describing clotting cascade, complement system, fibrinolytic system and their interrelations.

1.  
BY : Izatty Lim (0308188)

2.  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.

3.  Definition :any messenger that acts on blood vessels,
inflammatory cells or other cells to contribute
to an inflammatory response.
MEDIATORS

4.  Circulating protein of 3 interrelated system :
o Complement system
o Kinin system
o Coagulation system

6.  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

7. 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

8.  Vascular effects (C3a & C5a)
 Leukocyte activation, adhesion, chemotaxis
(C5a)
 Phagocytosis (C3b,iC3b)
 MAC ( C9)

9.  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)

10. (High molecular-weight
kininogen)

11.  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

12.  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

13.  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