Type II Hypersensitivity Reaction (Cytotoxic / Cytolytic Reaction)
Type II hypersensitivity is an antibody-mediated cytotoxic reaction where IgG or IgM antibodies bind to antigens on cell surfaces or extracellular matrix, leading to cell destruction, dysfunction, or inflammation.
Key Features
Involves antibodies directed against target antigens on cells or tissues.
Antibodies can be:
- Exogenous (e.g., drugs attached to cell surfaces).
- Endogenous (e.g., intrinsic cell membrane proteins).
Mechanisms of Type II Reaction
1 Complement- mediated cytolysis
IgG or IgM binding activates classical complement pathway → formation of membrane attack complex (MAC) → cell lysis.
Examples:
- Mismatched blood transfusion reaction (ABO incompatibility).
- Hemolytic disease of the newborn (Rh incompatibility )-
Maternal anti-Rh antibodies attack fetal RBCs.
2 Opsonization and phagocytosis
IgG and C3b coat target cells → recognized by phagocytes via Fc and complement receptors → phagocytosis.
Examples:
- Autoimmune hemolytic anemia.
3 Antibody- dependent cellular cytotoxicity (ADCC)
NK cells recognize antibody-coated cells via Fcγ receptors → release perforin and granzymes → apoptosis of target cell.
Examples:
- Some viral- infected cell destruction.
- Tumor cell killing.
4 Cellular dysfunction without lysis
Antibodies bind to cell surface receptors, altering their function rather than destroying the cell.
Examples:
- Graves’ disease: antibodies stimulate TSH receptor → hyperthyroidism.
- Myasthenia gravis: antibodies block acetylcholine receptors → muscle weakness.
Diagnostic Tests
Direct Coombs test: Detects antibodies or complement bound to patient's RBCs (e.g., autoimmune hemolytic anemia).
Indirect Coombs test: Detects free antibodies against RBC antigens in serum (e.g., prenatal screening for Rh incompatibility).
Treatment
Discontinue offending drug (if drug- induced).
Immunosuppression: corticosteroids, immunoglobulins.
Plasmapheresis (to remove antibodies).
Specific therapy for underlying disease (e.g., antithyroid drugs in Graves’ disease).