What is the Mechanism of Antibody Dependent Cytotoxic Hypersensitivity?

Type II or cytotoxic hypersensitivity reactions develop when interaction of serum IgG Abs & IgM Abs with foreign antigens on the cell membrane.

The Ag & Ab complex initiates activation and fixation of complement system enzymes on the surface of foreign cell.

The fixed complement enzymes such as C4b, C5b, C6, 7, 8, 9 produce membrane attack complex on foreign cell surface and develop a pore, leading to death of the cell due to leakage of cytoplasm.

In addition to activated complement enzymes activity, some of the fragments of activated complement enzymes such as C3a, C5b, etc. are released in to the surroundings.

Since these fragments are chemotactic for phagocytic cells, a phagocytic response is generated against the target cell. In addition to the complement dependent cytotoxic reactions, Ab dependent cytotoxic reactions are also induced due to the affinity of NK Cells to Fc region of IgG and IgM antibodies. If the foreign antigen happens to be a haptane and is adsorbed on to any of the cell, the cell with absorbed haptane also be removed by antibody dependent cytotoxic hypersensitivity reactions.

Drug induced immune hemolytic anemia is a familiar example for this kind of reactions.

Since penicillin like drug molecules show characters of heptane and bind to the surface of RBC and initiate Type II hyper sensitivity reactions leading to severe anemia. Individuals with this kind of problem show clinical symptoms like fever, weakness, jaundice etc.

Therapy:

Treatment for blood transfusion reactions involves prompt termination of transfusion and maintenance of urine flow with diuretic drugs to minimize stress on kidneys.

Treatment for hemolytic disease depends on the severity of the reactions. In severe cases the fetus can be given an intra uterine blood transfusion for every 10-21 days to replace fetal Rh+ red blood cells with Rh- cells until delivery.

In less severe conditions blood transfusion is not necessary, but after birth the infant has to be exposed to low levels of UV light to remove the bilurubin and to avoid cerebral damage by bilurubin (Exposing infants to UVradiation helps to reduce high bilirubin levels).

In certain cases mothers blood has to be screened for Rh+ antibodies by separating RBC and Plasma. If Rh+ antibodies are present, the plasma has to be replaced with fresh plasma solution without Rh+ antibodies.

The consequences of A, B, O and AB blood group incompatibility are very minor, in case bilurubin is produced due to their incompatibility; exposure to UV light is enough to break down the bilurubin.

Hemolytic disease can be prevented successfully through injection of Rh+ antibodies within 72 hours after delivery. Because the injected Rh+ Abs bind to Rh+ antigens of fetus, even before the activation of mother’s immune system.

When mother is not sensitized to Rh+ antigens, production of Rh+ Abs and memory cells does not take place to cause hemolytic disease.