Pathology1-2 - I Complement components(C a Requires a...

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I. Complement components (C’) a. Requires a trigger; consists of about 11 proteins b. Activated Complement i. Yields particles that coat microorganisms and function as adhesion molecules for neutrophils and macrophages (opsonins) ii. Leads to lysis of bacterial cell membranes via membrane attack complex (MAC) iii. Yields biologically active fragments influencing the vascular and cellular pathways of acute inflammation c. Complement cascade can be activated two ways: i. Classical pathway formation of antigen-antibody complex ii. Alternative pathway operates via direct cleavage of C3; can be activated by certain endotoxins, venom, yeast C1qrs travels as three separate parts (q, r, s); requires Ca++ to hold qrs together C1qrs C2, C4 show up as soon as C1qrs is activated; C1qrs cleaves C2 and C4 C2, C4 C2b and C4a float off, C2a and C4b activate C3 -components bind to wherever they were activated (e.g. bacteria, glomerulus, doesn’t matter) C3 splits into C3a and C3b; C3a enhances vasodilation – anaphylatoxin C3b C5 C5 C5a (anaphylatoxin), C5b C5b C678 C678 gather all the C9s C9 poke hole in cell; cell no longer maintains steady state; e.g. bacteria killed = endotoxins = inflammation = more proteins; most likely necrotic death C6789 membrane attack complex (MAC) II. Chemical Mediators – The Kinin System Coagulation Factor XII (series of proteins) = Hageman Factor -activated with glass, collagen, cartilage, endotoxins, plasmin - acts on 3 plasma proenzymes : clotting factor XI, plasminogen proactivator, and prekallikrein -activates Factor XI forms a clot -activates Plasminogen to break down clot Clotting: fibrinopeptides released from fibrinogen by action of thrombin -induced vascular leakage; chemotactic to neutrophils; more inflammation -Plasminogen Plasmin -Fibrinolytic system leads to production of plasmin -plasmin feeds back to activate more Hageman factor -plasmin digests Factor XII; leads to activation of pre-kallikrein -pre-kallikrein kallikrein kininogen bradykinin -kallikrein is a chemotactic compound for neutrophils -bradykinin vasodilation, vascular permeability, hypotensive (low blood pressure) -Plasmin activates Complement cascade (C’); can also cleave C3 directly (alternate pathway) -C’ activates C5a, C3a anaphylatoxins, etc. Factors that initiate inflammation: more than one mechanism/pathway in case one doesn’t work -clot, plasmin, fibrinolytic, bradykinin, C’
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III. Tissue Derived – all these processes try to clear whatever has perturbed the cell maintaining a steady state a. Vasoactive amines i. Histamine from mast cell ii. Mast cells line small vessels; release after physical injury (heat, cold, irradiation, mechanical) or chemical injury iii. Chemical injury: (all activate/enhance inflammation and vascular dilatation) 1. immunoglobulins (Ig’s) 2. venom 3. C3a, C5a 4. Chymotrypsin/trypsin 5. cationic lysosomal proteins (come from cell; hole or destruction of cell
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Pathology1-2 - I Complement components(C a Requires a...

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