Mechanism of clinical anaphylaxis

A detailed discussion of the mechanism of clinical anaphylaxis is given by FisheL(.l?.8Z.).. The classic description of types of immune response was given by Coombs and Gell.

Type I sensitivity is anaphylactic hypersensitivity. It is a result of mediator release from mast cells and basophils. The reactions are usually immediate, do not lead to cell lysis, and do not require complement activation. IgE and probably IgG antibodies mediate the reaction.

Type II sensitivity reactions are mediated by IgG or IgM antibodies directed against antigens on the surface of 'foreign cells'. The antigens may be part of the cell wall or haptens absorbed on the cell surface. The reactions are due to complement activation or phagocytosis by killer cells. The most common form are transfusion reactions, hemolytic anemias, idiopathic thrombocytopenic purpura, and Goodpasture's syndrome.

Type III reactions result from soluble antigen-antibody complexes or immune complexes. Complement is activated, and IgG and IgM antibodies participate. Examples include poststreptococcal glomerulonephritis and systemic lupus erythematosus.

Type IV reactions or delayed hypersensitivity are predominantly mononuclear and occur without the involvement of complement or antibodies. They result from the interaction between T lymphocytes and specific antigens. They are characteristically delayed by 24 to 48 h.

The Coombs and Gell classification is an oversimplification. For example, both type I and type IV reactions to the same drug have occurred in the same patient, IgE appears to be involved in some type III reactions, and complement activation has frequently been found in IgE-mediated reactions.

Late-phase reactions involving IgE can occur. The symptoms are not apparent until 2 to 4 h after exposure to antigen. Some reactions have a biphasic pattern characterized by initial resolution of manifestations with a subsequent reappearance. Aggregate anaphylaxis has been primarily described with polypeptides such as gammaglobulin; it has no latent period of sensitization and can be produced experimentally by injection of gammaglobulin from one species into another. Aggregated human gammaglobulin also produces clinical anaphylaxis probably involving complement.

Aspirin and other non-steroidal anti-inflammatory drugs produce clinical anaphylaxis, particularly in patients with respiratory allergy (asthma). The probable mechanism is inhibition of the cyclo-oxygenase pathway shunting arachadonic acid through lipo-oxgenase pathways, thus generating leukotrienes and platelet activating factor.

Kallikrein activation, producing kinins, has been implicated as a cause of reaction to plasma products. The role of the bradykinin system is important; patients using angiotensin-converting enzyme inhibitors for the first time can develop angioedema. Angiotensin-converting enzyme inhibitors block kininase, which promotes the conversion of angiotensin I to angiotensin II but is also responsible for the breakdown of bradykinin. Interactions between angiotensin-converting enzyme inhibitors and plasma products have been described.

Physical factors, exercise, osmolality, and temperature change may all produce clinical anaphylaxis. The mechanisms of exercise-induced anaphylaxis are complex and may represent prior antigen activation followed by mechanical injury to mast cells. Radiocontrast media, glucose solutions, and mannitol are hyperosmotic and can have direct effects on mast cells, producing clinical anaphylaxis.

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