Four separable jobs
Each effector function uses a different part of the antibody. Neutralization depends on the variable region. Opsonization, complement activation, and Fc-receptor engagement depend on the constant region and on which class the antibody belongs to. Because the parts are separable, a defect can remove one function while sparing another.
Function, mechanism, and what is lost when it fails
Neutralization
- Variable region blocks toxin or virus from host receptor
- Works without complement or phagocytes
- Loss allows toxin-mediated or viral disease despite normal immunoglobulin levels
Opsonization
- IgG constant region engages phagocyte Fc receptors
- Lowers the threshold for ingestion of encapsulated bacteria
- Loss allows recurrent infection with encapsulated organisms
Complement activation
- IgM or clustered IgG initiates the classical pathway
- Deposits C3b and assembles the membrane attack complex
- Loss impairs clearance and lysis of encapsulated bacteria
Why a normal level can still be a failure
Total immunoglobulin can be normal while functional antibody is defective, because the constant region or class needed for opsonization and complement activation may be missing or non-functional. Functional testing, not just quantitation, is required to detect this.