Which complement component, when deficient, leads to impaired opsonization and increased susceptibility to encapsulated bacterial infections, particularly Neisseria meningitidis?

Explanation

## C3 Deficiency and Complement-Mediated Immunity **Key Point:** C3 is the central hub of the complement cascade and is essential for opsonization, chemotaxis, and membrane attack complex formation. C3 deficiency results in severe immunodeficiency with recurrent pyogenic infections. ### Role of C3 in Immune Defense | Function | Mechanism | Clinical Consequence of Deficiency | | --- | --- | --- | | **Opsonization** | C3b binds to pathogen surface, enhances phagocytosis | Impaired bacterial clearance | | **Chemotaxis** | C3a recruits neutrophils to infection site | Delayed inflammatory response | | **MAC formation** | C3 cleavage initiates terminal pathway | No bactericidal activity | | **Complement amplification** | C3 feedback loop amplifies all pathways | Reduced complement activation | **High-Yield:** C3 deficiency is the most severe complement deficiency because C3 is required by ALL three pathways (classical, alternative, and lectin) and is the most abundant complement protein in serum (~1.2 mg/mL). ### Infection Pattern in C3 Deficiency 1. **Encapsulated bacteria:** *Neisseria meningitidis*, *Streptococcus pneumoniae*, *Haemophilus influenzae* 2. **Gram-negative organisms:** *Neisseria gonorrhoeae* 3. **Severity:** Recurrent, life-threatening infections despite normal antibody and T-cell function 4. **Timing:** Infections often begin in childhood and persist throughout life **Clinical Pearl:** Patients with C3 deficiency require prophylactic antibiotics (penicillin V) and meningococcal/pneumococcal vaccination, though vaccine efficacy is limited without functional C3. **Mnemonic:** **C3 = Central hub** — deficiency affects all three pathways and all complement functions (opsonization, chemotaxis, MAC).