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Acquired Immune Response

Acquired Immune Response. Sanjaya Adikari Department of Anatomy. Immune Response. Defense against foreign invaders or cancer cells. Immune Response. Innate Response. Acquired Response. Antibody Response. Cell mediated Response. Innate Response. Adaptive Response.

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Acquired Immune Response

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  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

  15. H2O2 O2- NO Neutrophil

  16. Body tissue Body tissue Body tissue

  17. Cytokines Cytokines activated Chemokines Chemokines Mediators of infl. activated Cytokines Cytokines activated Cytokines Mediators of Chemokines

  18. Pus cells Pus cells

  19. 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

  20. 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

  21. 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

  22. Trigger

  23. 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

  24. Body cells Kill

  25. Body cells Kill

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

  27. Adaptive Immune Response

  28. epithelium Dendritic cells

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

  30. 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

  31. 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

  32. Jefford et al., Lancet, June 2001

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

  34. 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

  35. 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

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

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

  38. 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)

  39. 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

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

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

  42. 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

  43. 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

  44. 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

  45. Humoral immune response

  46. BCR B cell MHC II

  47. BCR MHC II

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