Medical Microbiology

ofvarioustyrosinekinases(Fig.2. 11 )andmediatesstringentanddifferential

regulationofseveralsignalingsteps.T-cellinductionandactivationresult

fromtheactivationoftwosignals.InadditiontoTCRactivation(signal 1 =

antigen),acostimulatorysignal(signal2)isusuallyrequired.Importantcost-

imulatorysignalsaredeliveredbythebindingofB7(B7. 1 andB7.2)proteins

(presentontheAPCorBcell)toligandsontheTcells(CD28protein,CTLA-4),or

byCD40–CD40ligandinteractions.T-cellexpansionisalsoenhancedbyIL-2.

T-CellActivationbySuperantigens....................

InassociationwithMHCclassIImolecules,anumberofbacterialandpossibly

viralproductscanefficientlystimulatealargerepertoireofCD4+Tcellsatone

time.Thisisoftenmediatedbythebindingofthebacterialorviralproduct

totheconstantsegmentofcertainVbchains(andpossiblyVachains)witha

lowlevelofspecificity(seeFig.2.9a,p.65).Superantigensarecategorizedas

eitherexogenousorendogenous.Exogenoussuperantigensmainlyinclude

bacterialtoxins(staphylococcusenterotoxintypesA-E[SEA,SEB,etc.]),toxic

shocksyndrometoxin(TSST),toxinsfromStreptococcuspyogenes,andcertain

retroviruses.Endogenoussuperantigensarederivedfromcomponentsof

certainretrovirusesfoundinmice,andwhichdisplaysuperantigen-likebe-

havior(e.g.,murinemammarytumorvirus,MMTV).Thefunctionofsuper-

antigensduringTcellactivationcanbecomparedtotheeffectofbacterial

lipopolysaccharidesonBcells,inthatLPS-inducedBcellactivationisalso

polyclonal(althoughitfunctionsbywayoftheLPSreceptorsinsteadof

theIgreceptors(seebelow)).

InteractionsbetweenCellsoftheImmuneSystem.......

THelperCells(CD4+TCells)and

T-BCellCollaboration

MatureTcellsexpressingCD4arecalledThelper(Th)cells(seealsop. 6 4f.),

reflectingtheirroleinco-operatingwithBcells.Foreignantigens,whose

three-dimensionalstructuresarerecognizedbyBcells,alsocontainlinear

peptides.DuringtheinitialphaseoftheThelpercellresponse,theseanti-

gensaretakenupbyAPCs,processed,andpresentedaspeptidesinassocia-

tionwithMHCclassIImolecules—allowingtheirrecognitionbyThcells(see

Fig.2. 8 ,p. 61 andFig.2. 13 ,p. 7 6).PriortoourunderstandingofMHCrestric-

tion,B-cellepitopeswereknownashaptens,whilstthosepartsofthe

antigenswhichboretheT-cellepitopewereknownascarriers.Inorder

72 2 BasicPrinciplesofImmunology

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Kayser, Medical Microbiology © 2005 Thieme