T CELL lymphocyte , its function, production and types pptx

Production, function and types of T cells

1. T CELLS Dr SHEMEERA SAIDALAVI VP PG RESIDENT

2. CONTENTS INTRODUCTION DEVELOPMENT AND MATURATION T CELL DIFFERENTIATION/ DIFFERENT TYPES OF T CELLS CD4+T HELPER CELLS REGULATORY T CELLS CD8+ CYTOTOXIC CELLS MEMORY T CELLS PHASES OF T CELL ACTIVATION

3. INTRODUCTION T cells : Type of blood cell Belong to a group of white blood cells (WBCs) called lymphocytes . WBCs protect the body from infection  T-cells is to fight infection. Along with other WBCs, they play a major role in the immune system, which guards the body against infection.

4. 2–4% of the T cells succeed 96–98% of T cells die by  APOPTOSIS  and are phagocytosed by macrophages  in the thymus Lymphopoiesis for T cells

5. 96–98% of T cells die by  APOPTOSIS  I ntensive screening to make sure each thymocyte has the ability to recognise  self peptide: self MHC complex

6. CONTENTS INTRODUCTION DEVELOPMENT AND MATURATION T CELL DIFFERENTIATION/ DIFFERENT TYPES OF T CELLS CD4+T HELPER CELLS REGULATORY T CELLS CD8+ CYTOTOXIC CELLS MEMORY T CELLS PHASES OF T CELL ACTIVATION

7. T CELL - THYMUS Immature lymphocytes leave the bone marrow  thymus where they are “educated” to become mature T-lymphocytes . SCHOOL FOR TRAINING NURSE CELLS

8. THYMUS

9. LET’S DISCUSS :3 WEEKS TRAINING

10. WHY VDJ rearrangement? T CELLS NEED DIVERSITY

11. HOW DIVERSITY IS CREATING

12. TCR genes undergo rearrangement  results in diversity of TCR genes to interact with different peptides First beta chain of TCR gene is rearranged  eventually and sequentially alpha chain also ( not at the same time) Mature TCR- αβ are formed

13. 2 DISTINCT SELECTION PROCEDURE CORTEX

14. POSITIVE SELECTION: thymic epithelial cells ensure that the DP cells learned how to recognise the MHC molecules  ENSURE MHC RESTRICTION NEGATIVE SELECTION : Those high affinity interactions are removed Ensures SELF TOLERANCE is maintained and there is no autoreactive T cells are generated Negative selection failed in many autoimmune diseases

15. In the first selection round  just learn to recognise or gets familiarize with the MHC bound peptides  these peptides are self peptides produced by thymic epithelial cells 90% die

16. Now cortical part of maturation is over  migrate to medulla  interact with medullary epithelial cells  start recognizing class I &class II MHC molecules

17. LYMPH NODE After thymic selection T cells become  naïve T cells Class II MHC Class I MHC

18. CONTENTS INTRODUCTION DEVELOPMENT AND MATURATION T CELL DIFFERENTIATION/ DIFFERENT TYPES OF T CELLS CD4+T HELPER CELLS REGULATORY T CELLS CD8+ CYTOTOXIC CELLS MEMORY T CELLS PHASES OF T CELL ACTIVATION

19. CD4+T HELPER CELLS

20. CD4+T HELPER CELLS Develop in BM THYMUS (training )  naïve T helper cells move to LN  activated by APC After activation T cell interact with other cell types / differentiate into different subtypes

21. APC (Dendritic cells, macrophage )  along with pathogen  go to LN  interact with naïve T helper cells Depending on the polarizing cytokines they released  naïve T helper cells differentiate into several subtypes

22. Depending on type of cytokine + the type of master regulatory gene gets expressed + type of infection All 3  determine how a T cell further categorize into different subtypes

23. 1. TH 1 CELLS

24. 2. TH 2 CELLS

25. 3. TH 17 CELLS

26. 4. REGULATORY T LYMPHOCYTES

27. If T reg cells are absent  balance move more towards the inflammatory responses increases chance of severe inflammation + autoimmune disorders  DANGEROUS

28. T reg DEVELOPMENT

29. CD4+ T helper cells Some of CD4+ T helper cells become T reg cells

30. How it different from CD4+T helper cells CD25

31. Once CD4+T helper cells  switch into T reg cells they maintain the level of Fox p3 throughout their life

32. Maintenance of Treg identity  depends on signals from IL2R α , TCR, TGF β Increases Fox P3

33. T- reg cells has anti inflammatory function T reg interact with macrophage  prevent it from interaction with other CD4+ T helper cell T reg directly compete with CD4+ T helper cell for IL-2 (IL- 2 is necessary for the devp . of both cells) If IL-2 is low  CD4+ T cell do not develop that much Macrophage  secrete proinflammatory cytokines like IL1 & IL6  regulate and activate CD4+ T helper cells  thereby activate other immune complex

34. Perforin granzyme pathway Compete for IL-2 Directly inhibit macrophage Immunosuppressing agents

35. T reg cell suppress function of APC

36. T reg : prevent early onset of autoimmune disorders by providing its anti inflammatory resposes

37. T Helper cells in DISEASE

38. CONTENTS INTRODUCTION DEVELOPMENT AND MATURATION T CELL DIFFERENTIATION/ DIFFERENT TYPES OF T CELLS CD4+T HELPER CELLS REGULATORY T CELLS CD8+ CYTOTOXIC CELLS MEMORY T CELLS PHASES OF T CELL ACTIVATION

39. CYTOTOXIC T CELLS Cytotoxic T cell has CD8 co-receptor

40. Perforin creates pores  Thereby granzymes enter the cell Interaction b/w cytotoxic T cell & target cell FAS-FASL mediated interaction Perforin – granzyme mediated interaction

41. DEATH of virus infected cells  eliminate the virus

42. CONTENTS INTRODUCTION DEVELOPMENT AND MATURATION T CELL DIFFERENTIATION/ DIFFERENT TYPES OF T CELLS CD4+T HELPER CELLS REGULATORY T CELLS CD8+ CYTOTOXIC CELLS MEMORY T CELLS PHASES OF T CELL ACTIVATION

43. Memory T cells  less stringent reactivation criteria ie , they gets back to the cell cycle and proliferate rapidly Naïve T cells cant proliferate rapidly until it is activated by APC Memory T cells quickly gets activated by APC

44. CD8 + cells that are very tired

45. INTRODUCTION DEVELOPMENT AND MATURATION T CELL DIFFERENTIATION/ DIFFERENT TYPES OF T CELLS CD4+T HELPER CELLS REGULATORY T CELLS CD8+ CYTOTOXIC CELLS MEMORY T CELLS PHASES OF T CELL ACTIVATION

46. PHASES OF T CELL ACTIVATION Activation phase Clonal expansion Effector phase Declining phase Memory phase

47. CLONAL EXPANSION

48. 3

49. CYTOTOXIC T CELL RESPONSE

50. Few cells remain will become the memory T cells Following second attack  these memory cells can easily identify attacking pathogen and become secondary effective T cells easily kill them

51. T CELL DEFICIENCY

52. T CELL MARKERS

53. B CELL MARKERS

54. Recent advances in T cells

55. REFERENCES