Complement System

Why the Name?

• Called "complement" because it complements the ability of antibodies to do their job.

Three Different Pathways

• Classical Pathway: Triggered by antigen-antibody complex.
• Alternative Pathway: Triggered by bacterial endotoxin.
• Lectin Pathway: Triggered by mannose-binding lectin.
• In Paroxysmal Nocturnal Hemoglobinuria (PNH), the problem usually lies in the alternative pathway.

Alternative Pathway of the Complement

Trigger

• Triggered by bacterial endotoxin (lipopolysaccharide) from the outer membrane of gram-negative bacteria.

Steps

1. **Factor C3 Hydrolysis: ** In the presence of water, Factor C3 hydrolyzes into Factor C3b.
2. Factor B Binding: C3b binds with Factor B.
3. Factor D Conversion: Factor D converts Factor B into Ba and Bb.
4. Formation of C3 Convertase: Factor Bb combines with C3b to form C3 convertase.
5. C3 Convertase Function: C3 convertase converts C3 into C3a and C3b.
6. Formation of C5 Convertase: C3b binds with C3 convertase to form C5 convertase.
7. C5 Convertase Function: C5 convertase converts C5 into C5a and C5b.
8. Formation of MAC: C5b, together with C6, C7, C8, and C9, forms the Membrane Attack Complex (MAC).

Membrane Attack Complex (MAC)

• Forms a pore in the bacterial cell membrane, disrupting the ionic and osmotic environment of the cell, leading to bacterial death.
• MAC is not related to Microsoft or McDonald's. It's a crucial part of the immune response.