医学免疫学英文版课件：Chapter13Recognition and Immune Response of T cells to Antigens

1、Chapter15 Recognition and Immune Response of T cells to AntigensContents Part Introduction Part T cells mediated immune responsePart Related conceptsPart Introduction Conception of immune response Sites of Immune response Stages of immune response Types of immune response Broad sense of immune respo

2、nse:Unspecific immune response (innate immunity) barrier structure immunocytes:M, DC,NK,NKT,B1, T immune molecules: C, CK, defensinSpecific immune response (adaptive immunity) T cell mediated immune response B cell mediated immune response1. Conception of immune responsePrevention from Infection1. C

3、onception of immune responseNarrow sense of immune response:specific immune response (Adaptive immunity)Definition: a process that ICC recognize the antigens specifically, then activate ( or lose ability to be activated), proliferate, differentiate and play immune effects.2. Sites of Immune response

4、-peripheral immune organs Spleen, lymph node, MALTDC elicit immune response被膜输出淋巴管Capture and presentation of exogenous Ags tissueLymphatic vesselDC antigenAfferentLymphatic vessel cortexLymph node 3. Stages of Immune response1) Induction stage: antigen presenting, presentation and recognition.2) Re

5、action stage: activation, proliferation and differentiation of ICC (dual signal, CK).3)Effect stage: play immune effect (Ab, lymph factor, CTL).4. Types of adaptive immune response By consequence positive Ir: Normal Irantitumor, antiinfection Abnormal Irhypersensitivity, autoimmunity negative Ir: No

6、rmal Irself immune tolerance, Abnormal Irtumor, infectionBy 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 responseThe process of T-cell

7、mediated Immune 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 pep

8、tide-MHC complex on APCs-MHC restriction(1) exogenous antigens-APCs (2) Ag recognition: TCR on T cells bind with Ag peptide-MHC complexes on professional APCs specifically.Dual recognition: CDR1, CDR2 recognize the helix of MHC and two ends of peptide, CDR3 recognizes central part of Ag peptide.MHC

9、restrictionCDR3CDR1,2CDR2,1Peptide-MHC complex-Helix of MHC 2. CD4+T cell Activation , proliferation and differentiation (1) Activation: dual signalFirst signal：specific antigen singal TCR peptide-MHC complexes CD4 MHC(2)Second signal：co-stimulatory signal CD28 B7（CD80、CD86） CD2（LFA-2） CD58（LFA-3） L

10、FA-1 ICAM-1APCblock Th activityDual signal model of Th cell activationIL-2RAPCThSignal 1Signal 2LPSC TNF-a IL-1 IL-6IL-2ThSignal 1Th activatedAPC（2）proliferation：CKsIL-2After first signal: T cells express CK receptor(IL-1R, IL-2R).After second signal: T cells secrete CKs such as IL-2.T cells prolife

11、rate and produce a lot of daughter cells under CKs by autocrine or paracrine.（3）Differentiation：Daughter cells differentiate into effector T cells and some differentiate into memory T cells (basis of vaccine). Th1(IL-2、INF-）Thp Th0 Th2（IL-4、5、6、10）IL-12 IL-4Ag3. The functions of effector Th cells (1

12、) Function of Th1 cellsActivate , recruit macrophages: IFN-, TNF- activate macrophages to enhance their phagocytosis, secrete cytokines (IFN-, TNF-) to recruit mononuclear cells to the infection sites .Help to activate Th1, CTL and B cells.Activate nutrophils, LT kill target cells directly. (2) Func

13、tion of Th2 cellsHelp to activate B cells, enhance HI: IL-4,5,10,13 help B cells differentiate into plasma and produce Ab.Take part in hypersensitivity: stimulate mast cell, esinophil etc.APC CD8+T cell mediated immune response1.CD8+T cells recognize Ag peptide-MHCI complex on APC-MHC restriction(1)

14、 endogenous antigens-APCs (2) Ag recognition: TCR on T cells bind with Ag peptide-MHCI complexes on APCs specifically.Dual recognition: CDR1, CDR2 recognize the helix of MHCI and two ends of peptide, CDR3 recognizes central part of Ag peptide.MHC restrictionb2mTCR-b chainTCR-a chain Homocysteine HLA

15、-A68PeptideInteraction between TCR and homocysteine presented by HLA-A68 C 2. CD8+T cell Activation , proliferation and differentiation (1) Activation: dual signalFirst signal：specific antigen signal TCR peptide-MHC CD8 MHCSecond signal：co-stimulatory signal？ CD28 B7（CD80,CD86） CD2（LFA-2） CD58（LFA-3

16、） LFA-1 ICAM-1 block activityDual signal model of Tc activationIL-2APC 1 activate, expansionThTcAPC 2TcActivation of CD8+T cellDCs infected virus activate CD8+T cell directly Help of CD4+Th cell to CD8+T cell: Enhance expression of co-stimulatory on APCSecreted IL-2 as the second signal（2）activated

17、CTL proliferation and differentiation to effector CTL need help of Th1 cell. （3）during the course of CTL differentiation, memory CTL cells develop (basis of vaccine).3Function of effector CTLs（1）the process of CTL killing target cellsSpecific recognition and binding of target cell by CTLLethal hit t

18、o target cell Lysis of target cell（2）characteristic of CTL killing target cells： Specific killingMHCrestrictionContinuous killing of target cells in short time, and no injury of CTL（3）Mechanism of CTL killing target cell:perforingranzymeFas/FasL pathway-apoptosisCTL cellTarget cellBiological effect

19、of CMI1. Play an important role in predefense resisting intracellular microbe infection2. Kill tumor cell or virus-infected cells 3. Participate in graft rejection and graft-versus-host disease, GVHD4. Mediate type IV hypersensitivity reaction Part Related concepts characteristic of memory T Cells (Tm): Long lived cells CD45RA-,CD45RO+ Easily triggered by low antigen Less depend on co-stimulatory molec