Inflammation Anti inflammatory agents PCOL 502 evolutionarily conserved response primarily a defense mechanism not a disease role is to restore normal function to infected or DR JOHN O BRYAN Email obryanj uic edu 4091 COMRB damaged tissue if healing incomplete chronic inflammation Assigned reading Rang 6th edition Chapter 13 pages 202 213 optional background inflammatory immune responses and mediators Rang Chapter 14 pages 226 245 NSAID anti rheumatoid drugs immunosuppressant drugs drugs used in gout Katzung 10th edition Chapter 36 pages 573 597 1 Three phases to inflammation 2 Inflammatory response 1 Acute inflammation autocoids innate responses Acute inflammatory response initial response to tissue injury induced by a pathogen or noxious substance 2 Immune response adaptive immune response induction and effector phases 1 Chemical mediators or autocoids bradykinin serotonin histamine NO prostaglandins leukotrienes ILs 2 Vascular system flow and permeability changes due to PGs histamine PAF and cytokine release 3 Chronic inflammation results if injurious agent persists 3 Migration of blood cells chemotaxis neutrophils mast cells NK cells Inflammation can be beneficial and or destructive clear infections hypersensitivity reactions autoimmune diseases 4 Innate response 5 Time course is minutes to hours 3 4 Inflammatory response con t Inflammatory Reactions Innate response Inflammatory response con t II Immune response or subacute inflammation immune competent cell activation Innate immune response Innate and adaptive responses to initiating antigen event is pattern recognition TOLL like receptors non adaptive primordial response 1 innate recognition by tissue M of specific pathogen evolutionarily conserved associated molecular patterns PAMPs pathogen associated molecular patterns PAMPs some aspects are non immunological adaptive induction and effector phase of both cell to classes of pathogens specific some comprise innate immune response knee jerk mediated and humoral mediated respose e g peptidoglycans bacterial lipopolysaccharides reaction of immune system bind TLRs on antigen presenting cells dendritic cells 2 Canresponse be beneficial and or destructive role in preventing host damage by adaptive hypersensitivity reactions Adaptive immune response autoimmune diseases induced following recognition of pathogen by innate system pathogen specific responses backup systems in place macrophages TLR binding stim response by APC or Macrophages secretion of pro inflammatory mediators PGs and histamine release vascular permeability exudation of factors inflammatory response 5 Innate immune response 6 Innate immunity Adaptive Immunity Natural or native immunity Adaptive immune response Rapid response to microbes Specific orimmunity acquired Specific or acquired Physical and chemical barriers immunity of sustained response Exquisite Phagocytic cells neutrophils and specificity organism to infection for a large diversity macrophages and NK cells of distinctfor foreign specificity large Exquisite Blood proteins complement antigens diversity of foreign antigens system and other mediators Memory and robust Natural or native immunity Rapid response to microbes physical and chemical barriers Phagocytic cells neutrophils macrophages and NK cells Blood proteins other mediators Cytokines Increase in vascular permeability Memory and robust response Cytokines secreted proteins response to 2nd exposure to 2nd exposure that regulate and control cells of and the immune Lymphocytes system Lymphocytes T and B cells their products T and B cells Increase inand vascular their permeability products 7 8 3 Immune System Immune System Innate Immunity Rapid kinetics non specific response baseline response ADAPTIVE IMMUNE RESPONSE Key players lymphocytes B cells produce antibodies T cells responsible for induction phase of immune response and cell mediated immune rxns NK cells specialized lymphoid cells active in nonimmunological innate response Adaptive Immunity Slower kinetics specific response response with exposure mediated by phagocytes mediated by lymphocytes T physical and chemical and B cells and their products barriers and blood proteins 9 ADAPTIVE IMMUNE RESPONSE 10 ADAPTIVE IMMUNE RESPONSE Humoral and Cell mediated Immunity Response occurs in two phases 1 induction phase antigen presented to T cells by dendritic cell T cells interact with other T and B cells clonal expansion of cells that recognize antigen 2 effector phase antigen recognizing B cells differentiate into plasma cells produce antibodies antigen recognizing T cells cell mediated immune Hypersensitivity reactions inappropriately deployed responses activating macrophages killing virus infected cells memmory cells enhance response upon re exposure immune reactions anti inflammatory and immunosuppressive drugs used to counter these inappropriate immune reactions 11 12 Inflammatory Mediators Signaling Molecules Inflammatory response con t Arachidonic acid derivatives prostaglandins thromboxanes leukotrines vasodilation bloodflow redness edema fever vascular permeability WBC migration pain Chronic inflammation Vascular system flow and permeability changes EC Migration of blood cells infiltrate of lymphocytes Bradykinin vasoactive plasma peptides formed from kininogens vasodilator vascular permeability pain monocytes Chemical mediators chemokines cytokines Igs coagulation Adaptive immune response Time course is weeks to years Tissue proliferation and destruction Cytokines IL 1 and TNF released from tissue macrophages and see vascular permeability and adhesion molecule expression Chemokines chemoattractants IL 8 RANTES MCP 1 Complement lyse bacteria EC permeability opsonization Clotting mediators activated by platelets or collagen Hageman Factor XII 13 Inflammatory Mediators Signaling Molecules 14 Two Sides of the Inflammatory Response Thromboxanes platelets aggregation vasoconstriction Histamine IgE mediated or complement C3a and C5a mediated release from mast cells and basophils causes vasodilation permeability gastric acid secretion Protective controls infection and promotes tissue repair Serotonin vasoconstrictor released by platelets vascular permeability Destructive causes tissue damage necrosis and disease Angiogenic factors VEGF FGF Platelet activating factor released from platelets EC mast cells vasodilator stimulates prostaglandin syn Nitric oxide NO released from EC and causes smooth muscles to relax and vasodilation and PGs syn
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