1. 1 Circulating T cells Ag in the Inflammatory tissue Ch 9 T Cell-Mediated Immunity Ag-specific T cell response

2. Entry of APC (DC) and naïve T cells into peripheral lymphoid organs Priming of naïve T cells by DC Clonal expansion & differentiation Signal 1, 2, 3 Egress 2

3. Entry of DC into draining LN 3 Inflammation Immature DC: Ag uptake CCR7 Ag presentation (signal 1) B7 (signal 2) Mature DC (T cell zone) CCL21

4. Naïve T cell activation in peripheral lymphoid organs 4 Naïve Activated Effector 500 T cells/hr for 1 DC Naïve T: CCR7

5. T-APC interaction: activation of LFA1 Signal 1 5 Ag specificity

6. Three signals in naïve T cell priming Signal 2: proliferation 6

7. IL2 autocrine Signal 1+2 7 CD28-dependent clonal expansion of CD4 T cells

8. Signal 3: differentiation Adaptive Treg 8 Transcription factor Effector T subsets Induced Treg

9. 9 Colgate Immunology (and Virology) Blog CD40L-CD40 2. IL2 CD4 Th1-dependent CD8 T cell activation CD8 T 1. DC (APC) activation

10. DC CD8T APC 10

11. TRA: Tissue restricted antigen mTEC: AIRE transcription factor 2011, 32: 188 Thymic negative selection : Self tolerance

12. Effector T cell response CD8 T cytotoxic response CD4 T effector & Macrophage activation Homing 12 Entry of APC and naïve T cells into peripheral lymphoid organs Priming of naïve T cells by DC

13. Homing Effector response CD4 Th1/ Th2 CD8 Tc B cells 13

14. Where to go ?

15. CD4 T activation Within LN 15

16. Ig domain Addressin Guiding lymphocytes to tissues Homing Vascular addressin (VA) 16

17. Ag-specific recognition of CD8 T cells 17

18. Microtubule-organizing center Cytotoxic mechanisms of CD8 T cells (NK) Membrane effector molecule CTL Cytotoxic granules 18

19. Membrane molecules Effector molecules Soluble mediators 19

20. 20 APC Inflammatory site

21. Macrophage activation by Th1 Reciprocal activation 21

22. Th1 coordinates a macrophage response 22 Collaboration of adaptive and innate immunity tissue Systemic

23. The course of immune response to infection Immunological memory Ch 11 23

24. Innate immunity Humoral immunity CMI Sequential activation and regulation of T cell subsets 24

25. Amplifier of acute inflammation (local site, BM) 25

26. T H 17 Neutrophils Activation of macrophages Antimicrobial peptides Ubiquitous expression of IL17R on tissue cells: fibroblasts, epithelial cells, keratinocytes, etc. Cytokines: G-CSF, GM-CSF No IL4, IFNg, IL12) Chemokines: CXCL8, CXCL2 Proinflammatory cytokine Antimicrobial peptidesPhagocytosis Inflammed site Signal 1+2 26

27. Adaptive Treg T H 17 Rapid response to infection Preventing anti-self response Inhibition of proliferation & differentiation T H 17 27

28. 28 In the later stages of infection Polarization IL12 – Th1IL4 – Th2 Intracellular infectionExtracellular infection

29. Regulation among CD4 T subsets Cytokine pattern of the dominant response Inhibition of early Th17 response 29 IL4

30. Th1 30

31. Th1 CMI Intracellular infection: Virus Intracellular bacteria Protozoa 31

32. Th2 Humoral response Mast cells Extracellular infection: Helminths Parasites Protozoa Bacteria Neutralizing Ab IL10 Early IL4 & Th2 polarization 32

33. Natural/adaptive Treg

34. Sequential activation and regulation of T cell subsets Survival and sequential activation of B cell subsets T/B cell activation & differentiation 34 Barrier immunity

35. Professional APC 35

36. Induction of antibody response in LN (Th2) B cell response B cell as APC Ag-specific 5 days Isotype switching Somatic hypermutation 36

37. Ab response are sustained in medullary cords and BM In situ 2-3 days, 6-7 cell divisions Plasma cells Life span: 2-4 days Germinal center BM Plasmablasts Life span: months - years Plasma cells 37

38. Adhesion molecules Homing R / addressin Chemokine & R Migration of immune cells 38 Sequential activation and regulation

39. CD5 B cells 39

40. CD5 B cells 40

41. Early blocking Reinfection Effector response 41

42. 42

44. The course of immune response to infection Immunological memory 44

45. Two types of memory T cells Central memory T Effector memory T 45

46. Maintenance of memory T cells TCR, IL7, IL15 46 Homeostasis

47. The role of IL7 in memory response 47

48. CD4 T-dependent CD8 T cell memory response Promote efficient effector activity Maintain memory T cell numbers 48

49. Memory T cells Balance of cell proliferation and death 49 Long-lived

50. Memory B cell response 50 Somatic hypermutation Isotype switching

51. 51 Barrier immunity

53. Regulation of signal 2 53

54. Effector T cells recruitment Apoptosis of effectors 54

55. Continuous regulation of the expansion and effector activity in inflammatory sites 55

56. Protective immunity & time Apoptosis of effectors Long-lived 56

57. 57

58. Stages of infection and immune response Local inflammation Macrophage activation Activation of APC Activation of lymphocytes Homing of effectors Endothelial cells Collaboration with innate and tissue cells Endothelial cells 58