Antigen recognition and immune response of T lymphocytes

1. Antigen recognition and immune response of T lymphocytes

2. Contents Ⅰ.Recognition of antigen by T lymphocytes Ⅱ.The course of T lymphocytes activation Ⅲ.Responses of effector T lymphocytes

3. The course of immune response Antigen recognition specific binding of antigen to antigen receptor Immune response activation of lymphocytes and production of effector agents Immune reaction antigen elimination or neutralization by effector agents

4. Ⅰ. Antigen recognition Characteristics of  TCR antigen recognition • recognize MHC-peptide complex on APC cells • recognize linear amino acid antigen determinants • MHC restriction—— CD4+T--MHC-II-peptide CD8+T --MHC-I-peptide

6. (Ⅰ) Nonspecific binding between T cell and APC

7. Nonspecific binding between T and APC

8. (Ⅱ) Specific binding between T cell and APC

9. TCR and CD4 coreceptor recognize MHC-peptide complex TCR signaling enhance the affinity between LFA-1 and ICAM-1 low affinity binding between LFA-1and ICAM-1 T cell T cell T cell APC APC APC Stable binding between T and APC

10. (Ⅲ)Binding of costimulatory molecules between T cell and APC CD28/B7、LFA-1/ICAM-1、CD2/CD58…

11. (Ⅳ) immunological synapse Raft-like structure: Centre----TCR:MHC-peptide complex Surrounding ----pairs of adhension molecules

12. Ⅱ.signals essential for the activation of T cell (Ⅰ) The first signal

13. dual recognition of CD4+T cell

14. (Ⅱ) The second signal CD28/B7 LFA-1/ICAM-1 or ICAM-2 CD2/LFA-3 CD40/CD40L

15. dual signals in the activation of T cell

16. CD28/B7, promotes the gene transcription of IL-2 Without CD28/B7，T cell anergy CTLA4, high homology withCD28, with the affinity to B7 20 folds higher than that of CD28, restrict the over expansion of T cell through inhibitory signaling

17. (Ⅲ) cytokine promote the full activation of T cell IL-1、IL-2、IL-6、IL-12 ……

18. Ⅲ. signal transduction in the activation of T lymphocyte multimerization: Clustering of TCR/CD3,CD4 or CD8 and CD45

19. ……D/Exx YxxL/V x(7~11) YxxL/V …… Immunoreceptor tyrosine-based activation motif, ITAM Y：tyrosine L：leucine V：valine D：aspartic acid E：glutamic acid

20. Signal transduction in T cell activation

21. Ⅳ. transcription factor activation and gene expression (Ⅰ)activationof transcription factors • AP-1 (Fos、Jun) • NF-B • Oct-1 • NFAT (nuclear factor of activated T cell )

22. (Ⅱ) gene expression of T cell • cytokine gene expression • cytokine receptor gene expression • adhesion molecule gene expression • MHC

23. (Ⅲ) proliferation and diferentiation of T cell • CD4＋T cell proliferation and diferentiation • CD8＋T cell proliferation and diferentiation

24. IL-12 Th1－－cell mediated immunity Th0 IL-4 Th2－－humoral immunity Ⅴ. Function of effector T cell

25. 1. Effects of Th1CD4＋T cell • Induced delayed type hypersencitivity, activate and recruit Mφto local inflammation • Enhanced expression of MHC and adhension molecules on APC • Activate CD8＋T and NK cell，enhance killing activity

26. Effect phase of TH1 immune response Macrophage,neutrophil activation,recruitment and local infiltration DTH IL-2 IFN- TNF- GM-CSF IL-3 … Macrophage activation, Expression of MHC-II and adhension molecules Antigen presentation TH1 Activate Mφ NK cell Tc cell TH cell Cell mediated effects Memory TH

27. Mechanism of Mφactivation by Th1 T cell

28. activated Th1 cell IFN-γand CD40L FasL or TGF-β Lumen of blood vessel chemoattractive exudation Infected site kill infected cell and released bacterias were killed by Mφ induce differentiation of bone marrow Mφ Induce Mφexudation by endothelial cell activation activate Mφ to kill phagocyted bacterias recruitment of Mφto local infected site induce T cell proliferation Biological roles of Th1 cell secreted cytokines

29. 2. Function of Th2 CD4＋T cell • Regulate Mφ(recruitment, inhibition：IL-10/FasL/TGF-) • B cell activation, Ig isotype switching

30. B cell T cell Interaction between B and Th2 CD4+ T cell

31. 3.Effects of CD8＋CTL necrosis、apoptosis Activation Induced Cell Death

32. activation of naive T cell Killing of infected cell Proliferation and differentiation R killing T cell proliferation cytotoxic recognition differentiation CD8+CTL cytotoxic effect

33. effector phase of CD8+T cell mediated immune response • release of granule substances • perforin • granzyme • release of TNF • switch on apoptosis signaling • FasL →Fas →FADD→Caspase8→ DNA incision enzyme

34. cytotoxic cell cytotoxic cell vesicle enzyme release enzymic polymerization perforin cell damage polyperforin channels target cell target cell Granule-associated killing mechanism

36. T cell mediated immune response and immune effects • antigen： TD-Ag • cell： T cell and APC • effect agent： Th/CTL（Tc） • immune effects: anti-intracellular infection • anti-tumor • immunological injury • delayed type hypersencitivity, DTH • graft exclusion reaction • autoimmune disease

37. IL-2 IFN- TNF IL-2 IL-3 IL-2 IFN- TNF IL－2 IFN- TNF IL-2 IL-4 IL-5 IL-10 Roles of effector T cells

38. Ⅵ. outcomeof activated T cells • (Ⅰ) Memory T cell • (Ⅱ) Apoptosis • activation induced cell death, AICD • passive cell death, PCD

39. proliferation Persistent stimulation Deprived of growth factors mitochondria cytochrome C Activation induced cell death Passive cell death Two mechanisms of lymphocyte apoptosis

40. master the Characteristics of TCR • antigen recognition • master the requirment of T cell activation • master the function of effector CD4+T • and CD8+T cells • understand signal transduction of T cell • activation