Summary
Since the demonstration of the lymphocyte as a mediator of delayed hypersensitivity our understanding of this immune response has advanced tremendously. It is now recognised that the lymphocyte acts as the sensitized cell and the macrophage as the indicator cell. The following mechanism for delayed hypersensitivity has been suggested. Antigen→macrophage super antigen→lymphoblast→sensitized lymphocyte→migration inhibitory factor→macrophage. The anergy to tuberculin testing in active tuberculosis and other states is better understood. It is believed that in active tuberculosis there is an inhibitory factor in the serum. The recognition of thein vitro correlates of delayed hypersensitivity has provided yet another method of detecting this immune response. It is more sensitive than the dermal tests. It is hoped that this will prove useful in the diagnosis and management of tuberculosis, a disease where hypersensitivity plays a large part in the pathological process.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Baram, P., Yuan, L. and Mosko, M. M. (1966). Studies on the transfer of human delayed type hypersensitivity. Partial purification and characterisation of two active components.J. Immunol. 86, 177.
Berkovich, S. and Starr. (1966). Effect of live type 1 polio virus vaccine and other viruses on tuberculin test.New Engl. J. Med. 274, 67.
Bloch, H. (1968). Allergic manifestations in tuberculosis. in ‘Text book of Immunopathology’ ed. by Miescher, P. A. & Muller-Eberhard, H. J.Grune and Stratton, New York.
Bloom, B. R., Hamilton, L. D. and Chase, M. W. (1964). Effects of mitomycin C on the cellular transfer of delayed type hypersensitivity in the guineapig.Nature,201, 689.
Bloom, B. R., and Bennett, B. (1966). Mechanism of a reaction in vitro associated with delayed type hypersensitivity.Science,153, 80.
Cannon, G. A., Sarkany, I., Williams, H. S. and Todd, A. P. (1965). Radioactive method for the measurement of lymphocyte transformation in vitro.Lancet,2, 1266.
Carpenter, R. R. (1963). In vitro studies of cellular hypersensitivity. 1: Specific inhibition of migration of cells from adjuvant-immunised animals by purified protein derivative and other protein antigens.J. Immunol. 91, 803.
Chase, M. W. (1945). The cellular transfer of cutaneous hypersensitivity to tuberculin.Proc. Soc. Exptl. Biol. Med. 59, 134.
Choremis, C., Matsaniotis, N., Tsenghi, C. and Tsatsikas, J. (1964). Report given at IV Middle East Mediterranean Pediatric Congress, Athens.
Cowling, D. C., Quaglino, D. and Davidson, E. (1963). Changes induced by tuberculin in cultures.Lancet,2, 1091.
David, J. R., Al-Askari, S., Lawrence, H. S., and Thomas, L. (1964a). Delayed hypersensitivity in vitro. 1: The specificity of inhibition of cell migration by antigens.J. Immunol. 93, 264.
David, J. R., Lawrence, H. S., and Thomas, L. (1964b). Delayed hypersensitivity in vitro. II: Effect of sensitive cells on normal cells in the presence of antigen.J. Immunol. 93, 274.
David, J. R., Lawrence, H. S. and Thomas, L. (1964c). The in vitro densitization of sensitive cells by trypsin.J. Exptl. Med. 120, 1189.
David, J. R. (1965). Suppression of delayed hypersensitivity in vitro by inhibition of protein synthesis.J. Explt. Med. 122, 1125.
David, J. R. (1966). Delayed hypersensitivity in vitro: its mediation by cell free substances formed by lymphoid cell-antigen interaction.Proc. Natl. Acad. Sci. U. S. 56, 72.
Dutton, R. W., and Eady, J. (1964). An in vitro system for the study of the mechanism of antigenic stimulation in the secondary response.Immunol. 7, 40.
Elves, M. W., Roath, S., and Israels, M. C. G. (1963). The response of lymphocytes to antigenic challenge in vivo.Lancet,1, 806.
Fireman, P., Boesman, M., Haddad, Z. H. and Gitlin, D. (1967). Passive transfer of tuberculin reactivity in vitro.Science,155, 337.
Fireman, P., Boesman, M., Haddad, Z. and Gitlin, D. (1968). In vitro passive transfer of tuberculin reactivity.Federation Proc. 27, 29.
Friedman, R. M., Buckler, C. E. and Baron, S. (1961). The effect of amino-methyl pteroyl glutamic acid on the development of skin hypersensitivity and on antibody formation in guineapigs.J. Exptl. Med. 114, 173.
Friedman, R. M. (1964). Inhibition of established tuberculin hypersensitivity by methotrexate.Proc. Soc. Exptl. Biol. Med.,116, 471.
George, M. and Vaughan, J. H. (1962). In vitro cell migration as a model for delayed hypersensitivity.Proc. Soc. Exptl. Biol. Med. 111, 514.
Good, R. A., Kelly, W. D., Rotstein, J. and Varco, R. L. (1962). Immunological deficiency diseases: agammaglobulineamia, Hodgkins disease and sarcoidosis.Prog. Allergy,6, 187.
Harland, P. S. E. G. (1965). Tuberculin reaction in malnourished children.Lancet,2, 719.
Heilman, D. H. and McFarland, W. (1966). Inhibition of tuberculin induced mitogenesis in cultures of lymphocytes from tuberculous donors.Inter. Arch. Allergy,30, 58.
Hirschhorn, K., Bach, F., Kolodny, R. L., Firschein, I. L. and Hashem, N. (1963). Immune response and mitosis of human peripheral blood lymphocytes in vitro.Science,142, 1185.
Hirschhorn, K., Schreibman, R. R., Bach, F. H. and Silzbach, L. E. (1964). In vitro studies of lymphocytes from patients with sarcoidosis and lymphoproliferative disorders.Lancet,2, 842.
Hirschhorn, K. (1968). Discussion of lymphocyte transformation.Federation Proc. 27, 31.
Kent, D. and Shwartz, R. (1967). Active pulmonary tuberculosis with negative tuberculin skin reactions.Amer. Rev. Resp. Dis.,95, 411.
Kempe, C. H. (1960). Studies on smallpox and complications of small pox vaccination.Pediatrics,26, 176.
Kipps, A., Stern, L., and Vaughan, E. G. (1966). The duration and the possible significance of the depression of tuberculin sensitivity following measles.South African Med. J. 40, 104.
Landsteiner, K. and Chase, M. W. (1942). Experiments on transfer of cutaneous sensitivity to simple compounds.Proc. Soc. Exptl. Biol. Med. 49, 688.
Lawrence, H. S. (1955). The transfer in humans of delayed cutaneous sensitivity to streptococcal M substance and to tuberculin with disrupted leukocytes.J. Clin. Invest. 34, 219.
Lawrence, H. S. (1960). Some biological and immunological properties of transfer factor, in CIBA Foundation symposium on ‘Cellular aspects of immunity, ed. by G. E. Wolstenholme and M. O'Connor.Little Bown, Boston, p. 243.
Lawrence, H. S., Al-Askari, S., David, J., Franklin, E. C. and Zweiman, B. (1963). Transfer of immunological information in humans with dialysates of leukocyte extracts.Trans. Ass. Amer. Physicians,76, 84.
Lincoln, E. and Sewell, E. (1963). Tuberculosis in children.McGraw Hill Book Company. New York
Marshall, W. and Robersts, K. B. (1963). Tuberculin induced mitosis in peripheral blood leukocytes.Lancet,1, 773.
Matsaniotis, N., Tsenghi, C., E-Mavrou, C. and M-Stavridi, C. (1968). Skin hypersensitivity and in vitro lymphocyte reactivity to tuberculin in childhood.J. Pediat. 72, 599.
Matsaniotis, N., Tsenghi, C., Economou-Mavro, C. and M-Stavridaki, C. (1969). B. C. G. and the tuberculin test.Lancet,1, 892.
Maurer, P. H. (1961). Immunological studies with ethylene oxide treated human serum.J. Exptl. Med. 113, 1029.
McCluskey, R. T., Benacerraf, B. and McCluskey, J. W. (1963). Studies on the specificity of the cellular infiltrate in delayed hypersensitivity reactions.J. Immunol. 90, 466.
Metaxus, M. N., and Metaxus-Buhler, M. (1955). Studies on the cellular transfer of tuberculin sensitivity into guineapigs.J. Immunol. 75, 333.
Mueller, P. S., and Kies, M. W. (1962). Suppression of tuberculin reaction in scorbutic guieapigs.Nature,195, 813.
Muftuoglu, A. U. and Balkuv, S. (1967). Passive transfer of tuberculin sensitivity to patients with Hodgkins' disease.New. Engl. J. Med. 277, 126.
Nowell, P. C. (1960). Phytohemagglutinin: An initiator of mitosis in cultures of normal human leukocytes.Cancer Res. 20, 462.
Oliveira-Lima, A. (1958). Passive transfer of the delayed dermal sensitivity by means of blood leukocytes.Amer. Rev. Tuberc. 78, 346.
Oppenheim, J. J. (1968). Relationship of in vitro lymphocyte transformation to delayed hypersensitivity in guineapigs and man.Fed. Proc. 27, 21.
Pearmain, G., Lycette, R. R. and Fitzgerald, P. H. (1963). Tuberculin induced mitosis in peripheral blood leukocytes.Lancet,1, 637.
Parrot, D. M. and deSouza, M. A. B., (1966). Changes in the thymus dependent areas of lymphnodes after immunological stimulation.Nature,212, 1316.
Pochyly, D. F. (1967). The role of trypsin in interfering with in vitro delayed hypersensitivity reactions.Federation Proc. 26, 478.
Rapaport, F. T., Lawrence, H. S., Millar, J. W., Pappagianis, D. and Smith, C. E. (1960). Transfer of delayed hypersensitivity to occidiodin in man.J. Immunol. 84, 358.
Rich, A. R. and Lewis, M. R. (1932). The nature of allergy in tuberculosis as revealed by tissue culture studies.Bull. Johns Hopkins Hosp. 50, 115.
Robbins, J. H. (1964). Tissue culture studies of the human lymphocyte.Science,146, 1648.
Shrek, R. (1963). Cell transformation and mitosis produced in vitro by tuberculin purified protein derivative in human blood cells.Amer. Rev. Resp. Dis. 87, 734.
Starr, S. and Berkovich, S. (1964). Effect of measles, gammaglobulin modified measles and vaccine measles on tuberculin test.New Engl. J. Med. 270, 386.
Stefani, S. (1966). Old tuberculin induced radio-resistance in human leukocytes in vitro.Brit. J. Hemat. 12, 345.
Thor, D. E. (1968). Human delayed hypersensitivity: an in vitro correlate and transfer by an R. N. A. extract.Federation Proc. 27, 16.
Urbach, F., Sones, M., and Israel, W. L. (1962). Passive transfer of tuberculin sensitivity to patients with sarcoidosis.New Engl. J. Med. 247, 794.
Author information
Authors and Affiliations
Additional information
From the Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-16.
Rights and permissions
About this article
Cite this article
Verma, I.C. In vitro correlates of delayed hypersensitivity in tuberculosis. Indian J Pediatr 37, 337–346 (1970). https://doi.org/10.1007/BF02801350
Issue Date:
DOI: https://doi.org/10.1007/BF02801350