Tuberculosis is one of the most serious infections in the world, killing almost 3 million people worldwide annually. Thus, it is important to understand how this mycobacterium is pathogenic and the defence mechanisms it has in order to try and manage this potentially fatal disease. Mycobacterium tuberculosis, the causative agent of tuberculosis is a pathogen that can infect its host for decades without causing clinical disease, only to reactivate when host immunity is compromised. Recent work has begun to outline the complexity of this host-pathogen interaction and to reveal how the homeostatic balance between the two is achieved.
Normal Physiology of Macrophages
Macrophages, produced by the division of monocytes, are white blood cells within tissues; essentially, an immuno-defence mechanism. Macrophages are vital to the regulation of immune responses and the development of inflammation. After insult, macrophages normally become active to remove debris. Macrophages function in innate natural immunity by destroying microbes and in acquired immunity as an antigen-presenting cell.
During phagocytosis, macrophages are activated to destroy (consume) the bacteria devouring many times their own body mass in bacteria, essentially killing them with the macrophage’s acid-filled vacuoles. The ingested pathogen becomes trapped in a phagosome, which fuses with lysosome; from this enzymes and toxic peroxides digest and kill the pathogen. However, some advance pathogens such as Mycobacterium Tuberculosis have become resistant to the immune-defence mechanisms of the macrophage.
Structure of Mycobacterium Tuberculosis
Mycobacterium Tuberculosis is a gram positive, rod-shaped bacteria.(Reece, 2011, pp 579) M. Tuberculosis has the potential to produce all of its essential vitamins, amino acids, and enzyme co-factors by itself. The cell wall of M. Tuberculosis contains a variety of lipopeptides and liposaccharides that are type 2 toll-like receptors. (Goering, 2008) The engagement of this TLR can case the inhibition of cytokine synthesis and thus decreased cytokine responsiveness.
The transmission of M Tuberculosis occurs via air which is particularly effective because infected people cough up the bacteria into the environment. The mycobacteria has a waxy outer coat which allows is to resist for longer periods of time increasing the chance of spread.
Pathogenesis of M. Tuberculosis
Mycobacterium tuberculosis almost exclusively infects the macrophages of a cell. After one is infected, usually through inhalation, macrophages at the epithelial barrier are affected. The mycobacteria enter the cell via endocytosis where the bacteria can survive and multiply. Macrophages affected releases signals to attracts monocytes and inflammatory and present the antigen to a T cell to develop immunity.
Eventually a helper T cell activates the macrophages to become destructive- bactericidal. This response only occurs after antigens from the bacteria reach the lymph nodes draining from the infection. Because of this, inflammatory signals as a result of the initial infection endorse the flow of additional monocytes (an immune-defence mechanism and type of white blood cell) and macrophages. Inside the macrophages the inflammatory mediator prompts the formation of a phagolysosome producing an inhospitable acidic environment.
T helper cells are also important in the formation of caseating granulomas. The purpose of this process is to hold the bacterial infection before severe destruction of the tissue occurs. Granulomas, a collection of immune cells, collect around infected macrophages, undergoing premature death of the cells, or necrosis.
Tuberculosis can then remain inactive within the body for a...