1. Immunol mol med 2 Conleth Feighery 2010

2. This lecture ….. Importance of lymphocytes in immune system Identification of T and B cells How these cells bind antigen - receptors How cells become activated The involvement of MHC molecules in T cell function

3. Medical journals It is never too early to start …. dipping into journals 2 you might consider - New England Journal of Medicine Lancet

4. Major cells of the immune system T cell B cell lymphocytes neutrophil monocyte dendritic cell

5. 2 types of lymphocytes T B Mature in thymus - regulate, kill Mature in the bursa - antibody

6. Neutrophils ingest foreign material digest it “phagocytosis” Neutrophils most numerous white cell in circulation Short lived - 1 day Non-specific

7. Monocytes Macrophage in tissue “present” antigen monocyte Phagocytic cells 5 % of circulating cells

8. Macrophage

9. Dendritic cells T cell - help - suppress - kill B cell antibody Ingested antigen is presented Major antigen presenting cell in tissues

10. Monocytes / macrophages T cell - help - suppress - kill B cell antibody Ingested antigen is presented

11. Antigen presenting cells - APC Dendritic cells Macrophages B cells

12. B cell identification B cells have a specific receptor for antigen antibody molecule

13. B cell identification B cells have a specific receptor for antigen antibody receptor binds antigen directly

14. T cell identification T cells have a specific receptor for antigen TCR = T cell receptor

15. CD3 on T cells CD3 molecule bound to TCR CD3 signals to cell interior

16. T cell receptor - 2 chains alpha chain beta chain

17. TCR - alpha, beta chains alpha chain beta chain variable region constant region

18. TCR - alpha, beta chains The shape of the variable region binds to shape of different antigens. variable region constant region

19. B cell receptor The shape of the variable region binds to shape of different antigens. Variable region constant

20. T helper cells - CD4+ T cells CD4 molecules on T helper cells

21. T cytotoxic cells - CD8+ T cells CD8 molecules on T cytotoxic cells

22. T cell molecules T cell receptor = TCR CD3 - signaling molecule CD4 - on T helper cells CD8 - on T cytotoxic cells “CD” = cluster of differentiation - used in describing many molecules of immune system

23. For T cells to function …. Need TCR - binds antigen Need CD3 - signals binding via TCR Need antigen to be “presented” APC Antigen has to be bound to “MHC” mols.

24. MHC molecules Major Histocompatability Complex = MHC 2 types MHC class I MHC class II Enable T cells to react with antigen MHC = transplantation antigens - also called HLA molecules = human leucocyte antigens

25. CD8+ T cells - MHC I interaction APC T cytx TARGET CELL CD8 CD8+ T cells interact with antigen bound to MHC class I The CD8 molecule binds exclusively to MHC class I

26. MHC class I Found on all cells in the body Essential for function of T cytotoxic cells Viral peptides bind to MHC I Top end of a MHC class I molecule

27. Don Wiley, died 2001 I'm sorry, but I just don't understand anything in biology unless I know what it looks like.' Scientist, crystallographer

28. Don Wiley - appreciation "Wiley was a crystallographer: this is the ultimate molecular biology....The image of a class I MHC protein with its peptide cargo firmly in place will stand as a landmark Wiley discovery that forever changed the field of immunology.…”

29. MHC class I on target cell APC MHC I molecule TARGET CELL peptide

30. CD4+ T cells - MHC II interaction APC MHC II with peptide T h CD4

31. CD4+ T cells - MHC II interaction APC T h CD4 CD4+ T cells interact with antigen bound to MHC class II molecules

32. MHC class II Found on few cells in body - Macrophages Dendritic cells B cells All these cells present antigen = antigen presenting cells or APC

33. MHC class II on APC APC MHC II with peptide

34. MHC class II on B cells MHC II with peptide B antibody

35. B cells act as APC T h B antibody

36. T cell stimulation T cells bind to antigen and MHC Need to bind to a second molecule for full stimulation

37. CD4+ T cells - activation requires 2 signals APC T h CD4 T cell receptor binding to antigen = signal 1 CD28 B7 CD28 binds to B7 = signal 2

38. Activation of T cells Requires 2 signals Signal 1 - TCR, MHC, antigen Signal 2 - CD28 binding to B7 Both signals must be from the same APC ONLY now can T cell proliferation start

39. CD8+ T cells can kill target cells by inserting a ‘perforating hole’ in the cell, through which enzymes enter, damaging the cell APC T cytx TARGET CELL CD8 perforin enzymes

40. CD4+ T cells - MHC II interaction cytokines APC T h CD4 CD28 B7

41. CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines. cytokines The type of cytokines that are released are crucial to the type of immune response which results APC T h CD4 CD28 B7

42. Structure of molecules of IS T cell receptor MHC class I MHC class II Antibody molecules Knowledge of these structures helps understand how the immune system works !