The immune system distinguishes between its own healthy cells and foreign invaders. However, it can sometimes react to foreign elements from a member of the same species. This immune response, where the body reacts to antigens from another individual of the same species, is known as isoimmunity. This article explores isoimmunity, its common conditions, and how they are diagnosed and managed.
Understanding Isoimmunity
Isoimmunity, also called alloimmunity, describes an immune response directed against alloantigens. These are antigens from another individual of the same species, representing genetically determined differences like blood group antigens or human leukocyte antigens (HLA). The human body develops antibodies, known as alloantibodies, against these alloantigens.
The mechanism of isoimmunity involves exposure to these foreign alloantigens. This exposure can occur through various routes, including pregnancy, blood transfusions, or organ transplantation. Upon exposure, the recipient’s immune system recognizes these alloantigens as foreign, leading to the production of antibodies that specifically target them. This differs from autoimmunity, where the immune system targets its own tissues, and heterologous immunity, a reaction against antigens from different species.
Alloimmunization, the process of becoming isoimmune, involves the development of these alloantibodies. These reactions can lead to various outcomes, from mild effects to severe complications, depending on the specific alloantigens involved and the intensity of the immune response. For instance, in transplantation, alloantigens, particularly HLA molecules, determine compatibility between donor and recipient.
Common Isoimmune Conditions
Isoimmunity underlies several clinically relevant conditions, often involving reactions against blood cells or platelets due to genetic differences.
Hemolytic Disease of the Newborn (HDN), also known as Rh disease, is primarily caused by Rh incompatibility. This occurs when an Rh-negative mother carries an Rh-positive fetus, inheriting the Rh-D antigen from the father. During pregnancy or childbirth, fetal red blood cells can enter the mother’s bloodstream, causing her immune system to produce anti-D antibodies. These antibodies can then cross the placenta in subsequent Rh-positive pregnancies and attack the fetal red blood cells, leading to their destruction and causing anemia in the baby. While Rh incompatibility is the most common cause, other blood group incompatibilities can also lead to HDN.
Transfusion reactions are another instance of isoimmunity, occurring when a recipient receives incompatible blood. An acute hemolytic transfusion reaction happens when antibodies in the recipient’s blood destroy transfused red blood cells that carry specific antigens, typically due to ABO blood group incompatibility. This destruction, often mediated by IgM antibodies, can activate the complement system, leading to the lysis of red blood cells and the release of free hemoglobin. Symptoms can range from fever and chills to severe manifestations like low blood pressure and kidney injury.
Neonatal Alloimmune Thrombocytopenia (NAIT) results from maternal antibodies targeting fetal platelet antigens. The maternal alloantibodies cross the placenta, leading to the destruction of fetal platelets and causing a low platelet count in the newborn. NAIT can lead to bleeding complications, including intracranial hemorrhage, and can occur even in a first pregnancy.
Diagnosis and Management
Diagnosis of isoimmune conditions involves blood tests to identify specific antibodies and determine antigen types. The Coombs test is a common procedure used to detect antibodies attached to red blood cells or freely circulating in the bloodstream. A direct Coombs test identifies antibodies already bound to red blood cells, while an indirect Coombs test screens for antibodies in the blood that could react with foreign red blood cells, often used in prenatal testing or before transfusions. Antigen typing, such as blood group or HLA typing, helps determine the genetic differences triggering the immune response.
Management strategies often prioritize prevention. For Rh incompatibility, prevention is achieved through administering Rh immune globulin (RhoGAM or Anti-D immunoglobulin) to Rh-negative mothers. This injection, given around 28 weeks of pregnancy and again within 72 hours after delivery if the baby is Rh-positive, contains antibodies that bind to and neutralize any Rh-positive fetal red blood cells. This prevents the mother’s immune system from developing lasting anti-D antibodies, protecting future Rh-positive pregnancies.
For active isoimmune conditions, treatment depends on the specific condition and its severity. In severe Hemolytic Disease of the Newborn, therapies may include phototherapy to manage jaundice or exchange transfusions to replace affected fetal red blood cells. Intravenous immunoglobulin (IVIG) may also be administered, particularly in HDN, to help reduce red blood cell destruction. For NAIT, treatment can involve transfusions of compatible platelets or IVIG to the mother or newborn.