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. 1963 Mar 31;117(4):633–646. doi: 10.1084/jem.117.4.633

INHIBITION OF THE LESIONS OF PRIMARY VACCINIA AND OF DELAYED HYPERSENSITIVITY THROUGH IMMUNOLOGICAL TOLERANCE IN RABBITS

John A Flick 1, William B Pincus 1
PMCID: PMC2137618  PMID: 13945543

Abstract

In order to gain insight into the pathogenesis of the vesicular lesion of local primary vaccinia infection, newborn rabbits were injected with 0.5 mg of purified inactivated vaccinia virus in an attempt to render them immunologically tolerant. Within a few days these, and control normal rabbits of the same age, were infected on the skin with active vaccinia virus. Most of the tolerant-prepared rabbits failed to develop a local lesion of vaccinia but some developed a very atypical lesion. Successful virus isolation from some, and the presence of inclusions in the tissues of others, indicated successful infection with the virus. Skin allergy to the active virus failed to develop in the test animals but did in the controls. Thus, there was a high degree of correlation between inability to produce delayed hypersensitivity to the viral antigens and failure to develop a vaccinial skin lesion, indicating the probable allergic nature of the primary lesion. There was also a high mortality rate in the group of tolerant-prepared, infected animals. It was associated with a spreading of the virus from the site of infection to the organs, suggesting that generalized vaccinial infection was the cause of death. The observations were compatible with the hypothesis that death was due to viral toxicity. The observations also suggest that, in the animal possessing normal immunological function, active immunity develops rapidly, perhaps at the level of the draining lymph node, to prevent appreciable virus from leaving the site of infection. The absence of detectable immunological activity toward vaccinia virus early in the tolerant-prepared animals and even after 1 month in some of the survivors, indicates that a high degree of immunological tolerance was produced against these microbial antigens.

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Selected References

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

  1. BARTELL P., ROSANOFF E., WARRENT G. H. Propagation and titration of vaccinia virus in bovine epidermal cells. Am J Vet Res. 1960 Nov;21:1062–1065. [PubMed] [Google Scholar]
  2. BROWN A., MAYYASI S. A., OFFICER J. E. The toxic activity of vaccinia virus in tissue culture. J Infect Dis. 1959 Mar-Apr;104(2):193–202. doi: 10.1093/infdis/104.2.193. [DOI] [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. COHN M. The problem of specific inhibition of antibody synthesis in adult animals by immunization of embryos. Ann N Y Acad Sci. 1957 Mar 22;64(5):859–876. doi: 10.1111/j.1749-6632.1957.tb52480.x. [DOI] [PubMed] [Google Scholar]
  5. CUTCHINS E., WARREN J. Comparative susceptibility of cell cultures to vaccinia virus: application to the standardization of smallpox vaccine. Proc Soc Exp Biol Med. 1958 Feb;97(2):456–462. doi: 10.3181/00379727-97-23774. [DOI] [PubMed] [Google Scholar]
  6. DIXON F. J., MAURER P. H., WEIGLE W. O. Immunologic activity of pneumococcal polysaccharide fixed in the tissues of the mouse. J Immunol. 1955 Mar;74(3):188–191. [PubMed] [Google Scholar]
  7. FELTON L. D. The significance of antigen in animal tissues. J Immunol. 1949 Jan;61(1):107–117. [PubMed] [Google Scholar]
  8. FESTENSTEIN H., BOKKENHEUSER V. Attempted induction of immunological tolerance in rabbits using living Treponema pallidum. Br J Exp Pathol. 1961 Apr;42:158–165. [PMC free article] [PubMed] [Google Scholar]
  9. FRIEDMAN H., GABY W. L. Immunologic unresponsiveness to Shigella antigens in chickens. J Immunol. 1960 May;84:441–448. [PubMed] [Google Scholar]
  10. GOWLAND G., OAKLEY C. L. Acquired immunological tolerance of diphtheria alum-precipitated toxoid in the domestic fowl. J Pathol Bacteriol. 1960 Oct;80:373–378. doi: 10.1002/path.1700800221. [DOI] [PubMed] [Google Scholar]
  11. HASEK M., HRABA T. Immunological effects of experimental embryonal parabiosis. Nature. 1955 Apr 30;175(4461):764–765. doi: 10.1038/175764a0. [DOI] [PubMed] [Google Scholar]
  12. LINDORFER R. K., SUBRAMANYAM P. Induced immunological unresponsiveness to staphylococcus toxoid in rabbits. Proc Soc Exp Biol Med. 1959 Oct;102:168–170. doi: 10.3181/00379727-102-25179. [DOI] [PubMed] [Google Scholar]
  13. McMaster P. D., Kidd J. G. LYMPH NODES AS A SOURCE OF NEUTRALIZING PRINCIPLE FOR VACCINIA. J Exp Med. 1937 Jun 30;66(1):73–100. doi: 10.1084/jem.66.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. NISHMI M., BERNKOPF H. The toxic effect of vaccinia virus on leucocytes in vitro. J Immunol. 1958 Dec;81(6):460–466. [PubMed] [Google Scholar]
  15. NOBLE R. L., BEER C. T., CUTTS J. H. Role of chance observations in chemotherapy: Vinca rosea. Ann N Y Acad Sci. 1958 Dec 5;76(3):882–894. doi: 10.1111/j.1749-6632.1958.tb54906.x. [DOI] [PubMed] [Google Scholar]
  16. NOSSAL G. J. The induction of immunological tolerance in rats to foreign erythrocytes. Aust J Exp Biol Med Sci. 1958 Jun;36(3):235–244. doi: 10.1038/icb.1958.25. [DOI] [PubMed] [Google Scholar]
  17. Olitsky P. K., Long P. H. RELATION OF VACCINAL IMMUNITY TO THE PERSISTENCE OF THE VIRUS IN RABBITS. J Exp Med. 1929 Aug 31;50(3):263–272. doi: 10.1084/jem.50.3.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. PINCUS W. B., FLICK J. A. The role of hypersensitivity in the pathogenesis of vaccinia virus infection in humans. J Pediatr. 1963 Jan;62:57–62. doi: 10.1016/s0022-3476(63)80071-2. [DOI] [PubMed] [Google Scholar]
  19. RYDEN F. W., RANDALL C. C. A study of three strains of vaccinia virus in stable cell strains L, LLC-M1, and HeLa. Am J Pathol. 1957 Mar-Apr;33(2):293–311. [PMC free article] [PubMed] [Google Scholar]
  20. Rivers T. M., Smadel J. E., Chambers L. A. EFFECT OF INTENSE SONIC VIBRATIONS ON ELEMENTARY BODIES OF VACCINIA. J Exp Med. 1937 Apr 30;65(5):677–685. doi: 10.1084/jem.65.5.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. SCHERER W. F., SYVERTON J. T. The viral range in vitro of a malignant human epithelial cell (strain HeLa, Gel). I. Multiplication of herpes simplex, pseudorabies, and vaccinia viruses. Am J Pathol. 1954 Nov-Dec;30(6):1057–1073. [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. STERZL J., TRNKA Z. Effect of very large doses of bacterial antigen on antibody production in newborn rabbits. Nature. 1957 May 4;179(4566):918–919. doi: 10.1038/179918a0. [DOI] [PubMed] [Google Scholar]
  24. WARREN J., CUTCHINS E. C. General characteristics and viral susceptibility of bovine embryonic tissue cultures. Virology. 1957 Oct;4(2):297–304. doi: 10.1016/0042-6822(57)90064-8. [DOI] [PubMed] [Google Scholar]
  25. WEISS D. W. Inhibition of tuberculin skin hypersensitivity in guinea pigs by injection of tuberculin and intact tubercle bacilli during fetal life. J Exp Med. 1958 Jul 1;108(1):83–104. doi: 10.1084/jem.108.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]

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