Complement System
One-Sentence Definition
The complement system is a cascade of plasma proteins that opsonizes pathogens, recruits inflammation, and lyses susceptible cells — bridging Innate Immunity and Antibodies and Immunoglobulin Classes-mediated defense.
Simple Explanation
A cascade of blood proteins that punch holes in bacteria, coat them for eating, and amplify inflammation when antibodies or microbes trigger it.
Detailed Scientific Explanation
Three activation pathways
| Pathway | Trigger | Classic micro example |
|---|---|---|
| Classical | IgM/IgG + antigen | Encapsulated bacteria after antibody binding |
| Alternative | Microbial surfaces directly | Neisseria (when unprotected) |
| Lectin | Mannose on microbes | Gram-negative surfaces |
Effector functions
- C3b opsonization — enhanced phagocytosis
- C5a — chemotaxis, anaphylatoxin
- MAC (C5b-9) — lysis of susceptible cells (especially Gram-negative, some enveloped viruses)
Clinical deficiencies
- C5–C9 / terminal pathway → recurrent Neisseria bacteremia/meningitis (Neisseria meningitidis, Neisseria gonorrhoeae)
- C3 deficiency → pyogenic infections broadly
- Properdin (alternative) → Neisseria susceptibility
Microbial evasion
- Capsule (pneumococcus, meningococcus)
- Surface proteins that bind factor H (some Gram-negatives)
- Intracellular location avoids lysis
Mechanism
Proteolytic cascade amplifies cleavage of C3 → opsonins and lytic complex; tightly regulated to limit host damage.
Clinical Importance
- Explains why asplenic and complement-deficient patients need meningococcal vaccination
- Complement consumption in severe sepsis (CH50 low — research/clinical context)
Research Importance
- Vaccine design against encapsulated organisms targets antibody + complement synergy
Diagnostic Relevance
- Complement levels in recurrent Neisseria workups (specialist)
AMR Relevance
- None direct — immunologic, not pharmacologic
Related MOCs
Active Recall Questions
- Which pathway is antibody-initiated?
- Why are Neisseria infections classic in terminal complement deficiency?
- How does capsule interfere with complement?