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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 Cells of the immune system Properties of Immune cells Inactive/Naive Few surface molecules Activated cells Effector cells Many surface molecules Becomes larger in size Proliferate and produce more cells Release peptides and lipids Increased ability to migrate epithelium Macrophage Macrophage Common receptors for immune cells of many animals Detect pathogen associated molecular patterns epithelium Opsonization by Complement proteins Toll-like receptor Macrophages Toll-like receptors Pathogen-associated molecular patterns Lysosomes Phagosome Phagolysosome H2O2 O2- NO Activated macrophage Prostaglandins, Leukotrienes and Platelet activating factor Flow increased Velocity reduced Lipid mediators of inflammation Increased diameter Increased permeability Increased expression of adhesion molecules Lysosomes Phagosome Phagolysosome H2O2 O2- NO Activated macrophage Cytokines Chemokines 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 A A Neutrophil H2O2 O2- NO Body tissue Body tissue Body tissue Cytokines Cytokines activated Chemokines Chemokines Mediators of infl. Cytokines Cytokines activated activated Cytokines Chemokines Mediators of Pus cells Pus cells 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 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 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 Trigger 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 Body cells Kill Body cells Kill From Innate to Adaptive Cells activated during the innate immune response bridge the gap between the innate and the adaptive systems Dendritic cells and Macrophages Adaptive Immune Response epithelium Dendritic cells Toll-like receptors Dendritic cell or macrophage Antigen presentation Antigen presenting cells (APC) T T T T T Clonal expansion of lymphocytes 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 Mature DC T B B T B T B T T T T B T B Circulation T T Immature DC T B B B Jefford et al., Lancet, June 2001 Surface molecules on DC and T cells Cell-cell interaction molecules Receptors for cytokines Receptors for chemokines Cell adhesion molecules Cell-cell interaction molecules on DC and T cells Antigen presenting cell CD4 CD8 B-7 CD28 CD28 B7= CD80 & CD86 CD4+ helper T cell CD8+cytotoxic T cell 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 DC-T cell interaction Dendritic cells send two signals to T cells 1st signal – determines antigen specificity 2nd signal – triggers T cell proliferation immature DC CD4 1st signal CD4+ helper T cell mature DC B-7 CD4 2nd signal CD28 CD4+ helper T cell Increase proliferation Secrete IL-2 (growth factor of T cells) Cell-cell interaction molecules on DC and T cells Antigen presenting cell CD4 CD8 B-7 CD28 CD28 B7= CD80 & CD86 CD4+ helper T cell CD8+cytotoxic T cell Intravesicular pathogens Extracellular pathogens Toxins APC CD4 CD8 Th1 cells T helper cells (Th cells) Th2 cells Th0 cells Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines IFN- IFN- IFN- IFN- IFN- IL-5 IL-10 IL-4 IL-4 IL-10 Th1 cells Macrophage Activation IL-4 IL-10 IL-5 Th2 cells B cell Activation 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 Clinical relevance of Th1 vs Th2 Mycobacterium leprae grows in macrophage vesicles. To destroy bact. need to activate macrophages by Th1 cells Th2 response is a waste Th2 response Lepromatous leprosy Th1 response Tuberculoid leprosy - Numerous live bacteria - Few live bacteria - Lot of Ab in serum (ineffective) - Little Ab in serum - Gross tissue damage & death - Skin & PN damage due to Mac. activation - Slow disease, patient survives Humoral immune response B cell B cell CD4 IL-4 IL-5 IL-6 IL-10 CD4+ T helper cell Th2 IL-4, IL-5, IL-10 Plasma cell B cell Ab mediated response (Humoral immunity) B cell CD4 Inhibition Inhibition IFN- IFN- CD4+ T helper cell Th1 Cell mediated response immature DC CD8 1st signal CD8+cytotoxic T cell mature DC B-7 CD8 2nd signal CD28 CD8+cytotoxic T cell Increase proliferation Secrete IL-2 matureTissue DC Infected CD8 Kill IFN- effector CD8+cytotoxic T cell Kills virus or intracellular pathogen infected body cells MHC I CD8 T cells Cell mediated response Immunological memmory cytokines MHC I MHC II chemokines cytokines CD4 T cells chemokines B cells Antibody mediated response Immunological memory The ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously Both T cells and B cells are left behind as memory cells following the primary immune response These are a distinct populations of long lived cells, without the need to getting exposed to residual antigen, in the body Immunological memory…cont. In the presence of memory T and B cells, the naïve T and B cells are not activated upon exposure to the same antigen again (would be a waste) Adaptive immunity - summary The immune cells need to specifically identify the pathogen Clonal expansion of specific immune cells Takes few days to build up T and B lymphocytes are key players Leaves behind memory cells