Occurrence of Delayed Hypersensitivity During the Development of Arthus Type Hypersensitivity

Abstract

Guinea pigs were injected in the footpads with either purified diphtheria toxoid or recrystallized egg albumin in Freund adjuvant without mycobacteria. Each guinea pig was then skin-tested only once with the specific antigen and bled for antibody determination. After injection of the sensitizing antigen, a latent period occurred during which neither sensitivity nor circulating antibody could be detected. A period of delayed sensitivity followed wherein circulating antibody could not be discerned and which could be transferred by lymph node cells. Ultimately, the Arthus type sensitivity developed, accompanied by circulating antibody. The duration and severity of reactions to homologous antigens during the last 2 phases varied with the antigen and with the dose. An increase in the sensitizing dose decreased the duration of the delayed type of allergy, a decrease in the dose prolonged the delayed type. Inclusion of mycobacterium in the sensitizing inoculum tended to introduce delayed sensitivity earlier and delay the onset of Arthus type sensitivity. When specific precipitate in antibody excess was included with the toxoid in the sensitizing dose, the onset of the Arthus phase was hastened. When lymph nodes from a large number of sensitized donors were removed during the latter part of the latent period, recipients of the cells showed a delayed type sensitivity.

Immune Response to Chemically Modified Flagellin

“…This hypothesis readily explains the observation that the specificity requirements for antibody tolerance and delayed hypersensitivity are much lower than those required for antibody formation. It is also consistent with the observation that low doses of antigen preferentially induce cell-mediated immunity (26) and antibody tolerance (37), whereas particulate antigens (e.g., pol)maerized flagellin) preferentially develop humoral antibodies. SUMMARY Flagellin (mol.wt.…”

The Number of Responding CD4 T Cells and the Dose of Antigen Conjointly Determine the Th1/Th2 Phenotype by Modulating B7/CD28 Interactions

“…In vivo, low and higher doses of protein Ag or pathogens give rise to Th1 and Th2 cells, respectively. Furthermore, it is known that the immune response to diverse Ags, both living and nonliving, often goes through an exclusive Th1 phase before a Th2 component develops (67). Both the effect of Ag dose on the Th1/Th2 phenotype of the immune response as well as the evolution of the immune response from a Th1 to a Th1/Th2 mode with time are understandable in terms of the mechanism outlined in this study.…”

A Transient Stage of Suspected Delayed Sensitivity During the Early Induction Phase of Immediate Corneal Sensitivity

“…However, failure to reproduce a similar reaction with non-allergenic reagents or with homologous or autologous proteins mediated against this supposition. The presence of a concomitant delayed skin hypersensitivity to the specific antigen in these animals suggested the possibility that the corneal reaction was a manifestation of "delayed hypersensitivity" in the sense of Dienes and others (5)(6)(7)(8)(9)(10).…”

“…Many investigators believe that delayed sensitivity of this type represents a state of altered reactivity of the cells of the lymphoid-mononuclear series to the inciting antigen and, that this is an integral step in the development of circulating antibody (7,16). There is a natural reluctance to equate delayed hypersensitivity of this nature with that obtained classically with particulate antigens, especially tubercle bacilli.…”

“…Evidence is presented for placing this early reaction into the category of "delayed sensitivity" as described by Dienes and others (5)(6)(7)(8)(9)(10).…”