Inbred C3H mouse substrain differences demonstrated in experimental murine leprosy.
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Biomedical subjects
Publications and source records attributed to M Løvik.
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Delayed-type hypersensitivity was induced in cyclophosphamide-pretreated C3H/TifBom mice by subcutaneous immunization in the thorax with ultrasonicated Mycobacterium lepraemurium bacilli in Freund incomplete adjuvant. Seven weeks after immunization, 2.5 X 10(7) acid-fast M. lepraemurium bacilli suspended in diluted sonicate were injected into one hind footpad, and during the next 6 weeks three additional infections of sonicate were given at intervals into the infected footpad. After each injection a strong local reaction developed, which after the first three injections peaked at 24 h. The kinetics of the reaction was accelerated after the repeat injections. Each time the reaction subsided within 1 week. From 2 days to 11 weeks after the inoculation of bacilli there was a 10-fold increase in bacillary numbers in the footpad and a 3,000-fold increase in the draining popliteal lymph node. The degree of bacillary multiplication was the same in animals which had experienced repeated local reactions and in control animals. Thus, repeated strong delayed-type hypersensitivity reactions to M. lepraemurium antigens apparently were without any measurable effect on the bacillary multiplication. This observation provides further evidence for a dissociation in C3H/TifBom mice between delayed-type hypersensitivity to soluble mycobacterial antigens and protective immunity against mycobacteria. Possible explanations for our findings are discussed.
Upon infection with Mycobacterium lepraemurium (MLM) C3H mice develop a disease that has features in common with lepromatous leprosy in man. Intraperitoneal vaccination with a single dose of BCG four weeks before inoculation with MLM in the footpad significantly reduced the total bacillary load of the animals. In vaccinated animals there was a delay in the dissemination of bacilli to the popliteal lymph node, liver, and spleen. The growth rate of MLM in the footpad and the popliteal lymph node was not altered by BCG vaccination. Reduced dissemination of the bacilli seems to be a sensitive parameter of resistance in murine leprosy. The mechanism of the resistance observed is discussed mainly in relation to non-specific macrophage activation and T-cell mediated responses to cross-reactive antigens.
The immunizing effects of live Mycobacterium lepraemurium (MLM) and bacillary sonic extract (MLMSon) were compared in C57BL mice. MLMSon-immunized mice developed a delayed-type hypersensitivity (DTH) reaction when tested in the footpad with diluted MLMSon. The ability to develop a DTH reaction was transferable with immune cells but not with serum. Footpad testing with live MLM and MLMSon indicated that the specificity of the DTH response induced by MLMSon was different from that induced by infection with live bacilli. Two weeks after footpad inoculation with live MLM, MLMSon-immunized mice developed a strong local reaction to the bacilli. No local reaction developed in these mice after injection of the same number of heat-killed MLM. Studies of bacillary growth after inoculation with live MLM indicated that the bacilli did not multiply in micr previously inoculated with live MLM, but that they multiplied for about 2 weeks in LMLSon-immunized mice versus 4 weeks in the controls. The results suggest that immunization with MLMSon does not by itself induce a protective immune response, but creates a state in which the development of protective immunity is accelerated.
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