1. The Complement Cascade
The Classical Pathway
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2. Complement: The Classical Pathway
C1q Ab Ag
C1q binds to antibody/antigen complex
Antibody binds to antigen
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3. Complement: The Classical Pathway
C1q-Ab-Ag

4. Complement: The Classical Pathway
C1q-Ab-Ag
C1q/antibody/antigen complex activates C1r (bound to C1s)
C1r-C1s
C1r-C1s
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5. Complement: The Classical Pathway
C1r-C1s
C1q-Ab-Ag
Activated C1r cleaves C1r/C1s,
releasing Active C1s
C1s
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6. Complement: The Classical Pathway
C1r-C1s
C1q-Ab-Ag
C1s
C1s cleaves C4 C4
to C4a and C4b
C4a
C4b
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7. Complement: The Classical Pathway
C1r-C1s
C1q-Ab-Ag
C1s C4
C4b
C4b.2 C2
C4a
C4b binds to C2
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8. Complement: The Classical Pathway
C1r-C1s
C1q-Ab-Ag
C4b.2b
C2a
producing C4b.2b and C2a
C1s cleaves C2
C1s C4
C4b.2
C4a
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9. 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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10. Complement: The Classical Pathway
C1r-C1s
C1q-Ab-Ag
Cb4.2b cleaves C3
C4b.2b
C2a
C1s
C3a
C3b
producing C3a and C3b
C4b.2 C4
C4a
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11. Complement: The Classical Pathway
C1r-C1s
C1q-Ab-Ag
C4b.2b
C2a
C1s
C3a C4
C4b.2
C4a
C3b
C5b
C5a C5

12. Complement: The Classical Pathway
C1r-C1s
C1q-Ab-Ag
C4b.2b
C2a
C1s
C3a C4
C4b.2
C4a
C3b
C5b.6.7.8
C5b.6.7
C5b.6
C5b
C5a C5 C8 C7 C6
C9n
C5b n