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Chapter 14 T cell mediated immune response

Chapter 14 T cell mediated immune response. Immune response. Broad sense of immune response: non-specific immune response (innate immunity) barrier structure immunocytes:Mф, DC,NK,NKT,B1, γδT immune molecules: C, CK, defensin

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Chapter 14 T cell mediated immune response

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  1. Chapter 14 T cell mediated immune response

  2. Immune response

  3. Broad sense of immune response: non-specific immune response (innate immunity) barrier structure immunocytes:Mф, DC,NK,NKT,B1, γδT immune molecules: C, CK, defensin Specific immune response (adaptive immunity) T cell mediated immune response B cell mediated immune response 1. Concept of immune response

  4. 1. Conceptof immune response Narrow sense of immune response: specific immune response (Adaptive immunity) A specific response of the body's immune system to an antigen, involving the action of lymphocytes that eliminate antigen either by stimulating the production of antibodies (humoral immune response) or by a direct attack on foreign cells (cell-mediated immune response.)

  5. There are many different B cells. Each has an antibody with a unique specificity. The specificity of the antibody is determined before the antigen is encountered

  6. Antigen binding

  7. Proliferation of that B cell is called clonal expansion

  8. 2. Sites of Immune response ----peripheral immune organs Capture and presentation of exogenous Ags tissue DC antigen Lymphatic vessel 被膜 Lymph node Afferent Lymphatic vessel 输出淋巴管 cortex • Spleen, lymph node, MALT • Concentration of Ags • Lymphocyte recirculation

  9. 3. Stages of Immune response 1)Induction stage: antigen processing, presentation and recognition. 2) Reaction stage: activation, proliferation and differentiation of ICC (dual signal, CK). 3)Effect stage: immune effect (Ab, lymph factor, CTL).

  10. 4. Characteristics of Immune response Specificity MHC restriction Immunological memory Self-limitation

  11. Principle of T cell mediated immune response 感应阶段 1/100 Primary immunity Secondary immunity Ratio of specific T cells in blood 1/1000 1/10000 0 7 14 21 28 35 42 Days after immunity Immunological memory

  12. 5. Types of adaptive immune response By consequence positive IR: Normal IR—anti-tumor, anti-infection Abnormal IR—hypersensitivity, autoimmunity negative IR: Normal IR—self immune tolerance Abnormal IR—tumor, infection By mediating cells T cell mediated immune response--CMI B cell mediated immune response--HI

  13. PartⅡ Cellular immunity Tcell mediated immune response (CMI) CD4+T cell mediated immune response CD8+T cell mediated immune response

  14. T Cell surface peptides of Ag presented by cells that express MHC antigens Y Soluble native Ag Soluble peptides of Ag Cell surface peptides of Ag Cell surface native Ag Antigenic recognition by T lyphocytes ANTIGEN PROCESSING T cell response No T cell response No T cell response No T cell response No T cell response

  15. I. The process of T-cell mediated Immune response 1.T cells recognize the Ag peptide-MHC complex on APC ------double recognition and MHC restriction 2. Activation , proliferation and differentiation of T cells -------dual signals 3.Effect of effector T cells -------Th cell and CTL (Tc cell)

  16. 1. T cells recognize the Antigenic peptide-MHC complex on APC----dual recognition and MHC restriction TCR complex on CD4+ T cells recognizes the Ag peptide-MHC-II on professional APC TCR complex on CD8+ T cells recognizes the peptide-MHC-I on APC

  17. Dual Recognition : CDR1,CDR2 recognizes the  helix of MHC and two ends of peptide CDR3 recognizes central part of Ag peptide CDR3 CDR2,1 CDR1,2

  18. CDR3 CDR1,2 CDR2,1 -Helix of MHC Peptide-MHC complex

  19. MHC restriction:MHC genotype restrict recognition between T cell and antigen-presenting cell.

  20. Interaction between TCR and homocysteine presented by HLA-A68 TCR-a chain TCR-b chain Homocysteine C Peptide HLA-A68 b2m

  21. T cell synapse T cell synapse can be called immunological synapse. When TCR complex recognizes peptides-MHC on APC, several 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.

  22. 免疫突触的平面模式图

  23. APC

  24. 2. Activation , proliferation and differentiation of T cells (1) Activation: dual signal First signal：specific antigen singal TCR — peptide-MHC complexes CD4/CD8—peptide-MHCII/I ------- express IL-2R Second signal：co-stimulatory signal CD28 — B7（CD80、CD86） CD2（LFA-2）— CD58（LFA-3） LFA-1 — ICAM-1 --------enhance CK’s transcription(IL-2 expression) and decrease apoptosis of T cells

  25. (a) Activation of CD4+ T cell Dual signal between Th and APC 参与 Th细胞活化的膜表面分子 Dual signal model of Th cell activation Th细胞 APC Signal 1 IL-2R Th block Th activity CD4 APC TCR/CD3 MHC-II 1 LPS C TNF-a IL-1 IL-6 LFA-1 ICAM-1 Signal 1 IL-2 Th CD28 B7-1 APC Th activated 2 CD28 B7-2 Signal 2 LFA-1 ICAM-3 LFA-1 ICAM-3 CD2 LFA-3 B7-1 CTLA-4 —

  26. (b)Activation of CD8+T cell virus infected DCs activate CD8+T cell directly Help of CD4+Th cell to CD8+T cell: Enhance expression of co-stimulatory on APC Secreted IL-2 as the second signal

  27. （2）proliferation：CKs—IL-2 After first signal: T cells express CK receptor(IL-1R, IL-2R). After second signal: T cells secrete CKs such as IL-2. T cells proliferate and produce a lot of daughter cells under CKs by autocrine or paracrine.

  28. （3）Differentiation： Daughter cells differentiate into effector T cells and some differentiate into memory T cells (basis of vaccine). Th1(IL-2、IFN-γ） Thp Th0 Th2（IL-4、5、6、10） IL-12 Ag IL-4

  29. 3. Functions of effector T cells [1] Function of CD4+ T cells (1) Function of Th1 cells

  30. A. Effect of Th1 on macrophages (1)Th1 IL-8,other chemokines recruit more macrophages (2) Th1 IL-3, GM-CSF induce HSC to differentiate into more macrophages (3)Th1 IFN- ,CD40L activate macrophage Ag presentation more phagocytosis

  31. B. Effect of Th1 on T cells IL-2 released by effector Th1 cells binds to IL-2R----clonal expansion IL-2 , IFN- released by effector Th1 cells can induce CTL to proliferate

  32. (2) Function of Th2 cells Help to activate B cells, enhance HI: IL-4,5, 6 help B cells differentiate into plasma cells and produce Ab. Take part in hypersensitivity: Induce mast cell to release mediators to participate in Hypersensitivity I

  33. [2] Function of effector CTLs （1）Process of CTL killing target cells Specific recognition and binding of target cell by CTL Lethal hit to target cell Lysis of target cell

  34. （2）characteristic of CTL killing target cells： Specific killing MHCⅠ restriction Continuous killing of target cells in short time, and no injury of CTL

  35. （3）Mechanism of CTL killing target cell: perforin granzyme Fas/FasL pathway--apoptosis

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