The Complement Cascade

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The Complement Cascade

• The Alternative Pathway

2
Complement The Alternative Pathway
C3
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3
Complement The Alternative Pathway
C3b
(In the presence of Mg2 ions) Factor B binds to
C3b
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4
Complement The Alternative Pathway
C3b.B
C3b
Factor D cleaves C3b.B
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5
Complement The Alternative Pathway
C3b.Bb
FD
C3b.B
C3b
C3b.Bb is unstable, with a very short half life
It is stabilised by FP which is active of
microbial surfaces
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6
Complement The Alternative Pathway

• C3b.Bb is termed the Alternative C3 Convertase
• C3b.Bb cleaves C3 to produce C3b
• (C3a is released)
• C3b is the first molecule of the Terminal Pathway

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7
Complement The Alternative Pathway
C3
C3b.Bb
FD
C3a
C3b.B
C3b
C3b.Bb cleaves C3
producing C3a and C3b
Next
8
Complement The Alternative Pathway
C3
C3b.Bb

• This is a positive feedback mechanism
• It enables the amplification of the complement
  process
• Positive feedback mechanisms are relatively rare
  because they are inherently unstable
• Hence, positive feedback mechanisms have controls
  to regulate them and to maintain homeostasis.
• Factor H performs this role in the Alternative
  Pathway

FD
C3a
C3b.B
C3b
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9
Complement The Alternative Pathway
C3
C3b.Bb
FD
C3a
C3b.B
In the absence of infection, FH binds C3b in
preference to FB
If a bacterial surface is present, FB binds C3b
in preference to FH
C3b
C3b.H
Factor H competes with FB to bind C3b
forming C3b.H
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10
Complement The Alternative Pathway
C3
C3b.Bb
FD
FI
C3a
C3b.B
C3b.i.H
C3b
C3b.H
C3b.i
Factor I binds C3b.H forming C3b.i.H
FH is then released recycling FH
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11
Complement The Alternative Pathway
C3
C3b.Bb
FD
FI
C3a
C3b.B
C3b.i.H
C3b
C3b.H
C3b.i
C3b.i. spontaneously breaks down to C3c and C3d
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12
Complement The Alternative Pathway
C3
C3b.Bb
FD
C3a
C3b.B
C3b
C3b is the first component of the Terminal Pathway
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