Producción in vitro de interferón gamma en ratones vacunados con ´Mycobacterium habana´ frente a antígenos de Mycobacterium tuberculosis / In vitro interferon gamma production in mice vaccinated with ´Mycobacterium habana´ against Mycobacterium tuberculosis antigens

Introducción: el desarrollo de nuevas vacunas antituberculosas requiere de la caracterización de la respuesta de inmunidad celular, inducida por el nuevo candidato vacunal frente a los antígenos principales de Mycobacterium tuberculosis. Objetivo: determinar el potencial inmunogénico de ´Mycobacterium habana´ TMC-5135, cuando se usa como vacuna subcutánea en ratones Balb/c. Métodos: en este estudio se inocularon subcutáneamente ratones Balb/c con la cepa viva ´Mycobacterium habana´ TMC-5135 y se determinó la producción in vitro de IFN gamma en cultivos celulares de pulmón, bazo y ganglios inguinales estimulados con antígenos solubles totales y el antígeno 85b. Como grupo control se vacunaron ratones con BCG subcepa Phipps. Resultados: particularmente en los ganglios linfáticos inguinales, ambos antígenos indujeron mayor producción de IFN gamma en los ratones vacunados con ´Mycobacterium habana´que con BCG. Conclusiones: los resultados justifican la realización de nuevas investigaciones usando ´Mycobacterium habana´ TMC-5135 como candidato vacunal para prevenir la tuberculosis.

Introduction: development of new antituberculosis vaccines requires the characterization of the cell-mediated immune responses induced by mycobacterial antigens. Objective: to determine the immunogenic potential of ´Mycobacterium habana´ TMC-5135 when using subcutaneous vaccine in Balb/c mice. Methods: in this study, Balb/c mice were inoculated subcutaneously with live ´Mycobacterium habana´ TMC-5135. The production of IFN gamma in cell suspensions obtained from the lungs, the spleen and the lymph nodes after stimulation with mycobacterial antigens Ag85b or culture filtrate antigens (CFA) was recorded. Results: the production of IFN gamma after stimulation with CFA and Ag85b was higher in mice vaccinated with ´M. habana´ than in animals immunized with BCG. Conclusions: these results encourage new research on ´M. habana´ as vaccinal candidate against tuberculosis.

Quantificação dos niveis sericos de anticorpos anti-PGL-I, neopterina e proteina C reativa em pacientes com hanseniase durante a poliquimioterapia / ?

A hanseniase e doença infecciosa, causada pelo Mycobacterium leprae, um parasita intracelular obrigatorio nao cultivavel em meios artificiais. Esta doença pode se manifestar sob amplo espectro clinico, correspondendo a distintos padroes da resposta imunologica do hospedeiro ao M. leprae. Em um polo deste espectro, esta a forma de resistencia ao bacilo, a hanseniase tuberculoide (HT), na qual se desenvolve acentuada resposta imune celular especifica com efetivo controle da mutilaçao bacilar. O outro polo do espectro esta representado pela hanseniase virchoviana (HV), forma de baixa resistencia, em que a resposta imune celular seletivamente falha em eliminar o bacilo do organismo, resultando na disseminaçao da doença. O grupo dimorfo (HD) apresenta manifestaçoes intermediarias variaveis entre HT e HV, de acordo com o grau de resposta imune ao M. leprae. Considerando que na hanseniase existem poucos estudos avaliando os niveis sericos de anticorpos anti-PGL-I, neopterina e proteina C reativa (CRP) no momento do diagnostico e durante o tratamento poliquimioterapico, realizamos este estudo com os sguintes objetivos: A. Avaliar a resposta imune e inflamatoria de pacientes com hanseniase no momento do diagnostico e aos 2, 4, 6 e 12 meses de tratamento com poliquimioterapia (PQT) e nos estados reacionais, mediante a determinaçao dos niveis sericos de anti-PGL-I, de neopterina e de CRP....

Tuberculin and BCG tests.

The tuberculin test is widely used for the diagnosis of tuberculosis in children as it is the only one that provides evidence of infection with M. tuberculosis. Of the tuberculins that are available, the most widely used are PPDS and PPDRT 23, in various strengths. A positive test indicates prior infection with the tubercle bacillus but not necessarily active disease. A positive test may also result from BCG vaccination though the response is usually less than 10 mm and tends to wane with time. In areas with a high prevalence of atypical mycobacteria in the environment, positive reactions may also be due to cross-reactivity. BCG has been recommended by some workers as a diagnostic test but suffers from the disadvantages of low specificity.

Sensitization and reactogenicity of two doses of candidate antileprosy vaccine Mycobacterium w.

M.w vaccine is one of the antileprosy vaccines under test in an ongoing comparative vaccine trial in South India. The objective of the present study was to examine the sensitizing ability, as measured by skin test reactions to Rees' MLSA and lepromin, and reactogenicity of M.w vaccine in the local population. Two doses of M.w, 1 x 10(9) bacilli and 5 x 10(9) bacilli, were used, in two separate studies of 395 and 400 "healthy" individuals aged 1-65 years. In each study, the study subjects received either M.w vaccine or normal saline (control), by random allocation. The results showed that healing of vaccination lesions was uneventful although the healing process was somewhat prolonged with the higher dose. The mean size of lesions was 7.0 mm and 9.5 mm with the low and high doses of the vaccine, respectively. The results also showed that M.w vaccine in a dose of 1 x 10(9) bacilli, failed to induce post-vaccination sensitization as measured by reactions to Rees' MLSA and by Fernandez and Mitsuda reactions to lepromin-A. However, when the dose of the vaccine was increased to 5 x 10(9) bacilli the mean sizes of post-vaccination reactions to Rees' MLSA and lepromin-A (both early and late) were significantly larger in the vaccine group compared to that in the control group. The sensitizing effect attributable to the vaccine was of the order of 1.5 mm to 1.8 mm.

Immune response & modulation of immune response induced in the guinea-pigs by Mycobacterium avium complex (MAC) & M. fortuitum complex isolates from different sources in the south Indian BCG trial area.

A total of 139 guineapigs were used to study the immune response and its modulation induced by Mycobacterium avium complex (MAC) and M. fortuitum complex strains obtained from different sources in the south Indian BCG trial area. The guineapigs were divided into groups and some were directly sensitised/immunised with different MAC strains. M. fortuitum complex strain or BCG and others were sensitised with MAC or M. fortuitum complex and then immunised with BCG. The resulting delayed type hypersensitivity (DTH) response in the different groups of guineapigs was studied by skin tests using PPD-RT23 and PPD-B, and protective response was studied by challenging the guineapigs with a south Indian low virulent strain of M. tuberculosis and enumerating the bacilli in spleen at different points of time. The 3 strains of MAC induced similar low levels of DTH to PPD-RT23 but much higher and varying levels of DTH to PPD-B. MAC strains from soil and sputum induced different levels of immune modulation during subsequent immunisation with BCG on the DTH response to PPD-RT23 and PPD-B. At 2 wk after challenge, 23.8, 81 and 90.5 per cent protection was induced by the standard strain, soil isolate and sputum isolate of MAC, respectively, while 33.3 per cent protection was induced by the M. fortuitum complex strain compared to the protection induced by BCG alone. Prior exposure to MAC or M. fortuitum complex did not have any modulatory effect on the protective immunity due to BCG at this time point. However, at 6 wk after challenge, while the guineapigs immunised with BCG were protected, modulation of the protective response resulting from BCG was observed in the guineapigs sensitised with MAC and M. fortuitum from soil.

La intradermo-reacción con sensitinas en población paraguaya / The intradermal-reaction with sensitins in paraguayan population

La aplicación de Sensitinas utilizando la Intradermo-reacción de Mantoux nos permite investigar el perfil inmunológico de un organismo frente a determinadas cepas de Micobacterias no tuberculosas. La tasa de infección por estas Micobacterias no había sido estudiada hasta hoy en la población paraguaya, aunque nosotros ya habíamos comunicado el primer caso nacional de enfermedad por Mycobacterium fortuitum. La presente investigación nos permitió comprobar, sobre 210 pacientes estudiados, una tasa de reactores significativos de 24,7 por ciento a las sensitinas utilizadas, con neto predominio de reactores a M. avium y fortuitum

Maternal fetal immunological relationship particularly mycobacterial immunity.

Thirty-nine paired maternal and cord blood from normal full term deliveries were tested for lymphocyte function by proliferative response to mitogens-Phytohemagglutinin-P (PHA) and Poke week mitogens (PWM). Monocyte function was assessed by the ability of the monocytes to release hydrogen peroxide (H2O2) in response to standard stimulus (PMA). Mycobacterial immunity was assessed by lymphocyte proliferative response to purified proteins derivative (PPD) and IgM and IgG antibody response to H37Rv and 5 atypical mycobacteria. Lymphocyte functions were significantly lower in cord blood (PHA 20.6, PWM 21.2) as compared with maternal blood (PHA 65.8, PWM 37.8). The capacity of fetal monocytes to release H2O2 was comparable to maternal monocytes. The mean proliferative response of fetal lymphocytes to tubercular protein (PPD) was 0.67 as compared (P less than 0.01) to maternal lymphocytes (3.79). Nearly 86% of the cord blood did not show any response to PPD. None of the cord blood showed IgM antibody response to H37Rv nor to any of the range of 5 atypical mycobacteria though maternal IgM and IgG response was present. There was only passive transfer of IgG antibody from mother to fetus. Hence, though this is a highly endemic area for atypical mycobacteria and M. tuberculosis, there was apparently no transplacental transfer of antigen in normal sensitized mothers.

Draining lymph node enlargement produced by immunogenic strains of cultivable mycobacteria.

Lymphnode enlargement produced by strains of mycobacteria have a direct bearing on the immunogenicity characteristics. Two strains of mycobacteria namely M. habana TMC 5135 and M. marinum (SATO) have been studied for their property to produce enlargement of draining lymphnodes besides other cell-mediated immune responses. Both the strains are capable of producing the enlargements of inguinal and popliteal lymphnodes which is very significant. The enlargements of lymphnodes have been produced by these strains both in the live as well as killed state. Possibility of developing these strains as vaccine against leprosy has been discussed.

Possibilidades do G 30 320 no tratamento da hanseniase e da reação leprotica / Possibilities of G 30 320 me the treatment of leprosy and reaction leprosy

Os AA selecionaram doentes de lepra internados no Hospital Colonia Curupaiti e Hopsital Frei Antonio do Estado da Guanabara, Brasil, para experimentação da atividade antilepra do G 30 320. Todos oos pacinetes são da forma lepromatosa graus L1, L2,L3 e dimorfos, classificados nos seguinte Grupos:I - Doentes novos, virgens de tratamentoII - Doentes sulfono-resistentes com lepra progressiva avançadaIII - Doentes sujeitos a reação tipo ENL, talidomido dependentes. Desencadeia-se a reação sempre que se instituti tratamento sulfonico sem a respectiva e continua cobertura com talidomidaIV - Doentes talidomida insensiveis sujeitos a reação de ENI incontrolavel pelos metodos tradicionais inclusive talidomidaA experiencia tem por objetivo a verificação da utilidade do novo produito G 30 320 no controle do desenvvolvimento da Hanseniase e da reação leprotica. O esquema basico de administração tem sido 2 capisulas por dia durante 7 dias reduzindo-se então para l capsula diaria. Cada capsula contem l00 mg. de um derivado anilino aposafraninado G 30 320...