Biomedical subjects
Publications and source records attributed to M Metzger.
From experimental work to determine the role of humoral and cell-mediated responses in the pathogenesis of syphilis evidence has been collected to indicate that both humoral and cell-mediated immunity have a protective function in syphilis.
The influence of various conditions of freezing in liquid nitrogen on the motility, virulence, antigens, and immunogenicity of Treponema pallidum was studied. The suspending medium, rate of freezing, kind and concentration of cryprotector, and duration of preincubation with cryoprotector were found to be critical. On the basis of the results obtained the optimal conditions of freezing of T. pallidum in liquid nitrogen were established. These are: the Nelson-Diesendruck medium with the addition of 10% DMSO; freezing rate 1 degree per min, and thawing rate between 12.6 degrees and 120 degrees per min.
Rabbits infected intradermally with T. pallidum at four sites on the clipped back were treated with cyclophosphamide, 1 mg/kg body weight, twice before and every two days after inoculation for five months, or 5-fluorouracil 2.5 mg/kg body weight, according to the same regimen. Humoral response, as measured repeatedly by VDRL, FTA, and hemagglutination tests, was not affected by the application of the immunosuppressors. In contrast, the cell-mediated response, as determined by the Macrophage Migration Inhibition test was completely abolished in the treated rabbits. In the group of rabbits which were given immunosuppressors, syphilitic lesions appeared not only at the challenge sites, as usual, but also multiple multiform lesions developed over the entire dorsum after healing of the primary lesions. Taking into account the fact that abolishment of the cell-mediated response led to an aggravated course of the syphilitic infection, the results of these experiments were interpreted as indicating the protective role of the cell mediated response in syphilis.
Numerous investigators tried over the years to induce artifically immunity against syphilis by use of a variety of treponema preparations. None of these immunization experiments performed by different means and routes provided clear evidence of acquired immunity in animals and humans given various vaccine preparations against challenge with even minimal doses of virulent T. pallidum. In recent years, however, promising results have been obtained in the immunization study. Two types of syphilis vaccine have been developed which were found very effective in conferring a protection against syphilitic infection on rabbits: (1) the first vaccine contains T. pallidum attenuated by gamma irradiation, and the other one (2) contains T. pallidum killed by penicillin. In addition, it has been demonstrated that the immunogenic activity of T. pallidum is related to their very labile protein component. Pretty much is also known on the factors influencing the immune response of artificially immunized rabbits, and on the immunological mechanisms underlying the development of syphilis immunity.
Experimental evidence has been obtained to show that the cell-mediated response in syphilis is protective. The use of chemical immunosuppressors (cyclophosphamide, 5-fluorouracil) resulted in the abolition of the cell-mediated response measured by the macrophage migration inhibition test (MMI test), and was accompanied by an enhancement in the severity of the lesions during the course of experimental syphilis in the rabbit. Successful adoptive transfer of resistance to syphilitic infection from immune donor rabbits to normal recipient rabbits employing lymph node lymphocytes was accomplished.
The development of cell-mediated immunity was studied in rabbits: a) experimentally injected with T. pallidum, and b) artificially immunized with nonviable T. pallidum. The macrophage migration inhibition test (MMI test) using ultrasonicate of T. pallidum as antigen was employed to demonstrate this type of immunologic response. Lymphocytes of syphilitic rabbits were found to exert a pronounced inhibitory effect upon macrophage migration as early as one month after infection; between the fourth and sixth month, a transient decrease of this capacity occurred, followed by a slow but steady increase during the next two years, i.e. until the end of the observation period. In rabbits in which the infection had been controlled by penicillin treatment in the fifth month, no increase but gradual diminution of this capacity was observed. In the group of rabbits artificially immunized with nonviable T. pallidum, the MMI response appeared very shortly after commencement of the immunization and persisted for about nine months after completion of the immunization procedure. Only a crude correlation could be established between levels of the MMI response of the immunized animals and their resistance to infection with T. pallidum.
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