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.
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Selected References
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- BOYDEN S. V., SORKIN E. Effect of neonatal injections of protein on the immune response to protein-hapten complexes. Immunology. 1962 May;5:370–377. [PMC free article] [PubMed] [Google Scholar]
- BOYDEN S. V. The adsorption of proteins on erythrocytes treated with tannic acid and subsequent hemagglutination by antiprotein sera. J Exp Med. 1951 Feb;93(2):107–120. doi: 10.1084/jem.93.2.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHASE M. W. Experimental sensitization with particular reference to picryl chloride. Int Arch Allergy Appl Immunol. 1954;5(2):163–191. doi: 10.1159/000228095. [DOI] [PubMed] [Google Scholar]
- CINADER B., PEARCE J. H. The specificity of acquired immunological tolerance to azo proteins. Br J Exp Pathol. 1958 Feb;39(1):8–29. [PMC free article] [PubMed] [Google Scholar]
- CURTAIN C. C. The use of acquired immunological tolerance and immunological paralysis in the study of the antigenic relationships of normal and abnormal serum globulins. Br J Exp Pathol. 1959 Jun;40(3):255–262. [PMC free article] [PubMed] [Google Scholar]
- DIXON F. J., MAUER P. H. Immunologic unresponsiveness induced by protein antigens. J Exp Med. 1955 Mar 1;101(3):245–257. doi: 10.1084/jem.101.3.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DOWNE A. E. Inhibition of the production of precipitating antibodies in young rabbits. Nature. 1955 Oct 15;176(4485):740–741. doi: 10.1038/176740a0. [DOI] [PubMed] [Google Scholar]
- EISEN H. N., ORRIS L., BELMAN S. Elicitation of delayed allergic skin reactions with haptens; the dependence of elicitation on hapten combination with protein. J Exp Med. 1952 May 1;95(5):473–487. doi: 10.1084/jem.95.5.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GOOD R. A., ZAK S. J. Disturbances in gamma globulin synthesis as experiments of nature. Pediatrics. 1956 Jul;18(1):109–149. [PubMed] [Google Scholar]
- HANAN R., OYAMA J. Inhibition of antibody formation in mature rabbits by contact with the antigen at an early age. J Immunol. 1954 Jul;73(1):49–53. [PubMed] [Google Scholar]
- Landsteiner K., Chase M. W. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS : IX. SKIN SENSITIZATION INDUCED BY INJECTION OF CONJUGATES. J Exp Med. 1941 Feb 28;73(3):431–438. doi: 10.1084/jem.73.3.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MAGUIRE H. C., Jr, MAIBACH H. I. Specific immune tolerance to anaphylactic sensitization (egg albumin) induced in the guinea pig by cyclophosphoramide (Cytoxan). J Allergy. 1961 Sep-Oct;32:406–408. doi: 10.1016/0021-8707(61)90018-1. [DOI] [PubMed] [Google Scholar]
- OVARY Z. Immediate reactions in the skin of experimental animals provoked by antibody-antigen interaction. Prog Allergy. 1958;5:459–508. [PubMed] [Google Scholar]
- SALVIN S. B., SMITH R. F. The specificity of allergic reactions. I. Delayed versus Arthus hypersensitivity. J Exp Med. 1960 Apr 1;111:465–483. doi: 10.1084/jem.111.4.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SALVIN S. B., SMITH R. F. The specificity of allergic reactions. III. Contact hypersensitivity. J Exp Med. 1961 Aug 1;114:185–194. doi: 10.1084/jem.114.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SCHWARTZ R., DAMESHEK W. Drug-induced immunological tolerance. Nature. 1959 Jun 13;183(4676):1682–1683. doi: 10.1038/1831682a0. [DOI] [PubMed] [Google Scholar]
- SILVERSTEIN A. M., GELL P. G. Delayed hypersensitivity to hapten-protein conjugates. II. Anti-hapten specificity and the heterogeneity of the delayed response. J Exp Med. 1962 May 1;115:1053–1064. doi: 10.1084/jem.115.5.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SMITH R. T., BRIDGES R. A. Immunological unresponsiveness in rabbits produced by neonatal injection of defined antigens. J Exp Med. 1958 Aug 1;108(2):227–250. doi: 10.1084/jem.108.2.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WEIGLE W. O. The immune response of rabbits tolerant to bovine serum albumin to the injection of other heterologous serum albumins. J Exp Med. 1961 Jul 1;114:111–125. doi: 10.1084/jem.114.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
