gen; it has been hypothesized to occur rarely after intramuscular or subcutaneous injection through rapid entry (within 1 to 5 minutes) of large amounts of the antigen into the venous circulation. This reaction in an infant presumably could be mediated by IgG antibody received transplacentally from the mother; such antibody would be expected to persist for the first 6 months of life and possibly longer (Benacerraf and Kabat, 1950; Cohen and Scadron, 1946). Anaphylaxis also can occur without an obvious cause (Wiggins et al., 1989).

INTERACTION OF ANTIBODY WITH NORMAL TISSUE ANTIGENS

In type II reactions, antibody combines with an antigen expressed on normal tissue cells, complement is activated, and the resultant inflammation damages the tissue. It is not clear whether this type of reaction is triggered by alteration in the expression of a tissue antigen or by the formation of an antibody to an antigen in food or an invading microorganism that then cross-reacts with a host antigen. Antigens in a vaccine could theoretically mimic a tissue antigen and elicit such a cross-reacting response, but this has not been shown. On first exposure to such an antigen, any resultant tissue reaction would be expected to develop in about 2 or 3 weeks; on reexposure, a tissue reaction might occur within a few days. (These estimates are hypothetical and are based on what is known about primary and secondary antibody responses to foreign antigens.) The basis for type II reactions is not understood.

ARTHUS REACTION

The Arthus reaction (Arthus, 1903) is mediated differently from either anaphylaxis or type II reactions. Basic to this type III or Arthus reaction is the formation of antigen-antibody complexes, with a moderate excess of antigen, with deposition in the walls of blood vessels, and consequent organ damage. This is not an acute, immediately overwhelming condition. It generally develops over 6 to 12 hours if antibody levels are already high, or it can develop over several days (e.g., in serum sickness) as antibody levels increase and antigen persists. In this reaction, immune complexes in the walls of blood vessels initiate an inflammatory reaction involving complement and leukocytes, particularly neutrophils. Tissue sections show acute inflammation, and profound tissue destruction can occur.

Localized Arthus reactions have been reported to be common at the site of injection of some vaccines and occur when reimmunization is performed in the presence of high levels of circulating IgG antibody (Facktor et al., 1973). They are characterized by pain, swelling, induration, and edema



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