The delayed type of allergic inflammatory response

Abstract

The delayed type of inflammatory response is the most common allergic response encountered in human disease states. It occurs extensively in man as a result of natural infections with bacteria. It does not affect only the genetically susceptible few. Although it is a highly specific altered immune response, the antigen which induces delayed allergy and the antibody which mediates it have not been detected. It differs from early allergic responses which are associated with a measurable serum antibody and are transferred by such sera. The induction of delayed allergy, the manifestations of its noxious effects and the capacity to transfer the response are intimately bound to the cells of the sensitive host. To date delayed allergic responses have been transferred only with cells of the leukocyte series or extracts prepared from cells. Conventional antibody has not been detected in the cell extracts which transfer this response, or in the recipients of such extracts at a time when delayed allergy is present. The exact mechanism by which minute amounts of cell fragments cause the human recipient to respond to specific test materials in the manner the donor responded to the specific bacterial infection is not known. The chemical nature of the transfer factor liberated from cells also is not known. Delayed allergy can be induced in and transferred from congenital agammaglobulinemic patients by means of cells in the absence of the capacity to produce serum antibody. A reevaluation of early and delayed reactions to serum antigens suggest that delayed allergy may be an initial and incomplete phase of the Arthus response. Investigations concerning the mechanism of delayed allergy of the contact type suggest that the type of response induced by sensitization depends upon the chemical structure of the sensitizing agent. Moreover, the type of response achieved following cellular transfer in turn depends upon the mode of sensitization of the donor animal. Although the mechanism by which this occurs is unknown, it is thought to be in the nature of an antibody response. In addition to its immunologic applications, the mechanism of delayed allergy has extensive biologic ramifications at a cellular level. It appears to be operative in such diverse phenomena as skin homograft rejection, tumor transplant rejection, encephalomyelitis, neuritis and uveitis, aspermatogenesis and the Shwartzman reaction. Finally, the relation of the delayed allergic inflammatory response to the pathogenesis, symptomatology and course of infectious disease is discussed, with tuberculosis as an example of the clinical application of this basic immunologic concept. That a similar conditioning to hemolytic streptococcal infections may result in rheumatic fever is considered to be probable but as yet is unproved.