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Hypersensitivity refers to abnormal reactions of the immune system against certain antigens. It includes exaggerated reactions to otherwise harmless environmental antigens, commonly known as allergies; and inappropriate reactions against the body’s own antigens, or autoimmune diseases.
Reactions can range from a mild rash, to damaged organs, to fatal anaphylactic shock.
There are 2 principal groups of factors contributing to hypersensitivity:
– Imbalance between effectors and regulators of immune response: in some people, mechanisms that normally moderate the immune system are compromised, causing it to overreact to harmless, non-infectious antigens.
– Self-reactivity of immune cells: during their development in the thymus and bone marrow, T-cells and B-cells learn to not react to the body’s own antigens; self-reactive cells are normally eliminated; but in some people, some of these cells escape and may attack their own tissues once activated.
Hypersensitivity reactions only occur in pre-sensitized individuals. Patients must have had a previous contact with the antigen, which produced no symptoms, but during which the body had started making antibodies or activated immune cells that may cause symptoms in subsequent exposures to the same antigen.
Hypersensitivity is classified into 4 types based on mechanisms of action:
In type I hypersensitivity, a previous exposure to the antigen results in production of a class of antibodies called IgE. IgE molecules bind to their receptors on the surface of mast cells and basophils. Upon re-exposure to the same antigen, or sometimes a similar antigen, the antigen binds to adjacent IgE molecules, bringing their receptors together, triggering a signaling cascade that induces the release of histamine and other inflammatory chemicals. These chemicals cause dilation of blood vessels, smooth muscle spasms, and are responsible for symptoms such as edema, rash, difficulty breathing due to bronchospasm, abdominal cramping, vomiting and diarrhea. The reactions are immediate, within minutes of contact with the antigen, and can range from mild to severe. Severe reactions may lead to anaphylactic shock, a life-threatening condition in which blood pressure drops and airways narrow to a dangerous level. Most allergies are type I hypersensitivity reactions.
In type II hypersensitivity, previously formed IgG or IgM antibodies bind to antigens on the surface of a particular cell type. Antibody binding marks the cells for destruction, either by the complement system or phagocytosis. The antibodies may also interfere with normal functions of the cells without killing them. Type II is at the basis of many autoimmune diseases, where the body produces antibodies to destroy its own cells. Another example is hemolytic disease of the newborn, where maternal antibodies bind to D-antigen on the surface of fetal red blood cells and destroy them.
Type III hypersensitivity reactions are also mediated by IgM or IgG, but in this case, the antibodies bind to free-floating antigens, forming antibody-antigen complexes. The complement system is activated and inflammation results, causing damage to the affected tissue. A typical example is serum sickness, induced by a large amount of antigens in the blood. Immune complexes are deposited in the walls of blood vessels, triggering their inflammation, or vasculitis.
Type IV hypersensitivity is a delayed reaction, mediated by T-cells. Pre-sensitized T-cells are produced during a previous contact with the antigen. Upon re-exposure to the same antigen, T-helper cells release inflammatory cytokines, while T-killers induce cytotoxic reactions. Typical examples are allergic reactions to substances that come into direct contact with the skin, known as contact dermatitis. Type IV is also the basis of the tuberculosis skin test.
