Plasma derived chemical mediators of inflammation - ttylim
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Transcript of Plasma derived chemical mediators of inflammation - ttylim
CHEMICAL MEDIATORS OF INFLAMMATION
( PLASMA PROTEIN DERIVED )
BY : Izatty Lim (0308188)
LEARNING OUTCOMES 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.
CHEMICAL MEDIATORS OF INFLAMMATION
Definition : any messenger that acts on blood vessels, inflammatory cells or other cells to contribute to an inflammatory response.
MEDIATORS
PLASMA PROTEIN-DERIVED MEDIATORS
Circulating protein of 3 interrelated system :o Complement systemo Kinin systemo Coagulation system
COMPLEMENT 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
COMPLEMENT SYSTEM
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)
COAGULATION & KININ SYSTEM
Hageman factor ( Factor XII )o A protein synthesized by the livero Circulate in inactive form in plasmao Activated by collagen, basement membrane or activated
plateletso 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)
KININ SYSTEM
Bradykinino ↑ vascular permeabilityo Arteriolar dilationo Branchial smooth muscle contractiono Pain
Kallikreino Chemotatic activityo Potent activator of Hageman factor link with clotting
system
HMW KININOGEN BRADYKININ
KALLIKREIN
CLOTTING SYSTEM
Activated thrombino Fibrin cloto Enhance leukocytes adhesiono Cleave C5 C5a ( link with complement system )
Fibrinopeptideo ↑ vascular permeabilityo Chemotatic for leukocytes
Factor Xa (intermediate in clotting cascade)o ↑ vascular permeability & leukocyte emigration
Fibrinogen
Activated thrombin
Thrombin
Fibrin Clot
Fibrinopeptide
FIBRINOLYTIC SYSTEM
Plasmin o Multifunctional protease that cleaves fibrino Fibrin degradation product will ↑ permeabilityo 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
The end.