Classical Pathway

• Trigger: Antigen–antibody complexes (IgG or IgM bound to antigens).
• Entry point: C1 complex (C1q, C1r, C1s) recognizes Fc regions of antibodies.
• Consumption: Burns through C4 and C2 first, then C3.
• Lab pattern: Low C3 and low C4.

Think: “Classic = needs classic antibodies.”

Alternative Pathway

• Trigger: Pathogen surfaces (endotoxin, fungal cell walls, some viruses) or abnormal host tissue. No antibody required.
• Entry point: Spontaneous low-level “tickover” of C3 in plasma → C3b binds surfaces → stabilized by factors B, D, and properdin.
• Consumption: Mostly chews up C3, leaving C4 untouched.
• Lab pattern: Low C3, normal C4.

Think: “Alternative = doesn’t need antibodies, just surfaces.”

Both pathways converge on C3 convertase → C5 convertase → MAC (C5b-9). That’s the common destructive engine.