hypersensitivity

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

Most hypersensitivity diseases show a genetic predisposition. Modern methods of mapping disease-associated susceptibility genes are revealing the complex nature of these genetic influences.

Many susceptibility loci have been identified in different diseases. Among the genes known to be associated with hypersensitivity diseases are MHC genes, but many non-MHC genes also play a role.

Classification

Hypersensitivity diseases can be classified on the basis of the immunologic mechanism that mediates the disease. 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 1 hypersensitivity), the immune response releases vasoactive and spasmogenic substances that act on vessels and smooth muscle and pro-inflammatory cytokines that recruit inflammatory cells.

 In antibody-mediated disorders (type 2 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 3 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 4 hypersensitivity), sensitized T lymphocytes are the cause of the cellular and tissue injury.