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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