No abstract

No abstract

THE PHENOMENON of delayed hypersensitivity (DH) has recently become more amenable to investigation because of the development of several new techniques with which it can be studied. DH is typified by the tuberculin reaction. Its chief hallmarks consist of the delayed appearance of a mononuclear inflammatory reaction, passive transfer of the reaction by lymphoid cells and inability to passively transfer DH with serum. These characteristics of the DH reactions are also similar to the cellular immune processes involved in such immunological reactions as contact hypersensitivity, homograft rejection and some autoimmune diseases. One can therefore learn about the mechanisms of cellular immunity in general by the study of DH. The best way to discuss recent advances in the study of DH in the short space available to us is to compare and contrast it with antibody mediated immediate hypersensitivity. For a more exhaustive treatment of the subject, the reader can refer to an excellent recent review 1 and monograph 2 that deal with the phenomenon in greater detail. HlSTOPATHOLOGY OF DHClassically, the DH reaction has been defined by the appearance of cutaneous reactions of induration > 5 mm diameter, with or without erythema, within 16-72 hours after an interacutaneous challenge dose of antigen in a sensitized host. Histologically, this reaction is characterized by capillary dilatation, some edema, and an early polymorphonuclear infiltrate which is superceded by a mononuclear infiltrate consisting of small lymphocytes, some larger proliferating (transforming) lymphoblasts and many macrophages. If severe, this reaction may culminate in local necrosis and ulceration.Intravenous challenge of a delayed hypersensitive host can produce chills, fever for 1-24 hours, lymphopenia, and occasionally culminates in generalized vasoconstriction and shock. If not fatal, such intravenous doses or higher doses administered orally, subcutaneously, or even intradermally, will temporarily desensitize the host so that he becomes unreactive to the specific antigen and also at times transiently anergic towards other antigens as well. INDUCTION OF DHIntradermal and subcutaneous routes and direct injection of lymph nodes are most effective in inducing DH. Addition of adjuvants (such as complete Freund's adjuvant) permits intramuscular and intraperitoneal routes to be used to induce DH. The antigen used to elicit DH rather than antibody production generally have a lower number of antigenic determinants and are less immunogenic than antigens that lead to antibody production. This can be achieved by using minute quantities of antigen (as in sensitization due to repeated skin tests), immunizing with antigens complexed to antibody in antibody excess, or use of homologous rather than heterologous carriers when sensitizing with hapten-protein conjugates. SPECIFICITY OF DHThere is a subtle, but probably important, difference between antigens that induce DH (capable of triggering in vivo lymphocyte proliferation) and those that react well with antibody. ...