Hypersensitivity describes an immune response that is exaggerated or inappropriate, reacting to typically harmless substances or the body’s own tissues. These overreactions can lead to tissue damage. Cytotoxic hypersensitivity, also known as Type II hypersensitivity, involves the immune system directly attacking and destroying cells. This reaction is characterized by antibodies binding to antigens on cell surfaces, marking them for destruction.
How the Immune System Targets Cells
Cytotoxic hypersensitivity reactions are driven by immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. These antibodies bind to antigens on cell surfaces, whether natural components of the body’s own cells or foreign substances. This binding initiates cell destruction.
One pathway for cell destruction involves the complement system. When IgG or IgM antibodies bind to a cell, they trigger complement activation. This leads to the formation of the membrane attack complex (MAC). The MAC inserts into the target cell’s membrane, creating pores that disrupt the cell’s integrity, causing it to swell and burst (lysis).
Another mechanism is antibody-dependent cell-mediated cytotoxicity (ADCC). Immune effector cells, such as natural killer (NK) cells, macrophages, or neutrophils, recognize antibodies attached to the target cell’s surface. These effector cells bind to the Fc portion of the antibodies, then release cytotoxic substances like perforins and granzymes, inducing programmed cell death (apoptosis) or lysis.
Conditions Linked to Cytotoxic Hypersensitivity
Cytotoxic hypersensitivity underlies several medical conditions where the immune system mistakenly targets and destroys cells. Transfusion reactions are a common example, occurring when a recipient receives incompatible blood. Antibodies in the recipient’s blood, typically anti-A or anti-B antibodies, bind to antigens on transfused red blood cells, leading to their rapid destruction.
Hemolytic disease of the newborn (HDN), also known as erythroblastosis fetalis, is another condition. It occurs when an Rh-negative mother is sensitized to Rh-positive red blood cells from a previous pregnancy or exposure. During a subsequent pregnancy with an Rh-positive fetus, the mother’s antibodies cross the placenta and attack the baby’s red blood cells, leading to anemia and jaundice.
Autoimmune hemolytic anemia (AIHA) involves the immune system producing antibodies against a person’s own red blood cells. These autoantibodies bind to red blood cells, marking them for destruction by the complement system or phagocytic cells. This results in a reduction in oxygen-carrying red blood cells and symptoms of anemia.
Certain drugs can also trigger cytotoxic hypersensitivity, leading to drug-induced hemolytic anemia. The drug or its metabolites can attach to red blood cells, making them appear foreign to the immune system. Antibodies then form against these drug-modified cells, leading to their destruction.
Diagnosing and Managing Cytotoxic Reactions
Symptoms of cytotoxic reactions vary based on the specific cells targeted, but commonly include signs of cell destruction. For instance, with red blood cell destruction, individuals may experience fatigue, pallor, shortness of breath due to anemia, and jaundice (yellowing of the skin or eyes). Fever and chills can also be present.
Diagnosis involves identifying antibodies directed against specific cell types. The Coombs test, also known as the antiglobulin test, is a diagnostic tool for red blood cell reactions. The direct Coombs test detects antibodies attached to a patient’s red blood cells, while the indirect Coombs test looks for circulating antibodies. Evidence of cell destruction, such as a low red blood cell count (anemia), is also an indicator.
Management strategies for cytotoxic hypersensitivity aim to mitigate the immune attack and address cell destruction. Removing the trigger, such as discontinuing an incompatible blood transfusion or stopping a causative drug, is a primary step. Immunosuppressive medications, particularly corticosteroids, are used to reduce immune system activity and antibody production.
Supportive care is also a component of management. Blood transfusions may be necessary to correct severe anemia resulting from red blood cell destruction. In some cases, plasmapheresis, which removes antibodies from the blood, may be employed to rapidly reduce the immune attack. The overall approach is tailored to the specific condition and severity of the reaction to preserve organ function and improve patient outcomes.