Current knowledge on the structure of lipoarabinomannan (LAM) has resulted primarily from detailed studies on a few selected laboratory strains of Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium smegmatis. Our previous work was the first to report on the salient structural features of M. tuberculosis clinical isolates and demonstrated significant structural variations. A prime effort is to correlate a particular structural characteristic with observed differences in eliciting an immunobiological response, especially in the context of CD1-restricted presentation of LAM to T cells. T cell clones derived from the cutaneous lesions of leprosy patients have been shown to recognize specifically LAM from Mycobacterium leprae and not from M. tuberculosis Erdman or H37Rv. Herein we provide further fine structural data on LAM from M. leprae (LepLAM) and a tuberculosis clinical isolate, CSU20 (CSU20LAM), which was unexpectedly recognized by the supposedly LepLAM-specific CD1-restricted T cell clones. In comparison with the de facto laboratory LAM standard from M. tuberculosis H37Rv (RvLAM), LepLAM derived from in vivo grown M. leprae is apparently simpler in its arabinan architecture with a high degree of exposed, non-mannose-capped termini. On the other hand, CSU20, an ethambutol-resistant clinical isolate, makes a vastly heterogeneous population of LAM ranging from rather small and non-mannose-capped to full-length and fully capped variants. LepLAM and CSU20LAM contain a higher level of succinylation than RvLAM, which, in the context of truncated or less elaborated arabinan, may contribute to selective recognition by T cells. LAM from all species could be resolved into discrete forms by isoelectric focusing based apparently on their arabinan heterogeneity. In the light of our current and more recent findings, we reason that all immunobiological data should be cautiously interpreted and that the actual LAM variants that may be present in vivo during infection and pathogenesis need to be taken into consideration.

Culture filtrate protein 10 (CFP-10) from Mycobacterium tuberculosis is a well-characterized immunodominant 10-kDa protein antigen known to elicit a very potent early gamma interferon response in T cells from M. tuberculosis-infected mice and humans. The sequence of the Mycobacterium leprae homologue of CFP-10 shows only 40% identity (60% homology) at the protein level with M. tuberculosis CFP-10 and thus has the potential for development as a T-or B-cell reactive antigen for specific diagnosis of leprosy. Antisera raised in mice or rabbits against recombinant M. leprae and M. tuberculosis CFP-10 proteins reacted only with homologous peptides from arrays of overlapping synthetic peptides, indicating that there was no detectable cross-reactivity at the antibody level. Sera from leprosy and tuberculosis patients were also specific for the homologous protein or peptides and showed distinct patterns of recognition for either M. leprae or M. tuberculosis CFP-10 peptides. At the cellular level, only 2 of 45 mouse T-cell hybridomas raised against either M. leprae or M. tuberculosis CFP-10 displayed a cross-reactive response against the N-terminal heterologous CFP-10 peptide, the region that exhibits the highest level of identity in the two proteins; however, the majority of peptide epitopes recognized by mouse T-cell hybridomas specific for each protein did not cross-react with heterologous peptides. Coupled with the human serology data, these results raise the possibility that peptides that could be used to differentiate infections caused by these two related microorganisms could be developed. Immunohistochemical staining of sections of M. leprae-infected nude mouse footpads resulted in strongly positive staining in macrophages and dendritic cells, as well as weaker staining in extracellular areas, suggesting that M. leprae CFP-10, like its homologue in M. tuberculosis, is a secreted protein.The number of cases of leprosy worldwide has been reduced dramatically through aggressive World Health Organizationsponsored multidrug therapy, from approximately 10 million cases in 1985 to a little fewer than 700,000 cases today (46-48). However, with the unabated emergence of more than 600,000 new cases per year, there is the possibility that the source of infection is not being addressed (16). The single greatest need in leprosy research is the development of definitive diagnostic tools that identify sources of leprosy and routes of transmission. The recent completion of the genome sequences of both Mycobacterium tuberculosis (8) and Mycobacterium leprae (9) provides an opportunity to identify leprosy-specific antigens that might serve this purpose. A similar comparative approach has allowed identification of genes in the RD1 region that are deleted from Mycobacterium bovis BCG but present in M. tuberculosis and can therefore distinguish between infection with M. tuberculosis and vaccination with BCG (22). Among the deleted antigens are two low-molecular-weight proteins, culture filtrate protein 10 (CFP-10) (Rv3874) and ESAT-6...

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O texto procura refletir acerca do processo de aparição do rosto (Lévinas) da personagem Domingas, no romance Dois Irmãos, de Milton Hatoum. A partir da abordagem filosófica da noção de reconhecimento por autores como Butler, Rancière, Honneth, Voirol e Renault discute-se como, na escrita, Domingas alcança a hospitalidade necessária para existir e resistir à violência e à injúria.

Baeninger, como parte dos requisitos para obtenc;;ao do titulo de Ooutora em Oemografia.Este exemplar corresponde a redac;;ao final da Tese defendida e aprovada pela Comissao Julgadora em 28 /05/2012 .