Acute inflammation II Flashcards
What is the effect of histamine and serotonin on arterioles?
Vasodilation
What is the effect of histamine and serotonin on large arteries?
Vasoconstriction
What is the effect of histamine and serotonin on postcapillarly venules?
Increased permeability
Where are vasoactive amines stored?
Preformed granules of mast cells, basophils, and platelets
What is the critical step of complement activation?
Cleavage of C3
What initiates the classical complement pathway?
Binding of an antigen-antibody complex to C1
What initiates the alternate complement pathway?
C3 directly activated by endotoxin, IgA
What initiates the lectin complement pathway?
C1 activation by binding of mannose-binding lectin to carbohydrates on microbes
C3a, C4a, and C5a stimulate release of what compound?
Histamine
What are the roles of C5a?
- Chemotaxis of monocytes and granulocytes 2. Increase surface expression of leukocyte CAM 3. Activate LOX pathway in neutrophils and monocytes
What does the activation of Hageman factor (XII) do?
Triggers kinin system and clotting cascade
Bradykinin is inactivated by what enzyme?
Plasma kininase
What are the roles of bradykinin?
- Increase vascular permeability 2. Dilate blood vessels 3. Contract non-vascular smooth muscle 4. Cause pain
What molecules links coagulation to inflammation?
Thrombin
What does thrombin bind to on platelets, endothelium, and smooth muscle cells?
Platelet activated receptors (PARs)
Once bound to thrombin, what are the functions of PARs?
- Mobilize P-selectin 2. Produce chemokines, PAF, NO 3. Stimulate endothelial adhesion molecule formation 4. induce COX-2 and production of PGs 5. Induce changes in endothelial shape
What is the main role of plasmin?
Lysyes fibrin clots to form fibrin split products to increase vascular permeability in skin and lung
What are the arachidonic acid metabolites of the COX pathway?
TXA-2, PGI-2, PGE-2, PGD-2, PGF-2
What is the function of TXA-2?
Potent platelet aggregator and VASOCONSTRICTOR
What is the function of PGI-2?
Inhibitor of platelet aggregation and VASODILATOR
What are the roles of PGD-2, PGF-2, and PGE-2?
Vasodilation and edema formation
What are the roles of PGE-2?
Sensitizes skin to painful stimuli, cytokine-induced fever, vasodilation, edema formation
What are the roles of leukotriene B4?
Potent chemoattractant for neutrophils, causes aggregation and adhesion to endothelial cells, generation of ROS, and release of lysosomes
What are the roles of leukotrienes C4, D4, E4?
Intense vasoconstriction and bronchospasm, and increase vascular permeability
What is the general role of lipoxins?
Neutralize the function of leukotrienes
What are the roles of lipoxin A4 and B4?
Inhibit neutrophil adhesion to endothelium and neutrophil chemotaxis
What is the function of platelet activating factors (PAFs) at normal or high concentrations?
Vasoconstriction, bronchoconstriction
What is the function of platelet activating factors (PAFs) at LOW concentrations?
Vasodilation and venular permeability
Activated macrophages produced which main cytokines?
IL-1 and TNFa
What are the effects of IL-1 and TNFa on endothelial cells?
- Increase leukocyte adherence 2. Stimulate PGI synthesis 3. Increase procoagulant activity 4. Increase production of IL-1, IL-6, IL-8, PDGF
What are the effects of IL-1 and TNFa on leukocytes?
Increased cytokine secretion of IL-1, IL-6
C-X-C or alpha chemokines act primarily on which cell type?
Neutrophils
C-C or beta chemokines act primarily on which cell type?
Many cells but NOT neutrophils
C or gamma chemokines act primarily on which cell type?
Specific for lymphocytes
C-X-3C chemokines act primarily on which cell type?
Monocytes and T cells
What are the general roles of NO?
Reduce aggregation and dilate vasculature
What are the outcomes of extracellular ROS release?
- Endothelial cell damage 2. Inactivation of antiproteases 3. Injury to other cells
In general, which compounds are involved in vasodilation during acute inflammation?
PG, NO
In general, which compounds are involved in vascular permeability during acute inflammation?
Histamine / serotonin, C3a / C5a, bradykinin, leukotrienes (C, D, E), PAF, substance P
In general, which compounds are involved in chemotaxis and leukocyte activation during acute inflammation?
C5a, LTB-4, chemokines
In general, which compounds are involved in fever during acute inflammation?
IL-1, IL-6, TNFa
In general, which compounds are involved in pain during acute inflammation?
PG, bradykinin
In general, which compounds are involved in tissue damage during acute inflammation?
Lysosomal enzymes, oxygen metabolites, NO
