《Chapter14Tcellmediatedimmuneresponse》由会员分享，可在线阅读，更多相关《Chapter14Tcellmediatedimmuneresponse（98页珍藏版）》请在金锄头文库上搜索。
1、Chapter14-T-cell-Chapter14-T-cell-mediated-immune-mediated-immune-responseresponseContentsu Part General introductionu Part T cells mediated immune responseu Part NKT cell and T cell mediated immune responseuPart Unspecific activation of T cellsChapter 14 Chapter 14 T Cell Mediated Immune T Cell Med
2、iated Immune ResponseResponse（CMICMI）Part Introduction Conception of immune response Stages of immune response Sites of Immune response Types of immune response Broad sense of immune response:Broad sense of immune response:Unspecific immune response (innate immunity) barrier structure immunocytes: N
3、K, M, DC, B1, T immune molecules: C, CK, lysozymesSpecific immune response (adaptive immunity) T cell mediated immune response B cell mediated immune response1. Conception of immune responsePrevention from Infection1. Conception of immune responseNarrow sense of immune response:Narrow sense of immun
4、e response:specific immune response (Adaptive immunity)Definition: a process that ICC recognize the antigens specifically, then activate (or lose their ability to be activated), proliferate, differentiate and play immunological effect. 2. Stages of Immune response(1) Induction stage: Ag processing,
5、presentation and recognition.(2) Reaction stage: activation, proliferation and differentiation of ICC (dual signals, CKs).(3)Effect stage: play immunological effect (CK, CTL, Ab).3. Sites of Immune response-peripheral immune organs Lymph node, Spleen, MALT被膜被膜输出淋巴管输出淋巴管Capture and presentation of ex
6、ogenous Ags tissueLymphatic vesselDC antigenAfferentLymphatic vessel cortexLymph node 4. Types of adaptive immune responseBy consequence Positive Ir: Normal Ir-anti-tumor, anti-infection Abnormal Ir-hypersensitivity, autoimmunity Negative Ir: Normal Ir-self immune tolerance Abnormal Ir-tumor, infect
7、ionBy mediating cells T cell mediated immune response-CMI B cell mediated immune response-HIPart Cellular immunity T cell mediated immune response (CMI) CD4+T cell mediated immune response CD8+T cell mediated immune responseCell surfacepeptidesof AgAntigens must be processed in orderto be recognised
8、 by T cellsYT T cellresponseNo T cellresponseNo T cellresponseNo T cellresponseNo T cellresponseSolublenative AgCell surfacenative AgSoluble peptidesof AgCell surface peptides of Ag presented by cells that express MHC moleculesANTIGENANTIGENPROCESSINGPROCESSINGAPCAPCThe process of T-cell mediated Im
9、mune response1.T cells recognize the Ag peptide-MHC complex on APC -MHC restriction2. Activation, proliferation and differentiation of T cells -Dual signals3.The functions of effector T cells -Th cell and CTL (Tc cell)CD4+T cell mediated immune response1. CD4+T cells recognize the Ag peptide-class M
10、HC complex on APCs-MHC restriction(1) Exogenous antigens-APCs (2) Ag recognition: TCR on T cells bind with Ag peptide-MHC complexes on APCs specifically.Dual recognition: CDR1, CDR2 recognize MHC-helix, CDR3 recognizes Ag peptide.MHC restrictionThree dimensional structure of TCRAnatomical mechanism
11、of TCR recognizes MHC/antigenic peptideMHC-a a helixAntigenic peptideCDR1CDR2CDR3CDR3CDR2CDR1TCR- chainTCR-a a chainMHC-a a helixCDR3CDR2,1CDR1,2T cell synapsea special structure between T and APCT cell synapse can be called immunological synapse. When TCR complex recognizes peptides/MHC on APC, sev
12、eral T cell surface proteins and intracellular signaling molecules (such as CD3,CD4,CD8,CD28) are rapidly mobilized to the site of T cell-APC contact. 2. Activation, proliferation and differentiation of CD4+T cell (1) Activation: dual signalsFirst signalFirst signal：specific antigen signal TCR pepti
13、de-class MHC complexesTCR peptide-class MHC complexes CD4 class MHC molecule( CD4 class MHC molecule(2)2)Second signalSecond signal：co-stimulatory signalco-stimulatory signal CD28 B7 CD28 B7（CD80CD80、CD86CD86） CD2 CD2（LFA-2LFA-2） CD58 CD58（LFA-3LFA-3） LFA-1 ICAM-1 LFA-1 ICAM-1TCR complexThe Two-Sign
14、al HypothesisCo-stimulatory signal(CD28/B7) 2. Activation, proliferation and differentiation of CD4+T cell (1) Activation: dual signalsFirst signalFirst signal：specific antigen singal TCR peptide-class MHC complexesTCR peptide-class MHC complexes CD4 class MHC molecule( CD4 class MHC molecule(2)2)Se
15、cond signalSecond signal：co-stimulatory signalco-stimulatory signal CD28 B7 CD28 B7（CD80CD80、CD86CD86） CD2 CD2（LFA-2LFA-2） CD58 CD58（LFA-3LFA-3） LFA-1 ICAM-1 LFA-1 ICAM-1 VLA-4 VCAM-1 VLA-4 VCAM-112CD4MHC-IITCR/CD31ICAM-1B7-1B7-2LFA-1LFA-1ICAM-3LFA-3B7-1CD28CD28LFA-1ICAM-3CD22Molecules associated wi
16、th T activation Th cellAPCCTLA-4APCblock Tblock Th activityactivityDual signal model of Th cell activationIL-2RAPCThSignal 1Signal 2LPSTNF-a IL-1 IL-6IL-2ThSignal 1Th activatedactivatedCD28CD28B7（2）proliferation：CKsIL-2Resting T cells express low affinity IL-2R.Activated T cells express high affinit
17、y IL-2R and secrete CKs such as IL-2.T cells proliferate and produce a lot of daughter cells under IL-2 by autocrine or paracrine.TmEffector TProliferation of T cell（3）Differentiation：Daughter cells differentiate into effector T cells and some differentiate into memory T cells (basis of vaccine). Th
18、1(IL-2、IFN-、TNF-）Thp Th0 Th2（IL-4、5、6、10、13）IL-12 IL- 4AgIL-23（IL-6，TGF-）Th17（IL-17）n characteristic of memory T Cells (Tm): Long lived cells CD45RA-,CD45RO+ Easily triggered by low antigen Less dependent on co-stimulatory molecules Sensitive to CKs Responsible for maintaining immunological memoryDa
19、ys after immunityRatio of specific T cells in blood感应阶段Primary immunitySecondary immunity1/100001/10001/1000 7 14 21 28 35 42 Principle of T cell mediated immune responsecell mediated immune response Immunological memory3. The functions of effector Th cells 3. The functions of effector Th cells Th1
20、Th2 Th1 Th2 CKsCKs IL-2 + IL-2 + IL-4 + IL-4 + IL-5 + IL-5 + IL-10 + IL-10 + IFN- IFN- + + TNF- TNF- + + CKs for proliferationCKs for proliferation IL-2 IL-2/IL-4 IL-2 IL-2/IL-4 Helping Helping IgG,DTH IgE/IgA IgG,DTH IgE/IgA Inhibition Inhibition Th2 Th1 Th2 Th1 （Th1，Tc）(1) The functions of Th1 cel
21、ls Th1 cells release IFN- to activate macrophage, mediate inflammatory reaction and inhibit the function of Th2 cells. Th1 cells release IL-2 to promote the proliferation, differentiation of Th1 cells and Tc cells.Effect of macrophage:Phagosize and kill pathogensPromote Th1 activationMediate delayed
22、 hypersensitivity(2) The functions of Th2 cellsTh2 cells release IL-4,5,6,10 to activate the B cells to produce Ab.Th2 cells release IL-4,5 to promote the differentiation and development of eosinophil and mast cell.Th2 cells release IL-10 to inhibit the activation of macrophage and function of Th1 c
23、ells. CD8+T cell mediated immune response1.CD8+T cells recognize Ag peptide-class MHC complex on APC-MHC restriction(1) Endogenous antigens-APCs (2) Ag recognition: TCR on T cells bind with Ag peptide-classMHC complexes on APCs specifically.Dual recognition: CDR1, CDR2 recognize MHC-helix, CDR3 reco
24、gnizes Ag peptide.MHC restriction 2mTCR- chainTCR-a a chain Homocysteine HLA-A68PeptideInteraction between TCR and homocysteine presented by HLA-A68 C 2. CD8+T cell Activation, proliferation and differentiation (1) Activation: dual signalFirst signalFirst signal：specific antigen signal TCR peptide-c
25、lass TCR peptide-class MHC CD8 class CD8 class MHCSecond signalSecond signal：co-stimulatory signalco-stimulatory signal？ CD28 B7CD28 B7（CD80,CD86CD80,CD86） CD2 CD2（LFA-2LFA-2） CD58 CD58（LFA-3LFA-3） LFA-1 ICAM-1 LFA-1 ICAM-1Signal 1Signal 2 ?APC block block block block activityactivityactivityactivit
26、yDual signal model of Tc activationIL-2IL-2Target cellTarget cell activate, activate, activate, activate, expansionexpansionexpansionexpansionThThTcTcAPC APC TcTcTumor celltumortumorDCCD28CD28B7B7CD28Activation of CD8+T cellVirus infected DCs activate CD8+T cell directly Help of CD4+Th cell to CD8+T
27、 cell: Secreted IL-2 acts as the second signal Enhance expression of co-stimulator on APC（2）Activated Tc cells proliferate and produce a lot of daughter cells under IL-2. （ 3） Daughter cells differentiate into effector CTL and some differentiate into memory Tc cells(basis of vaccine).3Function of ef
28、fector CTLsCTLp recognized peptide-class MHC proliferate and differentiate to effector CTL under action of IL-2 released by Th1.The effector CTLs specifically recognize and bind Ag on target cells.CTL releases perforin, granzymes and express Fas ligand to kill target cells. （1）The process of CTL kil
29、ling target cellsSpecific Specific recognition recognition and and binding binding of of target cell by CTLtarget cell by CTLLethal hit to target cell Lethal hit to target cell Lysis or apoptosis of target cellLysis or apoptosis of target cell（2）Characteristics of CTL killing target cells： Specific
30、killingClassMHC molecule restrictionContinuous killing of target cells in short time, and no injury of CTLNormal cell No injury No injury（3 3）Mechanism of CTL killing target cell:Mechanism of CTL killing target cell:Perforin - Perforin - osmotic lysisGranzyme and Fas/FasL - Granzyme and Fas/FasL - a
31、poptosisSecreted TNF and IFN-Secreted TNF and IFN- induce target induce target cells to diecells to die*Fas：Apo-1 or CD95 Cell deathCell death TNF and IFN-TNF and IFN- (minor pathway) (minor pathway)CTL cellTarget cellBiological effect of CMI1. Play an important role in defense agaist intracellular
32、microbe infection.2. Kill tumor cells or virus-infected cells. 3. Participate in graft rejection and graft-versus-host disease(GVHD).4. Mediate type hypersensitivity. Part NKT cell and T cell mediated immune response1. Ir mediated by NKT cellNKT cell: T cell which express molecules of NK cellsRecogn
33、ize lipid Ag presented by CD1 moleculeActivated NKT cells secrete IFN- and IL-4 NKTcells2. Ir mediated by T cellCD4- and CD8- T cellAntigens: bacteria, virusNot need APC No MHC restrictionPart Unspecific activation of T cellsSuperantigenUnspecific activationNeed APC, but not processing and presentingSecrete CK Superantigen(sAg) TCRVAntigenic peptideClass II MHC chainT cellAPCThe mechanism of superantigen activating T cellAg and SAgAntigenSuperantigenThe other activators of T cellsmitogen(PHA, ConA)anti-CD3, anti-TCR, , anti-TCR anti-CD28结束结束
