Chapter 12: Type II Hypersensitivity Reaction
Type II HYPERSENSITIVITY REACTION (CYTOTOXIC REACTION)
In type, II the target is fixed in tissue or on the cell surface.
Antigen: It is present or is a part of the cell membrane. It may be:
- Exogenous Ag: Microbes, parasites, drugs.
- Intrinsic Ag: Autoimmune diseases and these are self, Ag.
Antibody: This is mainly due to IgG and occasionally IgM. Rarely IgA can give this reaction.
Ab attaches to Ag on the surface of cells and activates the complement system which leads to lysis or phagocytosis. Sometime Ab is attached to Ag on the cell surface will bring this complex near to NK cells or other phagocytic cells possessing the Fc Receptor and leads to antibody dependant cellular cytotoxicity (ADCC).
There are the following examples of Type 11 Reactions.
- Blood transfusion reactions: This may take place because of mismatched blood transfusion.
- B. Hemolytic diseases of the newborn (HDN) e.g. Rh-incompatibility and ABO-Incompatibility.
- Autoimmune hemolytic anemia (AHA). This takes place due to the loss of immunologic tolerance.
The possibilities of RBC Ag and Ab reactions are:
- Complement dependant lysis.
- Neutrophils: – There may be the destruction of neutrophils in SLE or due to drugs.
- Platelets: – The platelets are destroyed in ITP(idiopathic thrombocytopenic purpura) and drugs like sedormid and quinidine.
- Lymphocytes: – Lymphopenia may be seen in SLE.
- Kidney: – Type II reaction gives anti-glomerular-basement membrane nephritis (anti-GBM nephritis) and Good Pasteur syndrome.
- Myasthenia Gravis where Ab reacts with acetylcholine receptors.
- Skin diseases like pemphigus Vulgaris. In this case, Ab is against dermo-epidermal junction.
- Drugs:- Alpha methyldopa (antihypertensive drug) gives hemolytic anemia. This drug acts as a hapten. Other drugs are phenacetin, amidopyrine, penicillin, and chlorpromazine.
- Infectious agents like salmonella infection and tuberculosis.
Hemolytic Diseases of Newborn
This is also called erythroblastosis fetalis or Hydrops foetalis. It is seen in 15% whites and 7% blacks.
This is because of the sensitization of Rh-negative mother by Rh +ve fetus, where the father is Rh +ve. Sensitivity is particularly to D-antigen (90%).
D-Ag is more potent, first, there is IgM anti-D formation followed by IgG anti-D. Anti-Rh Ab in mother appears after 6 weeks. This Ab leads to phagocytosis and hemolysis of fetal RBC due to the activation of the complement system. Because this IgG type Ab can cross the placental barrier.
Presensitization of the mother may occur due to the previous history of abortion or stillbirth.
Signs and Symptoms
These are due to hemolytic anemia, which are:
- Anemia causes low oxygen-carrying capacity and leads to heart failure.
- Increase bilirubin formation due to hemolysis causes jaundice and may lead to kernicterus.
- There is a hypoxic injury to the liver, heart, and brain.
- There is a low protein (only 2.0 G/dl) and this will lead to generalized edema (Anasarca) or Hydrops foetalis.
- Jaundice appears within 24 hours in the newborn.
Low weight babies and premature newborns are at greater risk as these babies conjugating and excretory systems of the liver are not fully developed.
2% of the fetus may sensitize the mother within 28-34 weeks of gestation and these mothers are at more risk to develop Ab so needs anti-IgG (RhoGAM) in the last trimester.
The First Rh+ve baby of Rh+ve father sensitizes the mother when his blood goes into Rh-negative Mother during the last trimester of the pregnancy when the cytotrophoblast is no longer present as a barrier or during childbirth itself. The amount of blood may be more than 1.0 ml. If the mother and fetus’s blood groups are different then there are chances that the mother may not be sensitized. In the case of compatible blood of mother and fetus, fetal RBC Rh +ve will survive and sensitize the mother. This first baby will escape hemolytic anemia. But the second baby will be the victim for anti-Rh Ab present in mother circulation. First IgM Ab forms and then IgG. These IgG type Ab, can cross the placental barrier and goes into the foetal circulation and causes hemolytic anemia.
If father genotype is Rh+ve /Rh+ve, = all children are Rh+ve
If father genotype is Rh+ve /Rh-ve = then 50% are Rh+ve.
Rh-positive baby mother should be given RhoGAM (anti-IgG) within 24-72 hours after the birth of the baby if delayed then there is no value or use.
The diagnosis of Ab in the mother can be detected by the indirect Combs test. For to find Rh antibodies in the baby, a direct Coombs test may be done.
It is quite common and is seen in 20-25% of pregnant women. Only 10% of newborn develops hemolytic anemia and only 1/200 needs treatments.
Most Abs is IgM against Ag A & Ag B and these can not cross the placental barrier. Due to unknown reasons, only O mother develops IgG type Ab against A and B Ag, without previous presentation. So may see reaction even in the first baby.
Fortunately, lysis of fetal RBC is less severe due to poor expression of Ag A & B on RBC and also due to presence of Ag A & B on other cells than only RBC e.g. epithelial cells.
The only fetus with strong Ag A & B shows evidence of hemolytic anemia.
There is no method of protection.
Coombs Test (Anti-Human Globulin Test)
This was first described by Morchu in 1908 and later on rediscovered in 1945 by Coomb, Morchu, and Race.
- Evaluation of hemolytic anemia of the newborn.
- Red cell typing in blood banks.
- Diagnosis of autoimmune hemolytic anemia.
- Drugs induced hemolytic anemia.
This test may be done as:
Direct:- When Abs are present on cells or Ab-coated RBC e.g. baby blood.
Indirect:- When Abs are free in the serum e.g. in mother serum.
The RBCs have a negative charge so IgG-Ab can not show agglutination. To overcome this negative charge and to see agglutination following means can be used:
- Addition of albumin(albumin phase).
- Addition of combs serum(Coombs phase).
Addition of enzymes (enzyme phase).
Coombs serum (prepared in rabbit by injecting IgG and will get anti-IgG or Ab against Ab( anti-anti-Ab).
Albumin will neutralize the negative charges and show agglutination. Coomb’s serum anti-IgG Ab form bridging between two Abs and show clumping.