Hypersensitive Reactions

An immune response mobilizes a battery of effector molecules that act to remove antigen by various mechanisms described in previous chapters. Generally, these effector molecules induce a localized inflammatory response that eliminates antigen without extensively damaging the host's tissue. Under certain circumstances, however, this inflammatory response can have deleterious effects, resulting in significant tissue damage or even death. This inappropriate immune response is termed hypersensitivity or allergy. Although the word hypersensitivity implies an increased response, the response is not always heightened but may, instead, be an inappropriate immune response to an antigen. Hypersensitive reactions may develop in the course of either humoral or cell-mediated responses.

The ability of the immune system to respond inappropriately to antigenic challenge was recognized early in this century. Two French scientists, Paul Portier and Charles Richet, investigated the problem of bathers in the Mediterranean reacting violently to the stings of Portuguese Man of War jellyfish. Portier and Richet concluded that the localized reaction of the bathers was the result of toxins. To counteract this reaction, the scientists experimented with the use of isolated jellyfish toxins as vaccines. Their first attempts met with disastrous results. Portier and Richet injected dogs with the purified toxins, followed later by a booster of toxins. Instead of reacting to the booster by producing antibodies against the toxins, the dogs immediately reacted with vomiting, diarrhea, asphyxia, and, in some instances, death. Clearly this was an instance where the animals "overreacted" to the antigen. Portier and Richet coined the term anaphylaxis, loosely translated from Greek to mean the opposite of prophylaxis, to describe this overreaction. Richet was subsequently awarded the Nobel Prize in Physiology or Medicine in 1913 for his work on anaphylaxis.

We currently refer to anaphylactic reactions within the humoral branch initiated by antibody or antigen-antibody complexes as immediate hypersensitivity, because the symptoms are manifest within minutes or hours after a sensitized recipient encounters antigen. Delayed-type hypersensitiv-ity (DTH) is so named in recognition of the delay of symptoms until days after exposure. This chapter examines the mechanisms and consequences of the four primary types of hypersensitive reactions.

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