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1

Murine models of susceptibility to tuberculosis

100%
Beamer G. L., Turner J.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
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issue 6
469-483
EN
Approximately one third of the world's population is infected with Mycobacterum tuberculosis, yet each year a small proportion of those individuals progress to an active disease state. Early identification and treatment of such individuals is essential to reduce transmission; however, genetic and immunological correlates of disease progression have not been well established in man. The murine model has been a central tool for the elucidation of protective immune mechanisms that are essential for controlling M. tuberculosis infection. Additionally, the study of inbred mice has revealed significant divergence in the susceptibility and disease progression of individual mouse strains to an infection with M. tuberculosis. The continued study of genetically disparate mouse strains has the potential to identify immune mechanisms that correlate with increasing susceptibility to tuberculosis. These mechanisms will be highly applicable to studies in man and assist in the early detection of individuals that are more vulnerable to the development of reactivation tuberculosis.
2

Mannose-binding lectin enhances the attachment and phagocytosis of mycobacteria in vitro

100%
Bonar A., Chmiela M., Rudnicka W., Rozalska B.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
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issue 5
437-441
EN
Phagocytosis is the critical first step in the Mycobacterium (M.) tuberculosis-phagocyte interaction. The process involves microbial ligands and phagocyte surface receptors. It is known that serum mannose-binding lectin (MBL), an innate immune system component, may enhance the uptake of microbes by phagocytic cells and activate the complement system. Since phagocytes are the replicative environment for mycobacteria and, as we described earlier, tuberculosis patients differ from controls in serum MBL level, we asked whether MBL plays a role in promoting M. tuberculosis access to phagocytic cells. To estimate the influence of MBL on the phagocytic process, FITC-labeled Mycobacterium bovis BCG was used as a model bacterium. Neutrophils from healthy individuals were used as phagocytes. Phagocytosis was performed in the presence or absence of recombinant MBL (rMBL; 2 or 20 g/ml). The activation of complement was determined by dot-blot immune assay with monoclonal antibodies against C5b-C9. We showed that phagocytosis of the bacteria was more intensive in the presence of human rMBL. Both attachment and ingestion of mycobacteria were enhanced when MBL and active complement components (fresh serum) were present in the medium. The dot-blot method showed that the bacteria slightly activated complement by themselves. This effect was enhanced in the phagocyte-bacteria co-cultures containing rMBL.It is possible that MBL may serve in vivo as one of the factors facilitating the entry of mycobacteria into phagocytes, pathogen spread, and the establishment of infection.
3

Serodiagnostic efficacy of Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex, ESAT-6, and CFP-10 in patients with active tuberculosis

100%
Kumar G., Dagur P. K., Singh P. K., Shankar H., Yadav V. S., Katoch V. M., Bajaj B., Gupta R., Sengupta U., Joshi B.
Archivum Immunologiae et Therapiae Experimentalis
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2010
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vol. 58
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issue 1
57-65
EN
Elimination of tuberculosis (TB) largely depends upon definitive rapid diagnosis and treatment. Widely used diagnostic tests do not qualify for use in a developing country due to lack of either desired accuracy or their cost. In the present study an enzyme-linked immunosorbent assay was used to evaluate the diagnostic potential of an immuno-dominant 30/32-kDa mycolyl transferase complex (Ag85 complex) and Mycobacterium tuberculosis-specific proteins (ESAT-6 and CFP-10) of the RD1 region. Higher sensitivity (84.1%) with Ag85 complex was observed compared with ESAT-6 (64.9%) and CFP-10 (66%), with almost similar specificity (Ag85: 85.2%, ESAT-6: 88.9%, CFP-10: 85.2%), whereas the individual components of Ag85 complex, i.e. Ag85A, Ag85B, and Ag85C, showed sensitivities of 44.6, 34, and 80.9% and specificities of 55.6, 74.1, and 40.7% respectively. A cocktail of Ag85 complex, ESAT-6, CFP-10, Ag85A, Ag85B, and Ag85C antigens also could not help in increasing either sensitivity (51.1%) or specificity (85.2%). Furthermore, immunoblot analysis using clinical isolates as well as a standard strain (H37Rv) of M. tuberculosis also showed strong reactivity of sera from TB patients to Ag85 complex and, to a lesser extent, also to ESAT-6. To conclude, use of Ag85 complex along with ESAT-6 and CFP-10 seems to be promising in minimizing the heterogeneous sero-responses of adult TB cases.
4

The inflammatory response in M. tuberculosis infection

75%
Toossi Z.
Archivum Immunologiae et Therapiae Experimentalis
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2000
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vol. 48
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issue 5
513-520
EN
Infection with Mycobacterium tuberculosis (MTB) is accompanied by an intense local inflammatory response which may be critical to the pathogenesis of tuberculosis. Activation of components of the innate immune response, such as recruitment of polymorphonuclear (PMN) and mononuclear phagocytes and induction of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), by MTB occurs early after MTB infection, however, may persist as the organism establishes itself within granulomas. MTB and its protein and non-protein components are potent in induction of cytokines and chemokines from PMN and monocytes. This review focuses on the interaction of MTB and the host with regard to activation of the innate immune response. It also attempts to identify the potential impact of this early response on the subsequent pathogenesis of MTB, and its role in development and extent of tuberculosis. Insights into the initiation and persistent of the inflammatory response may allow the application of anti-inflammatory agents as adjuncts in the treatment of tuberculosis.
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