Heterologous organisms (L. monocytogenes and S. typhimurium) were used to study the rate of development, magnitude, and persistence of the antimicrobial resistance engendered in mice by vaccination with BCG. These same methods were used to investigate the influence of prior vaccination on the host response to reinfection. The rate of onset and magnitude of the resistance produced by BCG varied with the vaccinating dose. Increased resistance was detected within 48 hr of injecting large numbers of BCG (approximately 108 viable units), but concurrent treatment with isoniazid interrupted its further development. An equal number of heat-killed organisms failed to influence host resistance significantly. The development of tuberculin sensitivity was also dependent upon the continued survival of the immunizing population of BCG. When vaccinated mice were reinfected with BCG, host resistance in spleen and liver was rapidly augmented to the accompaniment of striking changes in the morphology and microbicidal activity of the peritoneal macrophages. These changes occurred most rapidly in mice with a high level of delayed hypersensitivity at the time of reinfection.
A system is described for studying adoptive immunity to tuberculosis in syngeneic mice. Donor mice were immunized with 104 BCG intravenously, and lymphoid cells were harvested 28 days later. Adoptive immunity was measured in recipient mice in terms of the inhibition of growth of BCG in the liver and spleen following intravenous injection. Adoptive immunity was expressed optimally when recipients were sublethally irradiated (500 R), challenged with 104 to 105 viable organisms, and given sensitized lymphoid cells intravenously. Adoptive immunity was not manifest until 14 days after challenge and was effective against Mycobacterium tuberculosis H37Rv as well as BCG. Immunity could be conferred by spleen, lymph node, peritoneal exudate, and resident peritoneal (washout) cells. The lymphoid cells conferring immunity were shown to be thymus-dependent lymphocytes by virtue of their nonadherence to glass wool and sensitivity to anti-O serum plus complement. The sensitized cells were relatively susceptible to both in vitro and in vivo X-irradiation.
Random-bred mice were immunized with a nonliving antigen prepared from mixed-blood forms of Plasmodium berghei, strain NYU-2, in combination with Corynebacterium parvum and/or living BCG. A high proportion of intravenously immunized mice survived virulent challenge, but subcutaneous vaccination was less effective. Vaccinated mice developed a patent infection after challenge similar to that observed in normal controls. However, between days 12 to 20 postchallenge, infections in some vaccinated mice became subpatent, whereas infections in all normal controls progressed until death. The incidence of recrudescent infection was low and, eventually, a state of sterile immunity was established. The capacity of vaccinated mice to withstand P. berghei challenge was sustained at a fairly stable level for the 6-month period of observation. Mice that had survived a primary infection with P. berghei almost completely suppressed a second and larger challenge with the same organism.
An open-ended study has been initiated by the International Working Group on Mycobacterial Taxonomy to accommodate strains of slow growers that do not belong to well-established or throughly characterized species. Numerical taxonomic analysis of the data derived from the first series of cultures examined in this study has permitted preparation of expanded descriptions of Myco bacterium simiae and M. szulgai, and, to a lesser extent, M. asiaticum. The analysis also provides some support for revival of the name "M. shimoidei," which is presently without standing. Additional clusters have emerged which may represent new taxa; one of these includes a strain labeled "M. paraffinicum," a name which is also now without standing.Many commonly encountered species of slowly growing mycobacteria have been characterized in a series of cooperative taxonomic studies carried out by the International Working Group on Mycobacterial Taxonomy (IWGMT) (8,21,22). The rapid growers were characterized in two additional IWGMT studies (6, 12), as were members of the "rhodochrous" taxon (4) which is now recognized as Rhodococcus. In the original numerical taxonomic (NT) studies of the slow growers, some strains failed to aggregate with any of the major clusters and were too few in number to permit assignment to new taxa. To provide a mechanism for continuous introduction of unusual or rarely encountered strains into the mycobacterial taxonomic framework, the IWGMT has initiated a new effort, designated the Open-Ended Study of Slowly Growing Mycobacteria. Accession and detailed study of strains is an ongoing process; as new clusters emerge, their descriptions will be reported and, when appropriate, new species will be proposed. This is the first such report from the IWGMT open-ended study. MATERIALS AND METHODS Selection of strains.The data base for this study was derived from cultures meeting one of the following three criteria.(i) Reference marker strains. One culture was selected from a central position in each of the clusters that corresponded to named species in the three prior cooperative studies on slow growers (8,21,22). These 13 cultures, which are identified in the NT matrix (see Fig. l), were not redistributed for further examination; the data previously derived from them were transferred into the computer file reserved for the OpenEnded Study.(ii) Unclustered strains from the prior studies. These strains either appeared in an isolated position or were linked to one or two other strains in one or another of the previously reported studies. These cultures also were not redistributed, but the existing data were simply transferred into the new file.(iii) New accessions. Submission of strains for study was not limited to members of the IWGMT. Anyone wishing to submit a strain for consideration was required to forward it to one of the designated IWGMT transmitters
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