Step by Step
CP
Classical — triggered by antibody
The classical pathway is activated when antibody (IgG or IgM) binds an antigen, forming an immune complex that C1q recognizes. It's the one complement pathway that's technically part of the adaptive immune response, since it requires antibody to get started.
LP
Lectin — triggered by mannose
The lectin pathway is activated when mannose-binding lectin (MBL) recognizes mannose sugar residues on a microbial surface — no antibody required. This makes it a purely innate recognition mechanism, distinct from the antibody-dependent classical pathway.
AP
Alternative — spontaneous, always-on background activation
The alternative pathway activates spontaneously and continuously at a low level, providing a baseline surveillance system that gets amplified specifically on microbial surfaces lacking the regulatory proteins that protect host cells.
C3
Convergence — all roads lead to C3 — then three outcomes
All three pathways converge on C3 convertase, which cleaves C3 into C3b and C3a. C3b coats the pathogen for opsonization (making it easier for phagocytes to engulf). C3a (along with C5a) acts as an anaphylatoxin, triggering mast cell degranulation and chemotaxis. Finally, C5b through C9 assemble into the Membrane Attack Complex (MAC), which punches a lethal pore into the pathogen's membrane.
In a Gram-negative bacterial infection, the MAC (C5b-9) is what actually lyses the bacterial outer membrane — which is why deficiencies in these late complement components leave a patient specifically vulnerable to Neisseria species.
Applied Walkthrough
1
A patient with recurrent, severe bacterial infections is found to have very low C3 levels.
2
Ask: why does low C3 cause such broad susceptibility? Because C3 is the convergence point for all three pathways — without it, opsonization fails across the board, regardless of which pathway would have originally triggered the response.
3
Contrast: a different patient with recurrent Neisseria infections specifically (and normal C3) is found to have a C5-C9 deficiency — since the Membrane Attack Complex is what specifically kills Neisseria, a deficiency there causes a much narrower, more specific vulnerability.
4
This contrast — broad susceptibility with a C3 deficiency versus narrow, Neisseria-specific susceptibility with a C5-C9 deficiency — is exactly how exams differentiate complement deficiency questions from one another.
Exam Application
Exams test which pathway is antibody-dependent (classical) versus antibody-independent (lectin, alternative), what C3 convertase produces (C3b for opsonization, C3a/C5a as anaphylatoxins), and complement deficiency syndromes: C1q deficiency resembles SLE, C3 deficiency causes severe recurrent bacterial infections, and C5-C9 deficiency specifically predisposes to Neisseria infections.
⚠ Common Trap
The most common trap is assuming all complement activation requires antibody — only the classical pathway does. The lectin and alternative pathways are purely innate. A second trap: confusing C3 deficiency (broad susceptibility to many bacteria) with C5-C9 deficiency (narrow, Neisseria-specific susceptibility) — they're often tested against each other directly.
✓ Quick Self-Check
1. Which complement pathway requires antibody to activate?
The classical pathway — it's triggered by antibody (IgG or IgM) bound to antigen.
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2. What triggers the lectin pathway?
Mannose-binding lectin recognizing mannose sugar residues on a microbial surface, without antibody.
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3. What do all three complement pathways converge on?
C3 convertase, which cleaves C3 into C3b and C3a.
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4. What does C3b do, and what does the C5b-C9 complex do?
C3b opsonizes pathogens for phagocytosis; C5b-C9 forms the Membrane Attack Complex (MAC), which lyses the pathogen's membrane.
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5. What is the clinical difference between a C3 deficiency and a C5-C9 deficiency?
C3 deficiency causes broad, severe recurrent bacterial infections; C5-C9 deficiency causes a narrow, specific susceptibility to Neisseria infections.
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