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| Tuberculosis | ||||||||||||||||||||||||||
| Infectious Agents:Mycobacterium tuberculosis and Mycobacterium bovis | ||||||||||||||||||||||||||
| Route of transmission: | ||||||||||||||||||||||||||
| Mycobacterium tuberculosis is transmitted by inhalation of infective droplets coughed or sneezed into the air by an infected patient | ||||||||||||||||||||||||||
| Mycobacterium bovis is transmitted by milk from a cow that has been infected. In patients infected by Mycobacterium bovis the first clinical manifestation are intestinal and tonsillar lesions. | ||||||||||||||||||||||||||
| Incubation Period: The incubation period in tuberculosis may vary. It is possible to get get the disease several years after being infected with it. | ||||||||||||||||||||||||||
| Tuberculosis: | ||||||||||||||||||||||||||
| Tuberculosis is the most important infectious cause of death in the world. - 3 million people each year | ||||||||||||||||||||||||||
| Overcrowding increases the probability of spread | ||||||||||||||||||||||||||
| Antibiotics developed in the 1950s helped lower the number of incidents, however since the 1980s it is back on the rise, especially in Africa, because it can affect Immunosurpressed patients, mainly AIDS patients. Also antibiotics are old and the mycobacterium has gained resistance to many of the drugs. | ||||||||||||||||||||||||||
| Resistance to the common drugs rifampin and isoniazid arose from mutations in the RNA Polymerase and catalase, respectively. | ||||||||||||||||||||||||||
| Mycobacterium are aerobic, non spore forming, non motile bacilli with a waxy coat that causes them to retain the red dye when treated with acid (red snapppers) in the acid fast stain technique. | ||||||||||||||||||||||||||
| Mycobacterium tuberculosis has the ability to escape macrophages and induce delayed type hypersensitivity. It is able to do so because of certain components in its cell wall. | ||||||||||||||||||||||||||
| The virulent forms of Mycobacterium tuberculosis have a "cord factor," which is a surface glycolipid and allows it to grow in serpentine cords. | ||||||||||||||||||||||||||
| Second Lipoarabinomannan (LAM), a major heteropolysaccharide, inhibits macrophage being activated by INF-gamma. It also promotes release of TNF-alpha, which causes fever, weight loss and tissue damage. | ||||||||||||||||||||||||||
| Mycobacterium tuberculosis also induces release of IL-10and surpresses T-cell proliferation. | ||||||||||||||||||||||||||
| Thirdly complement activated on mycobacterial cell surface may opsonize the organism and facilitate uptake by macrophages complemene receptor CR-3 without killing the mycobacterium. | ||||||||||||||||||||||||||
| Fourth, a 65kD heat shock protein of tuberculosis is similar to the human heat shock protein and plays a mjor role in inducing an autoimmune response. | ||||||||||||||||||||||||||
| Primary Infection: | ||||||||||||||||||||||||||
| Begins with inhalation of mycobacterium and ends with T-cell mediated immune response | ||||||||||||||||||||||||||
| Induces Hypersensitivity to the organism in the perifery of the lung, where the mycobacterium is phagocytosed by alveolar macrophages and transported by these to the hilar lymph nodes. | ||||||||||||||||||||||||||
| These macrophages are not able to kill the infectious organism, mycobacterium tuberculosis will multiply and lyse the host cell and can then affect other macrophages. | ||||||||||||||||||||||||||
| Sometimes can enter blood stream and infect other parts of the lung. | ||||||||||||||||||||||||||
| T-cell mediated immunity can be demonstrated by a positive purified protein derivative test reaction (PPD test) | ||||||||||||||||||||||||||
| Mycobacterium and the T-cell interact with each other in 3 ways: | ||||||||||||||||||||||||||
| CD4+ T-cells release INF-gamma activating macrophages to kill the orgamism. The reaction that is used to kill these are nitrogen intermediates (NO, NO2, HNO3). This reaction is associated with epithelioid cell granulomas. | ||||||||||||||||||||||||||
| CD-8+ surpressor T-cells lyse macrophages infected with the mycobacterium through Fas-independent granule dependent reaction and kills organism. | ||||||||||||||||||||||||||
| CD4-CD8- T-cells lyse macrophages in a Fas-dependent manner, without killing it. This causes delayed type hypersensitivity creating necrotic caseous granulomas, which ultimately results in a calcified scar in the lung parenchyma and hilar lymph node (Ghon complex). | ||||||||||||||||||||||||||
| Secondary / Disseminated Tuberculosis��� | ||||||||||||||||||||||||||
| Happens to individuals that become reinfected with mycobacterium. | ||||||||||||||||||||||||||
| Reactivation of dormant disease or individuals that progress from primary to secondary by a virulent strain. | ||||||||||||||||||||||||||
| Infection can be determined autosomal dominant gene Bcg, which encodes a membrane transport protein | ||||||||||||||||||||||||||
| Granulomas occur in the apex of the lungs in secondary, but may widely disseminate in the lungs, kidney, meninges, bone marrow and other organs. These granulomas are the major cause of tissue damage and reflection of delayed type hypersensitivity | ||||||||||||||||||||||||||
| 2 features: | ||||||||||||||||||||||||||
| caseous necrosis and cavities - necrosis may cause rupture into the blood vessel, hence spreading mycobacterium throughout body | ||||||||||||||||||||||||||
| Also may enter into airways and cause mycobacterium to be released into aerosols | ||||||||||||||||||||||||||
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