Abstract
This chapter explores the genetic toolbox available for the study of Mycobacterium tuberculosis physiology, the immunology relating to M. tuberculosis infection, and relevant animal models to probe the corresponding disease course. The development of better vaccines is contingent on an understanding of the mechanisms by which M. tuberculosis evades the innate and adaptive immune responses. A primary tuberculosis (TB) infection in humans generally results from the inhalation of a small number of bacilli. These bacteria are deposited in the lungs and are taken up by alveolar macrophages and dendritic cells (DC). M. tuberculosis is moderately resistant to many forms of reactive oxygen intermediates (ROI) due to the expression of typical detoxification enzymes, such as superoxide dismutase and catalase-peroxidase-peroxinitrase (KatG). Transmission electron microscopy experiments performed in the late 1960s by D’Arcy Hart suggested that M. tuberculosis resides within tightly associated membranous vacuoles that fail to fuse with lysosomes. Programmed cell death has a role in controlling mycobacterial replication, as decreases in the bacterial burden are correlated with macrophage cell death. Infected cells are detected by T cells through the recognition of antigens presented on major histocompatibility complex class II (MHC-II) molecules by the receptor on the CD4 T cells, leading to the initiation of the bactericidal activity of macrophages. The immune-system evasion mechanisms of M. tuberculosis are fundamental for the success of the pathogen, and a clearer understanding of these processes will advance vaccine and chemotherapy development.
Original language | English (US) |
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Title of host publication | 4th Edition |
Subtitle of host publication | Virulence Mechanisms of Bacterial Pathogens |
Publisher | wiley |
Pages | 31-50 |
Number of pages | 20 |
ISBN (Electronic) | 9781683674191 |
ISBN (Print) | 9781555814694 |
DOIs | |
State | Published - Jan 1 2022 |
ASJC Scopus subject areas
- General Medicine
- General Immunology and Microbiology