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 responses 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 and tissue . Cross linkage of the receptor bound IgE molecules by subsequent exposure to  induces degranulation ofand  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  to enter sites of infection. The high-affinity receptor for IgE (Fc?RI) is the key molecule in the triggering of IGe-mediated allergic reaction. Mutlivalent allergesns bridge the creceptor-bound IgE and induce the aggregation of this receptor on the surface of mast cells and basophils, and trigger the subsequent release of mediators such as histamine that are responsible for allergic symptoms. Interfering with the binding of IgE to this receptor is considered to be a strategy for the specific prevention of the IgE mediated allergic reaction. For example, recombinant and synthetic peptides comprising structural elements of human IgE or human Fc?RI have been investigated as competitive inhibitors for the IgE-Fc?RI interaction. Searches have also been made for monoclonal antibodies against IgE or Fc?RI? (the extracellular portion). Takai (Japanese Bioch. Society, 129(1), 2001) report that a Fab fragment of a humainzed antibody against the membrane proximinal IgE-binding domain of human Fc?RI? inhibits the rlease of histamine from human basophils. Interesting this same article reports that secretion of Fabs without the Fc gene was remarkably enhanced compared to that when transfected with the Fc gene. 

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

Almost all current therapeutic efforts against allergic disease have been aimed at the control of the symptoms triggered by mast cell or basophil 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  creating pores in the membrane of a foreign cell, or it can mediate cell destruction by . 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.