Medical Microbiology

Thereisnosurfacemarkerwhichcanunequivocallydifferentiatebetween

memoryTandBcellsand“naive”(neverbeforeactivated)cells.Instead,im-

munologicalmemoryisnormallytakentocorrelatewithanincreasednum-

berofspecificprecursorTandBcells.Followinganinitialimmunizationwith

antigen,thisincreasedprecursorfrequencyofspecificcellsisthoughttobe

maintainedbyanantigen-independentprocess.Yettheprecursorcellscan

onlybeactivated(orre-activated)byantigen,andonlyactivatedTcellscan

provideimmediateprotectionagainstre-infectionoutsidethelymphoidor-

gans,e.g.,inthesolidperipheralorgans.Similarly,onlyantigenactivated

Bcellscanmaturetobecomeplasmacellswhichmaintaintheincreasedblood

antibodytitersresponsibleformediatingprotection.Thisindicatesthatre-

sidualantigenmustbepresenttomaintainprotectiveimmunologicalmem-

ory.Asageneralrule,thelevelofprotectiveimmunitymediatedbytheex-

istenceofmemoryTandBcellsperseisminimal.Highlyeffectiveimmunity

andresistancetore-infectionareinsteadprovidedbymigratoryTcellswhich

havebeenrecentlyactivated(orre-activated)byantigen,andbyantibody-

secretingBcells.B-cellandantibodymemoryismaintainedbyre-encoun-

terswithantigen,orbyantigen-IgGcomplexeswhichbyvirtueoftheir

FcportionsorbybindingtoC3barecapturedby-,andmaintainedfor

longperiodson-,folliculardendriticcellspresentingerminalcenters.Mem-

oryTcells,andinsomecasesBcells,canbere-stimulatedandmaintained

inanactivestateby:persistentinfections(e.g.,tuberculosis,hepatitisB,HIV);

antigendepositsinadjuvants;periodicantigenre-exposure;peptide-loaded

MHCmoleculeswithlonghalf-lives;orpossibly(butrarely)bycross-reactive

antigens.Thus,secondarilyactivated(protective)memoryTandBcellscan-

noteasilybedistinguishedfromprimarilyactivatedTandBcells.Theanti-

gen-dependentnatureofimmunologicalprotectionindeedquestionsthe

relevanceofaspecialized“memoryquality”ofBandTcells.

B-CellMemory.............................................

ItisimportanttodifferentiatebetweenthecharacteristicsofmemoryTand

Bcellsasdetectedinvitro,andthesalientin-vivoattributesofimproved

immunedefenses.Followingaprimaryimmuneresponse,increasednum-

bersofmemoryBcellscanofcoursebedetectedusinginvitroassaysor

bymurineexperimentsinvolvingthetransferofcellsintonaiverecipients.

However,theseincreasedBcellfrequenciesdonotnecessarilyensureim-

muneprotectionagainst,forinstance,viralre-infection.Suchprotection

requirestheexistenceofanincreasedtiterofprotectiveantibodieswithin

thehost.

96 2 BasicPrinciplesofImmunology

2

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Kayser, Medical Microbiology © 2005 Thieme

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