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MonocyteEosinophilMast cellMacrophageNeutrophilBasophilPhagocytes, granulocytes, and mast cells, all withdifferent methods of attack, demonstrate the immunesystem’s versatility.Both kinds of killer cells slay on contact.The deadly assassins bind to their targets,aim their weapons, and then deliver alethal burst of chemicals.Phagocytes and Their RelativesPhagocytes are large white cells that canswallow and digest microbes and otherforeign particles. Monocytes arephagocytes that circulate in the blood.When monocytes migrate into tissues,they develop into macrophages.Specialized types of macrophages can befound in many organs, including lungs,kidneys, brain, and liver.14

Macrophages play many roles. Asscavengers, they rid the body of worn-outcells and other debris. They display bitsof foreign antigen in a way that draws theattention of matching lymphocytes. Andthey churn out an amazing variety ofpowerful chemical signals, knownas monokines, which are vital to theimmune responses.Granulocytes are another kind of immunecell. They contain granules filled withpotent chemicals, which allow thegranulocytes to destroy microorganisms.Some of these chemicals, such ashistamine, also contribute to inflammationand allergy.One type of granulocyte, the neutrophil, isalso a phagocyte; it uses its prepackagedchemicals to break down the microbes itingests. Eosinophils and basophils aregranulocytes that “degranulate,” sprayingtheir chemicals onto harmful cells ormicrobes nearby.The mast cell is a twin of the basophil,except that it is not a blood cell. Rather, itis found in the lungs, skin, tongue, andlinings of the nose and intestinal tract,where it is responsible for the symptomsof allergy.A related structure, the blood platelet, is acell fragment. Platelets, too, contain15

granules. In addition to promoting bloodclotting and wound repair, plateletsactivate some of the immune defenses.CytokinesComponents of the immune systemcommunicate with one another byexchanging chemical messengers calledcytokines. These proteins are secreted bycells and act on other cells to coordinate anappropriate immune response. Cytokinesinclude a diverse assortment of interleukins,interferons, and growth factors.Some cytokines are chemical switches thatturn certain immune cell types on and off.One cytokine, interleukin 2 (IL-2), triggersthe immune system to produce T cells. IL2’s immunity-boosting properties havetraditionally made it a promising treatmentfor several illnesses. Clinical studies areongoing to test its benefits in otherdiseases such as cancer, hepatitis C, andCytokines includelymphokines,produced bylymphocytes, andmonokines, madeby monocytes andmacrophages.LymphokinesMature helper T cell16MonokinesMacrophage

HIV infection and AIDS. Other cytokinesalso are being studied for their potentialclinical benefit.Other cytokines chemically attract specificcell types. These so-called chemokines arereleased by cells at a site of injury orinfection and call other immune cells tothe region to help repair the damage orfight off the invader. Chemokines oftenplay a key role in inflammation and area promising target for new drugs to helpregulate immune responses.ComplementThe complement system is made up ofabout 25 proteins that work together to“complement” the action of antibodies indestroying bacteria. Complement also helpsto rid the body of antibody-coated antigens(antigen-antibody complexes). Complementproteins, which cause blood vessels tobecome dilated and then leaky, contributeto the redness, warmth, swelling, pain, andloss of function that characterize aninflammatory response.Complement proteins circulate in the bloodin an inactive form. When the first proteinin the complement series is activated—typically by antibody that has locked ontoan antigen—it sets in motion a dominoeffect. Each component takes its turn in aprecise chain of steps known as thecomplement cascade. The end product is a17

AntigenFirst complement proteinAntibody (IgG)Complement cascadeCellswellsandburstsCylindrical complexinserted in cell wallThe interlocking steps of the complement cascade end incell death.cylinder inserted into—and puncturing ahole in—the cell’s wall. With fluids andmolecules flowing in and out, the cellswells and bursts. Other components of thecomplement system make bacteria moresusceptible to phagocytosis or beckon othercells to the area.18

Mounting an Immune ResponseInfections are the most common cause ofhuman disease. They range from thecommon cold to debilitating conditions likechronic hepatitis to life-threateningdiseases such as AIDS. Disease-causingmicrobes (pathogens) attempting to getinto the body must first move past thebody’s external armor, usually the skin orcells lining the body’s internal passageways.The skin provides an imposing barrier toinvading microbes. It is generallypenetrable only through cuts or tinyabrasions. The digestive and respiratoryLymphokinesComplementT cellAntibodiesB cellMacrophageKiller cellVirusWhen challenged, the immune system has manyweapons to choose.19

tracts—both portals of entry for a numberof microbes—also have their own levels ofprotection. Microbes entering the noseoften cause the nasal surfaces to secretemore protective mucus, and attempts toenter the nose or lungs can trigger asneeze or cough reflex to force microbialinvaders out of the respiratorypassageways. The stomach contains astrong acid that destroys many pathogensthat are swallowed with food.If microbes survive the body’s front-linedefenses, they still have to find a waythrough the walls of the digestive,respiratory, or urogenital passageways tothe underlying cells. These passagewaysare lined with tightly packed epithelial cellscovered in a layer of mucus, effectivelyblocking the transport of many organisms.Mucosal surfaces also secrete a specialclass of antibody called IgA, which inmany cases is the first type of antibody toencounter an invading microbe.Underneath the epithelial layer a numberof cells, including macrophages, B cells,and T cells, lie in wait for any germ thatmight bypass the barriers at the surface.Next, invaders must escape a series ofgeneral defenses, which are ready toattack, without regard for specific antigenmarkers. These include patrollingphagocytes, NK cells, and complement.20

Microbes that cross the general barriersthen confront specific weapons tailoredjust for them. Specific weapons, whichinclude both antibodies and T cells, areequipped with singular receptor structuresthat allow them to recognize and interactwith their designated targets.Bacteria, Viruses, and ParasitesThe most common disease-causingmicrobes are bacteria, viruses, andparasites. Each uses a different tactic toinfect a person, and, therefore, each isthwarted by a different part of theimmune system.Most bacteria live in the spaces betweencells and are readily attacked byantibodies. When antibodies attach to abacterium, they send signals tocomplement proteins and phagocytic cellsto destroy the bound microbes. Somebacteria are eaten directly by phagocytes,which signal to certain T cells to jointhe attack.All viruses, plus a few types of bacteriaand parasites, must enter cells to survive,requiring a different approach. Infectedcells use their MHC molecules to putpieces of the invading microbes on thecell’s surface, flagging down cytotoxicT lymphocytes to destroy the infected cell.Antibodies also can assist in the immune21

Antibodies are triggered when a B cellencounters its matching antigen.The B cell takes in the antigenand digests it,then it displays antigen fragmentsbound to its own distinctiveMHC molecules.The combination of antigenfragment and MHCmolecule attractsthe help of amature, matchingT cell.Lymphokines secreted bythe T cell allow the B cell tomultiply and mature intoantibody-producing plasma cells.Released into the bloodstream, antibodies lock ontomatching antigens. These antigen-antibody complexesare soon eliminated, either by the complement cascadeor by the liver and the spleen.22

T cells are mobilizedwhen they encounter a cell such as a macrophageor a B cell that has digested an antigenand is displaying antigen fragmentsbound to its MHC molecules.Lymphokineshelp the T cellto matureThe T cell, alertedand activated,secreteslymphokines.InfectedcellsSome lymphokinesattract immune cells—fresh macrophages,granulocytes, andother lymphocytes—to the site of infection.Yet other lymphokinesdirect the recruits oncethey arrive on the scene.Somelymphokinesspur thegrowth ofmore T cells.Some T cellsbecome killer cellsand track downbody cells infectedby viruses.23

response, attaching to and clearing virusesbefore they have a chance to enter the cell.Parasites live either inside or outside cells.Intracellular parasites such as the organismthat causes malaria can trigger T-cellresponses. Extracellular parasites are oftenmuch larger than bacteria or viruses andrequire a much broader immune attack.Parasitic infections often trigger aninflammatory response when eosinophils,basophils, and other specialized granularcells rush to the scene and release theirstores of toxic chemicals in an attempt todestroy the invader. Antibodies also play arole in this attack, attracting the granularcells to the site of infection.Immunity: Natural and AcquiredLong ago, physicians realized that peoplewho had recovered from the plague wouldnever get it again—they had acquiredimmunity. This is because some of theactivated T and B cells become memory cells.The next time an individual meets up withthe same antigen, the immune system isset to demolish it.Immunity can be strong or weak, shortlived or long-lasting, depending on the typeof antigen, the amount of antigen, and theroute by which it enters the body.24

AntigenNaturalNaturalS E RU MAcquiredAcquiredImmunity can also be influenced byinherited genes. When faced with the sameantigen, some individuals will respondforcefully, others feebly, and some not at all.An immune response can be sparked notonly by infection but also by immunizationwith vaccines. Vaccines containmicroorganisms—or parts ofmicroorganisms—that have been treated sothey can provoke an immune response butnot full-blown disease.Immunity can also be transferred from oneindividual to another by injections ofserum rich in antibodies against aparticular microbe (antiserum).25

For example, immune serum is sometimesgiven to protect travelers to countrieswhere hepatitis A is widespread. Suchpassive immunity typically lasts only a fewweeks or months.Infants are born with weak immuneresponses but are protected for the first fewmonths of life by antibodies received fromtheir mothers before birth. Babies who arenursed can also receive some antibodiesfrom breast milk that help to protect theirdigestive tracts.Immune ToleranceImmune tolerance is the tendency of T orB lymphocytes to ignore the body’s owntissues. Maintaining tolerance is importantbecause it prevents the immune systemfrom attacking its fellow cells. Scientistsare hard at work trying to understand howthe immune system knows when torespond and when to ignore.Tolerance occurs in at least two ways.Central tolerance occurs during lymphocytedevelopment. Very early in each immunecell’s life, it is exposed to many of the selfmolecules in the body. If it encountersthese molecules before it has fullymatured, the encounter activates aninternal self-destruct pathway and theimmune cell dies. This process, called26

clonal deletion, helps ensure that selfreactive T cells and B cells do not matureand attack healthy tissues.Because maturing lymphocytes do notencounter every molecule in the body, theymust also learn to ignore mature cells andtissues. In peripheral tolerance, circulatinglymphocytes might recognize a selfmolecule but cannot respond because someof the chemical signals required to activatethe T or B cell are absent. So-called clonalanergy, therefore, keeps potentially harmfullymphocytes switched off. Peripheraltolerance may also be imposed by a specialclass of regulatory T cells that inhibitshelper or cytotoxic T-cell activation byself antigens.VaccinesMedical workers have long helped thebody’s immune system prepare for futureattacks through vaccination. Vaccinesconsist of killed or modified microbes,components of microbes, or microbial DNAthat trick the body into thinking aninfection has occurred. An immunizedperson’s immune system attacks theharmless vaccine and prepares forsubsequent invasions. Vaccines remain oneof the best ways to prevent infectiousdiseases and have an excellent safetyrecord. Previously devastating diseasessuch as smallpox, polio, and whooping27

cough have been greatly controlled oreliminated through worldwidevaccination programs.Disorders of the Immune SystemAllergic DiseasesThe most common types of allergicdiseases occur when the immune systemresponds to a false alarm. In an allergicperson, a normally harmless material suchas grass pollen or house dust is mistakenfor a threat and attacked.Allergies such as pollen allergy are relatedto the antibody known as IgE. Like otherantibodies, each IgE antibody is specific;one acts against oak pollen, anotheragainst ragweed.Autoimmune DiseasesSometimes the immune system’srecognition apparatus breaks down, andthe body begins to manufacture T cells andantibodies directed against its own cellsand organs. Misguided T cells andautoantibodies, as they are known,contribute to many diseases. For instance,T cells that attack pancreas cells contributeto diabetes, while an autoantibody knownas rheumatoid factor is common in peoplewith rheumatoid arthritis. People withsystemic lupus erythematosus (SLE) have28

RagweedpollenB cellThe first time the allergy-proneperson runs across an allergensuch as ragweed,IgEhe or she makes large amountsof ragweed IgE antibody.PlasmacellThese IgE molecules attachthemselves to mast cells.MastcellThe second time that personhas a brush with ragweed,the IgE-primed mast cell willrelease its powerful chemicals,ChemicalsSymptomsand the person will suffer thewheezing and/or sneezing,runny nose, watery eyes, anditching of allergy.29

PancreasMature T cellBeta cellMisguided T cells can attack insulin-producing cells ofthe pancreas, contributing to diabetes.antibodies to many types of their own cellsand cell components.No one knows exactly what causes anautoimmune disease, but multiple factorsare likely to be involved. These includeelements in the environment, such asviruses, certain drugs, and sunlight, all ofwhich may damage or alter normal bodycells. Hormones are suspected of playing arole, since most autoimmune diseases arefar more common in women than in men.Heredity, too, seems to be important.Many people with autoimmune diseaseshave characteristic types of selfmarker molecules.30

Immune Complex DiseasesImmune complexes are clusters ofinterlocking antigens and antibodies.Normally, immune complexes are rapidlyremoved from the bloodstream. Sometimes,however, they continue to circulate, andeventually become trapped in the tissues ofthe kidneys, the lungs, skin, joints, orblood vessels. There they set off reactionswith complement that lead to inflammationand tissue damage.Immune complexes work their mischief inmany diseases. These include malaria andviral hepatitis, as well as manyautoimmune diseases.LargecomplexEndothelial cellGlomerular basementmembrane of kidneySmall complexAntigen-antibody complexes can become trapped in,and damage, the kidneys and other organs.31

Immunodeficiency DisordersWhen the immune system is missing oneor more of its components, the result is animmunodeficiency disorder.Immunodeficiency disorders can beinherited, acquired through infection, orproduced unintentionally by drugs such asthose used to treat people with cancer orthose who have received transplants.Temporary immune deficiencies candevelop in the wake of common virusinfections, including influenza, infectiousmononucleosis, and measles. Immuneresponses can also be depressed by bloodtransfusions, surgery, malnutrition,smoking, and stress.Some children are born with poorlyfunctioning immune systems. Some haveflaws in the B cell system and cannotproduce antibodies. Others, whose thymusis either missing or small and abnormal,lack T cells. Very rarely, infants are bornlacking all of the major immune defenses.This condition is known as severe combinedimmunodeficiency disease or SCID.AIDS is an immunodeficiency disordercaused by a virus (HIV) that infectsimmune cells. HIV can destroy or disablevital T cells, paving the way for a varietyof immunologic shortcomings. HIV alsocan hide out for long periods in immune32

Virus componentsVirus DNAT cellNewvirusCell DNANew AIDSvirus buddingfrom T cellThe AIDS virus takes over the machinery of the T cells itinfects, using it to make new viruses.cells. As the immune defenses falter, aperson with AIDS falls prey to unusual,often life-threatening infections andrare cancers.A contagious disease, AIDS is spread byintimate sexual contact, transfer of thevirus from mother to infant duringpregnancy, or direct blood contamination.There is no cure for AIDS, but newlydeveloped antiviral drugs can slow theadvance of the disease, at least for a time.Researchers also are testing HIV vaccinesin clinical studies.33

Cancers of the Immune SystemThe cells of the immune system, like othercells, can grow uncontrollably, resulting incancer. Leukemias are caused by theproliferation of white blood cells, orleukocytes. The uncontrolled growth ofantibody-producing plasma cells can leadto multiple myeloma. Cancers of thelymphoid organs, known as lymphomas,include Hodgkin’s disease.Immunology and TransplantsEach year thousands of American lives areprolonged by transplanted organs—kidney, heart, lung, liver, and pancreas. Fora transplant to “take,” however, the body’snatural tendency to rid itself o

gradually drift back into the lymphatic system, to begin the cycle all over again. The spleen is a flattened organ at the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and work, and serves as