Published on May 31, 2014
BY : Izatty Lim (0308188)
Able to describe the 3 systems of the plasma protein- derived mediator of inflammation. Identify the plasma protein-derived mediator in the 3 systems and their actions.
Definition :any messenger that acts on blood vessels, inflammatory cells or other cells to contribute to an inflammatory response. MEDIATORS
Circulating protein of 3 interrelated system : o Complement system o Kinin system o Coagulation system
Consist of plasma protein that play important role in host defense & inflammation. C1 – C9 Activated by proteolysis to acquire their own proteolytic activity, thus setting up an enzymatic cascade. Critical step : activation of 3rd component, C3, by o Classical pathway • By fixation of C1 to antigen-antibody complexes o Alternative pathway • Triggered by bacterial polysaccharides (eg. Endotoxin) & other bacterial cell wall component • Involving distinct set of plasma protein including properdin & factors B and D. o Lectin pathway • Plasma lectin bind to mannose residues on microbes & activates the early component of classical pathway
CLASSICAL PATHWAY ALTERNATIVE PATHWAY LECTIN PATHWAY Formation of C3 Convertase C 3 a C 3 b C6 – C9 Formation of C5 Convertase C 5 bC 5 a Deposit on cell/microbial surface & bind with C3 convertase (4) MAC (made up of multiple copies of final component C9) create pores disrupt osmotic balance cell lysis (1) VASCULAR EFFECTS: -C3a & C5a induce release of histamine -↑ vascular permeability & cause vasodilation -C5a also activates lipoxygenase pathway of AA (2) LEUKOCYTE ACTIVATION, ADHESION & CHEMOTAXIS: -C5a, C3a & C4a (lesser extent) -potent chemotatic agent for neutrophils, monocytes, eosinophil & basophil. (3) PHAGOCYTOSIS: -C3b & iC3b act as opsonins - ↑ phagocytosis
Vascular effects (C3a & C5a) Leukocyte activation, adhesion, chemotaxis (C5a) Phagocytosis (C3b,iC3b) MAC ( C9)
Hageman factor ( Factor XII ) o A protein synthesized by the liver o Circulate in inactive form in plasma o Activated by collagen, basement membrane or activated platelets o Activated Hageman factor (factor XIIa) further actives: • Kinin system (vasoactive kinins) • Clotting system (activation of thrombin, fibrinopeptides & factor X) • Fibrinolytic system (plasmin production & inactivating thrombin) • Complement system (anaphylatoxins C3a & C5a)
(High molecular-weight kininogen)
Bradykinin o ↑ vascular permeability o Arteriolar dilation o Branchial smooth muscle contraction o Pain Kallikrein o Chemotatic activity o Potent activator of Hageman factor link with clotting system HMW KININOGEN BRADYKININ KALLIKREIN
Activated thrombin o Fibrin clot o Enhance leukocytes adhesion o Cleave C5 C5a ( link with complement system ) Fibrinopeptide o ↑ vascular permeability o Chemotatic for leukocytes Factor Xa (intermediate in clotting cascade) o ↑ vascular permeability & leukocyte emigration Fibrinogen Activated thrombinThrombin Fibrin Clot Fibrinopeptide
Plasmin o Multifunctional protease that cleaves fibrin o Fibrin degradation product will ↑ permeability o Cleaves C3 C3a (vasodilation & ↑ vascular permeability) o Activate Hageman factor, thus amplify the entire set of responses • Activated concurrently with activation of clotting system • Serve to limit clotting
Mitos y realidades de las sustancias psicoactivas
Mitos y realidades de las sustancias psicoactivas.
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