Objective and Design: To determine the alpha-2macroglobulin (alpha2M) levels in mice during acute... more Objective and Design: To determine the alpha-2macroglobulin (alpha2M) levels in mice during acute and chronic inflammatory responses. Materials and Methods: Inflammation was induced by one of the following stimuli: carrageenin, zymosan, lipopolysacharide, thioglycollate, bacilli Calmette Guerin, PPD (in preimmunized and non-immunized animals) and tumor cells. The concentration of alpha2M was determined in plasma or peritoneal liquid by electroimmunoassay. Results: In all the treatments employed, the plasma levels of alpha2M were higher than in untreated animals. This increase varied from 9%, 24 h after injection up a maximum of 66% 72 h post-injection. When compared to animals injected only with saline, the increases were significant 48 h after treatment with either zymosan or LPS, and 72 h after treatment with either thioglycollate or carrageenin. Treatment with BCG triggers an increase in alpha2M levels after 24 h (18.60%) and 48 h (27.90%). Immunized mice presented higher levels of this protein than non-immunized animals after challenge with PPD. The growth of Ehrlich tumor cells in the peritoneal cavity was directly correlated with the local levels of alpha2M which increased 3.5 fold, 10 days after injection. Conclusions: These results strongly indicate that in mice, the concentration of alpha2M can increase during acute and chronic inflammatory reactions with kinetics dependent on the particular kind of inflammatory agent.
The pathogenicity and immunogenicity of six recently isolated Paracoccidioides brasiliensis sampl... more The pathogenicity and immunogenicity of six recently isolated Paracoccidioides brasiliensis samples derived from patients presenting distinct and well defined clinical forms of paracoccidioidomycosis (PCM) were compared as to their virulence, tropism to different organs and ability to induce specific cellular and humoral immune response in susceptible (BIO.A) inbred mice. Isolates Pb44 and Pb47 were obtained from acute cases, Pb5O from a chronic severe form, Pb45 from a chronic moderate case and both Pb56 and Pb57 from chronic mild forms of PCM. Pathogenicity and tropism of each fungal sample were evaluated by LD50% estimation, examination of gross lesions on various organs at 2, 4, 12 and 16 weeks post-infection, and by colony-forming unit (CFU) counts in the lungs at week 16 post-infection of mice. Fungal tropism in human PCM and in B1O.A mice was always dissociated. A well defined relationship between virulence of the fungal sample and the clinical findings of the correspondent patient was not evident, although a tendency to higher LD50% and less intense paracoccidioidic lesions was observed in mice infected with Pb56 and Pb57. The specific DTH response patterns varied according to the infectant sample, but positive DTH reactions at the beginning of the infection and a tendency to anergy or low DTH responses at week 12 and/or week 16 post-infection were always observed. A correspondence between the DTH response in humans and in mice was noticeable only when the isolates from the most benign cases (Pb56 and Pb57) were considered. The specific antibody patterns in mice and in the correspondent patients were also not analogous. Collectively, these results indicate that an association between the fungal pathogenicity and immunogenicity in the human disease and in susceptible mice was discernible only when isolates obtained from very mild cases (Pb56 and Pb57) were considered. Keywords paracoccidioidomycosis isogenic murine model fungal virulence antibody response DTH reactions
Células envolvidas na resposta imunológica Na primeira e segunda parte dessa série a respeito dos... more Células envolvidas na resposta imunológica Na primeira e segunda parte dessa série a respeito dos termos, abreviações e acrônimos usados com freqüência em imunologia, apresentamos uma visão geral sobre a imunologia, sua importância e relações com outras áreas das ciências biomédicas. Discutimos alguns tópicos, como tolerância e reconhecimento do próprio e do não-próprio, inflamação, imunidade inata e adquirida enfatizando os mecanismos imunológicos e seu funcionamento orquestrado, que leva a respostas imu-nológicas eficazes. Vimos também que existem duas formas principais de imunidade adquirida (ou específica): a imunidade humoral basicamente mediada por anticorpos e a imunidade mediada por células, na qual os linfócitos respondedores são os linfócitos T. Os anticorpos mediadores das respostas humorais específicas são produzidos por células denominadas plasmócitos. Os plasmócitos derivam de linfócitos B que se tornam ativados após a interação com antígenos e capazes de produzir
No intuito de escolher entre métodos de concentração, aplicáveis ao LCR, aquele que, não provocan... more No intuito de escolher entre métodos de concentração, aplicáveis ao LCR, aquele que, não provocando desnaturação de proteínas, seja o mais exato, preciso e de fácil aplicação em laboratórios de rotina, foram estudados quatro procedimentos: diálise contra solução de goma-arábica, centrífugo-ultrafiltração, absorção de substâncias de baixo peso molecular por gel seco de poliacrilamida e ultrafiltração sob pressão positiva. Concluiu-se que a diálise contra solução de goma-arábica, por ser preciso, relativamente exato, simples e pouco oneroso, é o mais satisfatório dentre os métodos estudados.
The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitr... more The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitro (growth curve determination) and in vivo (pathogenicity to sensitive inbred mice) criteria. Strains Pb 18 and Pb 265 which behaved similarly in vitro, showing low counts of fungi and long mean generation times, were respectively the most and the least pathogenic strains. Strains Pb 2052 and IVIC Pb 267, which grow abundantly in vitro were, respectively virulent and avirulent. Strains Pb SN and IVIC Pb 9 behaved similarly both in vitro and in vivo displaying an intermediate pattern of virulence and growing conditions.
The specific delayed-type hypersensitivity (DTH) response was evaluated in resistant (A/SN) and s... more The specific delayed-type hypersensitivity (DTH) response was evaluated in resistant (A/SN) and susceptible (B10.A) mice intraperitoneally infected with yeasts from a virulent (Pbl8) or from a non-virulent (Pb265) Paracoccidioides brasiliensis isolates. Both strains of mice were footpad challenged with homologous antigens. Pb18 infected A/SN mice developed an evident and persistent DTH response late in the course of the disease (90th day on) whereas B10.A animals mounted a discrete and ephemeral DTH response at the 14th day post-infection. A/SN mice infected with Pb265 developed cellular immune responses whereas B10.A mice were almost always anergic. Histological analysis of the footpads of infected mice at 48 hours after challenge showed a mixed infiltrate consisting of predominantly mononuclear cells. Previous infection of resistant and susceptible mice with Pb18 did not alter their DTH responses against heterologous unrelated antigens (sheep red blood cells and dinitrofluorobenzene) indicating that the observed cellular anergy was antigen-specific. When fungal related antigens (candidin and histoplasmin) were tested in resistant mice, absence of cross-reactivity was noted. Thus, specific DTH responses against P. brasiliensis depend on both the host's genetically determined resistance and the virulence of the fungal isolate.
Female mice were fed a low fluoride diet (0.1 to 0.3 ppm fluoride) plus drinking water containing... more Female mice were fed a low fluoride diet (0.1 to 0.3 ppm fluoride) plus drinking water containing 0, 50, 100 or 200 ppm fluoride as sodium fluoride. Toxic effects of fluoride were evidenced by retarded growth and impaired reproduction in mice with intakes of 100 and 200 ppm fluoride, and the higher level resulted in a high mortality rate (50% deaths in 5 weeks). Mice with a low fluoride intake developed signs of fluorine deficiency, with a progressive development of infertility in two suc cessive generations. Growth rate and litter size were not affected by the low fluoride intake, but the percentage of mice producing litters was lower, and the age at delivery of the first litter was greater than in mice receiving 50 ppm fluoride.
... HH Messer, WD Armstrong, and Leon Singer Department of Biochemistry (Health Sciences), Univer... more ... HH Messer, WD Armstrong, and Leon Singer Department of Biochemistry (Health Sciences), University ... DE-01850, National Institute of Dental Research, Bethesda, Maryland 20014. ... Fluoride concentrations of 0.007% of the ash (Low ~luoride Group), 0,041% (Moderate Fluoride ...
... mm of Page 2. 544 ELIN, ARMSTRONG, AND SINGER 36Cl ... fluids. Morris and O'Dell (10... more ... mm of Page 2. 544 ELIN, ARMSTRONG, AND SINGER 36Cl ... fluids. Morris and O'Dell (10) found no significant changes in bone calcium and phosphorus concentrations after 30 days of magnesium deficiency in the guinea pig. In ...
We have developed a murine model of pulmonary infection by Paracoccidioides brasiliensis in which... more We have developed a murine model of pulmonary infection by Paracoccidioides brasiliensis in which resistance was associated with immunological activities governed by gamma interferon (IFN-gamma). To better characterize this model, we measured type 1 and type 2 cytokines in the lungs and investigated the effect of endogenous IFN-gamma depletion by monoclonal antibodies in the course of infection of susceptible (B10.A) and resistant (A/Sn) mice. At weeks 4 and 8 after infection, lungs from susceptible animals presented levels of IFN-gamma, interleukin-4 (IL-4), IL-5, and IL-10 higher than those in resistant mice. In both mouse strains, neutralization of endogenous IFN-gamma induced exacerbation of the pulmonary infection, earlier fungal dissemination to the liver and spleen, impairment of the specific cellular immune response resulting in significantly lower delayed-type hypersensitivity reactions, and increased levels of immunoglobulin G1 (IgG1)- and IgG2b-specific antibodies. Histop...
Female mice maintained on a low fluoride diet over two generations showed a progressive decline i... more Female mice maintained on a low fluoride diet over two generations showed a progressive decline in litter production. Mice receiving the same diet supplemented with fluoride reproduced normally and at consistent intervals. Addition of fluoride to the intake of females with demonstrated impaired fertility restored their reproductive capacity.
The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitr... more The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitro (growth curve determination) and in vivo (pathogenicity to sensitive inbred mice) criteria. Strains Pb 18 and Pb 265 which behaved similarly in vitro, showing low counts of fungi and long mean generation times, were respectively the most and the least pathogenic strains. Strains Pb 2052 and IVIC Pb 267, which grow abundantly in vitro were, respectively virulent and avirulent. Strains Pb SN and IVIC Pb 9 behaved similarly both in vitro and in vivo displaying an intermediate pattern of virulence and growing conditions.
The yeast phase of ten P. brasiliensis isolates were studied to characterize their growth pattern... more The yeast phase of ten P. brasiliensis isolates were studied to characterize their growth pattern, morphology and ultrastructure. Growth curves were determined after counts of total and viable fungi units (FU) during 20 days. Three growth patterns were observed: slow, reaching approximately 10-30 x 106 FU/tube (Pb 18, Pb 265 and PB 2); intermediate, reaching 60-150 • 106 FU/tube (IVIC Pb 9, IVIC Pb 267, Pb SN, Pb Vitor and Pb Campo Grande) and fast, reaching 180-370 x 106 FU/tube (Pb 2052 and Pb 192). The highest percentage of viable cells occurred on the 6th day of culture for Pb 192, Pb Campo Grande, Pb 2052 and IVIC Pb 9; on the 8th day for Pb Vitor, Pb SN, Pb 18 and IVIC Pb 267; on the 10th day for Pb 265 and on the 12th day of culture for Pb 2. Mean generation times varied from approximately 21.2 (Pb 2052) to 102.6 hours (Pb 265).
The effect of macrophage blockade on the natural resistance and on the adaptative immune response... more The effect of macrophage blockade on the natural resistance and on the adaptative immune response of susceptible (B 10.D2/oSn) and resistant (A/Sn) mice to Paracoccidioides brasiliensis infection was investigated. B 10.D2/oSn and A/Sn mice previously injected with colloidal carbon were infected ip with yeast cells to determine the 50% lethal dose, and to evaluate the anatomy and histopathology, macrophage activation, antibody production and DTH reactions. Macrophage blockade rendered both resistant and susceptible mice considerably more susceptible to infection, as evidenced by increased mortality and many disseminated lesions. P. brasiliensis infection and/or carbon treatment increased the ability of macrophages from resistant mice to spread up to 25 days after treatment. In susceptible mice the enhanced spreading capacity induced by carbon treatment was impaired at all assayed periods except at 1 week after infection. Macrophage blockade enhanced DTH reactions in resistant mice, but did not alter these reactions in susceptible mice, which remained anergic. To the contrary, macrophage blockade enhanced specific antibody production by susceptible mice, but did not affect the low levels produced by resistant mice. The effect of macrophage blockade confirms the natural tendency of resistant animals to mount DTH reactions in the course of the disease and the preferential antibody response developed by susceptible mice after P. brasiliensis infection. On the whole, macrophage functions appear to play a fundamental role in the natural and acquired resistance mechanisms to P. brasiliensis infection.
Objective and Design: To determine the alpha-2macroglobulin (alpha2M) levels in mice during acute... more Objective and Design: To determine the alpha-2macroglobulin (alpha2M) levels in mice during acute and chronic inflammatory responses. Materials and Methods: Inflammation was induced by one of the following stimuli: carrageenin, zymosan, lipopolysacharide, thioglycollate, bacilli Calmette Guerin, PPD (in preimmunized and non-immunized animals) and tumor cells. The concentration of alpha2M was determined in plasma or peritoneal liquid by electroimmunoassay. Results: In all the treatments employed, the plasma levels of alpha2M were higher than in untreated animals. This increase varied from 9%, 24 h after injection up a maximum of 66% 72 h post-injection. When compared to animals injected only with saline, the increases were significant 48 h after treatment with either zymosan or LPS, and 72 h after treatment with either thioglycollate or carrageenin. Treatment with BCG triggers an increase in alpha2M levels after 24 h (18.60%) and 48 h (27.90%). Immunized mice presented higher levels of this protein than non-immunized animals after challenge with PPD. The growth of Ehrlich tumor cells in the peritoneal cavity was directly correlated with the local levels of alpha2M which increased 3.5 fold, 10 days after injection. Conclusions: These results strongly indicate that in mice, the concentration of alpha2M can increase during acute and chronic inflammatory reactions with kinetics dependent on the particular kind of inflammatory agent.
The pathogenicity and immunogenicity of six recently isolated Paracoccidioides brasiliensis sampl... more The pathogenicity and immunogenicity of six recently isolated Paracoccidioides brasiliensis samples derived from patients presenting distinct and well defined clinical forms of paracoccidioidomycosis (PCM) were compared as to their virulence, tropism to different organs and ability to induce specific cellular and humoral immune response in susceptible (BIO.A) inbred mice. Isolates Pb44 and Pb47 were obtained from acute cases, Pb5O from a chronic severe form, Pb45 from a chronic moderate case and both Pb56 and Pb57 from chronic mild forms of PCM. Pathogenicity and tropism of each fungal sample were evaluated by LD50% estimation, examination of gross lesions on various organs at 2, 4, 12 and 16 weeks post-infection, and by colony-forming unit (CFU) counts in the lungs at week 16 post-infection of mice. Fungal tropism in human PCM and in B1O.A mice was always dissociated. A well defined relationship between virulence of the fungal sample and the clinical findings of the correspondent patient was not evident, although a tendency to higher LD50% and less intense paracoccidioidic lesions was observed in mice infected with Pb56 and Pb57. The specific DTH response patterns varied according to the infectant sample, but positive DTH reactions at the beginning of the infection and a tendency to anergy or low DTH responses at week 12 and/or week 16 post-infection were always observed. A correspondence between the DTH response in humans and in mice was noticeable only when the isolates from the most benign cases (Pb56 and Pb57) were considered. The specific antibody patterns in mice and in the correspondent patients were also not analogous. Collectively, these results indicate that an association between the fungal pathogenicity and immunogenicity in the human disease and in susceptible mice was discernible only when isolates obtained from very mild cases (Pb56 and Pb57) were considered. Keywords paracoccidioidomycosis isogenic murine model fungal virulence antibody response DTH reactions
Células envolvidas na resposta imunológica Na primeira e segunda parte dessa série a respeito dos... more Células envolvidas na resposta imunológica Na primeira e segunda parte dessa série a respeito dos termos, abreviações e acrônimos usados com freqüência em imunologia, apresentamos uma visão geral sobre a imunologia, sua importância e relações com outras áreas das ciências biomédicas. Discutimos alguns tópicos, como tolerância e reconhecimento do próprio e do não-próprio, inflamação, imunidade inata e adquirida enfatizando os mecanismos imunológicos e seu funcionamento orquestrado, que leva a respostas imu-nológicas eficazes. Vimos também que existem duas formas principais de imunidade adquirida (ou específica): a imunidade humoral basicamente mediada por anticorpos e a imunidade mediada por células, na qual os linfócitos respondedores são os linfócitos T. Os anticorpos mediadores das respostas humorais específicas são produzidos por células denominadas plasmócitos. Os plasmócitos derivam de linfócitos B que se tornam ativados após a interação com antígenos e capazes de produzir
No intuito de escolher entre métodos de concentração, aplicáveis ao LCR, aquele que, não provocan... more No intuito de escolher entre métodos de concentração, aplicáveis ao LCR, aquele que, não provocando desnaturação de proteínas, seja o mais exato, preciso e de fácil aplicação em laboratórios de rotina, foram estudados quatro procedimentos: diálise contra solução de goma-arábica, centrífugo-ultrafiltração, absorção de substâncias de baixo peso molecular por gel seco de poliacrilamida e ultrafiltração sob pressão positiva. Concluiu-se que a diálise contra solução de goma-arábica, por ser preciso, relativamente exato, simples e pouco oneroso, é o mais satisfatório dentre os métodos estudados.
The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitr... more The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitro (growth curve determination) and in vivo (pathogenicity to sensitive inbred mice) criteria. Strains Pb 18 and Pb 265 which behaved similarly in vitro, showing low counts of fungi and long mean generation times, were respectively the most and the least pathogenic strains. Strains Pb 2052 and IVIC Pb 267, which grow abundantly in vitro were, respectively virulent and avirulent. Strains Pb SN and IVIC Pb 9 behaved similarly both in vitro and in vivo displaying an intermediate pattern of virulence and growing conditions.
The specific delayed-type hypersensitivity (DTH) response was evaluated in resistant (A/SN) and s... more The specific delayed-type hypersensitivity (DTH) response was evaluated in resistant (A/SN) and susceptible (B10.A) mice intraperitoneally infected with yeasts from a virulent (Pbl8) or from a non-virulent (Pb265) Paracoccidioides brasiliensis isolates. Both strains of mice were footpad challenged with homologous antigens. Pb18 infected A/SN mice developed an evident and persistent DTH response late in the course of the disease (90th day on) whereas B10.A animals mounted a discrete and ephemeral DTH response at the 14th day post-infection. A/SN mice infected with Pb265 developed cellular immune responses whereas B10.A mice were almost always anergic. Histological analysis of the footpads of infected mice at 48 hours after challenge showed a mixed infiltrate consisting of predominantly mononuclear cells. Previous infection of resistant and susceptible mice with Pb18 did not alter their DTH responses against heterologous unrelated antigens (sheep red blood cells and dinitrofluorobenzene) indicating that the observed cellular anergy was antigen-specific. When fungal related antigens (candidin and histoplasmin) were tested in resistant mice, absence of cross-reactivity was noted. Thus, specific DTH responses against P. brasiliensis depend on both the host's genetically determined resistance and the virulence of the fungal isolate.
Female mice were fed a low fluoride diet (0.1 to 0.3 ppm fluoride) plus drinking water containing... more Female mice were fed a low fluoride diet (0.1 to 0.3 ppm fluoride) plus drinking water containing 0, 50, 100 or 200 ppm fluoride as sodium fluoride. Toxic effects of fluoride were evidenced by retarded growth and impaired reproduction in mice with intakes of 100 and 200 ppm fluoride, and the higher level resulted in a high mortality rate (50% deaths in 5 weeks). Mice with a low fluoride intake developed signs of fluorine deficiency, with a progressive development of infertility in two suc cessive generations. Growth rate and litter size were not affected by the low fluoride intake, but the percentage of mice producing litters was lower, and the age at delivery of the first litter was greater than in mice receiving 50 ppm fluoride.
... HH Messer, WD Armstrong, and Leon Singer Department of Biochemistry (Health Sciences), Univer... more ... HH Messer, WD Armstrong, and Leon Singer Department of Biochemistry (Health Sciences), University ... DE-01850, National Institute of Dental Research, Bethesda, Maryland 20014. ... Fluoride concentrations of 0.007% of the ash (Low ~luoride Group), 0,041% (Moderate Fluoride ...
... mm of Page 2. 544 ELIN, ARMSTRONG, AND SINGER 36Cl ... fluids. Morris and O'Dell (10... more ... mm of Page 2. 544 ELIN, ARMSTRONG, AND SINGER 36Cl ... fluids. Morris and O'Dell (10) found no significant changes in bone calcium and phosphorus concentrations after 30 days of magnesium deficiency in the guinea pig. In ...
We have developed a murine model of pulmonary infection by Paracoccidioides brasiliensis in which... more We have developed a murine model of pulmonary infection by Paracoccidioides brasiliensis in which resistance was associated with immunological activities governed by gamma interferon (IFN-gamma). To better characterize this model, we measured type 1 and type 2 cytokines in the lungs and investigated the effect of endogenous IFN-gamma depletion by monoclonal antibodies in the course of infection of susceptible (B10.A) and resistant (A/Sn) mice. At weeks 4 and 8 after infection, lungs from susceptible animals presented levels of IFN-gamma, interleukin-4 (IL-4), IL-5, and IL-10 higher than those in resistant mice. In both mouse strains, neutralization of endogenous IFN-gamma induced exacerbation of the pulmonary infection, earlier fungal dissemination to the liver and spleen, impairment of the specific cellular immune response resulting in significantly lower delayed-type hypersensitivity reactions, and increased levels of immunoglobulin G1 (IgG1)- and IgG2b-specific antibodies. Histop...
Female mice maintained on a low fluoride diet over two generations showed a progressive decline i... more Female mice maintained on a low fluoride diet over two generations showed a progressive decline in litter production. Mice receiving the same diet supplemented with fluoride reproduced normally and at consistent intervals. Addition of fluoride to the intake of females with demonstrated impaired fertility restored their reproductive capacity.
The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitr... more The yeast-like forms of six P. brasiliensis strains were characterized and compared using in vitro (growth curve determination) and in vivo (pathogenicity to sensitive inbred mice) criteria. Strains Pb 18 and Pb 265 which behaved similarly in vitro, showing low counts of fungi and long mean generation times, were respectively the most and the least pathogenic strains. Strains Pb 2052 and IVIC Pb 267, which grow abundantly in vitro were, respectively virulent and avirulent. Strains Pb SN and IVIC Pb 9 behaved similarly both in vitro and in vivo displaying an intermediate pattern of virulence and growing conditions.
The yeast phase of ten P. brasiliensis isolates were studied to characterize their growth pattern... more The yeast phase of ten P. brasiliensis isolates were studied to characterize their growth pattern, morphology and ultrastructure. Growth curves were determined after counts of total and viable fungi units (FU) during 20 days. Three growth patterns were observed: slow, reaching approximately 10-30 x 106 FU/tube (Pb 18, Pb 265 and PB 2); intermediate, reaching 60-150 • 106 FU/tube (IVIC Pb 9, IVIC Pb 267, Pb SN, Pb Vitor and Pb Campo Grande) and fast, reaching 180-370 x 106 FU/tube (Pb 2052 and Pb 192). The highest percentage of viable cells occurred on the 6th day of culture for Pb 192, Pb Campo Grande, Pb 2052 and IVIC Pb 9; on the 8th day for Pb Vitor, Pb SN, Pb 18 and IVIC Pb 267; on the 10th day for Pb 265 and on the 12th day of culture for Pb 2. Mean generation times varied from approximately 21.2 (Pb 2052) to 102.6 hours (Pb 265).
The effect of macrophage blockade on the natural resistance and on the adaptative immune response... more The effect of macrophage blockade on the natural resistance and on the adaptative immune response of susceptible (B 10.D2/oSn) and resistant (A/Sn) mice to Paracoccidioides brasiliensis infection was investigated. B 10.D2/oSn and A/Sn mice previously injected with colloidal carbon were infected ip with yeast cells to determine the 50% lethal dose, and to evaluate the anatomy and histopathology, macrophage activation, antibody production and DTH reactions. Macrophage blockade rendered both resistant and susceptible mice considerably more susceptible to infection, as evidenced by increased mortality and many disseminated lesions. P. brasiliensis infection and/or carbon treatment increased the ability of macrophages from resistant mice to spread up to 25 days after treatment. In susceptible mice the enhanced spreading capacity induced by carbon treatment was impaired at all assayed periods except at 1 week after infection. Macrophage blockade enhanced DTH reactions in resistant mice, but did not alter these reactions in susceptible mice, which remained anergic. To the contrary, macrophage blockade enhanced specific antibody production by susceptible mice, but did not affect the low levels produced by resistant mice. The effect of macrophage blockade confirms the natural tendency of resistant animals to mount DTH reactions in the course of the disease and the preferential antibody response developed by susceptible mice after P. brasiliensis infection. On the whole, macrophage functions appear to play a fundamental role in the natural and acquired resistance mechanisms to P. brasiliensis infection.
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