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Innate Immunity
Barriers
Epithelial layers
Defensins
Intraepithelial lymphocytes
Inflammation
Acute phase response
Fever
Complement system
Complement system contains more than 30 glycoprotein present in
the serum in the form of components and factors
Activation involves the sequential proteolysis of proteins to
generate proteolytic enzymes
The products of complement activation become covalently
attached to microbial cell surface or to antibodies bound to
microbial surface or other antigens
Complement activation is inhibited by regulatory proteins present
on normal host cell to minimize complement mediated damage to
host cell
Complement cascade also interact with other trigered-enzyme
cascade : coagulation, kinin and fibrinolysis
Complement activation
The central event of complement activation is
proteolysis of complement protein C3 to generate
biologically active product C3b
MBP
C1r C1r
C1s MASP C1s P
C4 C4 C4 D
C2 C2 C2 B
C3
C3b
Classical Pathway :
immune complex : IgG & IgM
Alternative Pathway :
endotoxin , CVF
virus , parasite , bacteria
Lectin pathway :
carbohydrate(mannose)
MAC : Membrane Attack Complex
C5a C9
C7
C6
C8
C5
C6 C6 C
C6
D
B
C3B
C3
C3
C3 Ba
D
Bb
C3B C3 convertase
C3a
C3a C3a
C3a
C3B
C3B
Bb C5 convertase
C3B C3B
Classical pathway
C1q r s
C4
C2
C4a
C4b
C2a
C4a
C3
C4b
C3 convertase
C2b
C2a
C3a C4a
C3b
C4b
C5 convertase C2b
C3b
MASP: MBL associated serine protease
MAC : Membrane Attack Complex
C9
C7
C6
C8
C5
C5 convertase
MAC : Membrane Attack
Complex
C5a C9
C7
C6
C8
C5b
C5 convertase
MAC : Membrane Attack Complex
C9
C8
C6
C5b
C5 convertase
C7
MAC : Membrane Attack Complex
C9
C6
C5b
C5 convertase
C7
C8
MAC : Membrane Attack Complex
C6
C
6
C5b
C5 convertase C9
C7
C8
MAC : Membrane Attack Complex
C6 C6 C6 C6
C6 C6 C6 C6
C6 C6 C6 C6
C1,4,2 C3,B,D
C 3 / C 5 convertase
C 4a , C 5a , C3a C 3b C 5b , C 6 --- C 9
Lysis of microbes
Inflammation
Phagocytosis of
opsonized microbes
The Complement system in Disease
C1q MBP
C3b
C1r C1r
C1s MASP C1s P
C4 C4 C4 D
C2 C2 C2 B
C3
C3b
C4 and C2 deficiencies :
50% associated with Auto Immune Disease (SLE)
Not usually associated with increased susceptibility
to infection
C3 deficiency :
Frequent pyogenic bacterial infection
Alternative Pathway deficiencies
Factor D, B and Properdin
Increased susceptibility to pyogenic bacterial infection
Terminal complement components deficiencies
C5, C6, C7, C8, C9
Increased susceptibility to Neisseria bacterium
Complement Regulators deficiencies :
DAF deficiency :
Paroxysmal nocturnal Hburia
C1INH deficiency
Hereditary angioneurotic edema
Regulators /
inhibitors of
complement
Complement Receptors