免疫应答概论 课件

The Immune SystemInnateAntimicrobial PeptidesPhagocytes(Macrophages,PMNs,Monocytes,DCs)Alternative Complement SystemAcquired(Adaptive)-B Lymphocytes Antibody-T Lymphocytes Cytotoxicity “Help”Antibody Cytokine SecretionBDCThe Immune SystemInnateAcquire12 light chains(or)2 heavy chains(5 isotypes:IgG,M,A,D,E)2 Binding sites(Divalent)Secreted into circulationBinds Soluble Antigen2 Chains/(95%)or/(5%)1 Binding site(Monovalent)Membrane Bound,Not SecretedBinds Antigen Complexed with MHCZap 70fynlckg ge ez zV V C C CH1CH2CH3CH2CH3CH1CLCLVLVLVHVHe ed dz zIg/IgIg/IgBlk,Fyn or LynB and T Lymphocyte Antigen ReceptorsBDC2 light chains(or)2 Chain2XPID:X-linked polyendocrinopathy,immune dysfunction and diarrheaXLAAD:“Autoimmunity Allergic Dysreg”Scurfin gene(Foxp3/JM2)Immunopathogenesis:Th2 Cytokines,abnormal activation(Il-4,5,13)-Scurfy+Nude:No Autoimmunity-CD4+into Nude:Disease-Bone Marrow into irradiated:No Disease-Require Antigen Stimulation for Disease-Mixed Chimera:No DiseaseBDCXPID:X-linked polyendocrinopa3Human Leukocyte Antigenhuman MHCcell-surface proteinsimportant in self vs.nonself distinctionpresent peptide antigens to T cellsCLASS I:A,B,CCLASS II:DR,DQ,DPHLAJ.NobleHuman Leukocyte AntigenCLASS I4The Human Leukocyte Antigen Complex (6p21.31)DP DQ DR B C AClass II (1.1 Mb)Class IIIClass I (2.2Mb)Complement and CytokinesClass I-like genesand pseudogenesFrequent Recombination Recombinationis RareTelomereCentromere Recombinationis Rare(0.7Mb)BDCThe Human Leukocyte Antigen Co5 3 211 2211221122Binds 8-10mersExpressed on most Nucleated cellsPresents Cytosolic Proteins to CD8+T cellsBinds 13-25mersExpressed on APCs,Macs,B cells,activated T cellsPresents Vesicular Proteins to CD4+T cellsClass IClass IIHLA Class I and II Molecules Have a Distinct Structure and FunctionBDCa3b2a1a2a1a2b1b2Binds 8-10mers60501 02010301 0302 ciscisDQA1 DQB1transDQA1*0301/DQB1*0201DQA1*0501/DQB1*0302DQA1*0501/DQB1*0201DQA1*0301/DQB1*0302MaternalPaternalCis and Trans-Class II DimerizationBDC0501 02010307DQB1*0402Asp57 Leu56 -chain-chainBDCBDCDQB1*0402Asp57Leu56-chain8HLA-Peptide:TCRCDR1CDR2CDR3CDR3CDR2CDR1NH3+COO-TCRalphaTCRbeta2 Helix1 HelixBDCHLA-Peptide:TCRCDR1CDR2CDR3CD9Co-Stimulation TCellAPCCTLA-4-CD28+CD154(CD40L)CD2CD58CD40B7(+)IL-1,IL-6,TNFIL-10TGF(-)TCR-MHCBDCCo-Stimulation TAPCCTLA-4-C10Absence of Signal 2ActivationClonal Anergy or DeletionTCRMHCAPCToleranceT CellTCRMHCAPCSignal 1+Signal 2B7T CellcytokinesCD28The 2-Signal Model of Lymphocyte ActivationBDCAbsence of Signal 2ActivationC11MHC/self-peptideCD4MHC/VCD4CD4+V x T cell APCActivated autoreactive CD4+TCR V x TH1 cell TCR VxTCR Vx(1)expansion of CD4+,autoreactive TH1 cells specific for autoantigens(2)migration and infiltration of these self reactive CD4+TH1 cells into tissues and induction of inflammation and autoimmunity(3)induction of regulatory cells which control the growth and activation of the pathogenic autoreactive repertoire of CD4+T cellsInduction of CD4+TH1 mediated autoimmunity:A paradigm for the pathogenesis of rheumatoid arthritis,multiple sclerosis and type I diabetesL.Chess 2002MHC/self-peptideCD4MHC/VbCD4CD12TH1 CD4+cellsTH2 CD4+cells CD8 or CD4 suppressor precursorCD8 or CD4 suppressor effectorActivated CD4 T cellspeptide/APC Regulatory immunityCD4/CD8 interactions(-)(-)The Control of Activated CD4+T Cells by Regulatory T cellsApoptosisResting CD4 T cellsIL-12/IFN-g gIL-4NKT cells/CD4+CD25+cellsCD4+CD25-cells(-)(-)IL-10IFN-g gL.Chess 2002TH1 CD4+cellsTH2 CD4+cells C13T cell activation is regulated by signals derived from the TCR/CD3/CD4 complex and the CD40L and CD28/CTLA-4 co-stimulatory molecules g ge ed dz z z zCD3MHC class II,TCRh h h hPeptide antigenCD4+T Cell Antigen Presenting Cell(APC)V V C C CD4Antigen specific TCR signalsCD40CD40LsignalCD28/CTLA-4CD80(B7.1)/CD86(B7.2)lckCo-stimulatory signals(-)/+L.Chess 2002T cell activation is regulated14g ge ed dV C C V z zz zp56 lck peptideCD3CD28CD40LFA-3LFA-1ICAM-1MHC IIB7CD40LCD4CD45TCRCD2CD4+T CellAPC/B cellh h h hMolecular Interactions of Helper T Cells and APCB7CTLA-4VLA-1CollagenCD80/CD86L.Chess 2002gedVaCaCbVbzzp56 lck peptid15MHC/peptideTCRQa-1/V Activated CD4+T cellRestingCD4+T cellDown-regulation of Activated CD4+T CellsT cell activation induces expression of functional T cell surface molecules Regulatory CD8+T cellTCR(anti-Qa-1/V)Activated CD8+T cell(+)(-)TCRAPCTCRLate Activated CD4+T cellVLA-1CollagenCD40LMigration of sites of inflammationInduction and activation of B cells APCsCD25L.Chess 2002MHC/peptideTCRQa-1/VbActivated16Activated TH1 CD4+T CellCD4+Cell(TH2)CD4+Cell(TH0)DR3,DR4,DQ8/insulin peptide CD2Macrophage/dendritic cellFc R IFN-g g IL-12CD40LCD40,TCRIL-1,TNF,LT,NO,PGE-2B Cell?anti-insulin,GAD ab anti-MogIL-4Immunopathophysiology of Diabetes?Antibody mediated injuryDendritic cell/APCCD40LIL-4CD40LCD8+CTLFasLperforin cell death islet cellsL.Chess 2002Activated TH1 CD4+T CellCD4+17Innate Immune System:Toll-like receptor activation of APC T CellCD28B7TCR-MHCLPSToll Like Receptor(pattern Recognition R)IL-1,6,12“Signal 3”Signal 2Signal 1Anitgen Presenting Cell(APC)BDCInnate Immune System:Toll-lik18Th1 vs.Th2 CD4 T CellsTh1Th1IL-12 for differentiationCytokines:Interferon-Interleukin-2Intracellular Pathogens CD8 CytotoxicityDelayed Type HypersensitivityMacrophage ActivationTh2Th2IL-4 for differentiationCytokines:Inerluekin-4Interleukin-5Interluekin-13Extracellular PathogensB Cell activation&IgEImmunoglobulinEosinophil responsesBDCTh1 vs.Th2 CD4 T CellsTh1Th2B19Tr:T Regulatory CellsReview:Roncarolo Curr Opinion Immunol 2000BDCTr:T Regulatory CellsReview:20AvidinDQDQDQ“Tetramer”for T Cell AnalysisDQPEPTIDEBDCAvidinDQDQDQ“Tetramer”for T C21此课件下载可自行编辑修改，供参考！感谢您的支持，我们努力做得更好！此课件下载可自行编辑修改，供参考！22