HomeCoursesMEDSCI 203: Mechanisms of DiseaseLecture 9 Lecture 9 1. What do cytokines do?= =Control inflammation What do cytokines do?= =Control inflammation 2. What do chemokines do? Recruit cells to sites of injury and infectionWhat do chemokines do?== Recruit cells to sites of injury and infection 3. What do TNF and IL-1 do (apart from causing tumour necrosis and cachexia)? "Vasodilation, vasopermeability, neutrophil recruitment, EC adhesion molecules"What do TNF and IL-1 do (apart from causing tumour necrosis and cachexia)?== "Vasodilation, vasopermeability, neutrophil recruitment, EC adhesion molecules" 4. What are the consequences of high levels of TNF? (4) "Fever, blood coagulation (intravascular), fibrosis, cachexia"What are the consequences of high levels of TNF?== (4) "Fever, blood coagulation (intravascular), fibrosis, cachexia" 5. Why is TNF limited as a cancer treatment today? (2) "Unpleasant symptoms, not effective against carcinoma cancer types"Why is TNF limited as a cancer treatment today? ==(2) "Unpleasant symptoms, not effective against carcinoma cancer types" 6. What DAMPs activate TLRs? "ECM fragments, intracellular proteins, DNA/RNA"What DAMPs activate TLRs?== "ECM fragments, intracellular proteins, DNA/RNA" 7. What DAMPs activate inflammasomes? "Crystals (MSU, cholersterol)"What DAMPs activate inflammasomes?== "Crystals (MSU, cholersterol)" 8. What DAMP activates P2X7 purinergic receptors? ATPWhat DAMP activates P2X7 purinergic receptors?== ATP 9. What does signalling from TLRs produce? Activation of inflammasomes and caspase -1 generating IL-1beta. IL-1alpha and IL-1beta induce endothelial cell adhesiveness for leukocytesWhat does signalling from TLRs produce?== Activation of inflammasomes and caspase -1 generating IL-1beta. IL-1alpha and IL-1beta induce endothelial cell adhesiveness for leukocytes 10. What is the result of inflammation that leads to decreased plasma and increased viscosity in venules? ==Neutrophils leave central stream and concentrate in plamatic zone 11. What causes rolling of neutrophils? "P selectins, E selectins bind sialyl lewis x on neutrophils"What causes rolling of neutrophils?== "P selectins, E selectins bind sialyl lewis x on neutrophils" 12. What causes adhesion of neutrophils to endothelial cells? ICAM-1 and VCAM-1 on endothelial cells bind LFA-1 on neutrophilsWhat causes adhesion of neutrophils to endothelial cells?== ICAM-1 and VCAM-1 on endothelial cells bind LFA-1 on neutrophils 13. How is diapedisis (transmigration) achieved? Release of elastase digests basement membrane to allow entry of neutrophils into tissueHow is diapedisis (transmigration) achieved?== Release of elastase digests basement membrane to allow entry of neutrophils into tissue 14. What chemokine guides leukocytes in the blood stream? IL-8What chemokine guides leukocytes in the blood stream? ==IL-8 15. What chemokines guide cells in tissues? "NFPs, C3a, C5a, bradykinin, LTB4"What chemokines guide cells in tissues? =="NFPs, C3a, C5a, bradykinin, LTB4" 16. What happens in respiratory burst? O2 reduced to superoxide > depolarisation of vacuole > K+ influx > proteases released from carriers > myeloperoxidase/superoxidedismutase activated > pH raised to 9.0 > proeolysisWhat happens in respiratory burst?== O2 reduced to superoxide > depolarisation of vacuole > K+ influx > proteases released from carriers > myeloperoxidase/superoxidedismutase activated > pH raised to 9.0 > proeolysis 17. What are the sytemic responses to acute inflammation? "TNF, IL-1, PGE2 cause fever, IL-6 causes acute phase response (coagulation factor and opsonin production), leukocytosis following leukocyte release from bone marrow"What are the sytemic responses to acute inflammation?== "TNF, IL-1, PGE2 cause fever, IL-6 causes acute phase response (coagulation factor and opsonin production), leukocytosis following leukocyte release from bone marrow" 18. What can result from pyogenic infection? "Suppuration, abscesses, cellulitis"What can result from pyogenic infection? =="Suppuration, abscesses, cellulitis" 19. What induces systemic inflammatory response syndrome and sepsis? "DAMPs, PAMPs, TNF, IL-1 into the circulation, ROS, activated complement, increase in ratio of pro to anti coagulants"What induces systemic inflammatory response syndrome and sepsis?== "DAMPs, PAMPs, TNF, IL-1 into the circulation, ROS, activated complement, increase in ratio of pro to anti coagulants" 20. What is the result of systemic inflammatory response syndrome? "Systemic vasodilation and permeability, thrombi formation, uncontrolled bleeding (inadequate clotting factors), inadequate perfusion, multi organ dysfunction failure and death (30%)"What is the result of systemic inflammatory response syndrome?== "Systemic vasodilation and permeability, thrombi formation, uncontrolled bleeding (inadequate clotting factors), inadequate perfusion, multi organ dysfunction failure and death (30%)" 21. How is inflammation turned off? "Eliminating stimulatory effects of DAMPs and PAMPs, anti inflammatory negative feedback loop"How is inflammation turned off?== "Eliminating stimulatory effects of DAMPs and PAMPs, anti inflammatory negative feedback loop" Loading...
