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Biomedical subjects

M J Lefford

Publications and source records attributed to M J Lefford.

At least 37 records · Page 2Linked to original sources
PubMed1978

Induction of cell-mediated immunity to Mycobacterium leprae in mice.

The immune response of mice to armadillo-derived, irradiation-killed Mycobacterium leprae (I-ML) was investigated. Following injection of 100 microgram of I-ML into the left hind footpads of mice, a state of cell-mediated immunity (CMI) was engendered to antigens of M. leprae. The evidence for CMI was as follows: (i) development of delayed-type hypersensitivity to both human tuberculin purified protein derivative and soluble M. leprae antigens; (ii) T-lymphocyte-dependent macrophage activation at the inoculation site; (iii) specific systemic resistance to the cross-reactive species M. tuberculosis; and (iv) immunopotentiation of the delayed-type hypersensitivity response to an unrelated antigen. The CMI induced by I-ML in aqueous suspension was greater than that obtained with the same antigen in water-in-oil emulsion, even though the latter generated a more severe reaction at the site of immunization. I-ML also induced a stronger CMI response than the corresponding dose of heat-killed BCG.

Animals↗
PubMed1978

Relationship between delayed-type hypersensitivity and the progression of Mycobacterium lepraemurium infection.

The relationship between the level of delayed-type hypersensitivity (DTH) and the progression of Mycobacterium lepraemurium infection was examined after inoculation of mice with 10(8) M. lepraemurium in the left hind footpad. The expression of DTH developed over the first 4 weeks of infection, remained high up to week 8, and then dropped to a low level at which it remained for 12 more weeks. The development of DTH was concordant with an initial swelling of the inoculated foot, the appearance of a mononuclear infiltrate at this site, and a prevention of any increase in the number of mycobacteria in this foot and in other tissues studied. A decay of DTH reactivity was associated with a progressive increase in the number of M. lepraemurium initially at the original site of inoculation and subsequently in all other tissues. Although the expression of DTH was lost, adoptive immunization experiments showed that a population of sensitized lymphocytes persisted within host. Further experimentation offered evidence to suggest that the level of systemic antigen may be in part responsible for the loss of DTH reactivity.

Animals↗
PubMed1978

Specific and nonspecific resistance in mice immunized with irradiated Myobacterium leprae.

Following subcutaneous inoculation of irradiated Mycobacterium leprae (I-ML) into the left hind footpad of mice, there was increased resistance to Listeria monocytogenes, indicative of macrophage activation, at the immunization site. In spite of the high level of localized macrophage activation which was proportioned to the immunizing dose of I-ML, no such activity could be demonstrated systemically in these mice, as evidenced by the absence of increased resistance to an intravenous challenge with L. monocytogenes. Under these conditions, I-ML-immunized mice were nonetheless resistant to intravenous infection with either M. tuberculosis or M. bovis BCG, and this immunity was transferred to normal recipients using spleen or lymph node cells. Neonatal thymectomy completely abolished the development of antimycobacterial immunity after vaccination with I-ML, but immunity was restored by an intraperitoneal infusion of syngeneic thymocytes. Systemic nonspecific resistance could be generated in I-ML-immunized mice by an intravenous injection of disrupted I-ML. This study reveals that, after subcutaneous vaccination with I-ML, there is local accumulation of activated macrophages at the inoculation site and a widespread distribution of lymphocytes which are sensitized to mycobacterial antigens. Nonspecific resistance is mediated by the former cells and specific antimycobacterial immunity by the latter.

Animals↗
PubMed1978

Listeria pneumonitis: induction of immunity after airborne infection with Listeria monocytogenes.

After implantation of approximately 10(3) Listeria monocytogenes organisms into the lungs, mice develop an acute pneumonitis with dissemination of infection to a mediastinal lymph node (MedLN), liver, and spleen. The infections in a MedLN and spleen resolve in approximately 7 days, but the lung infection persists for a few days longer. Pneumonitis is accompanied by a lymphoproliferative response in a MedLN and spleen, and immunity to Listeria is conferred adoptively with MedLN and spleen cells but not with mesenteric lymph node cells. Although the spleen appears to be the major repository of sensitized lymphocytes, splenectomized mice combat Listeria pneumonitis as effectively as normal mice. It is concluded that the induction of immunity to lung infection with L. monocytogenes is efficient and that the cause for the rather protracted pneumonitis is due to a defect in the expression of the cell-mediated immunity effector mechanism.

Animals↗
PubMed1978

Host defenses in murine malaria: induction of a protracted state of immunity with a formalin-killed Plasmodium berghei blood parasite vaccine.

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.

Animals↗
PubMed1978

Immunization of mice after airborne infection with various strains of BCG.

The growth of 6 strains of bacillus Calmette-Guérin (BCG) in the lungs of mice was compared after direct implantation into those organs. Bacilli of the Connaught, Pasteur, Phipps, and Tice strains multiplied appreciably in the lungs and disseminated into the spleen In contrast, BCG Birkhaug and Glaxo strains did not replicate in the lungs or spread to the spleen. The immunizing ability of 3 of these strains was examined in more detail. Aerosol infection with BCG Glaxo, Pasteur, or Phipps strains produced resistance to subsequent pulmonary challenge with Mycobacterium tuberculosis RIRv. Such immunity was significantly greater in mice immunized with the Pasteur and Phipps strains and was not attributable to nonspecific resistance. Spleen cells from mice immunized with these 3 strains of BCG conferred similar degrees of immunity to intravenous challenge with M. tuberculosis on syngenic recipients. It was concluded that growth of BCG in the lungs influenced the degree of local immunity but not the degree of systemic immunity.

Aerosols↗
PubMed1978

The lymphocyte mediators of delayed hypersensitivity: the early phase cells.

Inbred rats were immunized with living BCG and lymphocytes which mediate tuberculin DTH and anti-tuberculosis immunity were found 10 days later in the draining lymph nodes, thoracic duct, blood, spleen and acute peritoneal exudates. The lymphocytes that mediated DTH incorporated 3HT in vitro, were large in size, sensitive to vinblastine but relatively resistant to irradiation, and had a short effective lifespan in syngeneic recipients. These properties characterize the cells as short-lived, nonrecirculating immunoblasts. In some experimental situations it was possible to dissociate the expression of DTH and immunity following the transfer of sensitized lymphocytes.

Animals↗
PubMed1977

Development of delayed-type hypersensitivity during Mycobacterium lepraemurium infection in mice.

Various preparations of Mycobacterium lepraemurium were used to elicit delayed-type hypersensitivity in the footpad of mice infected with this organism. With a sonicated preparation of the mycobacterium, a significant increase in footpad swelling was elicited in mice infected with M. lepraemurium 5 weeks previously, but not in BCG-infected animals or uninfected controls. This footpad reaction was shown to peak at 24 h and to be associated with an infiltration of mononuclear cells. The kinetics of footpad swelling, its association with lymphoproliferation, and its dependence on T lymphocytes were each examined. The results support the hypothesis that this is a delayed-type hypersensitivity reaction. The ability to transfer this reactivity to normal mice with cells but not serum offers further confirmation that this hypersensitivity is dependent on cell-mediated immunological mechanisms rather than humoral antibody. The relevance of this to the study of the immunological response of mice to murine leprosy is discussed.

Animals↗
PubMed1977

Suppression of immunity to Mycobacterium lepraemurium infection.

After injection of 10(8) live Mycobacterium lepraemurium (MLM) into the left hind footpad of mice, there is development of local swelling attributable to a granuloma of the cell-mediated immunity type. Concomitant intravenous inoculation of live MLM delays and may even suppress footpad swelling, the effects being proportional to the intravenous dose of organisms. Concomitant footpad infection and intravenous inoculation of 10(9) dead MLM also delays footpad swelling, but over a period of months the feet become excessively swollen. The excessive swelling is due to local enhancement of infection as evidenced by an increase in the number of MLM per footpad. Attempts were made to prevent such immunosuppression by splenectomy or treatment with BCG. Splenectomy was entirely without effect, but 10(7) live BCG administered intravenously 2 to 4 weeks before dead MLM prevented enhancement of infection. The mediator of the immunosuppressive mechanism that results in enhanced infection remains to be elucidated, but it is unlikely to be antibody or immune complexes.

Animals↗
PubMed1977

Induction and expression of immunity after BCG immunization.

The induction and expression of immunity to Mycobacterium tuberculosis after BCG immunization by intravenous, subcutaneous, and pulmonary routes has been investigated in mice. The speed with which protective immunity was engendered was a function of inoculum size; the immunization route was a less influential factor. Tuberculin hypersensitivity varied both with the inoculim size and immunization route, being least after pulmonary immunization. Once immunity was established, a steady state ensued in which the number of sensitized lymphocytes in the spleen was similar, regardless of the route or dose of vaccination. Actively immunized animals controlled intravenous and subcutaneous challenge infections, regardless of the method of vaccination. However, pulmonary challenge was resisted most efficiently by mice immunized by the pulmonary route. Adoptive immunity was well expressed in the spleen only, but the lungs were no more deficient in this regard than the footpad. It is suggested that enhanced immunity in the lungs depends on a population of resident sensitized lymphocytes.

Animals↗
PubMed1977

Induction of cell-mediated immunity to Mycobacterium lepraemurium in susceptible mice.

A mouse strain (CB6) that is highly susceptible to Mycobacterium lepraemurium was infected with 10(8) bacilli into the hind footpad. These mice developed cell-mediated immunity to M. lepraemurium, as expressed by the development of a granulomatous lesion at the site of inoculation in normal but not in T-lymphocyte-depleted mice, a proliferative response in the paracortical zone of the draining lymph node, delayed-type hypersensitivity to a sonic extract of M. lepraemurium, and immunopotentiation of the delayed hypersensitivity response to sheep erythrocytes. Resistance to a second challenge infection with M. lepraemurium was not demonstrated.

Animals↗
PubMed1975

Transfer of adoptive immunity to tuberculosis in mice.

A system is described for studying adoptive immunity to tuberculosis in syngeneic mice. Donor mice were immunized with 10(4) 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 10(4) to 10(5) 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-theta serum plus complement. The sensitized cells were relatively susceptible to both in vitro and in vivo X-irradiation.

Animals↗