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. 1958 Aug 1;108(2):227–250. doi: 10.1084/jem.108.2.227

IMMUNOLOGICAL UNRESPONSIVENESS IN RABBITS PRODUCED BY NEONATAL INJECTION OF DEFINED ANTIGENS

Richard T Smith 1, Robert A Bridges 1; With the Technical Assistance of Enid Thomson1
PMCID: PMC2136862  PMID: 13563758

Abstract

The phenomenon of immunological unresponsiveness induced in the neonatal rabbit by a single injection of a defined protein antigen, has been characterized semiquantitatively, and studies bearing upon the mechanism of such unresponsiveness have been presented. A single intraperitoneal injection at birth of 10 to 100 mg. BSA, HGG, ovalbumin, or a human macroglobulin, or an oral feeding of 100 mg. BSA, induced a state of unresponsiveness lasting at least 90 to 120 days. 100 mg. BSA given from birth to 17 days of age, but not later, produced unresponsiveness of 90 to 120 days' duration. Data are presented which show that the duration of unresponsiveness is finite and related to the amount of antigen given at birth, and that it may be indefinitely prolonged by repeated injections of antigen. Disappearance of injected antigen in the unresponsive animal was exponential with time, with no accelerated or immune phase. Administration of the antigen in adjuvants resulted in significant shortening of the duration of unresponsiveness. The transfer of immune cells to the unresponsive host while resulting in vicarious antibody formation, did not affect the underlying unresponsive state. Negative results of attempts to produce unresponsiveness to a variety of bacterial antigens are presented. The implications of the data are discussed, particularly in reference to the other experimental models of immunological tolerance, and to the various theories of acquired immunity. It is clear that any satisfactory theoretical explanation of acquired immunity will have to account simultaneously for the phenomena of immune tolerance.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AUST J. B., MARTINEZ C., BITTNER J. J., GOOD R. A. Tolerance in pure strain newborn mice to tumor homografts. Proc Soc Exp Biol Med. 1956 May;92(1):27–29. doi: 10.3181/00379727-92-22373. [DOI] [PubMed] [Google Scholar]
  2. BILLINGHAM R. E., BRENT L. A simple method for inducing tolerance of skin homografts in mice. Transplant Bull. 1957 Apr;4(2):67–71. [PubMed] [Google Scholar]
  3. BUXTON A. Antibody production in avian embryos and young chicks. J Gen Microbiol. 1954 Jun;10(3):398–410. doi: 10.1099/00221287-10-3-398. [DOI] [PubMed] [Google Scholar]
  4. CINADER B., DUBERT J. M. Acquired immune tolerance to human albumin and the response to subsequent injections of diazo human albumin. Br J Exp Pathol. 1955 Oct;36(5):515–529. [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. DIXON F. J., MAURER P. H., DEICHMILLER M. P. Half-lives of homologous serum albumins in several species. Proc Soc Exp Biol Med. 1953 Jun;83(2):287–288. doi: 10.3181/00379727-83-20336. [DOI] [PubMed] [Google Scholar]
  7. DIXON F. J., TALMAGE D. W. Catabolism of I131 labelled bovine gamma globulin in immune and non-immune rabbits. Proc Soc Exp Biol Med. 1951 Oct;78(1):123–125. doi: 10.3181/00379727-78-18996. [DOI] [PubMed] [Google Scholar]
  8. FELTON L. D. The significance of antigen in animal tissues. J Immunol. 1949 Jan;61(1):107–117. [PubMed] [Google Scholar]
  9. GARVEY J. S., CAMPBELL D. H. The retention of S35-labelled bovine serum albumin in normal and immunized rabbit liver tissue. J Exp Med. 1957 Apr 1;105(4):361–372. doi: 10.1084/jem.105.4.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GERMUTH F. G., Jr A comparative histologic and immunologic study in rabbits of induced hypersensitivity of the serum sickness type. J Exp Med. 1953 Feb 1;97(2):257–282. doi: 10.1084/jem.97.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. GRUSKAY F. L., COOKE R. E. The gastrointestinal absorption of unaltered protein in normal infants and in infants recovering from diarrhea. Pediatrics. 1955 Dec;16(6):763–769. [PubMed] [Google Scholar]
  13. 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]
  14. HARRIS S., HARRIS T. N., FARBER M. B. Studies on the transfer of lymph node cells. I. Appearance of antibody in recipients of cells from donor rabbits injected with antigen. J Immunol. 1954 Feb;72(2):161–171. [PubMed] [Google Scholar]
  15. Heidelberger M., Macpherson C. F. QUANTITATIVE MICRO-ESTIMATION OF ANTIBODIES IN THE SERA OF MAN AND OTHER ANIMALS. Science. 1943 Apr 30;97(2522):405–406. doi: 10.1126/science.97.2522.405. [DOI] [PubMed] [Google Scholar]
  16. JOHNSON A. G., WATSON D. W., CROMARTIE W. J. Effect of massive antigen dosage on antigen retention and antibody response in rabbits. Proc Soc Exp Biol Med. 1955 Mar;88(3):421–427. doi: 10.3181/00379727-88-21607. [DOI] [PubMed] [Google Scholar]
  17. Jerne N. K. THE NATURAL-SELECTION THEORY OF ANTIBODY FORMATION. Proc Natl Acad Sci U S A. 1955 Nov 15;41(11):849–857. doi: 10.1073/pnas.41.11.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. KAMINSKI M., OUCHTERLONY O. Etudes immunochimiques, qualitatives et quantitatives des protéides du blanc d'oeuf. Bull Soc Chim Biol (Paris) 1951;33(7):758–770. [PubMed] [Google Scholar]
  19. KERR W. R., ROBERTSON M. Passively and actively acquired antibodies for Trichomonas foetus in very young calves. J Hyg (Lond) 1954 Jun;52(2):253–263. doi: 10.1017/s0022172400027455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. KOPROWSKI H. Actively acquired tolerance to a mouse tumour. Nature. 1955 Jun 18;175(4468):1087–1088. doi: 10.1038/1751087b0. [DOI] [PubMed] [Google Scholar]
  21. OSBORN J. J., DANCIS J., JULIA J. F. Studies of the immunology of the newborn infant. I. Age and antibody production. Pediatrics. 1952 Jun;9(6):736–744. [PubMed] [Google Scholar]
  22. Owen R. D. IMMUNOGENETIC CONSEQUENCES OF VASCULAR ANASTOMOSES BETWEEN BOVINE TWINS. Science. 1945 Oct 19;102(2651):400–401. doi: 10.1126/science.102.2651.400. [DOI] [PubMed] [Google Scholar]
  23. ROBERTS J. C., Jr, DIXON F. J. The transfer of lymph node cells in the study of the immune response to foreign proteins. J Exp Med. 1955 Oct 1;102(4):379–392. doi: 10.1084/jem.102.4.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. SIMONSEN M. Artificial production of immunological tolerance; induced tolerance to heterologous cells and induced susceptibility to virus. Nature. 1955 Apr 30;175(4461):763–764. doi: 10.1038/175763a0. [DOI] [PubMed] [Google Scholar]
  25. STARK O. K. Studies on pneumococcal polysaccharide. II. Mechanism involved in production of immunological paralysis by type I pneumococcal polysaccharide. J Immunol. 1955 Feb;74(2):130–133. [PubMed] [Google Scholar]
  26. TALMAGE D. W. Allergy and immunology. Annu Rev Med. 1957;8:239–256. doi: 10.1146/annurev.me.08.020157.001323. [DOI] [PubMed] [Google Scholar]
  27. TALMAGE D. W., DIXON F. J., BUKANTZ S. C., DAMMIN G. J. Antigen elimination from the blood as an early manifestation of the immune response. J Immunol. 1951 Oct;67(4):243–255. [PubMed] [Google Scholar]
  28. THOMAS L., GOOD R. A. Studies on the generalized Shwartzman reaction: I. General observations concerning the phenomenon. J Exp Med. 1952 Dec;96(6):605–624. doi: 10.1084/jem.96.6.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. WOLFE H. R., TEMPELIS C., MUELLER A., REIBEL S. Precipitin production in chickens. XVIL The effect of massive injections of bovine serum albumin at hatching on subsequent antibody production. J Immunol. 1957 Aug;79(2):147–153. [PubMed] [Google Scholar]
  30. WOODRUFF M. F., SIMPSON L. O. Induction of tolerance to skin homografts in rats by injection of cells from the prospective donor soon after birth. Br J Exp Pathol. 1955 Oct;36(5):494–499. [PMC free article] [PubMed] [Google Scholar]
  31. YUILE C. L., LUCAS F. V., JONES C. K., CHAPIN S. J., WHIPPLE G. H. Inflammation and protein metabolism studies of carbon-14-labeled proteins in dogs with sterile abscesses. J Exp Med. 1953 Aug;98(2):173–194. doi: 10.1084/jem.98.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]

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