Delayed Hypersensitivity

Abstract

In the previous paper (1) it was reported that guinea pigs infected intraderreally with a living toxigenic strain of C. diphtheria~ developed delayed hypersensitivity to diphtheria toxin even when treated with antitoxin before infection. The present paper describes experiments which show that small amounts of diphtheria toxoid or of ovalbumin are capable of inducing a high degree of tuberculin type hypersensitivity in guinea pigs ff the antigen is injected intradermally in the form of a complex with excess homologous antibody. Maximum sensitization is achieved several weeks before circulating antibody can be detected. Materials and MethodsA ntigens.--Schick test materials and purified toxoid KP28 were the same as described in the preceding paper (1). Ovalbumin, three times recrystallized, was supplied by Dr. Milton Levy in the form of a dry powder. It was dissolved in saline or in phosphate buffer, filtered, and the protein concentration determined by measuring the absorption at 277 m/~ of aliquots diluted in 0.25 N acetic acid.AnHsem.--Rabbit antitoxin 379-380, horse antitoxic gamma globulin 5353AD, and human precipitating antitoxic gamma globulin were the same materials used in the preceding study (1). Human skin-sensitizing antitoxin ltu (2) was used without fractionation. This serum was from a recent bleeding taken from subject Hu who had received an immunizing dose of alum toxoid 5 years previously. The serum still contained 20 units of non-precipitating, skin-sensitizing antitoxin per ml.

Influence of Dose and Route of Antigen Injection on the Immunological Induction of T Cells

“…This is another way of saying that we do not know what regulates the production of activated T cells. However, the present investigation recalls with some emphasis what Uhr, et al had clearly established (8), namely that the induction of DTH depends critically cn antigenic dose and route of immunization. SRBC, in the absence cf adjuvant, ~-ere found in the present study to produce DTH even when administered intravenously.…”

“…The Effect of Antigen Dose on the Induction of DTH.--It was known from the early studies of Salvin (7) and of Uhr et al (8) that dose and route of injection have a marked effect upon whether or not an immunological stimulus gives rise to delayed-type hypersensitivity (9). When varying doses of SRBC were injected intravenously or into one hind footpad, two different but highly reproducible patterns of response were found (Fig.…”

“…There are, however, some artificial ways of inducing DTH. The addition of mycobacteria to Freund-type adjuvants is, for example, the conventional method of producing DTH (9) ; but minute doses of antigen, particularly when complexed with antibody, cause DTH of somewhat limited duration (7,8); and macrophage-associated (19)(20)(21) or macrophage-processed (22) antigens have also been found to favor the induction of DTH, sometimes without evidence of antibody formation (22). In contrast to this last finding, an ongoing response to living BCG, like that observed originally in tuberculous animals by Dienes and Schoenheit (23), conditions the immunological apparatus for an accentuated T-cell response despite a marked increase in antibody production (5).…”

Cutaneous Basophil Hypersensitivity

“…Similarly, groups of animals receiving antigen in IFA were retested on the same and new sites 4 and 6 days later with identical doses of skin test antigen as used initially. Evolution of reactions was observed at 2, 4,6,8,24, and 48 hr.…”

Aggregated Immunoglobulin Protects Immune T Cells from Suppression: Dependence on Isotype, Fc Portion, and Macrophage FcγR

“…Regulation of the immune response by antigen-antibody (Ag-Ab) immune complexes (IC) has been a subject of interest for many years [13][14][15][16][17][18]. An extensive literature indicates the potential role of circulating IC in the pathogenesis of different infections, cancers, and autoimmune phenomena [19][20][21].…”