HomeCoursesMEDSCI 203: Mechanisms of DiseaseLecture 8 Lecture 8 1. What are the cardinal signs of inflammation? "Heat, redness, swelling, pain"What are the cardinal signs of inflammation?== "Heat, redness, swelling, pain" 2. What does inflammation bring to a site of injury? "Nutrients, oxygen, exudate (antibodies), leukocytes (defence), phagocytes (cleanup), fibrin mesh"What does inflammation bring to a site of injury?== "Nutrients, oxygen, exudate (antibodies), leukocytes (defence), phagocytes (cleanup), fibrin mesh" 3. What does inflammation remove from a site of injury? "Toxins (via exudate, lymph)"What does inflammation remove from a site of injury?== "Toxins (via exudate, lymph)" 4. What are pro inflammatory signals following tissue damage? "Neurons release peptides, DAMPs, PAMPs (endotoxin, LPS)"What are pro inflammatory signals following tissue damage?== "Neurons release peptides, DAMPs, PAMPs (endotoxin, LPS)" 5. "What are DAMPs, PAMPs sensed by?" Pattern recognition receptors (PPRs)"What are DAMPs, PAMPs sensed by?"== Pattern recognition receptors (PPRs) 6. What are soluble PRRs? ComplementWhat are soluble PRRs?== Complement 7. What are cell bound PRRs? Toll like receptors (TLRs)What are cell bound PRRs?== Toll like receptors (TLRs) 8. What cells respond to proinflammatory signals? "Macrophages, mast cells"What cells respond to proinflammatory signals?== "Macrophages, mast cells" 9. What granule inflammatory mediators do mast cells release on stimulation? "Histamines, proteases, TNF"What granule inflammatory mediators do mast cells release on stimulation?== "Histamines, proteases, TNF" 10. What causes redness and heat in inflammation? Vasodilation > hyperaemiaWhat causes redness and heat in inflammation? ==Vasodilation > hyperaemia 11. What happens in the case of an insect bite? "Endothelial cells retract, creating gaps (0.1-0.4microns) allowing exudate to pass"What happens in the case of an insect bite?== "Endothelial cells retract, creating gaps (0.1-0.4microns) allowing exudate to pass" 12. What happens in the case of sever injury? Endothelial damage leads to their detachment from the basement membrane > leaking until clot or repair takes placeWhat happens in the case of sever injury?== Endothelial damage leads to their detachment from the basement membrane > leaking until clot or repair takes place 13. What causes swelling and pain? "Increased hydrostatic pressure in capillaries, permeability, water binding of exudate proteins > intertitial oedema > stretching of tissue causes pain"What causes swelling and pain?== "Increased hydrostatic pressure in capillaries, permeability, water binding of exudate proteins > intertitial oedema > stretching of tissue causes pain" 14. What are vasoactive amines? Preformed histamine stored in granules of mast cells/basophils/plateletsWhat are vasoactive amines?== Preformed histamine stored in granules of mast cells/basophils/platelets 15. What are tryptases? Proteases that cleave protease activated receptors which induces inflammationWhat are tryptases?== Proteases that cleave protease activated receptors which induces inflammation 16. How do lipids mediate inflammation? "Inflammatory signals activate phospholipase A to create lysophophatidylcholine and arachidonic acidHow do lipids mediate inflammation?== "Inflammatory signals activate phospholipase A to create lysophophatidylcholine and arachidonic acid 17. Lysophosphatidylcholine is converted into PAF which induces platelet aggregation, leukocyte adhesion, chemotaxis and activation. Lysophosphatidylcholine is converted into PAF ==which induces platelet aggregation, leukocyte adhesion, chemotaxis and activation. 18. Arachidonic acid forms 1. Cyclooxygenases (COX1, COX2) which generate prostaglandins and 2. 5-lipoxygenase which generates leukotrienes."Arachidonic acid forms== 1. Cyclooxygenases (COX1, COX2) which generate prostaglandins and 2. 5-lipoxygenase which generates leukotrienes." 19. What do prostaglandins do? "Vasodilation and platelet disaggregation ( PCI2, PGE2), vasoconstriction and platelet aggregation (TXA2)"What do prostaglandins do?== "Vasodilation and platelet disaggregation ( PCI2, PGE2), vasoconstriction and platelet aggregation (TXA2)" 20. What do leukotrienes do? "Neutrophil chemotaxis and activation (LTB4), vasopermeability, mucus, bronchconstriction (CysLTC4, D4, E4)"What do leukotrienes do?== "Neutrophil chemotaxis and activation (LTB4), vasopermeability, mucus, bronchconstriction (CysLTC4, D4, E4)" 21. What are circulating inflammatory mediators? "Coagulation, fibrinolytic, kinin and complement cascades"What are circulating inflammatory mediators?== "Coagulation, fibrinolytic, kinin and complement cascades" 22. Describe the coagulation cascade?== "Damage to endothelium > release of tissue factor > activation of thrombin > cleaves 1. fibrinogen to fibrin > haemostasis 2. PARs > permeability, vasodilation, leukocyte adhesion" 23. What does the Hageman (FXII) factor do? Activates thrombin to propagate thrombiWhat does the Hageman (FXII) factor do?== Activates thrombin to propagate thrombi 24. What does the fibrinolytic pathway do? "Generates plasmin that degrades fibrin, ECM proteins and activates MMPs for remodelling"What does the fibrinolytic pathway do?== "Generates plasmin that degrades fibrin, ECM proteins and activates MMPs for remodelling" 25. What does the kinin pathway do? "FXII activates kallikrein protease > release of bradykinin > vasodilation, permeability, neutrophil chemotaxis"What does the kinin pathway do? =="FXII activates kallikrein protease > release of bradykinin > vasodilation, permeability, neutrophil chemotaxis" 26. Describe the complement pathway? "Proteases, antigen - antibody complexes, bacterial products >Describe the complement pathway?== "Proteases, antigen - antibody complexes, bacterial products > 27. C3 -> C3a (mast cell degranulation, permeability, chemotaxis) ,C3b (opsonistation)C3 -> C3a ==(mast cell degranulation, permeability, chemotaxis) ,C3b (opsonistation) 28. C3b + C5 -> C5a (mast cell degranulation, permeability, chemotaxis), C5b (membrane attack complex)"C3b + C5 -> C5a ==(mast cell degranulation, permeability, chemotaxis), C5b (membrane attack complex)" Loading...