Acquired Immune Response

1. Acquired Immune Response Sanjaya Adikari Department of Anatomy

2. Immune Response • Defense against foreign invaders or cancer cells Immune Response Innate Response Acquired Response Antibody Response Cell mediated Response

3. Innate Response Adaptive Response

4. Cells of the immune system

5. Properties of Immune cells Activated cells Effector cells Inactive/Naive Many surface molecules Few surface molecules Becomes larger in size Proliferate and produce more cells Release peptides and lipids Increased ability to migrate

6. epithelium Macrophage

7. Macrophage Common receptors for immune cells of many animals Detect pathogen associated molecular patterns

8. Opsonization by Complement proteins epithelium Toll-like receptor Macrophages

9. Toll-like receptors Pathogen-associated molecular patterns

10. Phagolysosome H2O2 O2- NO Lysosomes Phagosome Activated macrophage Prostaglandins, Leukotrienes and Platelet activating factor

11. Flow increased Velocity reduced Lipid mediators of inflammation Increased diameter Increased permeability

12. Increased expression of adhesion molecules

13. Phagolysosome H2O2 O2- NO Lysosomes Phagosome Activated macrophage Cytokines Chemokines

14. A A Cytokines Proteins released by cells that affect the behavior of other cells that bear receptors for them Chemokines Proteins released by cells that attract other cells that bear receptors for them

16. H2O2 O2- NO Neutrophil

17. Body tissue Body tissue Body tissue

18. Cytokines Cytokines activated Chemokines Chemokines Mediators of infl. activated Cytokines Cytokines activated Cytokines Mediators of Chemokines

20. Pus cells Pus cells

21. Natural Killer cells Also called NK T cells Larger than T and B cells Activated during the innate response by macrophage derived cytokines Eg. IL-12 and Interferons Produce IFN- when activated Kills cells infected with intracellular pathogens Mechanism of Killing is similar to that of cytotoxic T cells

22. Complement system • Augments the opsonization of bacteria by antibodies. Hence, the name, meaning that it complements the antibodies • Large number of plasma proteins that react with each other following a trigger • Most of them are proteases that are themselves activated by proteolytic cleavage

23. Complement system….cont. • Precursor proteins are widely distributed in body fluids and tissues • Only activated on the surface of the pathogens • Once triggered it becomes a huge reaction in its successive steps

24. Trigger

25. Innate immunity - summary • Immune cells identify the ‘pathogen-associated molecular patterns’ on the cell membrane of pathogens • Pathogen is immediately destroyed • Neutrophils and macrophages are key players • Complement system plays an important role • Activated dendritic cells present antigens

26. Body cells Kill

27. Body cells Kill

28. From Innate to Adaptive • Cells activated during the innate immune response bridge the gap between the innate and the adaptive systems • Dendritic cellsandMacrophages

29. Adaptive Immune Response

30. epithelium Dendritic cells

31. Antigen presentation Antigen presenting cells (APC) Toll-like receptors Dendritic cell or macrophage T T T T T Clonal expansion of lymphocytes

33. Dendritic Cells (DC) • Most potent APC (>>> macrophages) • Designated as professional APC • Main function is to control T and B cells through presentation of different antigens

34. Mature DC B B T B B T T T T B T B Circulation T B T T B T B T Immature DC

35. Jefford et al., Lancet, June 2001

36. Surface molecules on DC and T cells • Cell-cell interaction molecules • Receptors for cytokines • Receptors for chemokines • Cell adhesion molecules

37. MHC I MHC II CD8 CD4 Antigen presenting cell B-7 TCR TCR CD28 CD28 B7= CD80 & CD86 CD4+ helper T cell CD8+cytotoxic T cell Cell-cell interaction molecules on DC and T cells

38. MHC molecules • Two types: MHC type I and MHC type II • MHC type I: Expressed in all body cells • MHC type II: Expressed in some immune cells • Dendritic cells, macrophages and B cells • Human counterpart is called HLA MHC – Major histocompatibility complex HLA – Human leukocyte antigen

39. DC-T cell interaction Dendritic cells send two signals to T cells • 1st signal – determines antigen specificity • 2nd signal – triggers T cell proliferation

40. immature DC CD4 MHC II 1st signal TCR CD4+ helper T cell

41. mature DC MHC II CD4 B-7 2nd signal TCR CD28 CD4+ helper T cell Increase proliferation Secrete IL-2 (growth factor of T cells)

42. MHC I MHC II CD8 CD4 Antigen presenting cell B-7 TCR TCR CD28 CD28 B7= CD80 & CD86 CD4+ helper T cell CD8+cytotoxic T cell Cell-cell interaction molecules on DC and T cells

43. APC CD8 CD4 MHC I MHC II TCR TCR Intravesicular pathogens Extracellular pathogens Toxins Vesicle Cytoplasm

44. Th1 cells T helper cells (Th cells) Th2 cells Th0 cells

45. Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines IFN- IL-4 IFN- IL-5 IFN- IL-4 IL-10 IL-10 IFN- IFN- IL-4 IL-5 IL-10 Th1 cells Th2 cells Macrophage Activation B cell Activation

46. Th1 cells Produce IFN-, the main macrophage-activating cytokine. It inhibits B cells Th2 cells Produce IL-4, IL-5 that activates B cells and IL-10 that inhibits macrophages Th0 cells Produce both Th1 and Th2 cytokines and therefore have a mixed effect

47. Clinical relevance of Th1 vs Th2 To destroy bact. need to activate macrophages by Th1 cells Th2 response is a waste Mycobacterium leprae grows in macrophage vesicles. • Th1 response • Tuberculoid leprosy • Few live bacteria • Little Ab in serum • Skin & PN damage due to Mac. activation • Slow disease, patient survives • Th2 response • Lepromatous leprosy • Numerous live bacteria • Lot of Ab in serum (ineffective) • Gross tissue damage & death

48. Humoral immune response

49. BCR B cell MHC II

50. BCR MHC II