The Complement Cascade
The Classical Pathway
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Complement: The Classical Pathway
C1q
Ab
Ag
C1q binds
Antibody
to antibody/antigen
binds to antigen
complex
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Complement: The Classical Pathway
C1q-Ab-Ag
Complement: The Classical Pathway
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C1q/antibody/antigen complex activates
C1r (bound to C1s)
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Complement: The Classical Pathway
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C1s
Activated C1r cleaves C1r/C1s,
releasing Active C1s
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Complement: The Classical Pathway
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C1s
C4
C4b
C4a
C1s cleaves C4 to C4a and C4b
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Complement: The Classical Pathway
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C1s
C4b
C4b.2 C2
C4
C4a
C4b binds to C2
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Complement: The Classical Pathway
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C4b.2b
C2a
C1s
C4
C4b.2
C4a
C1s cleaves C2 producing C4b.2b and C2a
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Complement: The Classical Pathway
• C4b.2b is termed the Classical C3 Convertase
• C4b.2b cleaves C3 to produce C3b
• (C3a is released)
• C3b is the first molecule of the Terminal Pathway
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Complement: The Classical Pathway
C3
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C4b.2b
C2a
C1s
C4
C3a
C4b.2
C4a
C3b
Cb4.2b cleaves C3 producing C3a and C3b
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Complement: The Classical Pathway
C3
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C4b.2b
C2a
C1s
C3a
C4
C4b.2
C4a
C3b
C5b
C5
C5a
Complement: The Classical Pathway
C3
C1q-Ab-Ag
C1r-C1s
C1r-C1s
C4b.2b
C2a
C1s
C3a
C4
C4b.2
C4a
C3b
C5b.6.7
C5b.6.7.8
C8
C5b.6.7.8.9n
C9n
C5b.6
C7
C5b
C6
C5
C5a