Hypersensitivity Reactions

Hypersensitive reactions are inflammatory reactions within the humoral (Types I-III) or cell-mediated branches of the immune system that lead to extensive tissue damage. Inflammation is a complex process, accompanied by the release of mediators, which, by chemotaxix, attract luekocytes to the point of invasion, create local pain and raise body temperature.

IgE-Mediated (Type I) Hypersensitivity

Allergic diseases such as asthma result from Th2-type immune responses against otherwise harmless environmental antigens. Such resposnes lead to the generation of Th2 T cells, which produce IL-4 and IL-5 and promote the differentiation of B cells into IgE secreting cells.

This IgE binds to Fc receptors on the membranes of blood basophils and tissue mast cells. Cross linkage of the receptor bound IgE molecules by subsequent exposure to antigen induces degranulation of basophils and mast cells releasing various granules (histamine) that give rise to allergic manifestations. These molecules cause blood vessels to dilate and become leaky, which in turn helps white blood cells, antibodies and complement components to enter sites of infection.

Clinical manifestations of type I reactions include hay fever and asthma.

Almost all current therapeutic efforts against alergic disease have been aimed at the control of the symptoms triggered by mast cell or bsophil degranulation. However, a more fundamental approach to disease therapy might be to prevent the initial generation of the Th2 like immune response against the allergen, or to induce a Th1 like response against the allergen since Th1 and Th2 immune responses are typically mutually inhibitory.

Antibody-Mediated Cytotoxic (Type II) Hypersensitivity

Type II hypersensitivity reactions involve antibody-mediated destruction of cells. Antibody can activate the complement system, creating pores in the membrane of a foreign cell, or it can mediate cell destruction by antibody-dependent cell-mediated cytotoxicity (ADCC). Antibody bound to a foreign cell can also serve as an opsonin, enabling phagocytic cells with Cc or C3b receptors to bind and phagocytose the antibody-coated cell.

Transfusion reactions are Type II Reactions. For example, if a type A person is transfused with blood containing type B cells, anti-B iso-hemagglutinins bind to the B blood cells and mediate their destruction by means of complement mediated lysis.

Immune Complex Mediated (Type III) Hypersensitivity

The reaction of antibody with antigen generates immune complexes which usually facilitates the clearance of antigen by phagocytic cells. In some cases, however, large amounts of immune complexes lead to tissue damaging type III hypersensitive reactions. Much of the tissue damage in type III reactions occurs from release of lytic enzymes by neutrophils as they attempt to phagocytose immune complexes.

Delayed-Type (Type IV) Hypersensitivity

"Delayed" refers to the fact that induration slowly develops over 24-48 hr, and "hypersnsitivity" refers to inappropriate damage of tissues by the immune system.

When some subpopulations of activated T_H cells encounter certain types of antigens, they secrete cytokines that induce a localized inflammatory reaction which is characterized by large influxes of nonspecific inflammatory cells like macrophages. In contrast to a Type III reaction then, there is recruitment of macrophages as opposed to neutrophils and also there is a delay in time required for the reaction to develop.