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    Subjects/Microbiology/Complement System
    Complement System
    hard
    bug Microbiology

    A 32-year-old woman with recurrent Neisseria meningitidis infections is evaluated for complement deficiency. Laboratory tests show normal C3 and C4 levels, but serum bactericidal activity is absent. All of the following complement components are involved in the membrane attack complex (MAC) formation EXCEPT:

    A. C6 and C7 bind sequentially to C5b to form the C5b-6-7 complex
    B. C8 insertion into the lipid bilayer creates a small pore permeable to ions and small molecules
    C. C2 is the final component that polymerizes to form the complete pore in the lipid membrane
    D. C5b acts as the nucleation site for MAC assembly by binding to the cell membrane

    Explanation

    ## Membrane Attack Complex (MAC) Formation ### Sequential Assembly of MAC The membrane attack complex is the terminal effector of complement, formed by sequential binding of C5b through C9: ```mermaid flowchart LR A[C5 cleavage] -->|C5a + C5b| B[C5b binds membrane]:::action B --> C[C6 + C7 bind]:::action C --> D[C5b-6-7 complex]:::outcome D --> E[C8 inserts into bilayer]:::action E --> F[Small pore formed]:::outcome F --> G[C9 polymerizes]:::action G --> H[Complete MAC pore]:::outcome H --> I[Cell lysis]:::urgent ``` ### Components of MAC | Component | Role | Function | | --- | --- | --- | | **C5b** | Nucleation site | Anchors complex to membrane; initiates assembly | | **C6** | Binding partner | Stabilizes C5b; prevents inactivation | | **C7** | Binding partner | Increases hydrophobicity; inserts into bilayer | | **C8** | Pore initiator | Creates small pore (10 Å); allows ion leakage | | **C9** | Pore enlarger | Polymerizes (10–16 molecules); enlarges pore to 100 Å | **Key Point:** C9 (not C2) is the final component that polymerizes to form the complete, large pore. C2 is a component of the **classical and lectin pathway C3 convertase** (C4b2a), NOT the MAC. ### Why This Patient Has Recurrent Meningitis **High-Yield:** Deficiencies in **terminal complement components (C5–C9)** or **alternative pathway components (Factor H, Factor I, Properdin)** specifically increase susceptibility to **Neisseria meningitidis** and **Neisseria gonorrhoeae**. This patient's normal C3/C4 but absent bactericidal activity suggests a terminal pathway defect (likely C5–C9 or C3b deposition defect). **Clinical Pearl:** Patients with recurrent meningococcal infections should receive meningococcal vaccination and prophylactic antibiotics. Complement deficiency screening includes hemolytic assay (CH50 for classical, AP50 for alternative).

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