Genetic influences on the granulatomous inflammatory response in a murine model of tuberculosis
Başlık:
Genetic influences on the granulatomous inflammatory response in a murine model of tuberculosis
Yazar:
Orrell, Julian M., author.
ISBN:
9780438082830
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (218 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
Only a small proportion of humans exposed to Mycobacterium tuberculosis develop clinical disease. As well as nutrition and general health, host genetic factors are implicated. Possession of a particular allele at one genetic locus may dramatically influence the course of disease in certain individuals and study of these genetic factors can give insight into the pathogenesis of tuberculosis and may lead to the development of more effective vaccines. Genetic factors are most readily studied in animal models of tuberculosis. Both innate resistance and acquired cellular immunity have been studied in congenic strains of mice. This thesis describes one particular aspect of tuberculosis infection in several inbred strains of mice; the granulomatous inflammatory response in the liver and lung following intraperitoneal inoculation with M. tuberculosis, strain H37Rv. The strains of mice used are all innately susceptible to infection (Bcgs) with either a B10 or Balb nonH2 background and variable H-2 haplotype (H-2b, H-2k, H-2d). The extent of the inflammatory response was measured by planimetry of granulomas in histological sections. A consistent pattern emerged of early self-healing granulomatous inflammation in the liver and a later progressive inflammatory reaction in the lung. The granuloma fraction in the liver was greater in BIO strains compared to Balb strains with H-2 haplotype having a negligible influence. Backcross experiments suggested that multiple genes were involved. In contrast late infection in the lung appears to be influenced by H-2 haplotype and there is some evidence that late expansion of tuberculosis infection is due to lack of expressed I-E molecule or with expression of Db molecule. T cells and macrophages within liver granulomata were demonstrated by immunohistochemistry. TH cells outnumber TS cells but with no differences between strains of mice. Macrophages were identified using antibodies against F4/80, Cathepsin B and CDI 11b/CD18. CD11lb/CD18 staining demonstrates two populations of cells within granulomata; central epithelioid cells and peripheral newly recruited macrophages. Using quantitative image analysis there were more epithelioid cells in B10 mice and an increase in newly recruited macrophages as the granuloma fraction declined in both strains. In an attempt to establish whether these differences could be accounted for by differential expression of cytokines in the liver granulomata immunohistochemistry for cytokine proteins was attempted, particularly for TNFalpha TNFalpha could not be demonstrated in liver and lung granulomata although there was some success in endotoxin stimulated murine monocytic cell cultures. Mycobacterial load has been estimated in tissue sections by 1) counting the number of acid fast bacilli within granulomas and 2) measuring the amount of anti-BGG immunoperoxidase stain by quantitative image analysis. The latter method demonstrates degraded mycobacterial antigens rather than intact bacilli. The granulomas of Balb strains of mice contain relatively more immunoperoxidase stain to the numbers of acid fast bacilli compared to BIO strains. It is suggested that granulomas of Balb strains are more effective (at least initially) at mycobacterial degradation. The image analysis techniques developed for the study of this murine model of tuberculosis were also applied to human granulomatous disease. Macrophage subpopulations were identified in sarcoid granuloma in lymph nodes. There appears to be a correlation between the number of newly recruited macrophages and disease activity. In another application the anti-BGG serum was used to offer some increase in sensitivity in the diagnosis of human mycobacterial infection.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(686847.1) | 686847-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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