Deficiency of C3 leads to increased susceptibility to which type of hypersensitivity?

• A. Type III hypersensitivity
• B. Type I hypersensitivity
• C. Type II hypersensitivity
• D. Type IV hypersensitivity

Answer: (A)

C3 is a central player in the complement system, crucial for opsonizing pathogens and, importantly, for clearing immune complexes from the circulation (immune complex–clearance via C3b and CR1 on red cells). When C3 is deficient, immune complexes are not efficiently removed and can accumulate and deposit in tissues. Those deposits trigger inflammation through complement activation and leukocyte recruitment, which is the hallmark of Type III hypersensitivity (immune complex–mediated). Diseases such as serum sickness or immune complex–mediated glomerulonephritis illustrate this mechanism.

The other hypersensitivity types involve different pathways: Type I is IgE-mediated allergic reactions, Type II is antibody-dependent cytotoxicity against cell or matrix antigens, and Type IV is T-cell–mediated delayed-type hypersensitivity.