免疫应答概论PPT课件

-,1,TheImmuneSystem,InnateAntimicrobialPeptidesPhagocytes(Macrophages,PMNs,Monocytes,DCs)AlternativeComplementSystem,Acquired(Adaptive)-BLymphocytesAntibody-TLymphocytesCytotoxicity“Help”AntibodyCytokineSecretion,BDC,-,2,2lightchains(or)2heavychains(5isotypes:IgG,M,A,D,E)2Bindingsites(Divalent)SecretedintocirculationBindsSolubleAntigen,2Chains/(95%)or/(5%)1Bindingsite(Monovalent)MembraneBound,NotSecretedBindsAntigenComplexedwithMHC,BandTLymphocyteAntigenReceptors,BDC,-,3,XPID:X-linkedpolyendocrinopathy,immunedysfunctionanddiarrhea,XLAAD:“AutoimmunityAllergicDysreg”Scurfingene(Foxp3/JM2)Immunopathogenesis:Th2Cytokines,abnormalactivation(Il-4,5,13)-Scurfy+Nude:NoAutoimmunity-CD4+intoNude:Disease-BoneMarrowintoirradiated:NoDisease-RequireAntigenStimulationforDisease-MixedChimera:NoDisease,BDC,-,4,HumanLeukocyteAntigenhumanMHCcell-surfaceproteinsimportantinselfvs.nonselfdistinctionpresentpeptideantigenstoTcells,CLASSI:A,B,C,CLASSII:DR,DQ,DP,HLA,J.Noble,-,5,TheHumanLeukocyteAntigenComplex(6p21.31),BDC,HLAClassIandIIMoleculesHaveaDistinctStructureandFunction,BDC,-,7,CisandTrans-ClassIIDimerization,BDC,DQB1*0402,Asp57,Leu56,-chain,-chain,BDC,BDC,-,9,HLA-Peptide:TCR,CDR1,CDR2,CDR3,CDR3,CDR2,CDR1,NH3+,COO-,TCRalpha,TCRbeta,2Helix,1Helix,BDC,-,10,Co-Stimulation,TCell,APC,CTLA-4-,CD28+,CD154,(CD40L),CD2,CD58,CD40,B7,(+)IL-1,IL-6,TNF,IL-10,TGF,(-),TCR-MHC,BDC,-,11,The2-SignalModelofLymphocyteActivation,BDC,-,12,MHC/self-peptide,CD4,MHC/Vb,CD4,CD4+VbxTcell,APC,ActivatedautoreactiveCD4+TCRVbxTH1cell,TCRVbx,TCRVbx,(1)expansionofCD4+,autoreactiveTH1cellsspecificforautoantigens(2)migrationandinfiltrationoftheseselfreactiveCD4+TH1cellsintotissuesandinductionofinflammationandautoimmunity(3)inductionofregulatorycellswhichcontrolthegrowthandactivationofthepathogenicautoreactiverepertoireofCD4+Tcells,InductionofCD4+TH1mediatedautoimmunity:Aparadigmforthepathogenesisofrheumatoidarthritis,multiplesclerosisandtypeIdiabetes,L.Chess2002,-,13,TH1CD4+cells,TH2CD4+cells,CD8orCD4suppressorprecursor,CD8orCD4suppressoreffector,ActivatedCD4Tcells,peptide/APC,RegulatoryimmunityCD4/CD8interactions,(-),(-),TheControlofActivatedCD4+TCellsbyRegulatoryTcells,Apoptosis,RestingCD4Tcells,IL-12/IFN-g,IL-4,NKTcells/CD4+CD25+cellsCD4+CD25-cells,(-),(-),IL-10,IFN-g,L.Chess2002,-,14,TcellactivationisregulatedbysignalsderivedfromtheTCR/CD3/CD4complexandtheCD40LandCD28/CTLA-4co-stimulatorymolecules,L.Chess2002,-,15,g,e,d,V,a,C,a,C,b,V,b,z,z,p56lck,peptide,CD3,CD28,CD40,LFA-3,LFA-1,ICAM-1,MHCII,B7,CD40L,CD4,CD45,TCR,CD2,CD4+TCell,APC/Bcell,h,h,MolecularInteractionsofHelperTCellsandAPC,B7,CTLA-4,VLA-1,Collagen,CD80/CD86,L.Chess2002,-,16,MHC/peptide,TCR,Qa-1/Vb,ActivatedCD4+Tcell,RestingCD4+Tcell,Down-regulationofActivatedCD4+TCells,TcellactivationinducesexpressionoffunctionalTcellsurfacemolecules,RegulatoryCD8+Tcell,TCR(anti-Qa-1/Vb),ActivatedCD8+Tcell,(+),(-),TCR,APC,TCR,LateActivatedCD4+Tcell,VLA-1,Collagen,CD40L,Migrationofsitesofinflammation,InductionandactivationofBcellsAPCs,CD25,L.Chess2002,-,17,ActivatedTH1CD4+TCell,CD4+Cell(TH2),CD4+Cell(TH0),DR3,DR4,DQ8/insulinpeptide,CD2,Macrophage/dendriticcell,FcR,IFN-g,IL-12,CD40L,CD40,a,b,TCR,IL-1,TNF,LT,NO,PGE-2,BCell,?anti-insulin,GADabanti-Mog,IL-4,ImmunopathophysiologyofDiabetes,?Antibodymediatedinjury,Dendriticcell/APC,CD40L,IL-4CD40L,CD8+CTL,FasLperforin,bcelldeath,bisletcells,L.Chess2002,-,18,InnateImmuneSystem:Toll-likereceptoractivationofAPC,TCell,CD28,B7,TCR-MHC,LPS,TollLikeReceptor(patternRecognitionR),IL-1,6,12“Signal3”,Signal2,Signal1,AnitgenPresentingCell(APC),BDC,-,19,Th1vs.Th2CD4TCells,Th1IL-12fordifferentiationCytokines:Interferon-Interleukin-2IntracellularPathogensCD8CytotoxicityDelayedTypeHypersensitivityMacrophageActivation,Th2IL-4fordifferentiationCytokines:Inerluekin-4Interleukin-5Interluekin-13Extracellu