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1
One Step Further
Complement Activation
OSF - 6
Pages 84 - 86
2
Complement Activation - 2
Two enzymatic pathways available:
eClassical pathway
eAlternative pathway
ˇfirst one discovered
ˇactivated by immune complexes
ˇactivated primarily by polysaccharide structures
¸microbial cell walls is an example
Two enzymatic pathways join at:
eClevage of C5 which results in:
ˇformation of the Membrane Attack Complex (MAC)
¸this results in lysis of cell
3
Complement Activation - 3
Classical pathway activation:
ethe sequence of activation is:
Immune complex
\
C1q of C1 complex
\
C4
-
C4a
\
C4b
\
C2
-
C2a
\
C2b
C4b
\
C2b
-
C3 convertase
C3 convertase
\
C3
-
C3b
C3b
\
C3 convertase
-
C5 convertase
C5 convertase
\
C5
-
C5b
C5b
\
C6
\
C7
\
C8
\
C9
MAC
cell lysis
4
Complement Activation - 4
Alternative pathway activation:
ethe sequence of activation is:
C3
-
C3b
(C3b is found normally in the blood due to hydrolysis of C3)
C3b
-
binds to microbial surface
C3b
\
Factor D
\
Factor B
-
C3 convertase
C3 convertase
\
C3
-
C3b
C3b
\
C3 convertase
-
C5 convertase
C5 convertase
\
C5
-
C5b
C5b
\
C6
\
\
\
C7
C8
C9
MAC
cell lysis
5
Complement Activation - 5
Regulation of pathways:
eC1 INH
eFactor I
eFactor H
eC4bp
ˇinhibits C1 binding with immune complex
ˇinhibits C3b
ˇinhibits C3 convertase formation
ˇinhibits C3b + Factor B & Factor D interaction
ˇinhibits C3 convertase formation
ˇbinds with C4
ˇinhibits C3 convertase formation
6
Complement Activation - 6