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Biomedical subjects

F M Collins

Publications and source records attributed to F M Collins.

At least 55 records · Page 3Linked to original sources
PubMed1986

Crossprotection against nontuberculous mycobacterial infections by Mycobacterium tuberculosis memory immune T lymphocytes.

Adoptive immunization of T cell-deficient recipient mice with M. tuberculosis-specific memory immune T lymphocytes conferred upon these animals the ability to express significantly enhanced resistance both to the homologous infection, and to three strains of nontuberculous mycobacteria. These results support the hypothesis, therefore, that antigenic determinants possessed by the four mycobacterial strains that are relevant to the generation of protective cellular immunity are identical or closely crossreactive.

Air Microbiology↗
PubMed1986

Aerogenic vaccination of mice with Mycobacterium bovis BCG.

The course of infection with Mycobacterium bovis BCG Pasteur was followed against time in groups of mice vaccinated by either the aerogenic or subcutaneous route. The generation of acquired protective immunity and immunological memory was determined in each group by adoptive immunisation procedures. In addition, subcutaneously vaccinated mice were tested for their ability to resist an aerogenic challenge with a lethal dose of M. tuberculosis. No overall qualitative differences in the magnitude or longevity of antituberculosis immunity in mice vaccinated by the two procedures were observed. It is concluded that aerogenic vaccination offers no immunological advantage over vaccination by the subcutaneous route.

Aerosols↗
PubMed1986

Lack of evidence for a reduction in the efficacy of subcutaneous BCG vaccination in mice infected with nontuberculous mycobacteria.

Subcutaneous BCG vaccination of mice several weeks after intravenous or subcutaneous infection with either M. avium or M. kansasii had no effect on the subsequent course of these nontuberculous mycobacterial infections. In some animals the growth of the BCG infection in the draining popliteal lymph nodes was reduced compared with the growth in controls, although these mice were as resistant as BCG-vaccinated controls to a subsequent airborne challenge infection with M. tuberculosis. Nonvaccinated previously infected mice also showed some degree of resistance to the airborne challenge infection; this resistance was more pronounced in mice infected with nontuberculous mycobacteria intravenously than in those infected subcutaneously.

Animals↗
PubMed1986

Kinetics of the tuberculocidal response by alkaline glutaraldehyde in solution and on an inert surface.

Single cell suspensions of BCG and Mycobacterium tuberculosis were exposed to 2% alkaline glutaraldehyde solution (pH 8.0) and the rate of kill measured at intervals up to 30 min. Residual glutaraldehyde was neutralized with freshly prepared 1% sodium bisulphite. The rate of kill was directly proportional to the temperature and independent of the inoculum size whether the organism was tested in suspension or attached to an inert surface. Glutaraldehyde was slightly more bactericidal for the virulent M. tuberculosis than for the attenuated BCG. A substantial proportion of the mycobacterial population on an inert surface floated off during its exposure to the glutaraldehyde solution but the 'floaters' were killed at an equivalent rate to the attached bacilli. Complete sterility of a standardized suspension of M. tuberculosis could not be achieved within the 10 min period specified by the tuberculocidal assay, although it was usually attained within 20 min.

Aldehydes↗
PubMed1986

Bactericidal activity of alkaline glutaraldehyde solution against a number of atypical mycobacterial species.

The mycobactericidal activity of 2% alkaline glutaraldehyde solution was determined using standardized suspensions of 10 species of atypical mycobacteria and compared with that for virulent Mycobacterium tuberculosis. Suspensions of M. avium, M. intracellulare and M. gordonae were more resistant to disinfection by the glutaraldehyde than were virulent tubercle bacilli while M. kansasii, M. scrofulaceum and M. szulgae were somewhat more susceptible. Mycobacterium marinum, M. smegmatis and M. fortuitum were highly sensitive to the disinfectant action of the alkaline glutaraldehyde solution. This variation in sensitivity shown by apparently closely related strains of mycobacteria to this disinfectant has important practical implications.

Aldehydes↗
PubMed1986

Genetic control of natural resistance to nontuberculous mycobacterial infections in mice.

Results show that various inbred strains of mice can be segregated into two distinct groups, based on their capacity to allow a number of nontuberculous mycobacterial infections to grow in target organs following experimental intravenous infection. The first group, which allowed these infections to grow progressively, was thus designated as naturally susceptible to these infections; in contrast, those strains which were able to exert detectable bacteriostasis were designated as naturally resistant. It was then found that segregation of mouse strains based on this distinction also mirrored the capacity of these animals to generate acquired immunity to the mycobacterial infections. For example, Mycobacterium simiae grew progressively in susceptible C57BL/6 mice, subsequently triggering acquired mechanisms of immunity, whereas no evidence for acquired immunity could be found in resistant A/Tru mice infected with this organism. The possibility that acquired immunity could not be expressed in the latter strain as a result of a defect in macrophage activation was excluded. Moreover, it was found that the trait of resistance to these infections could be transferred by bone marrow cells into radiation chimeras, thus indicating that this trait was expressed by the progeny of hemopoietic precursor cells. Subsequent backcross analysis to determine the mode of inheritance of the trait of resistance to these mycobacterial infections revealed data that were consistent with the hypothesis that this resistance is controlled by more than one gene. Statistical analysis of the data by the maximum likelihood method suggested polygenic control, although in some cases the probability values suggested control by a major gene, influenced by modifier genes. These findings suggest that the previous hypothesis that the growth of mycobacterial infections in inbred strains of mice is controlled by a single gene should be reevaluated.

Animals↗
PubMed1986

Role of mononuclear phagocytes in expression of resistance and susceptibility to Mycobacterium avium infections in mice.

The growth of Mycobacterium avium 702 in the spleens and livers of four inbred strains of mice varied such that the mice could be separated into naturally susceptible (BALB/c and C57BL/6) and naturally resistant (A/Tru and DBA/2) strains. This phenomenon was independent of the size of the infecting inoculum of bacteria in that both low (10(4))- and high (10(7))-dose inocula of M. avium grew progressively in susceptible strains and were eliminated from the target organs of resistant strains. Resistance and susceptibility were also demonstrated in in vitro preparations of macrophages from these strains of mice. Over a 7-day period, replication of M. avium in susceptible mouse macrophages was far greater than that in resistant macrophages. Evidence was obtained to suggest that toxic oxygen metabolites were not responsible for this difference. Though no difference was found in the rate of clearance of M. avium from the blood of susceptible or resistant mice, resident macrophages from susceptible mice ingested more M. avium in vitro than did resident macrophages from resistant animals. Growth of M. avium in spleens of susceptible mice induced a large influx of phagocytes, whereas this was not observed in resistant mice. In contrast to this it was found that, after injection of a variety of inflammatory agents, influx of leukocytes into the peritoneal cavity could not be used to distinguish susceptible and resistant strains of mice.

Animals↗
PubMed1985

Protection to mice afforded by BCG vaccines against an aerogenic challenge by three mycobacteria of decreasing virulence.

Specific pathogen-free mice were vaccinated subcutaneously with 10(7) CFU of BCG Pasteur or BCG Glaxo and 30 or 90 days later, the mice were challenged aerogenically with Mycobacterium tuberculosis (Erdman or South Indian strains) or with M. avium. Both vaccines induced substantial levels of resistance to tuberculosis and tuberculin hypersensitivity. There was no detectable difference in the host response to the three aerogenic challenges which could be related in any way to the immunogenicity of the BCG strain or to the mouse virulence of the challenge organism. These results do not support the hypothesis that the protective activity of BCG vaccines varies, depending upon the virulence of the infecting organism.

Animals↗
PubMed1985

Prophylactic effect in mice of BCG vaccination against nontuberculous mycobacterial infections.

The effect of prior vaccination of mice with Mycobacterium bovis BCG on the subsequent course of acute aerogenic infection with various environmental mycobacteria was tested. A protective effect was recorded against infection with M. avium, and M. kansasii; by contrast no effect was noted against M. simiae or M. intracellulare. The prophylactic effects of BCG were demonstrated regardless of whether vaccination was given by the intravenous or aerogenic routes. These findings support the hypothesis that BCG vaccination, if given prior to contact, can provide some degree of protection against certain non-tuberculous mycobacterial infections.

Animals↗
PubMed1984

Acquired immunity to heavy infection with Mycobacterium bovis bacillus Calmette-Guérin and its relationship to the development of nonspecific unresponsiveness in vitro.

Mice heavily infected with Mycobacterium bovis bacillus Calmette-Guérin (BCG) rapidly generated an acquired cellular immune response to this infection, as characterized primarily by the emergence of a splenic T-cell population capable of passively transferring substantial levels of adoptive protection against a challenge infection with M. tuberculosis. The emergence of this protective T-cell population was temporally associated with considerable levels of DNA synthesis in vivo in both the spleen and liver, and with the development of an acquired capacity within the animal to express very high levels of nonspecific resistance to secondary intracellular bacterial infection. Concomitant with the emergence of this acquired response, splenic T cells from infected animals became severely unresponsive to blastogenic in vitro stimulation with the mitogen phytohemagglutinin, and possessed the capacity to suppress the responsiveness of normal T cells in cocultures. Both the unresponsiveness of T cells from infected mice and their immunosuppressive activity in vitro could be essentially ablated by supplementation of the tissue culture medium with a supernatant containing very high titers of the T-cell growth factor interleukin 2 (IL-2). Furthermore, T cells harvested from these animals at the peak of in vitro unresponsiveness exhibited a substantial capacity to absorb or consume IL-2 from IL-2-containing supernatants. It is hypothesized, on the basis of these findings, that mice heavily infected with BCG acquire an IL-2-dependent T-cell population within the spleen in response to this infection, and that the observed in vitro blastogenic unresponsiveness of spleen cells which contain this population may be an artefactual effect arising from the reduction or consumption of available IL-2 within the sustaining culture medium. The relevance of these findings is discussed with particular regard to clinical situations, such as lepromatous leprosy, in which restorative strategies involving the in vivo use of IL-2 are presently being postulated.

Animals↗
PubMed1984

Effect of mycobacterium bovis (BCG) infection on the kinetics of the mononuclear cell response within the lung.

Specific pathogen-free LBN rats were parabiotically linked and the monocyte donor animal was labeled with multiple pulses of tritiated thymidine (1 microCi/g body weight). The right-hand (recipient) rat lungs were infected with 10(5) viable Mycobacterium bovis (BCG) Pasteur by the intravenous, aerogenic, or intratracheal routes. Control animals received heat-killed BCG or saline only, given intratracheally. The BCG infection resulted in a ten-fold increase in the number of heavily labeled, blood-derived monocytes recovered 24 hr later in the lung lavage fluid. The percentage of labeled cells peaked on day 3 and then declined slowly. Introduction of heat-killed BCG into the lung produced a smaller mononuclear cell influx but a marked polymorphonuclear phagocyte response that persisted for several days. The labeled monocyte counts for the infected recipient rat lung washouts were five to ten times those for the uninfected donor parabiont, except when the aerogenic infection route was used, when both donor and recipient rats were equally infected and both showed substantial increases in labeled monocytes in the lung washouts.

Animals↗
PubMed1984

Adoptive protection of the Mycobacterium tuberculosis-infected lung. Dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hypersensitivity to tuberculin.

Adoptive transfer of protective immunity to an aerogenic infection with the facultative intracellular bacterium Mycobacterium tuberculosis was mediated by a population of T cells acquired in the spleen of donor mice at the height of the primary cell-mediated immune response to an immunizing infection with M. bovis bacillus Calmette-Guerin. Successful adoptive immunotherapy was ablated by prior exposure of immune donor cells to ionizing radiation or by treatment of these cells with antibody raised against the Ly-2 marker. In contrast, however, the capacity of immune donor cells to passively transfer delayed-type hypersensitivity (DTH) responses to tuberculin was unaffected by prior treatment with antibody to Ly-2, but was completely ablated by treatment by antibody to Ly-1. These results indicate, that DTH and protective anti-tuberculous immunity are dissociable phenomena, mediated by separate populations of T lymphocytes.

Animals↗
PubMed1984

Immune response to atypical mycobacteria: immunocompetence of heavily infected mice measured in vivo fails to substantiate immunosuppression data obtained in vitro.

The results of in vitro experiments designed to measure the immunocompetence of mice heavily infected with the atypical mycobacterial pathogens Mycobacterium avium and Mycobacterium simiae were compared with the results of experiments which used in vivo approaches. Blastogenic responsiveness in vitro both to mitogen and to alloantigen was severely depressed in the heavily infected mice; this responsiveness could be restored by removal of an inhibitory Thy-1.2-, nylon wool-adherent cell population. No evidence was found to support the previous contention that suppressor T cells may play a role in the inhibition of this responsiveness. These results were then compared with experiments which measured the ability of the infected animal to elicit a delayed-type hypersensitivity response to sheep erythrocytes in vivo. However, although delayed-type hypersensitivity responses in vivo were also depressed, evidence was obtained which suggested that this unresponsiveness was due to inadequate sensitization of T cells, possibly due to catabolism of antigen, rather than due to the influence of an active, immunosuppressive mechanism. Finally, despite the severely depressed ability of cells from infected mice to respond to alloantigenic stimulation in vitro, infected animals were fully able to cause the regression of a tumor implant in vivo.

Animals↗
PubMed1984

Efficacy of Mycobacterium bovis BCG vaccination in mice undergoing prior pulmonary infection with atypical mycobacteria.

The efficacy of Mycobacterium bovis BCG immunization in mice with established pulmonary infections caused by atypical mycobacteria was studied. In all four strains of Mycobacterium tested (M. kansasii, M. simiae, M. avium, and M. scrofulaceum), intravenous inoculation with 10(6) BCG had no discernible effect upon the course of atypical mycobacterial infection within the lungs; despite this, however, all BCG-vaccinated groups of mice were fully resistant to a subsequent acute aerogenic challenge with M. tuberculosis H37Rv, regardless of the presence of the pulmonary atypical mycobacterial infections. Furthermore, animals infected with M. kansasii, M. simiae, or M. avium but not vaccinated with BCG expressed considerable antituberculous resistance within the lungs, resulting in significant prolonged survival of these animals. The relevance of these findings to the expression of antituberculous resistance in human populations in areas in which atypical mycobacteria are endemic and the failure of these findings to support the hypothesis that prior contact with atypical mycobacteria might in some way jeopardize or interfere with the efficacy of subsequent BCG vaccination are discussed.

Animals↗
PubMed1984

Passive transfer of tuberculin sensitivity from anergic mice.

Mice heavily infected with Mycobacterium bovis BCG rapidly became anergic to cutaneous injection with tuberculin. Evidence is presented suggesting that this anergy reflects an adaptive physiological change within the host in which antigen-reactive Thy-1.2+ cells become sequestered in central lymphoid tissues, with a concomitant reduction in the circulating pool. No evidence could be provided to support the suggestion that anergy was a consequence of an acquired immunosuppressive mechanism.

Animals↗
PubMed1984

Adoptive transfer of acquired resistance to Mycobacterium kansasii by T cells harvested from chronically-infected mice.

Growth of Mycobacterium kansasii in intravenously infected mice ceases when the spleen cells express an enhanced non-specific resistance to a secondary challenge. Mice inoculated with 10(6) CFU M. kanasii 1203 develop a population of splenic T cells which are able to transfer protection passively to sublethally-irradiated syngeneic recipients when challenged with M. kansasii. Although the T-cell activated macrophages were unable to eliminate the mycobacteria from the spleen, they were able to prevent further growth of the organism in vivo. When mice which lack T cells (congenitally athymic, or 'nude' mice) were infected with M. kansasii, the cellular defences were unable to halt the progressive growth of the challenge organisms within the tissues. When normal mice were inoculated with large numbers of viable M. kansasii 1203 (up to 5 X 10(7) CFU), the activated macrophages within the spleen were capable of limiting the further growth of the bacterial population in vivo, but with no T-cell response capable of adoptively immunizing naive recipients against a secondary M. kansasii challenge. Thus, it seems likely that M. kansasii can induce the formation of activated macrophages by two separate mechanisms: one is a T-cell dependent process which occurs in mice inoculated with moderate doses (10(6) CFU) of M. kansasii, while the other is T-cell independent and occurs when a large infectious inoculum is employed.

Animals↗
PubMed1984

Effect of aztreonam on the growth of Pasteurella multocida in the lung.

Specific-pathogen-free ICR mice were infected aerogenically with Pasteurella multocida and, beginning 1 hour later, were treated with aztreonam (50 mg/kg of body weight). The number of viable bacilli in the lungs, liver, and spleen were determined at intervals for up to 36 hours. Aztreonam was bactericidal for growing bacilli in vitro and, when injected 1 and 5 hours after aerogenic exposure, provided greater than 80% protection after dosage at the level of 12.5 mg/kg. Below this dosage level, viable organisms persisted in the lungs and the spleen and many of the minimally treated mice eventually died of pasteurellosis. The survivors developed active immunity as a result of the continued sublethal infection. Aztreonam protects mice against an aerogenic infection with highly virulent P multocida and may be useful in the prevention and treatment of pasteurellosis in cattle.

Animals↗