Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1982 May;36(2):768–774. doi: 10.1128/iai.36.2.768-774.1982

Repeated delayed-type hypersensitivity reactions against Mycobacterium lepraemurium antigens at the infection site do not affect bacillary multiplication in C3H mice.

M Løvik, O Closs
PMCID: PMC351296  PMID: 7044977

Abstract

Delayed-type hypersensitivity was induced in cyclophosphamide-pretreated C3H/TifBom mice by subcutaneous immunization in the thorax with ultrasonicated Mycobacterium lepraemurium bacilli in Freund incomplete adjuvant. Seven weeks after immunization, 2.5 X 10(7) acid-fast M. lepraemurium bacilli suspended in diluted sonicate were injected into one hind footpad, and during the next 6 weeks three additional infections of sonicate were given at intervals into the infected footpad. After each injection a strong local reaction developed, which after the first three injections peaked at 24 h. The kinetics of the reaction was accelerated after the repeat injections. Each time the reaction subsided within 1 week. From 2 days to 11 weeks after the inoculation of bacilli there was a 10-fold increase in bacillary numbers in the footpad and a 3,000-fold increase in the draining popliteal lymph node. The degree of bacillary multiplication was the same in animals which had experienced repeated local reactions and in control animals. Thus, repeated strong delayed-type hypersensitivity reactions to M. lepraemurium antigens apparently were without any measurable effect on the bacillary multiplication. This observation provides further evidence for a dissociation in C3H/TifBom mice between delayed-type hypersensitivity to soluble mycobacterial antigens and protective immunity against mycobacteria. Possible explanations for our findings are discussed.

Full text

PDF
768

Images in this article

Selected References

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

  1. Alexander J., Curtis J. Development of delayed hypersensitivity responses in Mycobacterium lepraemurium infections in resistant and susceptible strains of mice. Immunology. 1979 Mar;36(3):563–567. [PMC free article] [PubMed] [Google Scholar]
  2. Anderson D. W., Crowle A. J. Evans blue dye adjuvant enhances delayed hypersensitivity while blocking immunity to Mycobacterium tuberculosis in mice. Infect Immun. 1981 Jan;31(1):413–418. doi: 10.1128/iai.31.1.413-418.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blanden R. V., Mackaness G. B., Collins F. M. Mechanisms of acquired resistance in mouse typhoid. J Exp Med. 1966 Oct 1;124(4):585–600. doi: 10.1084/jem.124.4.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cahall D. L., Youmans G. P. Conditions for production, and some characteristics, of mycobacterial growth inhibitory factor produced by spleen cells from mice immunized with viable cells of the attenuated H37Ra strain of Mycobacterium tuberculosis. Infect Immun. 1975 Oct;12(4):833–840. doi: 10.1128/iai.12.4.833-840.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Closs O. Experimental murine leprosy: growth of Mycobacterium lepraemurium in C3H and C57/BL mice after footpad inoculation. Infect Immun. 1975 Sep;12(3):480–489. doi: 10.1128/iai.12.3.480-489.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Closs O., Haugen O. A. Experimental murine leprosy. 3. Early local reaction to mycobacterium lepraemurium in C3H and C57/BL mice. Acta Pathol Microbiol Scand A. 1975 Jan;83(1):51–58. [PubMed] [Google Scholar]
  7. Closs O., Haugen O. A. Experimental murine leprosy. 4. The gross appearance and microscopic features of the local infiltrate after subcutaneous inoculation of C3H and C57/BL mice with mycobacterium lepraemurium. Acta Pathol Microbiol Scand A. 1975 Jan;83(1):59–68. [PubMed] [Google Scholar]
  8. Closs O., Kronvall G. Experimental murine leprosy. IX. Antibodies against Mycobacterium lepraemurium in C3H and C57BL mice with murine leprosy and in patients with lepromatous leprosy. Scand J Immunol. 1975;4(7):735–740. doi: 10.1111/j.1365-3083.1975.tb02681.x. [DOI] [PubMed] [Google Scholar]
  9. Closs O., Løvik M. Protective immunity and delayed-type hypersensitivity in C57BL mice after immunization with live Mycobacterium lepraemurium and sonicated bacilli. Infect Immun. 1980 Jul;29(1):17–23. doi: 10.1128/iai.29.1.17-23.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gogi R., Rahi A. H., Garner A. The nature of retest reaction in delayed hypersensitivity. I. Light microscopic changes in the skin of the eyelid. Histopathology. 1979 Jan;3(1):51–67. doi: 10.1111/j.1365-2559.1979.tb02981.x. [DOI] [PubMed] [Google Scholar]
  11. HART P. D., REES R. J. Effect of macrocyclon in acute and chronic pulmonary tuberculous infection in mice as shown by viable and total bacterial counts. Br J Exp Pathol. 1960 Aug;41:414–421. [PMC free article] [PubMed] [Google Scholar]
  12. KAWAGUCHI Y. Classification of mouse leprosy. Jpn J Exp Med. 1959 Dec;29:651–663. [PubMed] [Google Scholar]
  13. LEVY F. M., CONGE G. A., PASQUIER J. F., MAUSS H., DUBOS R. J., SCHAEDLER R. W. The effect of BCG vaccination on the fate of virulent tubercle bacilli in mice. Am Rev Respir Dis. 1961 Jul;84:28–36. doi: 10.1164/arrd.1961.84.1.28. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lagrange P. H., Thickstun P. M. In vivo antitumor activity of various forms of delayed-type hypersensitivity in mice. J Natl Cancer Inst. 1979 Feb;62(2):429–436. [PubMed] [Google Scholar]
  16. Lefford M. J. Editorial: Delayed hypersensitivity and immunity in tuberculosis. Am Rev Respir Dis. 1975 Mar;111(3):243–246. doi: 10.1164/arrd.1975.111.3.243. [DOI] [PubMed] [Google Scholar]
  17. Lefford M. J., Patel P. J., Poulter L. W., Mackaness G. B. Induction of cell-mediated immunity to Mycobacterium lepraemurium in susceptible mice. Infect Immun. 1977 Dec;18(3):654–659. doi: 10.1128/iai.18.3.654-659.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lenzini L., Rottoli P., Rottoli L. The spectrum of human tuberculosis. Clin Exp Immunol. 1977 Feb;27(2):230–237. [PMC free article] [PubMed] [Google Scholar]
  19. Løvik M., Closs O. Delayed type hypersensitivity to mycobacterial antigens without protective immunity: a failure to produce the right specificity or the right type of immune reaction? Scand J Infect Dis Suppl. 1980;Suppl 24:224–227. [PubMed] [Google Scholar]
  20. Løvik M., Closs O. Effect of BCG vaccination on Mycobacterium lepraemurium infection in a highly susceptible inbred mouse strain. Acta Pathol Microbiol Scand C. 1981 Apr;89(2):133–138. doi: 10.1111/j.1699-0463.1981.tb02676.x. [DOI] [PubMed] [Google Scholar]
  21. MACKANESS G. B. Cellular resistance to infection. J Exp Med. 1962 Sep 1;116:381–406. doi: 10.1084/jem.116.3.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mitsuyama M., Nomoto K., Akeda H., Takeya K. Enhanced elimination of Listeria monocytogenes at the site of delayed footpad reaction. Infect Immun. 1980 Oct;30(1):1–4. doi: 10.1128/iai.30.1.1-4.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nacy C. A., Leonard E. J., Meltzer M. S. Macrophages in resistance to rickettsial infections: characterization of lymphokines that induce rickettsiacidal activity in macrophages. J Immunol. 1981 Jan;126(1):204–207. [PubMed] [Google Scholar]
  25. Patel P. J. Expression of antibacterial resistance at the site of a delayed hypersensitivity reaction. Infect Immun. 1980 Jul;29(1):59–65. doi: 10.1128/iai.29.1.59-65.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. REES R. J., HART P. D. Analysis of the host-parasite equilibrium in chronic murine tuberculosis by total and viable bacillary counts. Br J Exp Pathol. 1961 Feb;42:83–88. [PMC free article] [PubMed] [Google Scholar]
  27. Rosenwasser L. J., Rosenthal A. S. Adherent cell function in murine T lymphocyte antigen recognition. I. A. macrophage-dependent T cell proliferation assay in the mouse. J Immunol. 1978 Jun;120(6):1991–1995. [PubMed] [Google Scholar]
  28. Turk J. L., Polak L., Parker D. Control mechanisms in delayed-type hypersensitivity. Br Med Bull. 1976 May;32(2):165–170. doi: 10.1093/oxfordjournals.bmb.a071350. [DOI] [PubMed] [Google Scholar]
  29. WALLACE J. G. The heat resistance of tubercle bacilli in the lungs of infected mice. Am Rev Respir Dis. 1961 Jun;83:866–871. doi: 10.1164/arrd.1961.83.6.866. [DOI] [PubMed] [Google Scholar]
  30. Waldron J. A., Jr, Horn R. G., Rosenthal A. S. Antigen-induced proliferation of guinea pig lymphocytes in vitro: obligatory role of macrophages in the recognition of antigen by immune T-lymphocytes. J Immunol. 1973 Jul;111(1):58–64. [PubMed] [Google Scholar]
  31. Wing E. J., Gardner I. D., Ryning F. W., Remington J. S. Dissociation of effector functions in populations of activated macrophages. Nature. 1977 Aug 18;268(5621):642–644. doi: 10.1038/268642a0. [DOI] [PubMed] [Google Scholar]
  32. Youmans G. P. Relation between delayed hypersensitivity and immunity in tuberculosis. Am Rev Respir Dis. 1975 Feb;111(2):109–118. doi: 10.1164/arrd.1975.111.2.109. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES