The Specificity of Allergic Reactions

Abstract

"Gastric feeding" of adult guinea pigs with dinitrochlorobenzene (DCB) resulted in a specific unresponsiveness to sensitization with the specific contact hapten. The more DCB gastric-fed to a guinea pig, the more complete the unresponsiveness to the hapten. When mycobacteria were incorporated into the sensitizing emulsion, the state of unresponsiveness to the dinitrophenyl (DNP) group was less apparent. When animals gastric-fed with DCB were later sensitized with an in vitro conjugate of the hapten combined with a heterologous protein such as dinitrophenyl-hen egg albumin (DNP·HEA), an immune response similar to that in the controls occurred both to the hapten and to the protein carrier. However, when the tolerant animals were sensitized with a conjugate containing a homologous protein carrier such as dinitrophenyl guinea pig serum (DNP·GPS), they showed diminished immune responses in comparison with those in the non-tolerant controls. The presence of circulating anti-DNP antibodies from sensitization with DNP-HEA did not affect the unresponsiveness to the specific contact hapten, regardless of whether these antibodies are present before or after induction of tolerance. Sensitization with picryl chloride (PiCl) (a cross-reacting hapten), either before or after gastric feeding of DCB, did not affect the state of unresponsiveness to DNP. Similarly when the DNP-tolerant animal was sensitized with PiCl, the subsequent immune response was similar to that in the controls; cross-reactions with the DNP group both in the contact and circulating antibody phase occurred at a rate similar to that in the controls. The foregoing relationships can be explained by presuming that, upon the gastric feeding of DCB, an in vivo conjugate is formed with a somatic protein, which determines the basic specificity of the tolerance. Acquired tolerance seems to manifest an immunologic specificity similar to that of delayed hypersensitivity, a relationship not unexpected if delayed hypersensitivity is an early phase of the immune response.

Some Effects of Oral Administration of Oxazolone to Mice

“…Attempts to sensitize ani mals by oral administration of sensitizers were generally unsuccessful, as were attempts to orally challenge skin-sensitized animals, even though several variations of dose, vehicle, and duration of administration were used. The tendency for orally administered sensitizing agents to produce a state of tolerance rather than allergy is in agreement with the results ob tained by several other groups of workers [Chase, 1946;Battisto and C hase, 1955; C oe and Salvin, 1963;P omeranz and N orman, 1966;A sherson and P tak, 1970;P omeranz, 1970].…”

“…Guinea pigs so treated failed to become sensitized, as assessed by skin testing, and furthermore, were refractory to subsequent attempts at sensitization by the more usual skin route, except when the most severe sensitizing tech niques were used [Battisto and C hase, 1955]. These results have since been confirmed by several workers using different contact sensitizers and different dosing regimes [Coe and Salvin, 1963;P omeranz and N or man, 1966]. Similar results have also been obtained in the mouse [A sherson and Ptak, 1970].…”

Development of Contact Sensitivity to DNFB in Guinea Pigs Genetically Differing in Their Response to DNP Skin Protein Conjugates

“…The formation of several DNP protein conjugates in situ with practi cally the same immunogenicity was demonstrated by P arker and T urk [10] and it does not seem that one particular conjugate is responsible for contact sensitivity as postulated by Coe and Salvin [5],…”

Selective Suppression of Delayed Hypersensitivity by the Induction of Immunologic Tolerance

“…However, when guinea pigs were immunized with picryl chloride conjugated in vitro to a heterologous protein carrier in Freund's adjuvant, only antibodies to the PC1 group were formed, but no contact sensitivity to cutaneous application of PC1 could be detected. It should be noted that the specificity of contact sensitivity is known to be directed to a combined hapten autologous carrier skin protein while the specificity of the antibody response is directed to the hapten or the hapten-carrier protein complex used for immunization (25). Thus two different antigenic determinants were involved in contact sensitivity and antibody formation which makes the interpretation of selective suppression of one of the two immune responses difficult.…”