Type II hypersensitivity reactions are mediated by IgG antibodies, raised against the allergen and activated complement enzymes. Lysis due to complement fixation is the cause for pathogenesis in this reaction.
Mechanism of Type II Hyper Sensitivity Reactions:
Antibodies present in the sensitized person bind to the antigen of the foreign cell and the antigen antibody complex triggers the cascade of complement system.
The activated components of the complement system binds to the membrane of the foreign cell as membrane associated complex, leading to the development of pore, that causes leakage of the cell contents resulting in its death.
In addition to this the released components of the complement system C3a,C5a express chemotactic action and induce accumulation of Tc cells, macrophages, phagocytes and other immunological cells near the area of reaction.
Since macrophages show affinity to FC region of IgG antibodies the cells bound with IgG are susceptible for phagocytosis. The remaining Killer cells of immune system also kill the foreign cells through surface bound antibody.
Since antibody binding with antigen makes the foreign cell cytotoxic, Type II Hyper sensitivity is also referred as antibody mediated cytotoxic reaction. The antigen inducing these reactions may be an isoantigen or an auto antigen (self antigen).
With reference to the type of antigen responsible for Type II Hyper sensitivity the reactions can be subdivided into (1) Isoimmune hyper sensitivity reactions and (2) auto immune hyper sensitivity reactions.
Isoimmune Hyper Sensitivity Reactions:
If hyper sensitivity reactions are induced by antigens derived from individuals of same species, the reactions are referred as isoimmune hyper sensitivity reactions. Blood transfusion reactions, graft rejection reactions, Rh incompatibility reactions are some of the examples for this hypersensitivity.
Blood Transfusion Reactions:
In blood transfusion procedures hemolytic reactions may develop due to mismatch of blood groups, between donor and recipient. In these reactions the serum factors of the recipient may agglutinate the RBCs of the donor, or serum of the donor may agglutinate RBCs of the recipient.
The agglutination of the red blood cells and their lysis in circulation leads to various pathological changes such as jaundice, fever, kidney failure etc.
Some times hemolytic reactions may lead to death of the recipient due to systemic shock brought about by massive erythrocyte destruction and kidney failure due to excessive function for the removal of debris of red blood cells. Minor hemolytic reactions like anemia occur when the lysis of RBCs is slow.
Rh Incompatibility / Erythroblastosis Fetalis:
If Rh women bear Rh+ fetus in her womb, Rh mother may get sensitized to Rh+ antigens produced by fetus and synthesize antibodies against to fetal Rh+ antigens.
Normally maternal circulation does not mix with fetal circulation during gestation period. Hence the first baby rarely gets affected, but at the time of parturition (delivery) rupture of blood vessels and excessive bleeding during placental separation ensures entry of fetal Rh+ antigens into mothers circulation, triggering production of antibodies against Rh+ antigens.
Once antibodies for Rh+ antigens are produced by mother subsequent pregnancy become risky.
Since maternal antibodies produced are IgG type, they can enter fetal circulation crossing the placental barrier and bound to fetal RBCs inducing Type II hypersensitive reactions.
As a consequence the baby may born with a disease called “Erythroblastosis fetalis” or “hemolytic disease” (Refer Chapter 20 for further information). The clinical symptoms include severe jaundice, enlargement of the infant spleen and liver.
The treatment of this disease depends upon the severity of symptoms. In extreme cases total blood transfusion might be performed in order to save the baby from death due to shock.
This disease is not common with the first pregnancy as there is no inter mixing of maternal and fetal blood before delivery. But rarely hemorrahage can occur during the last trimester when the fetus is relatively large.
However hemorrhage is usually slight and the concentration of fetal Rh+ factor is too low to induce Ab production in the mother.
Since HLA antigens present on all nucleated cells are diverse in different individuals, immune system recognizes them on the graft tissue and triggers cytotoxic response against the graft (Refer Chapter 16 for transplantation).
Auto Immune Reactions
Immune system can distinguish self MHC antigens of their own cells from those of foreign cells and develop tolerance to self antigens. Yet some physiological autoimmune reactions against self antigens can occur and serve as physiological regulators of the immune system and are carefully controlled.
But some times this carefully controlled activity goes away and large quantities of auto antibodies are produced leading to auto immune reactions.