免疫應答課件(英文)

Chapter11.Immuneresponse(1)I.IntroductionII.Antibody-mediatedHumoralImmunityI.Introduction1.ConceptofImmuneResponse2.TypesofImmuneResponse3.ProcessofImmuneResponse1.ImmuneresponseTheimmunesystemofbodyisabletorecognizesubtlechemicaldifferencesthatdistinguishoneforeignpathogenfromanother.Atthesametime,thesystemisabletodiscriminatebetweenforeignmoleculesandthebody’sowncellsandproteins.Onceaforeignorganismisrecognized,theimmunesystemeliminateorneutralizetheorganism,finally.2.TypesofImmuneResponse

Autoimmunity

selectionImmune“Self”AgAutoimmuneTolerance

Agsystem:

activation“non-self”AgHI/CMI

ImmuneTolerance

HypersensitivityReactionII.Antibody-mediatedHumoralImmunity

conceptofHI，simpleprocessofHI1.CommonruleofAbproduction2.InteractionbetweenimmunecellsinprocessofproducingAb

3.ImmuneMemory4.EffectofHumoralImmunity

HumoralImmunity，HI

Humoralimmunityismediatedbyantibodiesofvariousdifferentclasses;whichAbareproducedbycellsoftheBcelllineageinresponsetostimulationbyAg.SimpleprocessofHI:1、TD—AgAPCTHBL2

THm

BLm2、TI—AgBL1MatureBcellPlasmacells

Ab

HI1.CommonruleofAbproductiona.TheregularityofIgproductioninphylogenicevolutionanddevelopment,andontogenesis.b.TheregularityofAbproductionintheprimaryandsecondaryresponse。SecondaryImmuneResponse

Whentheimmunizedindividualafteraprimarycontactwithantigenisinjectedbyasecondinjection

ofthesameantigen,productionofantibodybecomesapparent,thisresponseiscalledthesecondaryresponse.

PrimaryIR

SecondaryIRAntigenThefirstcontactofanAsecondinjectionoftheindividualwithanAgsameAglatentperiodlong(1W，2-3W)short(1-3day)slowofAbproductionAbConc.lowinserumhighinserumMaintainTimeshort,decreasequicklylongertypeofIg

IgM

IgGAffinitylowerhigherpresentofAgM,DCBcellConcentrationofIg

IgIgMIgG10day3dayLatentperiodPrimarystimulationofAgSecondarystimulationofAg2.Interactionbetweenimmunecells

intheprocessofproducingAbTD—Agresponsea.InteractionbetweenMandThcells

*MpresentedAg*Interactionbetweencells

b.InteractionbetweenThcellandBcells*BcellpresentedAg*Interactionbetween

cellsc.InteractionbetweenMandBcellsTI—Agresponse

Bcell:responseofTI—Ag

Agsareingested,processed,presented

byM(primaryresponse)Ingestion：endocytosis,passiveadhesion。Processing：lysosomalenzymescondenseanddegradeAg,andcombinetoself-MHCIImolecules.Presentation：ThesecomplexesofpeptideandMHCmoleculesaretransportedtothesurfaceofthecellwheretheyarerecognizedbytheT-cellreceptor.ExogenousAgendosomeTransportationcombinationdegradationexpressionendocytosisAPCCD4TCRMHCIItranscriptionDNAmRNAVirus（endogenousAg）translationPrdegradationCD8CTLMHCITargetcellTCRInteractionbetweenMandThcells

（primaryresponse）

DoublesignalhypothesisofThcellactivation：Thefirstsignal：Th:TCR/CD3——APC:Ag-MHCIIcomplexesatthesametime,TH:CD4——APC:The2,2domainofMHCIIThesecondsignal：APC:B7/BB1（CM）——TH:CD28（CMR）THsecretedIL-2andexpressedIL-2RFinallycellsdivide,clonesproliferation,andproduceakindofCK.ICAM-1LFA-1

APC(CMs)MHC-IIAgB7/BB1VLA-4VCAM-1CD2CD58Cellactivation,（CK）celldifferentiationandcloneproliferation

TH(CMRs)TCRCD3CD4CD28CTLA4Signal1Signal2IL-2IL-2RInteractionbetweenAPCandThcellMHC-AgAPCTCR/CD3B7/BB1CD28THSignal1Signal2

IL-2productioncloneproliferationAPCTHSignal1Signal2

not

IL-2productioncloneanergyinactivationSuppressiveimmuneresponse：HypersensitivityDiseaseAutoimmunityDiseaseGraftrejectionresponsesAnti-B7AbCTLA4IgAnti-CD28Interdictionofco-stimulatorysignalsTHAPCMHCTCRAgCD28B7Enhancingimmuneresponse：TumorimmunitytreatmentB7TransfectionB7geneCTLMHCTCRAgCD28Tumorcellsignal1signal2CTLMHCTCRAgCD28Tumorcellsignal1signal2CTLactivatedKillertumorcellCTLactivatedKillertumorcell

InteractionbetweenThandBcells

（secondaryresponse）Thcellactivation：DoublesignalhypothesisSignal1：Th:TCR/CD3——Bcell:Ag-MHCIIcomplexes

Th:CD4——Bcell:The2,2domainofMHCIISignal2：Th:CD28molecule——Bcell:B7molecule.Bcellactivation：DoublesignalhypothesisSignal1：Bcell:BCR--Ag，Ig,Igtransferactivationsignal1Signal2：Bcell:CD40——Th:CD40LThandBcellinducingsignalofactivationeachother，ThproducedIL-4,5,6.BcellishelpedatThcell,finallyBcellproliferatedanddifferentiatedturnintotheplasmacellsofproducingakinkofIgs.

CD3singalBcellactivationBcellAgSIg12Signal1TcellB7CD28ICAM-1LFA-1CD3TCRCD4MHC-IICD40LCD40LFA-1ICAM-1Signal2ThactivationCKAgprocesspresentInteractionbetweenBcellandTcellCKRAgBmBBBBPCIgMIgGIgAIgEBmBmBmBmActivateThActivateBIL-2，4，5，6IL-1processpresentprocesspresentproliferationingestioningestionMHC-IIMHC-IITCRTCRMMdifferentiationc.InteractionbetweenMandBcellssignalsignalBcellBcell

Itype:TI—Agispolyclonalstimulator

IItype:multiplerepeat-linedantigenicdeterminantmakesreceptorlinkageTI-Agresponse3.ImmuneMemory-SecondaryresponseCharacteristic:a.Immunememorycellsb.ClassswitchingofIgc.AffinityMaturationofAbCharacteristic：

*

Immunememorycells:THm

Bm

*InvolvedinHumoralimmunityandcell-mediatedimmunty.*Abconc.increases，classswitchingofAb，

andaffinitymaturationofAb4.EffectofHumoralImmunityNeutralizationofAbOpsonizationofAbComplementdependentcell-mediatedcytotoxicity,CDCAntibodydependentcell-mediatedcytotoxicity,ADCCImmuneregulationofAbOpsonizationofAbBacteriaAnti-bacteriaAb

MFcrRBoostuplickupactionTargetcellM,NKDissolutionoftargetcellIgGSurfaceAgFcrRAntibody-dependentcell-mediatedcytotoxicity,ADCCChapter12.Immuneresponse(2)I.IntroductionII.CD4T-mediatedimmunityIII.CD8T-mediatedimmunityI.Introduction

1.Concept,Simpleprocess2.MajorfunctionsofCMISimpleprocess:TD-AgImmunesystemsecondaryTDTHTcCKCytotocixity2.MajorFunctionsofCMIDelayedTypeHypersensitivity,DTHIntracellularAnti-infectionAnti-tumorTransplantationrejectionreactionGraftVersusHostReaction,GVHRAutoimmunitydiseasesII.CD4T-mediatedimmunity

1.ActivationofCD4Tcells

2.FormationofDTHinflammation

*CKproduction*FunctionofM

ActivationofCD4TcellsDoublesignalhypothesisofCD4Tcellactivation：Thefirstsignal：Th:TCR/CD3——APC:Ag-MHCIIcomplexesatthesametime,TH:CD4——APC:The2,2domainofMHCIIThesecondsignal：APC:B7/BB1（CM）——TH:CD28（CMR）THsecretedIL-2andexpressedIL-2RFinallycellsdivide,clonesproliferation,andproduceakindofCK.IL-2RIL-2R

APC(CMs)

TH(CMRs)CD28CTLA4CD3TCRCD4ICAM-1LFA-1MHC-IIAgB7/BB1VLA-4VCAM-1CD2CD58Signal1Signal2IL-2IL-2RCellactivation,（CK）celldifferentiationandcloneproliferationAPCTAPCTAPCTTTTTIL-2IFNrTNFTM

restM

activationCKofDTHreactionIII.CD8T-mediatedimmunity1.ActivationofCD8T