MECHANISMS OF HYPERSENSITIVITY REACTIONS

Humans live in an environment teeming with substances capable of producing immunologic responses. Contact with antigen leads not only to induction of a protective immune response,

but also to reactions that can be damaging to tissues. Exogenous antigens occur in dust, pollens, foods, drugs, microbiologic agents, chemicals, and many blood products used in clinical

practice. The immune responses that may result from such exogenous antigens take a variety of forms, ranging from annoying but trivial discomforts, such as itching of the skin, to

potentially fatal diseases, such as bronchial asthma. The various reactions produced are called hypersensitivity reactions, and tissue injury in these reactions may be caused by humoral or

cell-mediated immune mechanisms.

Injurious immune reactions may be evoked not only by exogenous environmental antigens, but also by endogenous tissue antigens. Some of these immune reactions are triggered by

homologous antigens that differ among individuals with different genetic backgrounds. Transfusion reactions and graft rejection are examples of immunologic disorders evoked by

homologous antigens. Another category of disorders, those incited by self-, or autologous, antigens, constitutes the important group of autoimmune diseases (discussed later). These

diseases arise because of the emergence of immune responses against self-antigens.

Hypersensitivity diseases can be classified on the basis of the immunologic mechanism that mediates the disease ( Table 6-2 ). This classification is of value in distinguishing the manner in

which the immune response ultimately causes tissue injury and disease, and the accompanying pathologic alterations. Prototypes of each of these immune mechanisms are presented in the

subsequent sections.

• In immediate hypersensitivity (type I hypersensitivity), the immune response releases vasoactive and spasmogenic substances that act on vessels and smooth muscle and proinflammatory

cytokines that recruit inflammatory cells.

• In antibody-mediated disorders (type II hypersensitivity), secreted antibodies participate directly in injury to cells by promoting their phagocytosis or lysis and injury to tissues by

inducing inflammation. Antibodies may also interfere with cellular functions and cause disease without tissue injury.

• In immune complex-mediated disorders (type III hypersensitivity), antibodies bind antigens and then induce inflammation directly or by activating complement. The leukocytes

that are recruited (neutrophils and monocytes) produce tissue damage by release of lysosomal enzymes and generation of toxic free radicals.

• In cell-mediated immune disorders (type IV hypersensitivity), sensitized T lymphocytes are the cause of the cellular and tissue injury.

Most hypersensitivity diseases show a genetic predisposition. Modern methods of mapping disease-associated susceptibility

TABLE 6-2-- Mechanisms of Immunologically Mediated Diseases

Date: 2016-04-22; view: 792