1. T-LYMPHOCYTE 1 Lecture 8 Dr. Zahoor

2. Objectives T-cell Function – Cells mediated immunity Type of T-cells 1. Cytotoxic T-cell – CD8 (Killer T-cell) 2. Helper T-cell – CD4 3. Regulatory T-cell – CD4 + CD25 (Suppressor T-cell) Difference between T and B Lymphocyte 2

3. T-LYMPHOCYTE T – Lymphocyte are for cell mediated immunity T – Cell are important in defense of the body against most viral infections T – cell bind directly with their targets e.g. virus infected cells and cancer cells 3

4. T-LYMPHOCYTE On the surface of T-cell, there are receptors called T-cell receptors (TCRS) Immature T-cells acquire their TCRS in the thymus during their differentiation into T-cells during fetal life ( processing occurs in Thymus ). 4

5. T-LYMPHOCYTE T-cells are activated by foreign antigen only when it is on the surface of a cell that also carries markers of individual own identity also Both foreign antigen and self antigen are known as Major Histocompatibility Complex (MHC) 5

6. T-LYMPHOCYTE When T-cell is exposed to antigen, T-cell clone proliferate and differentiate for several days producing activated T-cells T-cell form memory cell and display both primary and secondary response (like B-cell) 6

7. T-LYMPHOCYTE After primary response, 90% of the T-cell die. The memory T-cells are long lived and give secondary response to same pathogen in future 7

8. T-LYMPHOCYTE T-cell are of 3 types: 1. Cytotoxic T-cell – CD8 (Killer T-cell) 2. Helper T-cell – CD4 3. Regulatory T-cell – CD4 + CD25 (Suppressor T-cell) CD means Cluster Designation We will discuss each type of T-cell 8

9. 1. Cytotoxic T-cell – CD8 These are also called Killer T-cell Cytotoxic T-cell have CD8 receptors in the plasma membrane, which were inserted as these cells passed through thymus Cytotoxic T-cell destroy virus infected cells, cancer cell, transplanted cells 9

10. 10 Cytotoxic T-cell lysing a virus invaded cell

11. 1. Cytotoxic T-cell – CD8 Cytotoxic T-cell can indirectly bring the death of infected virus cells by releasing digestive enzymes (granzymes) Digestive enzyme enter virus infected cells and cause destruction through APOPTOSIS 11

12. 1. Cytotoxic T-cell – CD8 What is APOPTOSIS?  A genetically determined process of cell self destruction due to DNA fragmentation. It is activated by the presence of a stimulus or removal of stimulus or suppressing agent 12

13. Other known specific mechanisms also help to kill virus infected cells e.g. NK-cell, interferon, macrophage and complement system 13

14. DEFENSE AGAINST VIRAL INFECTION Cytotoxic T-cell Helper T-cell Macrophage Plasma cells (derived from B-cell) Interferon Natural Killer Cell ( 0.2% ) What is Interferon?  It is lymphocyte product which participate in immune response e.g. destroying antigen coated cells 14

15. 2. Helper T-cell – CD4 15

16. 2. Helper T-cell – CD4 Helper T-cell do not directly participate in immune response, but activate other immune cells e.g. macrophage or activated lymphocyte Therefore, they are called Master switch T-helper cell make 60-80% of circulating T-lymphocyte 16

17. 2. Helper T-cell – CD4 Helper T-cell are not killer cells, but they secrete chemicals (cytokines) that amplify the activity of other immune cells T-Helper cells – help B-cells to develop into plasma cells T-Helper cell secrete interleukin (IL-4, IL-5 and IL-6) that serve as B- cell growth factor 17

18. 2. Helper T-cell – CD4 T-helper cells increase the activity of Cytotoxic T-cells, interleukin -2 (IL-2) T-helper cells activate macrophages T-helper cell secrete IL-3 to activate Eosinophil and IL-4 to promote IgE antibodies for defense against parasitic worms 18

19. Cytokines What are Cytokines?  Cytokines are soluble messenger molecules e.g. lymphokines and interleukins that act on other cells to stimulate or inhibit their function * Interleukins – are cytokine of low molecular weight protein produced by T-lymphocyte, macrophage and function in regulation of cell mediated immunity 19

20. T-Helper Cells How Helper T-Cell are activated ?  T-helper lymphocytes respond only to antigens presented to them by Antigen Presenting Cells (APCs) What are APCs?  They are Macrophage and Dendritic cells  Dendritic cells are present in skin, mucosa of lungs and digestive tract  Dendritic cells engulf bacteria and present it to T-helper cell as APC 20

21. 21 Antigen presenting Cell and T-cell

22. CLINICAL APPLICATION AIDS – Acquired Immuno Deficiency Syndrome It is caused by Human Immuno Deficiency Virus (HIV) AIDS virus selectively destroys T-helper cells AIDS virus also destroys macrophages 22

23. 3. Regulatory T-cell – CD4 + CD25 23

24. 3. Regulatory T-cell – CD4 + CD25 They were called Suppressor T-cells before. They have CD4 receptors like Helper T-cell, but in addition they have CD25 receptors Regulatory T-cell represent 5-10% of T-cell 24

25. 3. Regulatory T-cell – CD4 + CD25 (cont) Regulatory T-cells inhibit both innate and adaptive immune response and minimize harmful immune pathology Regulatory T-cell put brakes on Helper T-cell, B-cell, NK-cell and macrophage Note – Regulator T-cell, therefore, can be used therapeutically to stop auto immune disease and prevent rejection of transplanted organs 25

26. Β versus T Lymphocytes 26

27. Thank you 27