Medical Microbiology

thethree-dimensionalstructuresofcomplex,foldedproteins,andhydro-

carbons.Chemically,B-cellreceptorsareglobulins(“immunoglobulins”)

andcompriseanastoundingvarietyofspecifictypes.Despitethedivision

ofimmunoglobulinsintoclassesandsubclasses,theyallshareessentially

thesamestructure.SwitchingfromoneIgclasstoanothergenerallyrequires

T-cellhelp.

Tcellsrecognizepeptidespresentedonthecellsurfacebymajorhisto-

compatibility(gene)complex(MHC)molecules.AT-cellresponsecanonly

beinitiatedwithinorganizedlymphoidorgans.NaiveTcellscirculatethrough

theblood,spleen,andotherlymphoidtissues,butcannotleavethesecom-

partmentstomigratethroughperipheralnonlymphoidtissuesandorgans

unlesstheyareactivated.Selfantigens(autoantigens),presentedinthethy-

musandlympoidtissuesbymobilelymphohematopoieticcells,induceT-cell

destruction(so-callednegativeselection).Antigensthatareexpressedonly

intheperiphery,thatisoutsideofthethymusandsecondarylymphoidor-

gans,areignoredbyTcells;potentiallyautoreactiveTcellsarethusdirected

againstsuchselfantigens.Tcellsreacttopeptidesthatpenetrateintothe

organizedlymphoidtissues.Newantigensarefirstlocalizedwithinfewlym-

phoidtissuesbeforetheycanspreadsystemically.Thesemustbepresentin

lymphoidtissuesforthreetofivedaysinordertoelicitanimmuneresponse.

Animmuneresponsecanbeinducedagainstapreviouslyignoredselfantigen

thatdoesnotnormallyenterlymphoidtissuesifitsentryisinducedbycir-

cumstance,forinstance,becauseofcelldestructionresultingfromchronic

peripheralinfection.Itisimportanttorememberthatinductionofasmall

numberofTcellswillnotsufficetoprovideimmuneprotectionagainsta

pathogen.Suchprotectionnecessitatesacertainminimumsumofactivated

Tcells. &

Thefunctionoftheimmunologicalapparatusisbasedonacomplexseries

ofinteractionsbetweenhumoral,cellular,specific,andnonspecificmechan-

isms.Thiscanbebetterunderstoodbyexamininghowtheindividualcom-

ponentsoftheimmuneresponsefunction.

Thehumanimmunologicalsystemcanbeconceivedasawidelydis-

tributedorgancomprisingapproximately 1012 individualcells,mainlylym-

phocytes,withatotalweightofapproximately 1 kg.Leukocytesarisefrom

pluripotentstemcellsinthebonemarrow,thendifferentiatefurtherastwo

distinctlineages.Themyeloidlineageconstitutesgranulocytesandmono-

cytes,whichperformimportant basicdefensefunctionsas phagocytes

(“scavengercells”).Thelymphoidlineagegivesrisetotheeffectorcellsof

thespecificimmuneresponse,TandBlymphocytes.Thesecellsarecon-

stantlybeingrenewed(about 106 newlymphocytesareproducedinevery

minute)anddestroyedinlargenumbers(seeFig.2. 17 ,p.88).TandBlym-

phocytes,whilemorphologicallysimilar,undergodistinctmaturationpro-

46 2 BasicPrinciplesofImmunology

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Kayser, Medical Microbiology © 2005 Thieme