy treats disease by altering immune system

function or by directly attacking harmful cells.Some approaches

attempt to boost immune system function in general.For example,

administering cytokines or other agents can promote inﬂamma-

tion and the activation ofimmune cells, which can help in the de-

struction of tumor cells.On the other hand, sometimes inhibiting

the immune system is helpful.For example, multiple sclerosis is an

autoimmune disease in which the immune system treats self-

antigens as foreign antigens, thereby destroying the myelin that

covers axons. Interferon beta (IFN␤) blocks the expression of

MHC molecules that display self-antigens and is now being used to

treat multiple sclerosis.

Part4 Regulationsand Maintenance800

Some immunotherapy takes a more speciﬁc approach.For

example, vaccination can prevent many diseases (see section on

“Acquired Immunity”on p. 804). The ability to produce mono-

clonal antibodies may result in therapies that are effective for treat-

ing tumors.If an antigen unique to tumor cells can be found, then

monoclonal antibodies could be used to deliver radioactive iso-

topes,drugs, toxins, enzymes, or cytokines that can kill the tumor

cell or can activate the immune system to kill the cell.Unfortu-

nately,no antigen on tumor cells has been found that is not also

found on normal cells.Nonetheless, this approach may be useful if

damage to normal cells is minimal.For example, tumor cells may

have more surface antigens ofa particular ty pe than normal cells,

resulting in greater treatment delivery.Tumor cells may also be

more susceptible to damage,or normal cells may be better able to

recover from the treatment.

One problem with monoclonal antibody delivery systems is

that the immune system recognizes the monoclonal antibody as a

foreign antigen. After the ﬁrst exposure, a memory response

quickly destroys the monoclonal antibodies, rendering the treat-

ment ineffective. In a process called humanization, the mono-

clonal antibodies are modiﬁed to resemble human antibodies.This

approach has allowed monoclonal antibodies to sneak past the im-

mune system.

The use of monoclonal antibodies to treat tumors is mostly

in the research stage of development, but a few clinical trials are

now yielding promising results. For example,monoclonal anti-

bodies with radioactive iodine (

131

I) have caused regression ofB-

cell lymphomas and produced few side effects.Herceptin is a mon-

clonal antibody that binds to a growth factor that is overexpressed

in 25%–30% of primary breast cancers. The antibodies serve to

“tag”cancer cells, which are then lysed by natural killer cells. Her-

ceptin slows disease progression and increases survival time, but

it’s not a cure for breast cancer.

Many other approaches for immunotherapy are being stud-

ied,and the development of t reatments that use the immune sys-

tem are certain to increase in the future.Your knowledge of the

immune system will enable you to understand and appreciate these

therapies.

53. What is immunotherapy? Give examples.

Neuroendocrine Regulation ofImmunity

An intriguing possibilityfor reducing the severity of diseases or even

curing them isto use neuroendocrine regulation of immunity. The

nervoussystem regulates the secretion of hormones, such as cortisol,

epinephrine, endorphins, and enkephalins, for which lymphocyteshave

receptors. For example, cortisolreleased during times of stress inhibits

the immune system. In addition, mostlymphatic tissues, including some

individuallymphocytes, receive sympathetic innervation. That a

neuroendocrine connection existswith the immune system isclear. The

question we need to answer is: Can we use thisconnection to control our

own immunotherapy?

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Chapter 22 LymphaticSystem and Immunity 801

Innate Immunity

General response that

does not improve with

subsequent exposure

Mechanical

mechanisms

Neutrophils, macrophages,

basophils, and eosinophils

Inflammation and phagocytosis

cause destruction of the antigen

Macrophage presents

processed antigen to

helper T cell

Macrophage

Antigen

Helper T cell

Helper T cell Helper T cell

B cell

Plasma cell

Antibodies Cytokines

Direct effects

against antigen

Lysis of cells

expressing antigen

Memory B cell Memory T cell

T cell

B cell proliferates

and differentiates

T cell proliferates

and differentiates

Helper T cell proliferates and

secretes cytokines

Cytokines and antibodies

enhance inflammation

and phagocytosis

Chemical

mediators

Interferons prevent

viral infections

Adaptive Immunity

Specific response that

improves with

subsequent exposure

Begins with a

macrophage presenting

an antigen to a helper

T cell

Antibody-mediated immunity

Antibodies act against antigens in solution

or on the surfaces of extracellular

microorganisms.

Cell-mediated immunity

Effector T cells act against antigens bound to MHC

molecules on the surface of cells; effective against

intracellular microorganisms, tumors, and

transplanted cells.

Helper T cell

can activate

a B cell

Responsible

for adaptive immunity

Effector T cell

Helper T cell

can activate a

T cell

Figure 22.22

The Major Interactionsand Responses of Innate and Adaptive Immunity to an Antigen

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Clinical Focus Acquired ImmunodeﬁciencySyndrome

Acquired immunodeﬁciency syndrome

(AIDS)is a life-threatening disease caused

by the human immunodeﬁciency virus

(HIV). Two strains of HIV are recognized:

HIV-1 isresponsible for most cases of AIDS,

whereas HIV-2 isincreasingly being found

in West Africa. AIDSwas ﬁrst reported in

1981 in the United States. Since then, over

800,000 cases have been reported in the

United States to the Centers for Disease

Control and Prevention (CDC). The United

Nations Program on AIDS (UNAIDS) esti-

matesthat 60 million people have been in-

fected by HIV worldwide, and 18 million

have died. The course of HIV infection

varies. After contracting HIV, some people

die within a year; most, however, survive for

10 or 11 years, and some have survived be-

yond 20 years.

HIVis transmitted from an infected to a

noninfected person in bodyﬂuids, such as

blood, semen, or vaginal secretions. The

major methods of transmission are unpro-

tected intimate sexual contact, contami-

nated needles used by intravenous drug

users, tainted blood products, and from a

pregnant woman to her fetus. Present evi-

dence indicatesthat household, school, or

workcontacts do not result in transmission.

In the United States, most cases of

AIDSduring the 1980s occurred in homo-

sexualor bisexual men and in intravenous

drug users. A small percentage of cases

have resulted from transfusions or con-

taminated clotting factors used byhemo-

philiacs. Children can be infected before

birth, during delivery, or after birth from

breast- feeding. A few casesof AIDS have

occurred in health-care workersacciden-

tally exposed to HIV-infected blood or

body fluids, and even fewer cases of

health-care workers infecting patients

have been documented. The mostrapidly

increasing group of AIDS patientsin the

United States is heterosexual women or

men who have had sexualcontact with an

infected person. In other countriesthe pat-

tern ofAIDS cases is different from that in

the United States. UNAIDSestimates that

over 90% ofall HIV infections globally are

transmitted heterosexually.

Preventing transmission of HIV is

presentlythe only way to prevent AIDS. The

riskof transmission can be reduced by ed-

ucating the public about relatively safe

sexual practices, such as reducing the

number ofone’s sexual partners, avoiding

analintercourse, and using condoms. Pub-

liceducation also includes warnings to in-

travenous drug users of the dangers of

usingcontaminated needles. Ensuring the

safety of the blood supply isanother im-

portant preventive measure. In 1985, a

test for HIV antibodies in blood became

available. Heat treatment ofclotting fac-

torstaken from blood has also been effec-

tive in preventing transmission of HIV to

hemophiliacs.

HIVinfection begins when a protein on

the surface ofthe virus, called gp120, binds

to a CD4 molecule on the surface ofa cell.

The CD4 molecule is found primarily on

helper T cells, and it normally enables

helper T cellsto adhere to other lympho-

cytes, for example, during the process of

antigen presentation. Certain monocytes,

macrophages, neurons, and neuroglialcells

also have CD4 molecules. Once attached to

the CD4 molecules, the virusinjects its ge-

netic material(RNA) and enzymes into the

cell and beginsto replicate. Copies of the

virusare manufactured using the organelles

and materials within the cell. Replicated

viruses escape from the cell and infect

other cells.

Following infection by HIV, within

3 weeks to 3 months, many patients de-

velop mononuculeosis-like symptoms,

such asfever, sweats, fatigue, muscle and

joint aches, headache, sore throat, diar-

rhea, rash, and swollen lymph nodes.

Within 1–3 weeks, these symptomsdisap-

pear asthe immune system responds to the

virus byproducing antibodies and activat-

ing cytotoxic T cells thatkill HIV-infected

cells. The immune system is not able to

completelyeliminate HIV, however, and by

about 6 months a kind of “set point” is

achieved in which the virus continuesto

replicate at a low, but steady, rate. This

chronicstage of infection lasts, on the aver-

age, for 8–10 years, and the infected per-

son feels good and exhibits few, if any,

symptoms.

Although helper T cells are infected

and destroyed during the chronic stage of

HIVinfection, the body responds by produc-

ing large numbers of helper T cells.

Nonetheless, over a period ofyears the HIV

numbers gradually increase and helper T

cell numbers decrease. Normallyapproxi-

mately1200 helper T cells are present per

cubic millimeter of blood. An HIV-infected

person is considered to have AIDS when

one or more ofthe following conditions ap-

pear: the helper T cellcount fallsbelow 200

cells/mm

, an opportunistic infection oc-

curs, or Kaposi’ssarcoma develops.

Opportunisticinfections involve organ-

ismsthat normally don’t cause disease but

can do so when the immune system isde-

pressed. Withouthelper T cells, cytotoxic T-

and B-cell activation is impaired, and

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adaptive resistance issuppressed. Exam-

ples of opportunistic infections include

pneumocystis (noo-mo¯-sis⬘tis) pneumonia

(caused by an intracellular fungus, Pneu-

mocystis carinii), tuberculosis (caused by

an intracellular bacterium, Myocobacterium

tuberculosis), syphilis(caused bya sexually

transmitted bacterium, Treponema palli-

dum), candidiasis (kan-di-dı¯⬘a˘-sis; a yeast

infection ofthe mouth or vagina caused by

Candida albicans), and protozoans that

cause severe, persistentdiarrhea. Kaposi’s

sarcoma isa type of cancer that produces

lesionsin the skin, lymph nodes, and vis-

ceralorgans. Also associated with AIDS are

symptomsresulting from the effects of HIV

on the nervoussystem, including motor re-

tardation, behavioralchanges, progressive

dementia, and possiblypsychosis.

No cure for AIDShas yet been discov-

ered. Management ofAIDS can be divided

into two categories: (1) managementofsec-

ondary infections or malignancies associ-

ated with AIDSand (2) treatment of HIV. In

order for HIV to replicate, the viralRNA is

used to make viralDNA, which is inserted

into the host cell’sDNA. The inserted viral

DNA directsthe production of new viral RNA

and proteins, which are assembled to form

new HIV. Keysteps in the replication of HIV

require viral enzymes. Reverse transcrip-

tase promotes the formation of viral DNA

from viral RNA, and integrase (in⬘te-gra¯s)

inserts the viral DNA into the host cell’s

DNA. A viral protease (pro¯⬘te¯-a¯s) breaks

large viral proteins into smaller proteins,

which are incorporated into the new HIV.

Blocking the activity of HIV enzymes

can inhibitreplication of HIV. The ﬁrsteffec-

tive treatment of AIDS was the drug azi-

dothymidine (AZT) (az⬘i-do¯-thı¯⬘mi-de¯n),

also called zidovudine (zı¯-do¯⬘voo-de¯n). AZT

isa reverse transcriptase inhibitor,which

preventsHIV RNA from producing viral DNA.

AZT can delaythe onset of AIDS but doesn’t

appear to increase the survivaltime of AIDS

patients. However, the number of babies

who contract AIDSfrom their HIV-infected

mothers can be dramatically reduced by

giving AZT to the mothersduring pregnancy

and to the babies following birth. AZT can

produce serious side effects such asane-

mia or even totalbone marrow failure.

Often after 6–18 monthsof treatment

with AZT, viralmutations result in HIV that

are resistantto AZT. Other drugs that inhibit

viral nucleic acid replication, such as

dideoxyinosine (DDI) (dı¯⬘de¯-oks-e¯-ı¯⬘no¯-se¯n),

have been developed. These drugs have

been used for patientswho are resistant to,

or do notrespond to, AZT.

Proteaseinhibitors are drugsthat in-

terfere with viral proteases. Examples of

protease inhibitors are ritonavir and indi-

navir. The currenttreatment for suppressing

HIV replication is a combination of three

drugs, such astwo reverse transcriptase in-

hibitorsand one protease inhibitor. It’s less

likelythat HIV will develop resistance to all

three drugs. This strategy hasproven very

effective in reducing the death rate from

AIDSand partially restoring health in some

individuals.

Stillin the research stage are integrase

inhibitors,which prevent the insertion of vi-

ral DNA into the host cell’sDNA . Perhaps

somedayintegrase inhibitors will be part of

a combination drug therapyfor AIDS.

Another advance in AIDStreatment is a

test for measuring viral load, which mea-

suresthe number of viral RNA molecules in

a milliliter ofblood. The actuallevel of HIV is

one-half the RNA count because each HIV

has two RNA strands. Viralload is a good

predictor ofhow soon a person will develop

AIDS. Ifviral load is high, the onset of AIDS

ismuch sooner than if it islow. It’s also pos-

sible to detect developing viralresistance

byan increase in viral load. In response, a

change in drug dose or type mayslow viral

replication. Current treatment guidelines

are to keep viralload below 500 RNA mole-

culesper milliliter of blood.

An effective treatmentfor AIDS is not a

cure. Even ifviralload decreases to the point

thatthe virus is undetected in the blood, the

virus still remains in cellsthroughout the

body. It’spossible that the virus willeventu-

allymutate and escape drug suppression. In

addition, the long-term effectsof these drug

therapiesare unknown.

The long-term goal for dealing with

AIDSis to develop a vaccine that prevents

HIVinfection. Vaccines under development

stimulate the production of antibodies

against HIV, stimulate a cell-mediated re-

sponse againstHIV-infected cells, or both.

In June 1998, the ﬁrstlarge-scale testing of

a vaccine thatstimulates antibody produc-

tion againstHIV gp120 protein began in the

United States, Canada, and Thailand.

Because of improved treatment, peo-

ple with HIV/AIDS can now live for many

years. HIV/AIDSis, therefore, being viewed

increasinglyas a chronic disease, not as a

death sentence. A multidisciplinary team

that includes occupational therapists,

physical therapists, nutritionists/dieti-

cians, psychologists, infectious disease

physicians, and otherscan work together to

manage patients with HIV/AIDS to help

them have a better qualityof life.

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Acquired Immunity

Objective

■ Describe the waysin which adaptive immunity can be

acquired.

It’s possible to acquire adaptive immunity in four ways:ac-

tive natural,active artificial, passive natural, and passive artifi-

cial immunity (figure 22.23). The terms natural and artificial

refer to the method of exposure.Natural exposure implies that

contact with an antigen or antibody occurs as part of everyday

living and is not deliberate. Artificial exposure,also called im-

munization, is a deliberate introduction of an antigen or anti-

body into the body.

The terms activeand passive indicate whether or not an indi-

vidual’s immune system is directly responding to the antigen.

When an individual is naturally or artiﬁcially exposed to an anti-

gen,an adaptive immune system response can occur that produces

antibodies.This is called active immunity because the individual’s

own immune system is the cause ofthe immunity. Passive immu-

nity occurs when another person or animal develops antibodies

and the antibodies are transferred to a nonimmune individual.

This is called passive immunity because the nonimmune individ-

ual didn’t produce the antibodies.

How long the immunity lasts differs for active and passive

immunity.Active immunity can persist for a few weeks (common

cold) to a lifetime (whooping cough and chickenpox).Immunity

can be long lasting if enough B or T memory cells are produced

and persist to respond to later antigen exposure.Passive immunity

is not long lasting because the individual doesn’t produce his or her

own memory cells. Because active immunity can last longer than

passive immunity,it’s the preferred method. Passive immunity is

preferred,however, in some situations when immediate protection

is needed.

Part4 Regulationsand Maintenance804

Active NaturalImmunity

Natural exposure to an antigen,such as a disease-causing microor-

ganism, can cause an individual’s immune system to mount an

adaptive immune system response against the antigen and achieve

active natural immunity. Because the individual is not immune

during the ﬁrst exposure,he or she usually develops the symptoms of

the disease.Interestingly, exposure to an antigen doesn’t always pro-

duce symptoms.Many people, if exposed to the poliomyelitis virus

at an early age,have an immune system response and produce po-

liomyelitis antibodies,yet they don’t exhibit any disease symptoms.

Active ArtiﬁcialImmunity

In active artiﬁcial immunity, an antigen is deliberately intro-

duced into an individual to stimulate the immune system. This

process is vaccination,and the introduced antigen is a vaccine. In-

jection of the vaccine is the usual mode of administration. Exam-

ples of injected vaccinations are the DTP injection against

diphtheria, tetanus, and pertussis (whooping cough); and the

MMR injection against mumps, measles, and rubella (German

measles). Sometimes the vaccine is ingested, as in the oral po-

liomyelitis vaccine (OPV).

The vaccine usually consists ofsome part of a microorganism,

a dead microorganism,or a live, altered microorganism.The antigen

has been changed so that it will stimulate an immune response but

will not cause the symptoms of disease.Because active artiﬁcial im-

munity produces long-lasting immunity without disease symptoms,

it’s the preferred method ofacquiring adaptive immunity.

PREDICT

In some cases, a booster shotis used as part of a vaccination

procedure. A booster shotis another dose of the original vaccine given

some time after the originaldose was administered. Why are booster

shotsgiven?

Acquired adaptive

immunity

Active immunity

The individual’s own immune system

is the cause of the immunity.

Passive immunity

Immunity is transferred from another

person or an animal.

Artificial

Antibodies produced by

another person or an

animal are injected.

Natural

Antibodies from the mother

are transferred to her child

across the placenta or in milk.

Artificial

Antigens are

deliberately introduced

in a vaccine.

Natural

Antigens are introduced

through natural

exposure.

Figure 22.23

Waysto Acquire Adaptive Immunity

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Chapter 22 LymphaticSystem and Immunity 805

Passive Natural Immunity

Passive natural immunity results from the transfer of antibodies

from a mother to her child across the placenta before birth.During

her life,the mother has been exposed to many antigens, either natu-

rally or artiﬁcially,and she has antibodies against many of these anti-

gens.These antibodies protect the mother and the developing fetus

against disease.Some of the antibodies (IgG) can cross the placenta

and enter the fetal blood.Following birth, the antibodies provide pro-

tection for the ﬁrst few months ofthe baby’s life. Eventually the anti-

bodies are broken down,and the baby must rely on his or her own

immune system.If the mother nurses her baby, antibodies (IgA) in

the mother’s milk may also provide some protection for the baby.

Passive Artiﬁcial Immunity

Achieving passive artiﬁcial immunityusually begins with vaccinat-

ing an animal,such as a horse. After the animal’s immune system re-

sponds to the antigen, antibodies (sometimes T cells) are removed

from the animal and injected into the individual requiring immunity.

In some cases,a human who has developed immunity through natu-

ral exposure or vaccination is used as a source ofantibodies. Passive

artiﬁcial immunity provides immediate protection for the individual

receiving the antibodies and is therefore preferred when time might

not be available for the individual to develop his or her own immu-

nity.This technique provides only temporary immunity,however,be-

cause the antibodies are used or eliminated by the recipient.

Antiserum is the general term used for serum, which is

plasma minus the clotting factors,that contains antibodies respon-

sible for passive artiﬁcial immunity.Antisera are available against

microorganisms that cause diseases such as rabies, hepatitis,and

measles;bacterial toxins such as tetanus, diphtheria, and botulism;

and venoms from poisonous snakes and black widow spiders.

50. Distinguish between active and passive immunity.

51. State four general ways of acquiring adaptive immunity.

Which two provide the longestlasting immunity?

Effects of Aging on the Lymphatic

System and Immunity

Objective

■ Describe the effectsof aging on the lymphatic system and

the immune response.

Aging appears to have little effect on the ability of the lym-

phatic system to remove ﬂuid from tissues,absorb fats from the di-

gestive tract,or remove defective red blood cells from the blood.

Aging also seems to have little direct effect on the ability of

B cells to respond to antigens,and the number of circulating B

cells remains stable in most individuals.With age, thymic tissue is

replaced with adipose tissue,and the ability to produce new, ma-

ture T cells in the thymus is eventually lost.Nonetheless,the num-

ber of T cells remains stable in most individuals due to the

replication (not maturation) ofT cells in secondary lymphatic tis-

sues.In many individuals, however, there is a decreased ability of

helper T cells to proliferate in response to antigens.Thus, antigen

exposure produces fewer helper T cells,which results in less stim-

ulation of B cells and effector T cells. Consequently, both

antibody-mediated immunity and cell-mediated immunity re-

sponses to antigens decrease.

Primary and secondary antibody responses decrease with

age.More antigen is required to produce a response,the response is

slower,less antibody is produced, and fewer memory cells result.

Thus, the ability to resist infections and develop immunity de-

creases.It’s recommended that vaccinations should be given well

before age 60 because these declines are most evident after age 60.

Vaccinations,however,can be beneﬁcial at any age, especially if the

individual has reduced resistance to infection.

The ability of cell-mediated immunity to resist intracellular

pathogens decreases with age. For example,the elderly are more

susceptible to inﬂuenza (ﬂu) and should be vaccinated every year.

Some pathogens cause disease but are not eliminated from the

body.With age,a decrease in immunity can result in reactivation of

the pathogen. For example, the virus that causes chickenpox in

children can remain latent within nerve cells even though the dis-

ease seems to have disappeared.Later in life, the virus can leave the

nerve cells and infect skin cells,causing painful lesions known as

herpes zoster or shingles.

Autoimmune disease occurs when immune responses de-

stroy otherwise healthy tissue (see “Autoimmune Diseases”on

p.795). There is very little increase in the number of new-onset

autoimmune diseases in the elderly.However,the chronic inﬂam-

mation and immune responses that began earlier in life have a

cumulative,damag ing effect.The increased incidence of cancer

in the elderly is assumed to be related to a decrease in the im-

mune response.

52. What effect does aging have on the major functions of the

lymphaticsystem?

53. Describe the effects of aging on B cells and T cells. Give

examplesof how this affects antibody-mediated immunity

and cell-mediated immunityresponses.

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Systems Pathology

Systemic Lupus Erythematosus

Mrs. Lis a 30-year-old divorced woman with two children. Despite the

factthat she has to work to support herself and the children, she en-

tered college, determined to become a nurse and provide a better life

for her family. Mrs. Lwas an excellent student, but her class atten-

dance and her performance on tests were somewhaterratic. Some-

times she seemed very energeticand earned high grades, but other

timesshe seemed depressed and didn’t do as well. Toward the end of

the course, she developed a rash on her face (ﬁgure A), a large red le-

sion on her arm, and wasobviously not feeling well. Mrs. L went to the

instructor to askif she could take an incomplete grade and take the

lastexam at a later time. She explained that she has had lupus since

she was25 years old. Normally, medication helpsto control her symp-

toms, butthe stress of being a single parent combined with the chal-

lenges of school seemed to be making her condition worse. She

further explained thatthe symptoms of lupus come and go, and bed

rest wasoften helpful. Mrs. L ﬁnished the course requirements later

thatsummer. She went on to complete her education and now has a

full-time job asa nurse at a local hospital.

Background Information

Systemiclupus erythematosus (SLE) is a disease of unknown cause

in which tissuesand cells are damaged by the immune system. The

name describessome of the characteristics of the disease. The term

lupus literally means wolf and was originallyused to refer to eroded

(asif gnawed by a wolf) lesions of the skin. Erythematosus refers to a

rednessof the skin resulting from inﬂammation. Unfortunately, as the

termsystemic implies, the disorder is not conﬁned to the skin but can

affecttissues and cellsthroughout the body. Another systemic effect is

the presence oflow-grade fever in most cases of active SLE.

SLEis an autoimmune disorder in which a large variety of anti-

bodies are produced that recognize self-antigens, such asnucleic

acids, phospholipids, coagulation factors, red blood cells, and

platelets. The combination ofthe antibodies with self-antigens forms

immune complexesthat circulate throughoutthe body to be deposited

in varioustissues, in which theystimulate inﬂammation and tissue de-

struction. Thus, SLEis a disease thatcan affect many different systems

of the body. For example, the mostcommon antibodies act against

DNA thatis released from damaged cells. Normally the liver removes

the DNA, butwhen DNA and antibodies form immune complexes, they

tend to be deposited in the kidneysand other tissues. Approximately

40%–50% of individuals with SLE develop renaldisease. In some

cases, the antibodiescan bind to antigens on cells, resulting in lysisof

the cells. For example, the binding ofantibodies to red blood cells re-

sultsin hemolysis and the development of anemia.

The cause ofSLE is unknown. The most popular hypothesis is

thata viral infection disrupts the function of suppressor T cells, result-

ing in lossof tolerance to self-antigens. The picture is probably more

complicated, however, because not allSLE patients have reduced

numbers of suppressor T cells. In addition, some patientshave de-

creased numbersof the helper T cells thatnormally stimulate suppres-

sor T-cellactivity.

Genetic factorsprobably contribute to the development of the

disease. The likelihood ofdeveloping SLE is much higher if a family

member also hasit. In addition, family members of SLE patients who

Part4 Regulationsand Maintenance806

Figure A

SystemicLupus Erythematosus

The butterﬂyrash resulting from inﬂammation in the skin caused by systemic

lupuserythematosus.

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don’thave SLE are much more likelyto have DNA antibodies than does

the generalpopulation.

Approximately 1 out of2000 individuals in the United States

hasSLE. The ﬁrst symptoms usually appear between 15 and 25 years

ofage and affect women approximately nine times as often as men.

The progressof the disease is unpredictable, with ﬂare-ups of symp-

tomsfollowed by periods of remission. The survival after diagnosis is

greater than 90% after 10 years. The mostfrequent causesof death in-

volve kidney failure, centralnervous system dysfunction, infections,

and cardiovascular disease.

No cure for SLEexists, nor does one standard of treatment, be-

cause the course of the disease ishighly variable and many differ-

ences can be found among patients. Treatmentusually begins with

mild medicationsand proceeds to more and more potent therapies as

conditionswarrant. Aspirin and nonsteroidal anti-inﬂammatory drugs

are used to suppress inﬂammation. Antimalarial drugsare used to

treatskin rash and arthritis in SLE, but the mechanism of action is un-

known. Patientswho don’t respond to these drugs or those with se-

vere SLE are helped by steroids. Although steroids effectively

suppressinﬂammation, they can produce undesirable side effects, in-

cluding suppression of normal adrenalgland functions. In patients

with life-threatening SLE, veryhigh doses of steroids are used.

PREDICT

The red lesion Mrs. L developed on her arm is called purpura

(pu˘r⬘poo-ra˘), which iscaused bybleeding into the skin. The lesions

graduallychange color and disappear in 2–3 weeks. Explain how SLE

producespurpura.

Chapter 22 LymphaticSystem and Immunity 807

System Interactions

System The Effect of Systemic Lupus Erythematosus on Other Systems

Integumentary Skin lesions frequently occur and are made worse by exposure to the sun. There are three forms: (1) an inflammatory redness

that can take the form of the butterfly rash, which extends from the bridge of the nose to the cheeks; (2) small, localized

pimplelike eruptions accompaniedby scaling of the skin; (3) areas of atrophied, depigmented skin with borders of

increased pigmentation. Diffuse thinning of the hair results from hair loss.

Skeletal Arthritis, tendonitis, and death of bone tissue can occur.

Muscular Destruction of muscle tissue and muscular weakness can occur.

Nervous Memory loss, intellectual deterioration, disorientation, psychosis, reactive depression, headache, seizures, nausea, and loss of

appetite can occur. Stroke is a major cause of dysfunction and death. Cranial nerve involvement results in facial muscle

weakness, drooping of the eyelid, and double vision. Central nervous system lesion can cause paralysis.

Endocrine Sex hormones may play a role in SLE because 90% of the cases occur in females and females with SLE have reduced levels of

androgens.

Cardiovascular Inflammation of the pericardium (pericarditis) with chest pain can develop. Damage to heart valves, inflammation of cardiac

tissue, tachycardia, arrhythmias, angina, and myocardial infarction can also occur. Hemolytic anemia, and leukopenia can

be present (see chapter 19). Antiphospholipid antibody syndrome, through an unknown mechanism, increases coagulation

and thrombus formation, which increases the risk of stroke and heart attack.

Respiratory Chest pain caused by inflammation of the pleural membranes; fever, shortness of breath, and hypoxemia caused by

inflammation of the lungs; and alveolar hemorrhage can develop.

Digestive Ulcers develop in the oral cavity and pharynx. Abdominal pain and vomiting are common, but no cause can be found.

Inflammation of the pancreas and occasionally enlargement of the liver and minor abnormalities in liver function tests occur.

Urinary Renal lesions and glomerulonephritis can result in progressive failure of kidney function. Excess proteins are lost in the urine,

resulting in lower-than-normal blood proteins, which can produce edema.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

22. Lymphatic System and

Immunity

Companies, 2004

Part4 Regulationsand Maintenance808

LymphaticSystem

(p. 772)

The lymphatic system consists oflymph, lymphatic vessels, lymphatic tis-

sue,lymphatic nodules, lymph nodes, tonsils, the spleen, and the thymus.

Functionsof the Lymphatic System

The lymphatic system maintains ﬂuid balance in tissues,absorbs fats from

the small intestine,and defends against microorganisms and foreign sub-

stances.

LymphaticVessels

1. Lymphatic vessels carry lymph away from tissues.

2. Lymphatic capillaries lack a basement membrane and have loosely

overlapping epithelial cells.Fluids and other substances easily enter

the lymphatic capillary.

3. Lymphatic capillaries join to form lymphatic vessels.

• Lymphatic vessels have valves that ensure one-way ﬂow oflymph.

• Skeletal muscle action, contraction of lymphatic vessel smooth

muscle,and thoracic pressure changes move the lymph.

4. Lymph nodes are along the lymphatic vessels.After passing through

lymph nodes,lymphatic vessels form lymphatic trunks and

lymphatic ducts.

5. Lymphatic trunks and ducts empty into the blood at thoracic veins

(junctions ofthe internal jugular and subclavian veins).

• Lymph from the right thorax, the upper-right limb,and the right

side ofthe head and the neck enters right thoracic veins.

• Lymph from the lower limbs,pelvis, and abdomen; the left thorax;

the upper-left limb;and the left side of the head and the neck

enters left thoracic veins.

6. The jugular,subclavian,and brochomediastinal trunks may unite to

form the right lymphatic duct.

7. The thoracic duct is the largest lymphatic vessel.

8. The intestinal and lumbar trunks may converge on the cisterna

chyli,a sac that joins the inferior end of the thoracic duct.

LymphaticTissue and Organs

1. Lymphatic tissue is reticular connective tissue that contains

lymphocytes and other cells.

2. Lymphatic tissue can be surrounded by a capsule (lymph nodes,

spleen,thymus).

3. Lymphatic tissue can be nonencapsulated (diffuse lymphatic tissue,

lymphatic nodules,tonsils). Mucosa-associated lymphoid tissue is

nonencapsulated lymphatic tissue located in and below the mucous

membranes ofthe digestive, respiratory, urinary, and reproductive

tracts.

4. Diffuse lymphatic tissue consists ofdispersed lymphocytes and has

no clear boundaries.

5. Lymphatic nodules are small aggregates oflymphatic tissue (e.g.,

Peyer’s patches in the small intestines).

6. The tonsils

• The tonsils are large groups of lymphatic nodules in the oral cavity

and nasopharynx.

• The three groups of tonsils are the palatine, pharyngeal, and

lingual tonsils.

7. Lymph nodes

• Lymphatic tissue in the node is organized into the cortex and the

medulla.Lymphatic sinuses extend through the lymphatic tissue.

• Substances in lymph are removed by phagocytosis,or they

stimulate lymphocytes (or both).

• Lymphocytes leave the lymph node and circulate to other tissues.

8. The spleen

• The spleen is in the left superior side of the abdomen.

• Foreign substances stimulate lymphocytes in the white pulp

(periarterial lymphatic sheath and lymphatic nodules).

• Foreign substances and defective red blood cells are removed from

the blood by phagocytes in the red pulp (splenic cords and venous

sinuses).

• The spleen is a limited reservoir for blood.

• Most blood ﬂows through the spleen in a few seconds.About 20%

ofthe blood takes a few minutes to ﬂow through the spleen, and

about 2% takes an hour or more.

9. The thymus

• The thymus is a gland in the superior mediastinum and is divided

into a cortex and a medulla.

• Lymphocytes in the cortex are separated from the blood by

reticular cells.

• Lymphocytes produced in the cortex migrate through the medulla,

enter the blood,and travel to other lymphatic tissues, where they

can proliferate.

Immunity

(p. 779)

Immunity is the ability to resist the harmful effects ofmicroorganisms and

other foreign substances.

Innate Immunity

(p. 780)

MechanicalMechanisms

Mechanical mechanisms prevent the entry ofmicrobes (skin and mucous

membranes) or remove them (tears,saliva, and mucus).

ChemicalMediators

1. Chemical mediators promote phagocytosis and inﬂammation.

2. Complement can be activated by either the alternative or the

classical pathway.Complement lyses cells,increases phagocytosis,

attracts immune system cells,and promotes inﬂammation.

3. Interferons prevent viral replication.Interferons are produced by

virally infected cells and move to other cells,which are then

protected.

Cells

1. Chemotactic factors are parts ofmicroorganisms or chemicals that

are released by damaged tissues.Chemotaxis is the ability of white

blood cells to move to tissues that release chemotactic factors.

2. Phagocytosis is the ingestion and destruction ofmaterials.

3. Neutrophils are small phagocytic cells.

4. Macrophages are large phagocytic cells.

• Macrophages can engulf more than neutrophils can.

• Macrophages in connective tissue protect the body at locations

where microbes are likely to enter,and macrophages clean blood

and lymph.

5. Basophils and mast cells release chemicals that promote

inﬂammation.

6. Eosinophils release enzymes that reduce inﬂammation.

7. Natural killer cells lyse tumor cells and virus-infected cells.

InﬂammatoryResponse

1. The inﬂammatory response can be initiated in many ways.

• Chemical mediators cause vasodilation and increase vascular

permeability,which allows the entry of other chemical mediators.

• Chemical mediators attract phagocytes.

• The amount of chemical mediators and phagocytes increases until

the cause ofthe inﬂammation is destroyed. Then the tissue

undergoes repair.

SUMMARY

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

22. Lymphatic System and

Immunity

Companies, 2004

Chapter 22 LymphaticSystem and Immunity 809

2. Local inﬂammation produces the symptoms ofredness,heat,

swelling,pain, and loss of function. Symptoms of systemic

inﬂammation include an increase in neutrophil numbers,fever,and

shock.

Adaptive Immunity

(p. 785)

1. Antigens are large molecules that stimulate an adaptive immune

system response.Haptens are small molecules that combine with

large molecules to stimulate an adaptive immune system response.

2. B cells are responsible for humoral,or antibody-mediated,

immunity.T cells are involved with cell-mediated immunity.

Origin and Developmentof Lymphocytes

1. B cells and T cells originate in red bone marrow.T cells are

processed in the thymus,and B cells are processed in bone marrow.

2. Positive selection ensures the survival oflymphocytes that can react

against antigens,and negative selection eliminates lymphocytes that

react against self-antigens.

3. A clone is a group ofidentical lymphocytes that can respond to a

speciﬁc antigen.

4. B cells and T cells move to lymphatic tissue from their processing

sites.They continually circulate from one lymphatic tissue to

another.

5. Primary lymphatic organs (red bone marrow and thymus) are

where lymphocytes mature into functional cells.Secondary

lymphatic organs and tissues are where lymphocytes produce an

immune response.

Activation ofLymphocytes

1. The antigenic determinant is the speciﬁc part ofthe antigen to

which the lymphocyte responds.The antigen receptor (T-cell

receptor or B-cell receptor) on the surface oflymphocytes combines

with the antigenic determinant.

2. MHC class I molecules display antigens on the surface ofnucleated

cells,resulting in the destruction of the cells.

3. MHC class II molecules display antigens on the surface ofantigen-

presenting cells,resulting in the activation of immune cells.

4. MHCⲐantigen complex and costimulation are usually necessary to

activate lymphocytes.Costimulation involves cytokines and certain

surface molecules.

5. Antigen-presenting cells stimulate the proliferation ofhelper T cells,

which stimulate the proliferation ofB or T effector cells.

Inhibition ofLymphocytes

1. Tolerance is suppression ofthe immune system’s response to an

antigen.

2. Tolerance is produced by deletion ofself-reactive cells,by preventing

lymphocyte activation,and by suppressor T cells.

Antibody-Mediated Immunity

1. Antibodies are proteins.

• The variable region of an antibody combines with the antigen. The

constant region activates complement or binds to cells.

• Five classes of antibodies exist: IgG, IgM,IgA, IgE, and IgD.

2. Antibodies affect the antigen in many ways.

• Antibodies bind to the antigen and interfere with antigen activity

or bind the antigens together.

• Antibodies act as opsonins (a substance that increases

phagocytosis) by binding to the antigen and to macrophages.

• Antibodies can activate complement through the classical pathway.

• Antibodies attach to mast cells or basophils and cause the release

ofinﬂammatory chemicals when the antibody combines with the

antigen.

3. The primary response results from the ﬁrst exposure to an antigen.

B cells form plasma cells,which produce antibodies and memory

cells.

4. The secondary response results from exposure to an antigen after a

primary response,and memory B cells quickly form plasma cells

and additional memory cells.

Cell-Mediated Immunity

1. Antigen activates effector T cells and produces memory T cells.

2. Cytotoxic T cells lyse virus-infected cells,tumor cells,and tissue

transplants.

3. Cytotoxic T cells produce cytokines,which promote phagocytosis

and inﬂammation.

Immune Interactions

(p. 800)

Innate immunity, antibody-mediated immunity, and cell-mediated

immunity can function together to eliminate an antigen.

Immunotherapy

(p. 800)

Immunotherapy stimulates or inhibits the immune system to treat

diseases.

Acquired Immunity

(p. 804)

Active NaturalImmunity

Active natural immunity results from natural exposure to an antigen.

Active ArtiﬁcialImmunity

Active artiﬁcial immunity results from deliberate exposure to an antigen.

Passive NaturalImmunity

Passive natural immunity results from the transfer ofantibodies from a

mother to her fetus or baby.

Passive ArtiﬁcialImmunity

Passive artiﬁcial immunity results from transfer of antibodies (or cells)

from an immune animal to a nonimmune animal.

Effectsof Aging on the Lymphatic System

and Immunity

(p. 805)

1. Aging has little effect on the ability ofthe lymphatic system to

remove ﬂuid from tissues,absorb fats from the digestive tract, or

remove defective red blood cells from the blood.

2. Decreased helper T cell proliferation results in decreased antibody-

mediated immunity and cell-mediated immunity responses to

antigens.

3. The primary and secondary antibody responses decrease with age.

4. The ability to resist intracellular pathogens increases with age.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

22. Lymphatic System and

Immunity

Companies, 2004

Part4 Regulationsand Maintenance810

1. The lymphatic system

a. removes excess ﬂuid from tissues.

b. absorbs fats from the digestive tract.

c. defends the body against microorganisms and other foreign

substances.

d. all ofthe above.

2. Lymph capillaries

a. have a basement membrane.

b. are less permeable than blood capillaries.

c. prevent backﬂow oflymph into the tissues.

d. all ofthe above.

3. Lymph is moved through lymphatic vessels because of

a. contraction ofsurrounding skeletal muscles.

b. contraction ofthe heart.

c. pressure changes in the blood vessels.

d. ﬂapping ofthe lymph valves.

e. pumping by lymph nodes.

4. Which ofthe following statements is true?

a. Lymphatic vessels do not have valves.

b. Lymphatic vessels empty into lymph nodes.

c. Lymph from the right-lower limb passes into the right

lymphovenous portal.

d. Lymph from the jugular and subclavian trunks empties into the

cisterna chyli.

e. All ofthe above.

5. The tonsils

a. consist ofthree groups of lymphatic nodules.

b. are located in the nasal cavity.

c. are located in the oral cavity.

d. increase in size in adults.

e. all ofthe above.

6. Lymph nodes

a. ﬁlter lymph.

b. are where lymphocytes divide and increase in number.

c. contain a network ofreticular ﬁbers.

d. contain lymphatic sinuses.

e. all ofthe above.

7. Which ofthese statements about the spleen is not correct?

a. The spleen has white pulp associated with the arteries.

b. The spleen has red pulp associated with the veins.

c. The spleen destroys defective red blood cells.

d. The spleen is surrounded by trabeculae located outside the

capsule.

e. The spleen is a limited reservoir for blood.

8. The thymus

a. increases in size in adults.

b. produces macrophages that move to other lymphatic tissue.

c. responds to foreign substances in the blood.

d. has a blood–thymic barrier.

e. all ofthe above.

9. Which ofthese is an example of innate immunity?

a. Tears and saliva wash away microorganisms.

b. Basophils release histamine and leukotrienes.

c. Neutrophils phagocytize a microorganism.

d. The complement cascade is activated.

e. All ofthe above.

10. Neutrophils

a. enlarge to become macrophages.

b. account for most ofthe dead cells in pus.

c. are usually the last cell type to enter infected tissues.

d. are usually located in lymph and blood sinuses.

11. Macrophages

a. are large phagocytic cells that outlive neutrophils.

b. develop from mast cells.

c. often die after a single phagocytic event.

d. have the same function as eosinophils.

e. all ofthe above.

12. Which ofthese cells is the most important in the release of

histamine,which promotes inﬂammation?

a. monocyte

b. macrophage

c. eosinophil

d. mast cell

e. natural killer cell

13. Which ofthese conditions does notoccur during the inﬂammator y

response?

a. histamine and other chemical mediators are released

b. chemotaxis ofphagocytes

c. ﬁbrinogen enters tissues from the blood

d. vasoconstriction ofblood vessels

e. increased permeability ofblood vessels

14. Which ofthese is a symptom of systemic inﬂammation?

a. large numbers ofneutrophils are produced and released

b. pyrogens stimulate fever production

c. greatly increased vascular permeability

d. shock

e. all ofthe above

15. Antigens

a. are foreign substances introduced into the body.

b. are molecules produced by the body.

c. stimulate an adaptive immune system response.

d. all ofthe above.

16. B cells

a. are processed in the thymus.

b. originate in red bone marrow.

c. once released into the blood,remain in the blood.

d. are responsible for cell-mediated immunity.

e. all ofthe above.

17. MHC molecules

a. are glycoproteins.

b. attach to the plasma membrane.

c. have a variable region that can bind to foreign and self-antigens.

d. may form an MHC/antigen complex that activates T cells.

e. all ofthe above.

18. Antigen-presenting cells can

a. take in foreign antigens.

b. process antigens.

c. use MHC class II molecules to display the antigens.

d. stimulate other immune system cells.

e. all ofthe above.

19. Which ofthese participates in costimulation?

a. cytokines

b. complement

c. antibodies

d. histamine

e. natural killer cells

20. Helper T cells

a. respond to antigens from macrophages.

b. respond to cytokines from macrophages.

c. stimulate B cells with cytokines.

d. all ofthe above.

REVIEW AND COMPREHENSION

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

22. Lymphatic System and

Immunity

Companies, 2004

Chapter 22 LymphaticSystem and Immunity 811

21. The most important function oftolerance is to

a. increase lymphocyte activity.

b. increase complement activation.

c. prevent the immune system from responding to self-antigens.

d. prevent excessive immune system response to foreign antigens.

e. process antigens.

22. Variable amino acid sequences on the arms ofthe antibody

molecule

a. make the antibody speciﬁc for a given antigen.

b. enable the antibody to activate complement.

c. enable the antibody to attach to basophils and mast cells.

d. are part ofthe constant region.

e. all ofthe above.

23. Antibodies

a. prevent antigens from binding together.

b. promote phagocytosis.

c. inhibit inﬂammation.

d. block complement activation.

e. block the function ofopsonins.

24. The secondary antibody response

a. is slower than the primary response.

b. produces fewer antibodies than the primary response.

c. prevents disease symptoms from occurring.

d. occurs because ofcytotoxic T cells.

25. The type oflymphocyte that is responsible for the secondary

antibody response is the

a. memory B cell.

b. B cell.

c. T cell.

d. helper T cell.

26. The largest percentage ofantibodies in the blood are

a. IgA.

b. IgD.

c. IgE.

d. IgG.

e. IgM.

27. Antibody-mediated immunity

a. works best against intracellular antigens.

b. is involved in tumor control.

c. cannot be transferred from one person to another person.

d. is responsible for immediate hypersensitivity reactions.

28. The activation ofcytotoxic T cells can result in the

a. lysis ofvirus-infected cells.

b. production ofcytokines.

c. production ofmemory T cells.

d. all ofthe above.

29. Cytokines

a. promote inﬂammation.

b. activate macrophages.

c. kill target cells by causing them to lyse.

d. all ofthe above.

30. Delayed hypersensitivity is

a. caused by activation ofB cells.

b. a result ofantibodies reacting with an allergen.

c. mediated by T cells.

d. caused by natural killer cells.

e. caused by interferon.

Answers in Appendix F

CRITICAL THINKING

1. A patient is suffering from edema in the lower-right limb.Explain why

elevation ofthe limb and massage helps to remove the excess ﬂuid.

2. Ifthe thymus of an experimental animal is removed immediately

after its birth,the animal exhibits the following characteristics: (a) it

is more susceptible to infections,(b) it has decreased numbers of

lymphocytes in lymphatic tissue,and (c) its ability to reject grafts is

greatly decreased.Explain these observations.

3. Ifthe thymus of an adult experimental animal is removed,the

following observations can be made:(a) no immediate effect occurs

and (b) after 1 year,the number of lymphocytes in the blood

decreases,the ability to reject grafts decreases, and the ability to

produce antibodies decreases.Explain these observations.

4. Adjuvants are substances that slow but do not stop the release ofan

antigen from an injection site into the blood.Suppose injection A of a

given amount ofantigen is given without an adjuvant and injection B

ofthe same amount of antigen is given with an adjuvant that causes

the release ofantigen over a period of 2–3 weeks. Does injection A or

B result in the greater amount ofantibody production? Explain.

5. Tetanus is caused by bacteria that enter the body through wounds in

the skin.The bacteria produce a toxin that causes spastic muscle

contractions.Death often results from failure of the respiration

muscles.A patient comes to the emergency room after stepping on a

nail.If the patient has been vaccinated against tetanus, the patient is

given a tetanus booster shot,which consists of the toxin altered so that

it is harmless.If the patient has never been vaccinated against tetanus,

the patient is given an antiserum shot against tetanus.Explain the

rationale for this treatment strategy.Sometimes both a booster and an

antiserum shot are given,but at different locations of the body.Explain

why this is done,and why the shots are given in different locations.

6. An infant appears to be healthy until about 9 months ofage.Then

he develops severe bacterial infections,one after another.

Fortunately,the infections are successfully treated with antibiotics.

When infected with the measles and other viral diseases,the infant

recovers without unusual difﬁculty.Explain the different immune

responses to these infections.Why did it take so long for this

disorder to become apparent? (Hint:IgG.)

7. A baby is born with severe combined immunodeﬁciency disease

(SCID).In an attempt to save her life, a bone marrow transplant is

performed.Explain how this procedure might help the baby.

Unfortunately,there is a graft rejection, and the baby dies.Explain

what happened.

8. A patient has many allergic reactions.As part ofthe treatment

scheme,doctors decide to try to identify the allergen that stimulates

the immune system’s response.A series of solutions,each containing

an allergen that commonly causes a reaction,is composed. Each

solution is injected into the skin at different locations on the

patient’s back.The following results are obtained: (a) at one

location,the injection site becomes red and swollen within a few

minutes;(b) at another injection site, swelling and redness appear 2

days later;and (c) no redness or swelling develops at the other sites.

Explain what happened for each observation by describing what

part ofthe immune system was involved and what caused the

redness and swelling.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

22. Lymphatic System and

Immunity

Companies, 2004

Part4 Regulationsand Maintenance812

1. Cutting and tying offthe lymphatic vessels prevents the movement

ofinterstitial ﬂuid from the interstitial spaces. The small amount of

ﬂuid that fails to reenter the venous end ofthe capillaries after it

leaves the arteriolar end ofthe capillaries is normally carried by the

lymphatic vessels away from the tissue spaces and back to the

general circulation.If the lymphatic vessels are tied off, the ﬂuid

accumulates in the interstitial spaces and results in edema.

2 The T cells transferred to mouse B don’t respond to the antigen.The

T cells are MHC-restricted and must have the MHC proteins of

mouse A as well as antigen X to respond.

3. When the antigen is eliminated,it’s no longer available for

processing and combining with MHC class II molecules.

Consequently,no signal takes place to cause lymphocytes to

proliferate and produce antibodies.

4. The ﬁrst exposure to the disease-causing agent (antigen) evokes a

primary response.Gradually, however,antibodies degrade, and

memory cells die.If, before all the memory cells are eliminated, a

second exposure to the antigen occurs,a secondary response results.

The memory cells produced then could provide immunity until the

next exposure to the antigen.

5. With depression ofhelper T-cell activity,the ability of antigens to

activate effector T cells is greatly decreased.Depression of cell-

mediated immunity results in an inability to resist intracellular

microorganisms and cancer.

6. The booster shot stimulates a secondary (memory) response,

resulting in the formation oflarge amounts of antibodies and

memory cells.Consequently there is better, longer-lasting immunity.

7. SLE is an autoimmune disorder in which self-antigens activate

immune responses.Often, this results in the formation of immune

complexes and inﬂammation.But sometimes antibodies bind to

antigens on cells,resulting in the lysis of the cells. Purpura results

from bleeding into the skin,which means that platelet plug

formation,the normal mechanism for repairing small breaks in

blood vessels,is not working. In this case of SLE, antibodies are

causing the destruction ofplatelets, and the decreased number of

platelets results in decreased platelet plug formation and

coagulation (see chapter 19).The condition is called

thrombocytopenia.

ANSWERS TO PREDICT QUESTIONS

Visitthe Online Learning Center at www.mhhe.com/seeley6 for

chapter quizzes, interactive learning exercises, and other studytools.

9. Ivy Hurtt developed a poison ivy rash after a camping trip.Her

doctor prescribed a cortisol ointment to relieve the inﬂammation.A

few weeks later Ivy scraped her elbow,which became inﬂamed.

Because she had some ofthe cortisol ointment left over, she applied

it to the scrape.Explain why the ointment was or was not a good

idea for the poison ivy and for the scrape.

10. Suzy Withitt has just had her ears pierced.To her dismay,she ﬁnds

that when she wears inexpensive (but tasteful) jewelry,by the end of

the day there is an inﬂammatory (allergic) reaction to the metal in

the jewelry.Is this because of antibodies or cytokines?

Answers in Appendix G