Acute Inflammation II Flashcards
engulfment
pseudopods surround object forming phagosome that fuses with lysosome creating a phagolysosome
oxygen dependent pathway (respirtatory/oxidative burst)
- oxygen is reduced to superoxide via NADPH oxidase
- superoxide is then converted to H2O2 by superoxide dismutatse
- myelo-peroxidase form neutrophilic granules, catalyze reaction between Cl- and H2O2 forming HOCl
oxygen independent pathway
leukocyte granule proteins and enzymes
Histamine and Serotonin
immediate but transient effect causing arteriolar dilation and increased permeability of postcapillary venules
Where are histamine and serotonin stored
in preformed granules of mast cells and basophils and platelets
What is the critical step in complement activation
cleavage of C3
Classic pathway of complement activation
initiated by binding of an antigen antibody complex to C1
alternate pathway of complement activation
C3 directly activated by bacterial endotoxins, complex polysaccharides, aggregated globulins
lectin pathway of complement acitvation
C1 activation by binding of mannose-binding lectin to carbohydrates on microbes
C3a, C4a, C5a
stimulate histamine release form mast cells leading to increased vascular permeability and vasodilation
C5a
chemotaxis of monocytes and granulocytes, increases surface expression of leukocyte CAM, activates lipoxygenase pathway in neutrophils and monyctes
C3b
opsonization with recogniztion by receptors on neutrophils, macrophages, eosinophils
C5-9
membrane attack complex that inserts into lipid bilayer forming macropores that increase cell permeability and lead to lysis
Hageman factor (facor XII)
activated by direct contact with endotoxins, collagen, or basement membrane. triggers the kinin system and the clotting cascade
what does activated hageman factor do
convert prekallikrien into kallikriein
kallikrien
amplifies activation of Hagemant factor
cleaves high molecular weight kininogen forming the kinins incuding bradkinin
Bradykinin
a short lived vasoactive peptide
What is bradkinin quickly inactivated by
plasma kininase
Function of bradykinin
increased vascular permeability
dilates blood vessels
contracts non-vascular smooth muscle
causes pain
FUnction of thromibin
links the coagulation system and inflammation
cleaves circulating soluble fibrinogen to generate insoluble fibrin
plasmin
lyses fibrin clots
what is plasmin formed by
cleaving of plasminogen by kallikrein or plasminogen activator released by endothelium and leukocytes
what does plasmin do in inflammation
activates Hageman factor
cleaves C3 to C3a
degrades fibrin to form fibirin split produces
Arachidonic acid
normally bound to cell membrane phosphlipids and released by the action of cellular phospholipases
What pathways released arachidonic acid
COX and LOX
COX pathway
converts arachidonic acid into prostaglandin intermediates
What do the prostaglandin intermediated form
TXA2, PGI2, PGE2, PGD2, PGF2a,
TXA2
potent platelet aggregator and vasoconstrictor
PGI2
vasodilatior and inhibitor of platlet aggrestion
PGE2
sensitizes skin to painful stimuli and plays role in cytokine-induced fever
PGD2, PGF2a, PGE2
cause vasodilation and potentiate edema
LOX pathway
converts arachidonic acid to leukotrines and lipoxins
LT B4
potent chemoattractant causing neutrophil aggregation and adhesion to endothelial cells, generation of ROS, and release of lysosomes
LT C4, D4, E4
cause intense vasoconstriction and bronchospasm and increase vascular permeability
lipoxin A4, B4
inhibit neutrophil adhesion to endothelium and neutrophil chemotaxis
What does platelet acitvating factor do at low concentration
vasodilation and venular permeability
What are the key cytokines of inflammation
IL-1 and TNF
Acute phase reactions of IL-1 and TNF
prudce fever, affect sleep and appetite, produce acute-phase proteins, cause neutrophilia and hemodynamic effects in shock
endothelial effects of IL-1 and TNF
increase leukocyte adherence, stimulate PGI synthesis, increase procoagulant activity and increased productio nof IL1, IL6, IL8, PDGF
Fibroblast effects of IL-1 and TBF
increases proliferation, collagen synthesis, and PGE synthesis, increases protease and collagenase production
Leukocyte effects of IL-1 and TNF
increase cytokine secretion