Pulmonary tuberculosis (TB) remains one of the most infectious causes of death worldwide. Mycobacterium tuberculosis (M.tb), the causative agent of TB is transmitted via infectious aerosols, and in the majority of cases the bacteria is effectively controlled, by the host, resulting in a chronic latent infection. Currently, the only available vaccine is the Bacillus Calmette-Guérin (BCG), which despite being successful in preventing childhood disseminated forms of TB, has failed to control the adult pulmonary TB epidemic. One of the major contributing factors in the failure of the BCG is that although antigen-specific T cells are present at the time of M.tb infection, the recruitment of such T cells into the site of infection is significantly delayed. This delay, while reduced compared to non-vaccinated hosts, allows the bacteria to replicate unchecked within the lung and establish a “foothold” prior to the arrival of protective T cells and subsequent immune control. Thus, novel initiatives seek to close this “immunological gap” through increasing the level of protective T cell responses within the airway mucosa immediately following M.tb infection. We therefore investigated the impact of deliberate modulation of T cell geography following BCG vaccination on the outcome of pulmonary M.tb infection. In addition, a number of environmental factors are also thought to affect the site of M.tb infection: the respiratory mucosa. However, little is currently known about the effects of environmental exposure to allergens and other substances such as cigarette smoke on the outcome of pulmonary TB. Throughout this thesis we have investigated the mechanisms of immune protection and failure of protection against pulmonary M.tb infection within the respiratory mucosa. / Thesis / Doctor of Philosophy (Medical Science)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/15987 |
| Date | January 2014 |
| Creators | Horvath, Carly N. |
| Contributors | Xing, Zhou, Medical Sciences (Molecular Virology and Immunology Program) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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