The immune system defends the body against pathogens, but it can sometimes overreact to harmless substances or the body’s own cells, causing a hypersensitivity reaction. These reactions are categorized by the immune components involved and how they cause damage. This article focuses on Type II hypersensitivity, where antibodies mistakenly target and damage the body’s cells and tissues. This process is also known as cytotoxic hypersensitivity because it often results in cell death.
Antibodies and Antigens in Type II Reactions
Type II hypersensitivity reactions are driven by two classes of antibodies: Immunoglobulin G (IgG) and Immunoglobulin M (IgM). In these reactions, IgG and IgM incorrectly bind to antigens, which are molecular structures on cell surfaces or within the supportive network of tissues known as the extracellular matrix.
The targeted antigens can be intrinsic or extrinsic. Intrinsic, or “self,” antigens are normal parts of the body’s cells that the immune system mistakenly identifies as a threat. Extrinsic antigens are foreign molecules, like the drug penicillin, that attach to the surface of the body’s cells, making them appear foreign.
Regardless of the antigen’s origin, the binding of IgG or IgM antibodies marks the cell or tissue for a destructive immune response. This antibody-antigen interaction is the event that initiates the damage in a Type II reaction.
How Type II Hypersensitivity Causes Harm
Once IgG or IgM antibodies bind to antigens on cell surfaces or in tissues, they trigger damage through several distinct mechanisms. These pathways can lead to the destruction of cells, inflammation of tissues, or the disruption of normal cellular functions. The specific outcome depends on the location of the antigen and the immune components activated.
One primary mechanism is the direct destruction of targeted cells. This occurs when antibodies coat a cell (opsonization), flagging it for destruction by phagocytic cells like macrophages. Another method involves the complement system, a group of blood proteins that, when activated by antibodies, can form a Membrane Attack Complex (MAC) to puncture the cell’s membrane, causing it to rupture.
Harm also occurs through inflammation. When antibodies bind to antigens fixed within tissues, like the basement membranes of organs, they activate the complement system. This activation releases byproducts that attract inflammatory cells like neutrophils and macrophages, which then release enzymes and reactive oxygen species that damage the surrounding tissue.
A third mechanism alters a cell’s normal function without causing cell death. In these cases, antibodies bind to receptors on a cell’s surface. This binding can either block the receptor from receiving signals or inappropriately stimulate it, causing the cell to behave abnormally and leading to significant physiological consequences.
Conditions Caused by Type II Hypersensitivity
The mechanisms of Type II hypersensitivity are responsible for various diseases that occur when antibodies target specific cells or tissues. The resulting damage can be cell destruction, inflammation, or functional disruption, and the specific condition is determined by which tissue is attacked.
Examples of cell destruction include mismatched blood transfusions, where a recipient’s antibodies attack donor red blood cells. In Hemolytic Disease of the Newborn, a mother’s IgG antibodies cross the placenta and attack the fetus’s red blood cells, causing anemia. Autoimmune hemolytic anemia is a similar condition where an individual produces antibodies against their own red blood cells.
Tissue inflammation is the hallmark of conditions like Goodpasture’s syndrome. In this rare disease, antibodies target a specific type of collagen in the basement membranes of the kidneys and lungs. This antibody binding triggers an inflammatory response that damages these organs, potentially leading to kidney failure and bleeding in the lungs.
Cellular dysfunction caused by antibodies is seen in diseases like Myasthenia Gravis and Graves’ disease. In Myasthenia Gravis, antibodies block acetylcholine receptors on muscle cells, leading to muscle weakness. In Graves’ disease, antibodies stimulate the thyroid-stimulating hormone (TSH) receptor, causing the thyroid gland to become overactive and produce excessive hormones.