263 Chapter Concepts 14.1 Lymphatic System • The lymphatic vessels form a one-way system, which transports lymph from the tissues and fat from the lacteals to certain cardiovascular veins. 264 • The lymphoid organs (red bone marrow, spleen, thymus, and lymph nodes) play critical roles in defense mechanisms. 265 14.2 Nonspecific Defenses • Immunity consists of nonspecific and specific defenses to protect the body against disease. 266 • Nonspecific defenses consist of barriers to entry, the inflammatory reaction, natural killer cells, and protective proteins. 266 14.3 Specific Defenses • Specific defenses require two types of lymphocytes: B lymphocytes and T lymphocytes. 268 14.4 Induced Immunity • Induced immunity for medical purposes involves the use of vaccines to achieve long-lasting immunity and the use of antibodies to provide temporary immunity. 274 14.5 Immunity Side Effects • While immunity preserves life, it also is responsible for certain undesirable effects, such as allergies, autoimmune diseases, and tissue rejection. 276 Cancer cells (blue) divide as they course through a lymphatic vessel, which also contains normal lymphocytes (red). Lymphatic System and Immunity
Transcript
263
Chapter Concepts
14.1 Lymphatic System• The lymphatic vessels form a one-way system,
which transports lymph from the tissues and fat from the lacteals to certain cardiovascularveins. 264
• The lymphoid organs (red bone marrow, spleen,thymus, and lymph nodes) play critical roles indefense mechanisms. 265
14.2 Nonspecific Defenses• Immunity consists of nonspecific and specific
defenses to protect the body against disease. 266
• Nonspecific defenses consist of barriers to entry,the inflammatory reaction, natural killer cells,and protective proteins. 266
14.3 Specific Defenses• Specific defenses require two types of
lymphocytes: B lymphocytes and T lymphocytes.268
14.4 Induced Immunity• Induced immunity for medical purposes involves
the use of vaccines to achieve long-lastingimmunity and the use of antibodies to providetemporary immunity. 274
14.5 Immunity Side Effects• While immunity preserves life, it also is
responsible for certain undesirable effects, suchas allergies, autoimmune diseases, and tissuerejection. 276
Cancer cells (blue) divide as they course through a lymphaticvessel, which also contains normal lymphocytes (red).
14.1 Lymphatic SystemThe lymphatic system consists of lymphatic vessels and thelymphoid organs. This system, which is closely associated withthe cardiovascular system, has three main functions: (1) lym-phatic capillaries take up excess tissue fluid and return it tothe bloodstream; (2) lymphatic capillaries absorb fats at theintestinal villi and transport them to the bloodstream; and (3)the lymphatic system helps to defend the body against disease.
Lymphatic VesselsLymphatic vessels are quite extensive; most regions of thebody are richly supplied with lymphatic capillaries(Fig.14.1). The construction of the larger lymphatic vessels issimilar to that of cardiovascular veins, including the pres-ence of valves. Also, the movement of lymph within thesevessels is dependent upon skeletal muscle contraction. Whenthe muscles contract, the lymph is squeezed past a valve thatcloses, preventing the lymph from flowing backwards.
The lymphatic system is a one-way system that beginswith lymphatic capillaries. These capillaries take up fluid thathas diffused from and has not been reabsorbed by the bloodcapillaries. Edema is localized swelling caused by the accu-mulation of tissue fluid. This can happen if too much tissuefluid is made and/or not enough of it is drained away. Oncetissue fluid enters the lymphatic vessels, it is called lymph.The lymphatic capillaries join to form lymphatic vessels thatmerge before entering one of two ducts: the thoracic duct orthe right lymphatic duct. The thoracic duct is much larger thanthe right lymphatic duct. It serves the lower extremities, theabdomen, the left arm, and the left side of both the head andthe neck. The right lymphatic duct serves the right arm, theright side of both the head and the neck, and the right tho-racic area. The lymphatic ducts enter the subclavian veins,which are cardiovascular veins in the thoracic region.
Lymph flows one way from a capillary to ever-larger lymphatic vessels and finally to a lymphaticduct, which enters a subclavian vein.
264 Part 3 Maintenance of the Human Body 14-2
Karlin casually rubs her nose, unaware she is infectingherself with a cold virus picked up by shaking handswith a coworker. The viral particles slip past the pro-
tective mucous barrier of her nasal cavities, enter cells, andbegin to make copies of themselves. Just before the in-fected cells succumb, they secrete chemicals that alert herimmune system to the invaders. As newly made virusesburst forth killing the cells, antibodies latch onto them andmark them for destruction. This is the job of amoebae-likeimmune cells that rush to the infection site and devour suchcomplexes. Some other immune cells hereafter kill cells in-fected with the virus, and in this way prevent the productionof more viruses. After a week of sniffles, Karlin’s immunesystem wins its battle with the virus. This chapter explainshow the immune system, working with the lymphatic sys-tem, fights off bacteria, viruses, even cancer, and how vac-cines exploit these two systems to provide long-lastingprotection from many diseases.
right lymphaticduct
right subclavianvein
axillary lymph nodes
thymus
thoracic duct
spleen
Lymphatic Vessel
valve to prevent backflow
inguinal lymph nodes
tonsil
left subclavianvein
redbone marrow
Figure 14.1 Lymphatic system. The lymphatic vessels drain excess fluid from the tissues and return itto the cardiovascular system. The enlargement shows that lymphaticvessels have valves to prevent backward flow.
Lymphoid OrgansThe lymphoid organs of special interest are the lymphnodes, the tonsils, the spleen, the thymus gland, and thebone marrow (Fig. 14.2).
Lymph nodes, which are small (about 1–25 mm) ovoidor round structures, are found at certain points along lym-phatic vessels. A capsule surrounds two distinct regionsknown as the cortex and medulla which contain many lym-phocytes. Macrophages, which occur along lymph capillar-ies called lymph sinuses, purify lymph of infectiousorganisms and any debris. Antigens which leak into the cor-tex and medulla activate the lymphocytes to mount an im-mune response to them. Lymph nodes are named for theirlocation. Inguinal nodes are in the groin and axillary nodesare in the armpits. Physicians often feel for the presence ofswollen, tender lymph nodes in the neck as evidence thatthe body is fighting an infection. This is a noninvasive pre-liminary way to help make such a diagnosis.
The tonsils are partially encapsulated lymphatic tissuelocated in a ring about the pharynx. The well-known pha-
ryngeal tonsils are also called adenoids, while the larger pala-tine tonsils located on either side of the posterior oral cavityare most apt to be infected. The tonsils perform the samefunctions as lymph nodes inside the body, but because oftheir location they are the first to encounter pathogens andantigens that enter the body by way of the nose and mouth.
The spleen is located in the upper left region of the ab-dominal cavity just beneath the diaphragm. It is much largerthan a lymph node, about the size of a fist. Whereas thelymph nodes cleanse lymph, the spleen cleanses blood. Acapsule surrounds tissue known as white pulp and red pulp.White pulp contains lymphocytes and performs the im-mune functions of the spleen. The red pulp contains redblood cells and plentiful macrophages. The red pulp helps topurify blood that passes through the spleen by removingbacteria and worn-out or damaged red blood cells.
The spleen’s outer capsule is relatively thin, and an in-fection and/or a blow can cause the spleen to burst. Al-though its functions are replaced by other organs, a personwithout a spleen is often slightly more susceptible to infec-tions and may have to receive antibiotic therapy indefinitely.
Chapter 14 Lymphatic System and Immunity 26514-3
641 µm 641 µm
310 µm381 µm
lobule
medulla
cortex
Thymus Gland
capsule
white pulpred pulp
Spleen Bone Marrow
lymphatic vessel red bone marrow
lymphocyte
monocyte
Lymph Node
tonsil
medulla
capsule
cortex
Figure 14.2 The lymphoid organs.The lymphoid organs include the lymph nodes, the spleen, the thymus gland, and the red bone marrow, which all contain lymphocytes.
The thymus gland is located along the trachea behindthe sternum in the upper thoracic cavity. This gland varies insize, but it is larger in children than in adults and may dis-appear completely in old age. The thymus is divided intolobules by connective tissue. The T lymphocytes mature inthese lobules. The interior (medulla) of the lobule, whichconsists mostly of epithelial cells, stains lighter. It producesthymic hormones, such as thymosin, that are thought to aidin maturation of T lymphocytes. Thymosin may also haveother functions in immunity.
Red bone marrow is the site of origination for all typesof blood cells, including the five types of white blood cellspictured in Figure 13.10. The marrow contains stem cellsthat are ever capable of dividing and producing cells that goon to differentiate into the various types of blood cells (seeFigure 13.12). In a child, most bones have red bone marrow,but in an adult it is present only in the bones of the skull, thesternum (breastbone), the ribs, the clavicle, the pelvic bones,and the vertebral column. The red bone marrow consists ofa network of connective tissue fibers, called reticular fibers,which are produced by cells called reticular cells. These andthe stem cells and their progeny are packed around thin-walled sinuses filled with venous blood. Differentiatedblood cells enter the bloodstream at these sinuses.
The lymphoid organs have specific functions thatassist immunity. Lymph is cleansed in lymphnodes; blood is cleansed in the spleen; T lympho-cytes mature in the thymus; and white blood cellsare made in the bone marrow.
14.2 Nonspecific Defenses M
Immunity is the ability of the body to defend itself againstinfectious agents, foreign cells, and even abnormal bodycells, such as cancer cells. Thereby, the internal environmenthas a better chance of remaining stable. Immunity includesnonspecific and specific defenses. The four types of nonspe-cific defenses—barriers to entry, the inflammatory reaction,natural killer cells, and protective proteins—are effectiveagainst many types of infectious agents.
Barring EntrySkin and the mucous membranes lining the respiratory, di-gestive, and urinary tracts serve as mechanical barriers toentry by pathogens. Oil gland secretions contain chemicalsthat weaken or kill certain bacteria on skin. The upper respi-ratory tract is lined by ciliated cells that sweep mucus andtrapped particles up into the throat, where they can be swal-lowed, or expectorated (coughed out). The stomach has anacidic pH, which inhibits the growth of or kills many typesof bacteria. The various bacteria that normally reside in the
intestine and other areas, such as the vagina, preventpathogens from taking up residence. A pathogen is any dis-ease causing agent such as viruses and some bacteria.
Inflammatory ReactionWhenever the skin is broken due to a minor injury, a series ofevents occurs that is known as the inflammatory reaction.The inflamed area has four outward signs: redness, heat,swelling, and pain. Figure 14.3 illustrates the participants inthe inflammatory reaction. Mast cells, which occur in tissues,resemble basophils, one of the white cells found in the blood.
When an injury occurs, damaged tissue cells and mastcells release chemical mediators, such as histamine andkinins, which cause the capillaries to dilate and becomemore permeable. The enlarged capillaries cause the skin toredden, and the increased permeability allows proteins andfluids to escape and swelling results. A rise in temperatureincreases phagocytosis by white blood cells. The swollenarea as well as kinins stimulate free nerve endings, causingthe sensation of pain.
Neutrophils and monocytes migrate to the site of injury.They are amoeboid and can change shape to squeeze throughcapillary walls to enter tissue fluid. Neutrophils, and alsomast cells, can phagocytize bacteria. The engulfed bacteria aredestroyed by hydrolytic enzymes when the endocytic vesiclecombines with a lysosome, one of the cellular organelles.
Monocytes differentiate into macrophages, large phago-cytic cells that are able to devour a hundred bacteria orviruses and still survive. Some tissues, particularly connec-tive tissue, have resident macrophages, which routinely actas scavengers, devouring old blood cells, bits of dead tissue,and other debris. Macrophages can also bring about an ex-plosive increase in the number of leukocytes by liberatingcolony-stimulating hormones, which pass by way of blood tothe red bone marrow, where they stimulate the productionand the release of white blood cells, primarily neutrophils.
When a blood vessel ruptures, the blood clots to seal thebreak. The chemical mediators, mentioned earlier, and antigensmove through the tissue fluid and lymph to the lymph nodes.Now lymphocytes can also be activated to react to the threat ofan infection. As the infection is being overcome, some neu-trophils may die. These—along with dead tissue, cells, bacteria,and living white blood cells—form pus, a whitish material. Pusindicates that the body is trying to overcome the infection.
Sometimes inflammation persists and the result ischronic inflammation that is often treated by the administra-tion of anti-inflammatory agents such as aspirin, ibuprofen,or cortisone. They act against the chemical mediators re-leased by the white blood cells in the area.
The inflammatory reaction is a “call to arms”—itmarshals phagocytic white blood cells to the siteof bacterial invasion and stimulates the immunesystem to react against a possible infection.
Natural Killer CellsNatural killer (NK) cells kill virus-infected cells and tumorcells by cell-to-cell contact. They are large granular lympho-cytes. They have no specificity and no memory. Their num-ber is not increased by immunization.
Protective ProteinsThe complement system, often simply called complement,is a number of plasma proteins designated by the letter Cand a subscript. A limited amount of activated complementprotein is needed because a domino effect occurs: each acti-vated protein in a series is capable of activating many otherproteins.
Complement is activated when pathogens enter thebody. It “complements” certain immune responses, whichaccounts for its name. For example, it is involved in and am-plifies the inflammatory response because complement pro-teins attract phagocytes to the scene. Some complementproteins bind to the surface of pathogens already coatedwith antibodies, which ensures that the pathogens will bephagocytized by a neutrophil or macrophage.
Certain other complement proteins join to form a mem-brane attack complex that produces holes in bacterial cell wallsand plasma membranes of bacteria. Fluids and salts then en-ter the bacterial cell to the point that it bursts (Fig. 14.4).
Interferon is a protein produced by virus-infected cells.Interferon binds to receptors of noninfected cells, causingthem to prepare for possible attack by producing substancesthat interfere with viral replication. Interferon is specific tothe species; therefore, only human interferon can be used inhumans.
Immunity includes these nonspecific defenses:barriers to entry, the inflammatory reaction, naturalkiller cells, and protective proteins.
14.3 Specific Defenses M
When nonspecific defenses have failed to prevent an infec-tion, specific defenses come into play. An antigen is any for-eign substance (often a protein or polysaccharide) thatstimulates the immune system to react to it. Pathogens haveantigens, but antigens can also be part of a foreign cell or acancer cell. Because we do not ordinarily become immune toour own cells, it is said that the immune system is able todistinguish self from nonself.
Immunity usually lasts for some time. For example,once we recover from the measles, we usually do not get theillness a second time. Immunity is primarily the result of theaction of the B lymphocytes and the T lymphocytes. B lym-phocytes1 mature in the bone marrow, and T lymphocytesmature in the thymus gland. B lymphocytes, also called Bcells, give rise to plasma cells, which produce antibodies,proteins that are capable of combining with and neutraliz-ing antigens. These antibodies are secreted into the blood,lymph, and other body fluids. In contrast, T lymphocytes,also called T cells, do not produce antibodies. Instead, cer-tain T cells directly attack cells that bear antigens. Other Tcells regulate the immune response.
Lymphocytes are capable of recognizing an antigen be-cause they have receptor molecules on their surface. The shapeof the receptors on any particular lymphocyte is comple-mentary to a specific antigen. It is often said that the receptorand the antigen fit together like a lock and a key. It is estimatedthat during our lifetime, we encounter a million differentantigens, so we need a great diversity of lymphocytes to pro-tect us against antigens. It is remarkable that diversificationoccurs to such an extent during the maturation process thatthere is a lymphocyte type for any possible antigen. Just howthis occurs is discussed in the reading on page 271.
Complement proteins form holesin the bacterial cell wall and membrane.
Holes allow fluids and salts to enter thebacterium.
Bacterium expands until it bursts.
fluids and salts
complement
bacterium
Figure 14.4 Action of the complement system against a bacterium.When complement proteins in the plasma are activated by an immune reaction, they form holes in bacterial cell walls and plasma membranes,allowing fluids and salts to enter until the cell eventually bursts.
1Historically, the B stands for bursa of Fabricius, an organ in the chicken wherethese cells were first identified. As it turns out, however, the B can conveniently bethought of as referring to bone marrow.
B Cells and Antibody-Mediated ImmunityEach type of B cell carries its specific antibody, as amembrane-bound receptor, on its surface. When a B cell in alymph node or the spleen encounters a bacterial cell or atoxin bearing an appropriate antigen, it becomes activatedto divide many times. Most of the resulting cells are plasmacells, which secrete antibodies against this antigen. Aplasma cell is a mature B cell that mass-produces antibodiesin lymph nodes and in the spleen.
The clonal selection theory states that the antigen se-lects which lymphocyte will undergo clonal expansion andproduce more lymphocytes bearing the same type of recep-tor (Fig.14.5). Notice that a B cell does not divide until itsantigen is present and binds to its receptors. B cells are alsostimulated to divide and become plasma cells by helper Tcell secretions, as is discussed in the next section. Somemembers of the clone become memory cells which are themeans by which long-term immunity is possible. If the sameantigen enters the system again, memory cells quickly di-vide and give rise to more lymphocytes capable of quicklyproducing antibodies.
Once the threat of an infection has passed, the develop-ment of new plasma cells ceases and those present undergo
apoptosis. Apoptosis is a process of programmed cell death(PCD) involving a cascade of specific cellular events leadingto the death and destruction of the cell. The methodology ofPCD is still being worked out, but we know it is an essentialphysiological mechanism regulating the cell populationwithin an organ system. PCD normally plays a central rolein maintaining tissue homeostasis.
Defense by B cells is called antibody-mediated immu-nity because the various types of B cells produce antibodies.It is also called humoral immunity because these antibodiesare present in blood and lymph. A humor is any fluid nor-mally occurring in the body.
Characteristics of B cells:
• Antibody-mediated immunity• Produced and mature in bone marrow • Reside in spleen and lymph nodes, circulate in
blood and lymph• Directly recognize antigen and then undergo
Figure 14.5 Clonal selection theory as it applies to B cells.An antigen activates only the B cell whose receptors can combine with the antigen. This B cell then undergoes clonal expansion. During theprocess many plasma cells, which produce specific antibodies against this antigen, are produced. After the infection passes, they undergoapoptosis. Memory cells, which retain the ability to recognize this antigen, are retained in the body.
Structure of IgGThe most common type of antibody (IgG) is a Y-shaped pro-tein molecule with two arms. Each arm has a “heavy” (long)polypeptide chain and a “light” (short) polypeptide chain.These chains have constant regions, where the sequence ofamino acids is set, and variable regions, where the sequence ofamino acids varies between antibodies (Fig. 14.6). The con-stant regions are not identical among all the antibodies. In-stead, they are almost the same within different classes ofantibodies. The variable regions form an antigen-bindingsite, and their shape is specific to a particular antigen, as dis-cussed in the reading on the next page. The antigen com-bines with the antibody at the antigen-binding site in alock-and-key manner.
The antigen-antibody reaction can take several forms,but quite often the reaction produces complexes of antigenscombined with antibodies. Such antigen-antibody com-plexes, sometimes called immune complexes, mark the anti-gens for destruction. For example, an antigen-antibodycomplex may be engulfed by neutrophils or macrophages, orit may activate complement. Complement makes pathogensmore susceptible to phagocytosis, as discussed previously.
Other Types of AntibodiesThere are five different classes of circulating antibody pro-teins or immunoglobulins (Igs) (Table 14.1). IgG antibodiesare the major type in blood, and lesser amounts are alsofound in lymph and tissue fluid. IgG antibodies bind topathogens and their toxins. A toxin is a specific chemical(produced by bacteria, for example) that is poisonous toother living things. IgM antibodies are pentamers, meaningthat they contain five of the Y-shaped structures shown inFigure 14.6a. These antibodies appear in blood soon after aninfection begins and disappear before it is over. They aregood activators of the complement system. IgA antibodiesare monomers, dimers, or larger molecules containing twoY-shaped structures. They are the main type of antibodyfound in bodily secretions. They bind to pathogens beforethey reach the bloodstream. The main function of IgD anti-bodies seems to be to serve as receptors for antigens on ma-ture B cells. IgE antibodies, which are responsible forimmediate allergic responses, are discussed on page 277.
An antigen combines with an antibody at theantigen-binding site in a lock-and-key manner. Thereaction can produce antigen-antibody complexes,which contain several molecules of antibody andantigen.
270 Part 3 Maintenance of the Human Body 14-8
heavychain
antigen-bindingsites
lightchain
V
V
C
C C
V
V
C
a.
b.
Figure 14.6 Structure of the most common antibody (IgG).a. An IgG antibody contains two heavy (long) polypeptide chains andtwo light (short) chains arranged so there are two variable regions,where a particular antigen is capable of binding with the antibody.b. Computer model of an antibody molecule. In this model, theantigen combines with the two side branches.
Classes Presence Function
IgG Main antibody type in circulation Binds to pathogens, activates complement, and enhances phagocytosis
IgM Antibody type found in circulation; largest antibody Activates complement; clumps cells
IgA Main antibody type in secretions such as saliva and milk Prevents pathogens from attaching to epithelial cells in digestiveand respiratory tract
IgD Antibody type found in circulation in extremely low quantity Presence signifies maturity of B cell
IgE Antibody type found as membrane-bound receptor on Responsible for immediate allergic response and protection against basophils in blood and on mast cells in tissues certain parasitic worms
In 1987, Susumu Tonegawa became the first Japanese scientistto win the Nobel Prize in Physiology or Medicine. He had dedi-cated himself to finding the solution to an engrossing puzzle.Immunologists and geneticists knew that each B cell makes anantibody especially equipped to recognize the specific shape ofa particular antigen. But they did not know how the humangenome contained enough genetic information to permit theproduction of up to a million different antibody types needed tocombat all of the pathogens we are likely to encounter duringthe course of our lives.
An antibody is composed of two light and two heavypolypeptide chains, which are divided into constant and vari-able regions. The constant region determines the antibody classand the variable region determines the specificity of the anti-body, because this is where an antigen binds to a specific anti-body (see Fig. 14.6). Each B cell must have a genetic way to codefor the variable regions of both the light and heavy chains.
Tonegawa’s colleagues say that he is a creative genius whointuitively knows how to design experiments to answer specificquestions. In this instance, he examined the DNA sequences oflymphoblasts and compared them to mature B cells. He foundthat the DNA segments coding for the variable and constant re-gions were scattered throughout the genome in B lymphocytestem cells and that only certain of these segments appeared in
each mature antibody-secreting B cell where they randomlycame together and coded for a specific variable region. Later, thevariable and constant regions are joined to give a specific anti-body (Fig. 14Ab). As an analogy, consider that each person en-tering a supermarket chooses various items for purchase, andthat the possible combination of items in any particular grocerybag is astronomical. Tonegawa also found that mutations occuras the variable segments are undergoing rearrangements. Suchmutations are another source of antibody diversity.
Invariably some B cells with receptors that could bind to thebody’s own cell surface molecules arise. It is believed that thesecells undergo apoptosis, or programmed cell death.
Tonegawa received his B.S. in chemistry in 1963 at Kyoto Uni-versity and earned his Ph.D. in biology from the University ofCalifornia at San Diego (UCSD) in 1969. After that he worked as aresearch fellow at UCSD and the Salk Institute. In 1971, he movedto the Basel Institute for Immunology and began the experimentsthat eventually led to his Nobel Prize-winning discovery. Tone-gawa also contributed to the effort to decipher the receptors of Tcells. This was an even more challenging area of research than thediversity of antibodies produced by B cells. Since 1981, he hasbeen a full professor at the Massachusetts Institute of Technology(MIT), where he has a reputation for being an “aggressive, deter-mined researcher” who often works late into the night.
271
Susumu Tonegawa and Antibody Diversity
Figure 14A Antibody diversity.a. Susumu Tonegawa received a Nobel Prize for his findings regarding antibody diversity. b. Different genes for the variable regions ofheavy and light chains are brought together during the production of B lymphocytes so that their antigen receptors can combine with onlya particular antigen.
Z
Z Y X W V U
Y X V U Z Y X W
amino acids in variable regionof one B cell antigen receptor(heavy or light chain)
amino acids in variable regionof another B cell antigen receptor(heavy or light chain)
T Cells And Cell-Mediated ImmunityThe two main types of T cells are cytotoxic T cells and helperT cells. Cytotoxic T cells are the type of T cell responsible forcell-mediated immunity, so-called because T cells bringabout the destruction of antigen-bearing cells, such as virus-infected or cancer cells. Cytotoxic T cells have storage vac-uoles containing perforin molecules. Perforin moleculesperforate a plasma membrane, forming a pore that allowswater and salts to enter. The cell then swells and eventuallybursts (Fig. 14.7).
Helper T cells regulate immunity by enhancing the re-sponse of other immune cells. When exposed to an antigen,they enlarge and secrete cytokines, stimulatory moleculesthat cause helper T cells to divide and other immune cells toperform their functions. For example, cytokines stimulatemacrophages to phagocytize and stimulate B cells to becomeantibody-producing plasma cells. Because HIV, whichcauses AIDS, infects helper T cells and certain other cells ofthe immune system, it inactivates the immune response.
As we shall see, there are also memory T cells that
remain in the body and can jump-start an immune reactionto an antigen previously present in the body.
Activation of T CellsWhen T cells leave the thymus they have unique receptorsjust as B cells do. Unlike B cells, however, cytotoxic T cellsand helper T cells are unable to recognize an antigen presentin lymph, blood, or the tissues without help. The antigenmust be presented to them by an antigen-presenting cell(APC). When an APC, usually a macrophage, engulfs apathogen, the pathogen is broken down to fragments withinan endocytic vesicle. These fragments are antigenic; that is,they have the properties of an antigen. The fragments arelinked to a major histocompatibility complex (MHC) proteinin the plasma membrane and then they can be presented toa T cell.
Human MHC proteins are called HLA (human leuko-cyte associated) antigens. Because they mark the cell as be-longing to a particular individual, HLA proteins are self
272 Part 3 Maintenance of the Human Body 14-10
1 µma. b.
vacuoles
pores
T cells
target cell
T cell
target cell plasmamembrane
T cell plasmamembrane
perforinmolecule
nucleus
Target cell
Figure 14.7 Cell-mediated immunity.a. The scanning electron microscope shows cytotoxic T cells attacking and destroying a cancer cell. b. During the killing process, the vacuoles ina cytotoxic T cell release perforin molecules. These molecules combine to form pores in the target cell plasma membrane. Thereafter, fluid andsalts enter so that the target cell eventually bursts.
mune system. A few of the clonally expanded T cells donot undergo apoptosis. The survivors are memory cells—T cells that can rapidly respond should the same antigenbe present at a later time.
Apoptosis also occurs in the thymus as T cells are ma-turing. A T cell that bears a receptor with the potential to rec-ognize a self antigen undergoes suicide. When apoptosisdoes not occur as it should, T-cell cancers (i.e., lymphomasand leukemias) can result.
Characteristics of T cells:
• Cell-mediated immunity• Produced in bone marrow, mature in thymus• Antigen must be presented in groove of an HLA
molecule.• Cytotoxic T cells destroy antigen-bearing cells.• Helper T cells secrete cytokines that control the
immune response.
Chapter 14 Lymphatic System and Immunity 27314-11
antigens. The importance of self antigens in plasma mem-branes was first recognized when it was discovered thatthey contribute to the specificity of tissues and make it diffi-cult to transplant tissue from one human (or animal) to an-other. In other words, when the donor and the recipient arehisto (tissue)-compatible (the same or nearly so), a trans-plant is more likely to be successful.
Figure 14.8 shows a macrophage presenting an anti-gen to a T cell. Once a helper T cell recognizes an antigenand is stimulated to do so, it undergoes clonal expansionand produces cytokines that stimulate immune cells to re-main active. Once a cytotoxic T cell is activated in thismanner, it undergoes clonal expansion and destroys anycell infected with the same virus, if the cell bears the cor-rect HLA. As the infection disappears, the immune reac-tion wanes and fewer cytokines are produced. Now, theactivated T cells become susceptible to apoptosis. As men-tioned previously, apoptosis is a programmed cell deaththat contributes to homeostasis by regulating the numberof cells that are present in an organ, or in this case the im-
Figure 14.8 Clonal selection theory as it applies to T cells. Each type of T cell bears a specific antigen receptor. When this receptor binds to an antigen in the groove of an HLA molecule and is stimulatedto do so, it undergoes clonal expansion. After the immune response has been successful, the majority of T cells undergo apoptosis while a smallnumber may become memory cells. Memory cells provide protection should the same antigen enter the body again at a future time.
14.4 Induced ImmunityImmunity occurs naturally through infection or is broughtabout artificially by medical intervention. There are twotypes of induced immunity: active and passive. In active im-munity, the individual alone produces antibodies against anantigen; in passive immunity, the individual is given pre-pared antibodies.
Active Immunity Active immunity sometimes develops naturally after a per-son is infected with a pathogen. However, active immunityis often induced when a person is well so that possible fu-ture infection will not take place. To prevent infections, peo-ple can be artificially immunized against them. The UnitedStates is committed to the goal of immunizing all childrenagainst the common types of childhood diseases listed in theimmunization schedule given in Figure 14.9a.
Immunization involves the use of vaccines, substancesthat contain an antigen to which the immune system re-sponds. Traditionally, vaccines are the pathogens them-selves, or their products, that have been treated so they areno longer virulent (able to cause disease). Today, it is possi-ble to genetically engineer bacteria to mass-produce a pro-tein from pathogens, and this protein can be used as vaccine.This method now has been used to produce a vaccineagainst hepatitis B, a viral disease, and is being used to pre-pare a vaccine against malaria, a protozoan disease.
After a vaccine is given, it is possible to follow an im-mune response by determining the amount of antibodypresent in a sample of serum—this is called the antibody titer.After the first exposure to a vaccine, a primary response oc-curs. For a period of several days, no antibodies are present;then, there is a slow rise in the titer, followed by first aplateau and then a gradual decline as the antibodies bind tothe antigen or simply break down (Fig. 14.9b). After a secondexposure, a secondary response is expected. The titer risesrapidly to a plateau level much greater than before. The sec-ond exposure is called a “booster” because it boosts the anti-body titer to a high level. The high antibody titer now isexpected to help prevent disease symptoms even if the indi-vidual is exposed to the disease-causing antigen.
Active immunity is dependent upon the presence ofmemory B cells and memory T cells which are capable of re-sponding to lower doses of antigen. Active immunity is usu-ally long-lived, although a booster may be required every somany years.
Active (long-lived) immunity can be induced by theuse of vaccines. Active immunity is dependentupon the presence of memory B cells and memoryT cells in the body.
274 Part 3 Maintenance of the Human Body 14-12
Pla
sma
An
tib
od
y C
on
cen
trat
ion
primary response secondary response
first exposureto vaccine
Time (days)0 30 60 90 120 150 180
second exposureto vaccine
Vaccine Age (Months) Age (Years)
HepB* (hepatitis B)
OPV§ (oral polio vaccine)
Td‡ (adult tetanus)
DTP†
(diphtheria, tetanus,whooping cough)
Birth, 2, 4, 6, 12–15
2, 4, 6, 15–18
11–12
12–15 and 1 month later
4–6, 11–12
2, 4, 6, 12–15
2, 4, 6, 12–15
4–6
11–12, 14–16
4–6
Hib§ (Haemophilusinfluenza, type b)
MMR¶ (measles, mumps, rubella)
* Three doses will be required for kindergarten entry.† Five doses recommended for school entry.‡ First Td needed 10 years after last DTP.§ Doses 3 and 4 should be given according to manufacturer's guidelines.¶ A second dose given at least 1 month after first dose required for kindergarten entrySource: Iowa Department of Public Health, July 1998.
Figure 14.9 Active immunity due to immunizations.a. Suggested immunization schedule for infants and young children. b. During immunization, the primary response, after the first exposureto a vaccine, is minimal, but the secondary response, which mayoccur after the second exposure, shows a dramatic rise in theamount of antibody present in serum.
Passive ImmunityPassive immunity occurs when an individual is given pre-pared antibodies (immunoglobulins) to combat a disease.Since these antibodies are not produced by the individual’sB cells, passive immunity is short-lived. For example, new-born infants are passively immune to some diseases becauseantibodies have crossed the placenta from the mother’sblood. These antibodies soon disappear, however, so thatwithin a few months, infants become more susceptible to in-fections. Breast-feeding prolongs the natural passive immu-nity an infant receives from the mother because antibodiesare present in the mother’s milk (Fig. 14.10).
Even though passive immunity does not last, it some-times is used to prevent illness in a patient who has been un-expectedly exposed to an infectious disease. Usually, thepatient receives a gamma globulin injection (serum that con-tains antibodies), perhaps taken from individuals who haverecovered from the illness. In the past, horses were immu-nized, and serum was taken from them to provide theneeded antibodies against such diseases as diphtheria, botu-lism, and tetanus. In the past, a patient who received theseantibodies became ill about 50% of the time because theserum contained proteins that the individual’s immune sys-tem recognized as foreign. This was called serum sickness.But problems can still occur with products produced inother ways. An immunoglobulin intravenous product calledGammagard was withdrawn from the market because ofpossible implication in the transmission of hepatitis.
Passive immunity provides immediate protectionwhen an individual is in immediate danger ofsuccumbing to an infectious disease. Passiveimmunity is short-lived because there are nomemory cells.
Cytokines and ImmunityCytokines are messenger molecules produced by lympho-cytes, monocytes, or other cells. Because cytokines regulatewhite blood cell formation and/or function, they are beinginvestigated as possible adjunct therapy for cancer andAIDS. Both interferon and interleukins, which are cytokinesproduced by various white blood cells, have been used asimmunotherapeutic drugs, particularly to enhance the abil-ity of the individual’s own T cells (and possibly B cells) tofight cancer.
Interferon, discussed previously on page 268, is a sub-stance produced by leukocytes, fibroblasts, and probablymost cells in response to a viral infection. Interferon still isbeing investigated as a possible cancer drug, but so far it hasproven to be effective only in certain patients, and the exactreasons for this as yet cannot be discerned.
When and if cancer cells carry an altered protein on their
cell surface, they should be attacked and destroyed by cyto-toxic T cells. Whenever cancer does develop, it is possiblethat the cytotoxic T cells have not been activated. In thatcase, cytokines might awaken the immune system and leadto the destruction of the cancer. In one technique being in-vestigated, researchers first withdraw T cells from the pa-tient and activate the cells by culturing them in the presenceof an interleukin. The cells then are reinjected into the pa-tient, who is given doses of interleukin to maintain the killeractivity of the T cells.
Those who are actively engaged in interleukin researchbelieve that interleukins soon will be used as adjuncts forvaccines, for the treatment of chronic infectious diseases,and perhaps for the treatment of cancer. Interleukin antago-nists also may prove helpful in preventing skin and organrejection, autoimmune diseases, and allergies.
The interleukins and other cytokines show somepromise of potentiating the individual’s ownimmune system.
Chapter 14 Lymphatic System and Immunity 27514-13
Figure 14.10 Passive immunity.Breast-feeding is believed to prolong the passive immunity an infantreceives from the mother because antibodies are present in themother’s milk.
Monoclonal Antibodies Every plasma cell derived from the same B cell secretes anti-bodies against a specific antigen. These are monoclonal an-tibodies because all of them are the same type and becausethey are produced by plasma cells derived from the same Bcell. One method of producing monoclonal antibodies invitro (outside the body in glassware) is depicted in Figure14.11. B lymphocytes are removed from an animal (today,usually mice are used) and are exposed to a particular anti-gen. The activated B lymphocytes are fused with myelomacells (malignant plasma cells that live and divide indefi-nitely). The fused cells are called hybridomas; hybrid be-cause they result from the fusion of two different cells, andoma because one of the cells is a cancer cell.
At present, monoclonal antibodies are being used forquick and certain diagnosis of various conditions. For exam-ple, a particular hormone is present in the urine of a preg-nant woman. A monoclonal antibody can be used to detectthis hormone; if it is present, the woman knows she is preg-nant. Monoclonal antibodies also are used to identify infec-tions. And because they can distinguish between cancer andnormal tissue cells, they are used to carry radioactive iso-topes or toxic drugs to tumors so that they can be selectivelydestroyed.
14.5 Immunity Side EffectsThe immune system usually protects us from disease be-cause it can distinguish self from nonself. Sometimes, how-ever, it responds in a manner that does harm to the body, aswhen individuals develop allergies, receive the wrongblood type, suffer tissue rejection, or have an autoimmuneresponse.
AllergiesAllergies are hypersensitivities to substances such aspollen or animal hair that ordinarily would do no harm tothe body. The response to these antigens, called allergens,usually includes some degree of tissue damage. There arefour types of allergic responses, but we will consider onlytwo of these: immediate allergic responses and delayedallergic responses.
Immediate Allergic ResponseAn immediate allergic response occurs within seconds ofcontact with the antigen. As discussed in the reading onpage 277, coldlike symptoms are common. Anaphylacticshock is a severe reaction characterized by a sudden and life-threatening drop in blood pressure.
Immediate allergic responses are caused by antibodiesknown as IgE (see Table 14.1). IgE antibodies are attached tothe plasma membrane of mast cells in the tissues and ba-sophils in the blood. When an allergen attaches to the IgEantibodies on these cells, they release histamine and othersubstances that bring about the coldlike symptoms or,rarely, anaphylactic shock.
Allergy shots sometimes prevent the onset of an allergicresponse. It’s been suggested that injections of the allergenmay cause the body to build up high quantities of IgG anti-bodies, and these combine with allergens received from theenvironment before they have a chance to reach the IgE anti-bodies located in the membrane of mast cells and basophils.
Delayed Allergic ResponseDelayed allergic responses are initiated by sensitized Tcells at the site of allergen in the body. A sensitized T cell isone that is ready to respond to the antigen because it hasbeen present in the body before. T cells initiate the responseby recruiting the help of macrophages, which are able tophagocytize offending viral particles or infectious cells. Theoverall response is regulated by the cytokines secreted byboth the T cells and macrophages.
A classic example of a delayed allergic response is thetuberculin skin test. When the result of the test is positive,there is a reddening and hardening of tissue where the anti-gen was injected. This shows that there was prior exposureto tubercle bacilli which cause TB. Contact dermatitis, suchas occurs when one is allergic to poison ivy, jewelry, cos-metics, and so forth, is also an example of a delayed allergicresponse.
276 Part 3 Maintenance of the Human Body 14-14
Plasma cell
Cancerous myeloma cell
antigens
antibody
monoclonal antibody
Hybridomacell
Figure 14.11 Production of monoclonal antibodies.Plasma cells (derived from immunized mice) are fused with myeloma(cancerous) cells, producing hybridoma cells that are “immortal.”Hybridoma cells divide and continue to produce the same type ofantibody, called monoclonal antibodies.
The runny nose and watery eyes of hay fever are often causedby an allergic reaction to the pollen of trees, grasses, and rag-weed. Worse, the airways leading to the lungs constrict if onehas asthma, resulting in difficult breathing characterized bywheezing. Windblown pollen, particularly in the spring andfall, brings on the symptoms of hay fever. Most people can in-hale pollen with no ill effects. But others have developed a hy-persensitivity, meaning that their immune system responds in adeleterious manner. The problem stems from a type of antibodycalled immunoglobulin E (IgE) that causes the release of hista-mine from mast cells and basophils whenever they are exposedto an allergen. Histamine is a chemical that causes mucosalmembranes of the nose and eyes to release fluid as a defenseagainst pathogen invasion. But in the case of allergy, copiousfluid is released although no real danger is present.
Most food allergies are also due to the presence of IgE anti-bodies that bind usually to a protein in the food. The symptoms,such as nausea, vomiting, and diarrhea, are due to the mode ofentry of the allergen. Skin symptoms may also occur, however.Adults are often allergic to shellfish, nuts, eggs, cows’ milk, fish,and soybeans. Peanut allergy is a common food allergy in theUnited States possibly because peanut better is a staple in theUnited States. People seem to outgrow allergies to cows’ milkand eggs more often than allergies to peanuts and soybeans.
Celiac disease occurs in people who are al-lergic to wheat, rye, barley, and sometimesoats—in short, any grain that contains glutenproteins. It is thought that the gluten proteinselicit a delayed cell-mediated immune re-sponse by T cells with the resultant productionof cytokines. The symptoms of celiac diseasecan include diarrhea, bloating, weight loss, ane-mia, bone pain, chronic fatigue, and weakness.
People can reduce the chances of a reactionto airborne and food allergens by avoiding theoffending substances.The reaction to peanutscan be so severe that airlines are now requiredto have a peanut-free zone for those allergic.The people in Figure 14B are trying to avoidwindblown allergens. The taking of antihista-mines can also be helpful. If these proceduresare inadequate, patients can be tested to mea-sure their susceptibility to any number of pos-sible allergens. A small quantity of asuspected allergen is inserted just beneath theskin, and the strength of the subsequent reac-tion is noted. A wheal-and-flare response atthe skin prick site demonstrates that IgE anti-bodies attached to mast cells have reacted toan allergen. In an immunotherapy called hy-
posensitization, ever-increasing doses of the allergen are period-ically injected subcutaneously with the hope that the body willbuild up a supply of IgG. IgG, in contrast to IgE, does not causethe release of histamine after it combines with the allergen. If IgGcombines first upon exposure to the allergen, the allergic re-sponse does not occur. Patients know they are cured when the al-lergic symptoms no longer occur. Therapy may have to continuefor as long as two to three years.
Allergic-type reactions can occur without involving the im-mune system. Wasp and bee stings contain substances thatcause swellings, even in those whose immune system is not sen-sitized to substances in the sting. Also, jellyfish tentacles andfoods such as fish that is not fresh and strawberries contain his-tamine or closely related substances that can cause a reaction.Immunotherapy is also not possible in those who are allergic topenicillin and bee stings. High sensitivity has built up upon thefirst exposure, and when reexposed, anaphylactic shock can oc-cur. Among its many effects, histamine causes increased perme-ability of the smallest blood vessels, called capillaries. In theseindividuals, there is a drastic decrease in blood pressure that canbe fatal within a few minutes. People who know they are aller-gic to bee stings can obtain a syringe of epinephrine to carrywith them. This medication can delay the onset of anaphylacticshock until medical help is available.
Immediate Allergic Responses
Figure 14B Protection against allergies.The allergic reaction known as hay fever, and asthma attacks, can have many triggers,one of which is the pollen of a variety of plants. A dramatic solution to the problem hasbeen found by these people.
Blood TypesWhen blood transfusions were first attempted, illness andeven death sometimes resulted. Eventually, it was discov-ered that only certain types of blood are compatible becausered blood cell membranes carry proteins or sugar residuesthat are antigens to blood recipients. The ABO system of typ-ing blood is based on this principle.
ABO SystemBlood typing in the ABO system is based on two antigensknown as antigen A and antigen B. There are four bloodtypes: O, A, B, and AB. Type O has neither the A antigen northe B antigen on red blood cells; the other types of bloodhave antigen A, B, or both A and B, respectively (Table 14.2).
Within plasma, there are naturally occurring antibodiesto the antigens not present on the person’s red blood cells.This is reasonable, because if the same antigen and antibodyare present in blood, agglutination, or clumping of redblood cells, occurs. Agglutination causes blood to stop circu-lating and red blood cells to burst.
Figure 14.12 shows a way to use the antibodies derivedfrom plasma to determine the blood type. If agglutinationoccurs after a sample of blood is mixed with a particular an-tibody, the person has that type of blood.
Rh SystemAnother important antigen in matching blood types is the Rhfactor. Persons with the Rh factor on their red blood cells areRh positive (Rh�); those without it are Rh negative (Rh�).Rh-negative individuals normally do not have antibodies tothe Rh factor, but they may make them when exposed to theRh factor during pregnancy or blood transfusion.
If a mother is Rh negative and a father is Rh positive, achild may be Rh positive (Fig. 14.13). The Rh-positive redblood cells of the child may begin leaking across the pla-centa into the mother’s circulatory system, as placentaltissues normally break down before and at birth. This some-times causes the mother to produce anti-Rh antibodies. Inthis or a subsequent pregnancy with another Rh-positivechild, anti-Rh antibodies may cross the placenta and de-stroy the child’s red blood cells. This condition is called he-molytic disease of the newborn (HDN).
278 Part 3 Maintenance of the Human Body 14-16
Antigen % U.S. % NorthBlood on Red Antibody African % U.S. % U.S. American % Americans ofType Blood Cells in Plasma American Caucasian Asian Indians Chinese Descent
A A Anti-B 27 41 28 8 25
B B Anti-A 20 9 27 1 35
AB A,B None 4 3 5 0 10
O None Anti-A and 49 47 40 91 30anti-B
Table 14.2 The ABO System
anti-A
anti-B
anti-Rh
typeblood
O+
B+
A–
AB–
a. No agglutination Agglutination
b.
Figure 14.12 Blood typing. The standard test to determine ABO and Rh blood type consists ofputting a drop of anti-A antibodies, anti-B antibodies, and anti-Rhantibodies on a slide. To each of these, a drop of the person’s bloodis added. a. If agglutination occurs, as seen in the photo on the right,the person has this antigen on red blood cells. b. Several possibleresults.
The Rh problem has been solved by giving Rh-negativewomen an Rh-immunoglobulin injection (often a Rho-Gaminjection) either midway through the first pregnancy or nolater than 72 hours after giving birth to any Rh-positivechild. This injection contains anti-Rh antibodies, which at-tack any of the child’s red blood cells in the mother’s bloodbefore these cells can stimulate her immune system to pro-duce her own antibodies. This injection is not beneficial ifthe woman has already begun to produce antibodies; there-fore, the timing of the injection is most important.
Blood is often typed according to the ABO systemcombined with the Rh system. The possibility ofhemolytic disease of the newborn exists when themother is Rh negative and the father is Rh positive.
Autoimmune DiseasesWhen T cells or antibodies mistakenly attack the body’s owncells as if they bore foreign antigens, the resulting condition isknown as an autoimmune disease. Exactly what causes au-toimmune diseases is not known. However, sometimes theyoccur after an individual has recovered from an infection.
In the autoimmune disease myasthenia gravis, neuro-muscular junctions do not work properly and muscularweakness results. In multiple sclerosis, the myelin sheath ofnerve fibers breaks down, and this causes various neuro-muscular disorders. A person with systemic lupus erythe-matosus has various symptoms prior to death due to kidneydamage. In rheumatoid arthritis, the joints are affected. Re-searchers suggest that heart damage following rheumatic
fever and type I diabetes are also autoimmune illnesses. Asyet there are no cures for autoimmune diseases, but they canbe controlled with drugs.
Autoimmune diseases occur when antibodies andcytotoxic T cells recognize and destroy the body’sown cells.
Tissue RejectionCertain organs, such as skin, the heart, and the kidneys,could be transplanted easily from one person to another ifthe body did not attempt to reject them. Rejection occurs be-cause cytotoxic T cells bring about destruction of foreign tis-sue in the body.
Organ rejection can be controlled by careful selection ofthe organ to be transplanted and the administration of im-munosuppressive drugs. It is best if the transplanted organhas the same type of HLA antigens as those of the recipient,because cytotoxic T cells recognize foreign HLA antigens.The immunosuppressive drug cyclosporine has been usedfor many years. A new drug, tacrolimus (formerly known asFK-506), shows some promise, especially in liver transplantpatients. However both drugs, which act by inhibiting theresponse of T cells to cytokines, are known to adversely af-fect the kidneys.
When an organ is rejected, the immune systemhas recognized and destroyed cells that bear HLAantigens different from those of the individual.
Chapter 14 Lymphatic System and Immunity 27914-17
Figure 14.13 Hemolytic disease of the newborn.Due to a pregnancy in which the child is Rh positive, an Rh-negative mother can begin to produce antibodies against Rh-positive red blood cells.In another pregnancy, these antibodies can cross the placenta and cause hemolysis (bursting of red blood cells) in an Rh-positive child’s redblood cells.
Child is Rh positive;mother is Rh negative
Red blood cells leakacross placenta
Mother makes anti-Rhantibodies
Antibodies attack Rh-positivered blood cells in child
14.1 Lymphatic System The lymphatic system consists of lymphatic vessels and lymphoid or-gans. The lymphatic vessels collect fat molecules at intestinal villi andexcess tissue fluid at blood capillaries, and carry these to the blood-stream.
Lymphocytes are produced and accumulate in the lymphoid or-gans (red bone marrow, lymph nodes, spleen, and thymus gland).Lymph is cleansed of pathogens and/or their toxins in lymph nodes,and blood is cleansed of pathogens and/or their toxins in the spleen. Tlymphocytes mature in the thymus, while B lymphocytes mature in thered bone marrow where all blood cells are produced. White blood cellsare necessary for nonspecific and specific defenses.
14.2 Nonspecific DefensesImmunity involves nonspecific and specific defenses. Nonspecific de-fenses include barriers to entry, the inflammatory reaction, naturalkiller cells, and protective proteins.
14.3 Specific DefensesSpecific defenses require lymphocytes, which are produced in the bonemarrow. B cells mature in the bone marrow. They undergo clonal selec-tion with production of plasma cells and memory B cells after their spe-cific plasma membrane receptors directly combine with a particularantigen. Plasma cells secrete antibodies and eventually undergo apop-tosis. B cells are responsible for antibody-mediated immunity. IgG an-
280 Part 4 Maintenance of the Human Body 14-18
The United Nations estimates that16,000 people become newly infected
with the human immunodeficiency virus(HIV) each day, or 5.8 million per year.Ninety percent of these infections occur inthe less-developed countries1 where in-fected persons do not have access to an-tiviral therapy. In Uganda, for example,there is only one physician per 100,000people, and only $6.00 is spent annuallyon health care, per person. In contrast, inthe United States $12,000–$15,000 is some-times spent on treating an HIV infectedperson per year.
The only methodology to prevent thespread of HIV in a developing country iscounseling against behaviors that increasethe risk of infection. Clearly an effectivevaccine would be most beneficial to thesecountries. Several HIV vaccines are in var-ious stages of development, and all need
to be clinically tested in order to see if theyare effective. It seems reasonable to carryout such trials in developing countries, butthere are many ethical questions.
A possible way to carry out the trial isthis: vaccinate the uninfected sexual part-ners of HIV-infected individuals. After all,if the uninfected partner remains free ofthe disease, then the vaccine is effective.But is it ethical to allow a partner identi-fied as having an HIV infection to remainuntreated for the sake of the trial?
And should there be a placebogroup—a group that does not get the vac-cine? After all, if a greater number of per-sons in the placebo group become infectedthan those in the vaccine group, then thevaccine is effective. But if members of theplacebo group become infected, shouldn’tthey be given effective treatment? For thatmatter, even participants in the vaccine
group might become infected. Shouldn’tany participant of the trial be givenproper treatment if they become infected?Who would pay for such treatment whenthe trial could involve thousands ofpersons?
Questions1. Should HIV vaccine trials be done in
developing countries, which stand to gainthe most from an effective vaccine? Whyor why not?
2. Should the trial be carried out using thesame standards as in developedcountries? Why or why not?
3. Who should pay for the trial—the drugcompany, the participants, or the countryof the participants?
1Country that has only low to moderateindustrialization; usually located in the southernhemisphere.
tibody is a Y-shaped molecule that has two binding sites for a specificantigen. Memory B cells remain in the body and produce antibodies ifthe same antigen enters the body at a later date.
T cells, which are responsible for cell-mediated immunity, maturein the thymus. The two main types of T cells are cytotoxic T cells andhelper T cells. Cytotoxic T cells kill infected cells that bear a foreignantigen on contact; helper T cells stimulate other immune cells andproduce cytokines. Like B cells, each T cell bears a specific receptor.However, for a T cell to recognize an antigen, the antigen must be pre-sented by an antigen-presenting cell (APC), usually a macrophage,along with an HLA (human lymphocyte-associated) antigen. There-after the activated T cell undergoes clonal expansion until the infectionhas been stemmed. Then most of the activated T cells undergo apopto-sis. A few cells remain, however, as memory T cells.
14.4 Induced ImmunityImmunity can be induced in various ways. Vaccines are available to in-duce long-lived active immunity, and antibodies sometimes are avail-able to provide an individual with short-lived passive immunity.
Cytokines, including interferon, are used in an attempt to promotethe body’s ability to recover from cancer and to treat AIDS.
14.5 Immunity Side EffectsAllergic responses occur when the immune system reacts vigorously tosubstances not normally recognized as foreign. Immediate allergicresponses, usually consisting of coldlike symptoms, are due to the ac-tivity of antibodies. Delayed allergic responses, such as contact derma-titis, are due to the activity of T cells.
1. What is the lymphatic system, and what are its three func-tions? 264
2. Describe the structure and the function of lymph nodes, thespleen, the thymus, and red bone marrow. 265–66
3. What are the body’s nonspecific defense mechanisms?266–68
4. Describe the inflammatory reaction, and give a role for eachtype of cell and molecule that participates in the reaction.266
5. What is the clonal selection theory? B cells are responsible forwhich type of immunity? 269
6. Describe the structure of an antibody, and define the termsvariable regions and constant regions. 270
7. Name the two main types of T cells, and state their functions.272
8. Explain the process by which a T cell is able to recognize anantigen. 272–73
9. How is active immunity achieved? How is passive immunityachieved? 274–75
10. What are cytokines, and how are they used in immunother-apy? 275
11. How are monoclonal antibodies produced, and what are theirapplications? 276
12. Discuss allergies, tissue rejection, and autoimmune diseasesas they relate to the immune system. 276–77
Testing Yourself
Choose the best answer for each question.1. Use these terms to label this IgG molecule: antigen-binding
sites, light chain, heavy chain. d. What does V stand for in thediagram? e. What does C stand for in the diagram? f. Whatshape antigen would bind to this particular antigen-bindingsite?
2. Complementa. is a general defense mechanism.b. is involved in the inflammatory reaction.c. is a series of proteins present in the plasma.d. plays a role in destroying bacteria.e. All of these are correct.
3. Which of these pertain(s) to T cells?a. have specific receptorsb. are more than one typec. are responsible for cell-mediated immunity
c.
a.
b.
V
V
C
C C
V
V
C
Chapter 14 Lymphatic System and Immunity 28114-19
d. stimulate antibody production by B cellse. All of these are correct.
4. Which one of these does not pertain to B cells?a. have passed through the thymusb. have specific receptorsc. are responsible for antibody-mediated immunityd. synthesize and liberate antibodies
5. The clonal selection theory says thata. an antigen selects certain B cells and suppresses them.b. an antigen stimulates the multiplication of B cells that
produce antibodies against it.c. T cells select those B cells that should produce antibodies,
regardless of antigens present.d. T cells suppress all B cells except the ones that should
multiply and divide.e. Both b and c are correct.
6. Plasma cells area. the same as memory cells.b. formed from blood plasma.c. B cells that are actively secreting antibody.d. inactive T cells carried in the plasma.e. a type of red blood cell.
7. For a T cell to recognize an antigen, it usually interacts witha. complement.b. a macrophage.c. a B cell.d. a thymus cell.e. All of these are correct.
8. Antibodies combine with antigensa. at variable regions.b. at constant regions.c. only if macrophages are present.d. only if T cells are present.e. Both a and c are correct.
9. Which one of these is mismatched?a. helper T cells—help complement reactb. cytotoxic T cells—active in tissue rejectionc. macrophage—activate T cellsd. memory T cells—long-living line of T cellse. T cells—mature in thymus
10. Vaccines area. the same as monoclonal antibodies.b. treated bacteria or viruses, or one of their proteins.c. short-lived.d. MHC proteins.d. All of these are correct.
11. The theory behind the use of cytokines in cancer therapy isthata. if cancer develops, the immune system has been ineffec-
tive.b. cytokines stimulate the immune system.c. cancer cells bear antigens that should be recognizable by
cytotoxic T cells.d. cytokines can be isolated from the blood.e. All of these are correct.
12. During blood typing, agglutination indicates that thea. plasma contains certain antibodies.b. red blood cells carry certain antigens.c. plasma contains certain antigens.d. red blood cells carry certain antibodies.e. white blood cells fight infection.
Match the terms to these definitions:a. Antigens prepared in such a way that they can
promote active immunity without causing disease.b. Fluid, derived from tissue fluid, that is carried in
lymphatic vessels.c. Foreign substance, usually a protein or a polysac-
charide, that stimulates the immune system to react, such asto produce antibodies.
d. Process of programmed cell death involving acascade of specific cellular events leading to the death anddestruction of the cell.
e. Lymphocyte that matures in the thymus andexists in three varieties, one of which kills antigen-bearingcells outright.
Thinking Scientifically
1. Considering the action of B cells and T cells (page 268):a. A mouse is irradiated so that its bone marrow and thymus
are destroyed. It then is resupplied only with bone mar-row. The mouse is unable to form antibodies. Why?
b. A mixture of B cells is exposed to a specific radiolabeledantigen in vitro (within laboratory glassware). Would youexpect all B cells to bind with the antigen and to be radio-labeled?
c. When B cells and T cells are incubated in vitro with aradiolabeled antigen, binding to certain B cells occurs butnot to T cells. Why?
d. Human beings communicate by sight, sound, and touch.How do immune cells communicate with one another?
2. In this text, antigen originally was defined as a foreign sub-stance in the body.a. Expand this definition by telling what an antigen does in
the body.b. It is possible to tag different types of monoclonal antibod-
ies with different dyes so you can tell them apart. Knowingthis, how would you produce and use monoclonal anti-bodies to distinguish helper T cells and cytotoxic T cells ina blood sample?
c. How would you prove that a monoclonal antibody isspecific to the herpes virus (HSV-2) that causes genitalherpes, but not to the one (HSV-1) that causes cold sores?
d. In a manufacturing process called affinity purification, amixture that contains a desired substance is passedthrough a tube. In the tube, a large number of antibodymolecules are fixed to a solid support. Why will thisprocess result in purification of the product?
plasma cell 269red bone marrow 266spleen 265T lymphocyte 268
thymus gland 266tonsils 265vaccine 274
Using Technology
Your study of the lymphatic system and immunity issupported by these available technologies:
Essential Study Partner CD-ROMAnimals ££ Lymph and Immunity
Visit the Mader web site for related ESP activities.
Exploring the InternetThe Mader Home Page provides resources and tools asyou study this chapter.
http://www.mhhe.com/biosci/genbio/mader
Dynamic Human 2.0 CD-ROMLymphatic System
HealthQuest CD-ROM4 Communicable Diseases6 Cancer
Life Science Animations 3D Video33 Complement System34 How T Lymphocytes Work35 Clonal Selection
