Table of Contents
In 1882, Robert Koch first discovered Mycobacterium Tuberculosis. It has been in existence in the human population for many years and it is considered as one of the infectious diseases that kills humans irrespective of the global use of live attenuated vaccine and antibiotics. In Friedman, (2001) view, mycobacterium tuberculosis is a nonmotile, acid-fast and obligate pathogenic bacterial species and a causative agent of tuberculosis in the family of Mycobacteriaceae. The cell wall of this mycobacterium tuberculosis is mainly composed of acidic waxes in the form of mycolic acid. It was not until 1940 that physicians were able to discover and produce antibiotics that allowed patients to be effectively treated and this led to a massive drop in the mortality rate of the disease. Although the cure for tuberculosis has been found, the disease is still a major cause of death in people especially young adults in the developing countries. This essay will illustrate the clinical manifestation of tuberculosis, early and later events in infectious process, host genetics and DNA repair of tuberculosis.
Clinical manifestation of Mycobacterium Tuberculosis
The clinical manifestation of tuberculosis depends largely on factors such as age, immune system, co-existing diseases, and immunization status of the infected person. The most common presentation of the pulmonary tuberculosis is coughing of blood which is associated with later stages of the disease causing sputum to produce when inflammation and tissue necrosis ensue. (Hopewell, 1994). Sometimes hemoptysis is shown as a symptoms of tuberculosis from previous diseases. The infection of tuberculosis is initiated by exposing the respiratory route and it follows a general pattern. Kaplan et al. (2001), mentioned that the pattern of progression and resolution is divided into four stages. The first stage after the Mycobacterium Tuberculosis occur is from 3 to 8 weeks. Between the weeks, mycobacterium tuberculosis is contained in an inhaled aerosols and becomes implanted in the alveoli. A primary or Ghon complex is formed after the bacteria are spread by the lymphatic circulation to the lymph nodes regions in the lung causing a conversion of reactivity to the tuberculin. The second stage of progression according to Garay, (1996), last for about 3 months.
Within the 3 months, hematogenous circulate bacteria to many organs of the body and other parts of the lung. At this stage, some individuals experience acute and sometimes fatal disease in the form of tuberculosis meningitis or miliary tuberculosis. (Garay, 1996). At the third stage, there is an inflammation of the pleural surface lasting from 3 to 7 months. This stage also present a severe chest pain which can sometimes be delayed up to 2 years. According to Hopewell, (1994), this condition is caused by hemotogenous dissemination or by the release of bacteria into the pleural space and form subpleural concentrations of bacteria in the lung. The fourth stage which is the final stage of the primary complex takes up to 3 years. In this stage, there is a slow progress in the extrapulmonary lesions. The individual experiences frequent chronic back pain especially when the infection is in the bones and joints. Most of the individuals who are infected with tuberculosis also do not exhibit progression of the disease (Lounis et al., 2001).
Events in the infectious process
There are two broad events in the infectious processes associated with Mycobacterium Tuberculosis. These are early events and late events, each of which has been outlined and explained below.
It has already been established that mycobacterium tuberculosis enters humans through the alveolar passage in an aerosol droplet. In the early stage of infection, dendritic cell plays two important roles. One of the roles is to activate the T cells with specific antigens of the mycobacterium tuberculosis. The dendritic cell also helps in the spread of the mycobacterium tuberculosis since it is migatory. (Fenton & Vermeulen, 1996). To understand the interaction of mycobacterium tuberculosis at the early stage, the bacteria in a process initiate contact with macrophage mannose and surfactant protein A which is a glycoprotein found on the surface of alveolar enhance e binding and uptake of mycobacterium tuberculosis by increasing mannose receptor activity. Surfactant protein D which is also located at alveolae helps in the blockage of mannosyl oligosaccharide residuaes on the bacterial cell surface. (Fenton & Vermeulen, 1996). The cholesterol in the cell plasma is considered an important process for removing steroid from human neutrophils and decrease the phagocytosis of mycobacterium kansasii. It also cause depletion and prevent the entry of mycobacterium bovis from entering the mouse macrophages. In the early stage too, the human toll-like receptors 2 contribute to the increase in mycobacterium tuberculosis and causes an important interaction with bacterial component. When this happens, mycobacterium tuberculosis and other intracellar pathogens like phagosome reside in an endocytic vacuoule. After phagosomal maturation cycle occurs, bacteria like phagosme-lysosome fusion come into contact with hostile environment which include acid pH, reactive oxygen intermediates, lysosomal enzymes and toxic peptides. (Garay, 1996).
In the later events in the infectious process, Fenton & Vermeulen, (1996), stated that mycrophages in the lung which are infected through the production of chemokines, attract inactivated monocytes, lymphocytes and neutrophils. There is also the formation and composition of granulomatous focal lesions of mycrophage-derived giant cells and lymphocytes which is an effective means of containing the spread of the bacteria. Again, when cellular immunity develops, macrophages which contains bacilli are killed and out of this there is a formation of caseous center of granuloma occupied by a cellular zone of fibroblasts, lymphocytes and blood-derived monocytes. (Grange, 1996). Mycobacterium tuberculosis bacilli cannot multiply within the caseous tissue because of factors including the acidic pH, the low availability of oxygen and the presence of toxic fatty acids. Sometimes some of the organisms remains dormant and can live for decades. To determine whether an infection will progress to the next stage depends largely on the strength of the host cellular immune response. Individuals with strong cell-mediated immunity are able to arrest permanently the infection leaving the granulomas to subsequently heal and leaves small fibrous and calcified lesions. But when the infected individual is unable to control the initial stage of infection in the lung, the granuloma center can become prone to an unknown process which can serve as a medium through which the revive bacteria can multiply in an uncontrolled manner.
Because of the intracellular pathogen contain in mycobacterium tuberculosis, it is exposed to a lot of damages to the DNA basically from host-generated antimicrobial toxic radicals. According to Friedman, (2001), exposure of mycobacterium tuberculosis to reactive oxygen species causes different types of DNA damages which include oxidation, depurination, methylation and deamination which can lead to both single and double strand breaks. Bishai et al. (2002) stated that in mycobacterium tuberculosis, there is an increase in DnaE2 caused by several DNA-damaging agents. There is a decrease in the virulence of mycobacterium tuberculosis in mice when the DnaE2 polymerase is loss. Homologous recombinational repair and nonhomologous end joining are the two major pathways employed in the repair of double-strand break (DSB). The homologous recombination according to Bermudez & Goodman, (1996) is the type of genetic recombination which allows the exchange of nucleotide sequences between two similar or identical molecules of DNA and used by cells to repair harmful breaks that occur on the double strands of the DNA. The non-homologous end joining also repairs double-strand breaks in DNA. In the course of repairing the DNA, the nonhomologous end joining make use of short homologous DNA sequences in the form of microhomologies to guide the repair. When the intracellular is exposed, it courses the mycobacterium tuberculosis to reactivate oxygen and nitrogen species that result in the formation of double-strand break’s repair by homologous recombination repair or nonhomologous end joining.
In the study of mycobacterium tuberculosis, Robert Koch indicated that the bacteria has been in existence for so many years and is one of the leading causes of death. This was due to the fact that no vaccine was discovered until scientist were able to discover a vaccine to cure the disease. Although a vaccine has been found, the disease still kills people especially in the developing countries. The clinical manifestation of the disease present itself in four stages. The first stage occur between 3 to 8 weeks when mycobacterium tuberculosis is contained in an inhaled aerosols and become implanted in the alveoli. The second stage which last for 3 months causes hematogenous to circulate the bacteria to many organs of the body and lungs. The third and the fourth stage last from 7 months to 3 years and within this stage the infected individual experience severe chest pain and other complications and later the extrapulmonary lesions begins to show signs of slow progression. On the whole, gaining deeper understanding of how the disease manifests at different stages is a major step in fighting it.
One Page Summary
From the paper, it has been known that tuberculosis is a pulmonary disease which is caused by the deposition of Mycobacterium Tuberculosis contained in aerosol droplets onto the lung alveolar surface of the infected person. Formally, scientist did not have any means of treating the disease, the only preventive measure adopted in controlling the spread of the diseases was to isolate people who were infected. Before the twentieth century, it was recorded that more than 80% of the American population who were under the age of 20 years were infected and tuberculosis was considered as the leading cause of mortality in United State of America. (Friedman, 2001). There is evidence which indicates that host genetic influence the outcome of exposure to mycobacterium tuberculosis. The host-pathogen is considered to be a genetic component of tuberculosis interact with humans and mycobacterium tuberculosis. (Garay, 1996). This occur in individual with genetic defect when disorders like mendelian susceptibility and mycobacterial diseases are observed and this causes an increase in susceptibility to mycobacterial infection. Early cases of the disease shows that genetic component is an important host to mycobacterium tuberculosis. In the early stage the bacteria initiate contact with macrophage mannose and surfactant protein A causing an increase in mannose receptor activity. In the later events in infectious process, the mycrophages in the lung attract inactivated monocytes, lymphocytes and neutrophils and when this happens the individual will require antibiotic therapy to survive. The host pathogen is considered to be a genetic component which interact with both human and mycobacterium tuberculosis and it mostly occur in persons with genetic defect. Two major pathways adopted in the repair of the double strand breaks are the homologous recombinationa repair and the nonhomologous end joining. The reactivation of oxygen and nitrogen species helps in the repair of the homologous recombination repair and the nonhomologous end joining.
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