Core Framework & Diagram How Does the Complement System Attack Pathogens?

SLE patients have large amounts of autoantibodies against self-DNA and nuclear proteins. These autoantibodies combine with corresponding self-antigens, forming large amounts of immune complexes. These complexes continuously activate the classical complement pathway, consuming large amounts of C1q, C4, and C3, causing significant drops in serum concentrations. Therefore, active SLE typically accompanies C3 and C4 level drops — useful as one monitoring indicator for disease activity. Simultaneous C3 and C4 drops are more diagnostically meaningful than either alone.

Neisseria meningitidis is Gram-negative and highly sensitive to complement MAC killing — in normal circumstances, serum bactericidal activity is critical for controlling bacteremia. But Neisseria meningitidis replicates extremely rapidly (doubling time approximately 20–30 minutes). If complement responses can't prevent early blood dissemination, it can cause explosive septicemia within hours, leading to multi-organ failure and death. People with congenital terminal complement component deficiencies (C5-C9) are extremely susceptible to meningococcal infections — direct proof of MAC's indispensable role in fighting this bacterium.

Different complement component deficiencies present different clinical consequences: C1q/C4/C2 deficiency (classical pathway defect) — high susceptibility to SLE-like autoimmune diseases (classical pathway participates in immune complex clearance; deficiency causes immune complex accumulation). C3 deficiency — extremely susceptible to all types of pyogenic bacteria (particularly encapsulated bacteria) since C3 is the common node of all pathways; deficiency impairs both opsonization and MAC. C5-C9 deficiency (terminal complement defect) — specifically susceptible to Neisseria species (meningococcus, gonococcus); clearance of these two bacteria highly depends on MAC.

C3a and C5a produced by complement activation are both 'anaphylatoxins' — they can directly activate mast cells and basophils to release histamine and other inflammatory mediators, producing allergy-like symptoms (vasodilation, increased permeability, bronchospasm). Certain drugs (like contrast agents, vancomycin) can directly activate complement through non-IgE pathways, producing 'pseudoallergic reactions' — symptoms similar to IgE-mediated true allergy but with different mechanisms. This situation doesn't require a prior sensitization phase; it can occur on first exposure.