Path VI Flashcards
What causes chemotaxis, leukocyte recruitment, and activation?
TNF, IL1, chemokines, C2a, C5a, leukotriene B4,
what causes vasodilation?
prostaglandins, NO, histamines
Histamine: what releases it? what does it do?
relased by mast cells, basophils, and platelets
dilates arterioles but constricts larger arteries and bronchioles and incr. vascular permeability
What triggers histamine release?
physical or thermal truama, Ig biding of mast cells, effects of C3a, C5a, neuropeptides, IL1, and IL8
what causes incr. vascular permeability?
histamine, serotonin, C3a nad C5a, bradykinin, leukotrienes C4 D4 and E4, PAF, substance P
What are main mediators of tissue damage?
lysosomal enzymes of leukocytes
reactive oxygen species
nitric oxide
What releases serotonin? What does it do?
enterochrommafin cells and platelets
incr. vascular permability
induce platelet aggregation (less important)
vasodilation
What induces serotonin release?
PAF or trauma of enterochrommafin cells, platelet aggregation. platelet contact w/ collagen, thrombin
what are the maing mediators of fever?
IL1, TNF, IL6, prostaglandins
What factors activate C3 directly? What about C5 and C5a?
lysozome and plasmin can activate C3 directly
kallikrein can activate C5 and C5a directly
What do C3a, C4a, and C5a do?
induce histamine release from mast cells and cause vasodilation.
What does C5a do>
chemotaxin for leukocytes/ activatea arachidonic acid release and lipooxygenase path in tneurophils and macrophages to promote leukotriene production
What does C3b do?
opsonin for neutrophils and macrophages
What is kallikrein?
the active form of prekallikrein, wihch is present in plasma
it activates bradykinin, plasmin, and XIIa (Hageman factor). It also converts C5 to C5 a
What actiaves Kiallikrein?
hageman factor XIIa
What is bradykinin? In what form is it present in the plasma? What activates it?
HMWK= inactive plasma form
it causes smooth muscle contraction, vasodilation, and pain augmentation
it is activated by kallikrein
What is Hageman factor/ factor XIIa?
inactive form in plasma (factor XII)
it activates the clotting cascade/coagulation system, and the kinin system with activates the fibrinolytic system
also activates plasmin?
What factors activate hageman factor?
plasma protein activated by contact with negatively charged surfaces like the basement membranem collegen, elastin bacterial LPS proteolytic enzymes (less important)
What does thrombin do? (4 downstream effects)
converts fibrinogen to fibrin. this produces fibrinopeptides which increase vascular permeability and are chemotactic. it promotes leukocyte adhesion and stimulates fibroblast prolif.
What activates thrombin?
intrinsic and extrinsic clotting cascades
What is factor Xa? Inactive form? what does it do?
Factor X is the inactive form
it activates factor II to IIa.
it increases vasc. permeability
it promotes leukocyte transmigration and emigration
What activates factor X?
clotting cascad via intrisic (factor IX/VIIIa complex) and extrinsic cascades (factor VIIa/tissue factor complex)
What is plasmin? inactive form? what does it do?
inactive form is plasminogen
it lyses fibring clotes to make fibrin split products which increase vascular permeability
it activates C3 to C3a and C3b and activates Factor XII to factor XIIa.
What activates plasmin?
tissue plasminogen activator and kallikrein
What are prostaglandins? Where do they come from? What inhibits their production?
come from arachidonic action via cyclooxygenase
stimualted by activation of leukocytes and endothelial cells
inhibited by aspirin
What does PGE2 do?
edema, vasodilation, and pain
What does PGD2 do?
edema and vasodilation
What does PGI2 do? What cells produce it?
vasodilation and inhibition of platelet aggregation
produced by endothelial cells
What does TXA2 do? what cells produce it?
vasoconstriction and promotion of platelet aggregation
produced by platelets
Leukotrienes: origin and stimulus
origin: from arachidonic acid by actions of lipooxygense
stimulated by activation of neutrophils and made from neutrophils, plateltes, and macrophages
What dos LTB4 do?
chemotaxis and increasesa adhesion molecules. promotes oxidative burst and lysosomal function
What do LTC3, LTD4, and LTE4 do?
vasoconstriction, bronchospasm, and inc. vascular permeability
What is the origin of lipoxins LXA4 and LXB4?
platelets modify LTA4 from neutrophils- inverse of leukotrienes
What doe LXA4 and LXB3 do?
inhibit neutrophil migration and cause vasodilation.
What is PAF?
phosphlipid created upon cell activation
What does PAF do?
vasodilation. increases vascular permeability and promotes leukocyte aggregation and activation. it increases adhesion molecules. it is chemotactic and activates platelets. it stimulates oxidative burst and AA derivatives.
What can PAF do in very high concentrations?
vasoconstriction and bronchoconstriction
What makes IL6?
macrophages, endothelial cells, and fibroblasts. It sitmutes acute phase proteins by the liver and induces fever. inhibits TNFa production.
What stimulates IL6 production?
activation of macrophages, endothelial cells or fibroblasts by IL1 or TNFa
what are the main mediators of pain?
prostaglandins
bradykinin
What does IL1 do?
enhances histamine release, increases PGE2 production to produce fever. activates endothelium, all leukocyte types, and fibroblasts. produces other cytokines and acute phase proteins.
What makes TNFa?
macrophages
What does TNFa do?
activates neutrophils, endothelia, leukocytes, fibroblasts. aggregates neutrophils. induces loss of appetite, release of leukocytes from bone marrow, release of ACTH. stimualtes production of other cytokines and acute phase proteins.
Dangers of too much TNFa?
hypotension, low glucose, decreased myocardial contractility, and diffuse intravscular coagulation. major mediator of septic shock.
What does IL8 do?
endothelial activation. it activates and is chemotactic for neutrophils.
What stimulates IL8?
activation of macrophages or endothelial cells by IL1 and TNFa
What does NO do?
vasodilation. reduced platelte aggregation and adhesion. works with O2 to make antimicrobial metabolites
What makes stimulates NO production and who makes it?
endothelial cells, some macrophages (source)
stimulated by action of Ca influx brought on by Il1 and TNFalpha.
Who makes O2 free radicals?
neutrophils and macrophages
What do O2 free radicals do?
bacterial killing and induction of IL8 expression
How are O2 free radicals made?
activation of NADPH oxidative system.
What releases neuropeptides like substance p and neurokinin A?
peripheral nerve endings
what do neuropeptides like substance p and neurokinin A do?
augment pain, incr. vascular permeability, vasodilation
What is the stimulus for the release of neuropeptides like substance p and neurokinin A?
released by direct trauma/damage
What is the stimulus for the release of PAF
produced by the activation of all cells involved in inflammation, esp. mast cells and macrophages
What produces IL-1?
activated macrophages and fibroblasts
what stimulates release of IL1?
cell injury, immune complexes, bacterial cell walls, and endotoxin
what is the stimulus for the release of TNF alpha?
activation of macrophages, esp. bacterial LPS.
