## Complement System Activation Pathways ### Overview of Three Pathways The complement system has three distinct activation pathways, each with unique initiators but converging at C3 activation: | Pathway | Initiator | C3 Convertase | Requires Antibody | | --- | --- | --- | --- | | **Classical** | IgG/IgM + C1q | C4b2a | Yes | | **Alternative** | Microbial surfaces (polysaccharides, LPS) | C3bBb | No | | **Lectin** | MBL/Ficolins + carbohydrates | C4b2a | No | **Key Point:** All three pathways generate C3 convertase, though the classical and lectin pathways share the same C3 convertase (C4b2a), while the alternative pathway generates its own (C3bBb). ### Why the Correct Answer is Wrong The statement "C3 convertase formation occurs only in the classical pathway" is **FALSE**. This is the trap answer. - **Classical pathway:** C3 convertase = C4b2a (formed after C4 and C2 cleavage) - **Alternative pathway:** C3 convertase = C3bBb (formed by C3b + Factor B) - **Lectin pathway:** C3 convertase = C4b2a (identical to classical) All three pathways converge at C3 activation, making C3 convertase formation a universal feature, not exclusive to the classical pathway. **High-Yield:** The alternative pathway is the only one that does NOT require C1q or antibody and is constitutively active at low levels, providing the first line of defense against pathogens. **Clinical Pearl:** Deficiencies in classical pathway components (C1q, C2, C4) predispose to autoimmune diseases (SLE), while alternative pathway defects (Factor H, Factor I) increase susceptibility to Neisseria and other encapsulated organisms.
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