Step by Step
1
The classical pathway
Activated by antibody-antigen complexes (IgG or IgM), proceeding through C1, C4, and C2 to reach C3 — this pathway specifically links adaptive immunity (via antibodies) to the innate complement system.
2
The lectin pathway
Mannose-binding lectin (MBL) detects mannose sugars on bacterial surfaces, activating C4 and C2 to reach C3 — this pathway is entirely innate, requiring no antibody involvement.
3
The alternative pathway
Spontaneous, low-level C3 hydrolysis occurs constantly, but becomes amplified specifically on foreign surfaces — again, no antibody is needed for this pathway.
4
Four outcomes once all pathways converge at C3
Opsonization: C3b coats bacteria, helping phagocytes engulf them. Chemotaxis: C5a attracts neutrophils to the site. Mast cell degranulation: C3a and C5a (anaphylatoxins) trigger this. Lysis: C5b-9 forms the Membrane Attack Complex (MAC), punching holes directly in the pathogen's membrane.
Applied Walkthrough
1
When IgG antibodies bind a bacterial surface, this triggers the classical complement pathway, proceeding through C1, C4, and C2 to reach C3 — directly linking the adaptive immune response to complement activation.
2
Separately, even without any antibodies present, mannose-binding lectin can detect mannose sugars on that same bacterial surface, activating the lectin pathway to reach C3 through an entirely innate route.
3
Regardless of which pathway is used, once C3 is reached, several outcomes follow: C3b opsonizes the bacteria (helping phagocytes engulf them), C5a attracts neutrophils and triggers mast cell degranulation, and ultimately C5b-9 assembles into the Membrane Attack Complex, physically puncturing the bacterial membrane.
4
A patient with a C3 deficiency would be at risk for severe bacterial infections generally, since all three pathways converge at this single point — while a patient with a C5-C9 deficiency specifically would be vulnerable mainly to Neisseria infections, since MAC formation is especially important for defending against that particular organism.
Exam Application
Exams test whether you can distinguish the three complement activation pathways (classical, lectin, alternative) by what triggers each, and whether you know the four outcomes once they converge at C3 (opsonization, chemotaxis, mast cell degranulation, lysis via MAC).
⚠ Common Trap
The most common trap is assuming all three complement pathways require antibodies — only the classical pathway requires antibody-antigen complexes; the lectin and alternative pathways are both entirely innate, requiring no antibody involvement at all.
✓ Quick Self-Check
1. What activates the classical complement pathway?
Antibody-antigen complexes (IgG or IgM).
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2. What activates the lectin complement pathway?
Mannose-binding lectin (MBL) detecting mannose on bacterial surfaces.
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3. What activates the alternative complement pathway?
Spontaneous C3 hydrolysis, amplified on foreign surfaces — no antibody required.
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4. What are the four outcomes once the pathways converge at C3?
Opsonization, chemotaxis, mast cell degranulation, and lysis (via MAC).
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5. What specific infection risk is associated with C5-C9 deficiency?
Neisseria infections.
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