Infection with M. tuberculosis typically leads to the development of delayed hypersensitivity, which can be detected by the tuberculin (Mantoux) test. About 2 to 4 weeks after the infection has begun, intracutaneous injection of 0.1 mL of sterile purified protein derivative (PPD) induces a visible and palpable induration (at least 5 mm in diameter) that peaks in 48 to 72 hours. Sometimes, more PPD is required to elicit the reaction, and unfortunately, in some responders, the standard dose may produce a large, necrotizing lesion. A positive tuberculin skin test result signifies cell-mediated hypersensitivity to tubercular antigens, but does not differentiate between infection and disease. A well-recognized limitation of this test is that false-negative reactions (or skin test anergy) may be produced by certain viral infections, sarcoidosis, malnutrition, Hodgkin lymphoma, immunosuppression, and (notably) overwhelming active tuberculous disease. False-positive reactions may result from infection by atypical mycobacteria.
About 80% of the population in certain Asian and African countries is tuberculin-positive. In contrast, in 2012, approximately, 5% to 10% of the U.S. population was positive, indicating the marked difference in rates of exposure to the tubercle bacillus. In general, 3% to 4% of previously unexposed individuals acquire active tuberculosis during the first year after “tuberculin conversion,” and no more than 15% do so thereafter. Thus, only a small fraction of those who contract an infection develop active disease.
Mycobacteria are slender rods that are acid-fast (i.e., they have a high content of complex lipids that readily bind the Ziehl-Neelsen [carbol fuchsin] stain and subsequently stubbornly resist decolorization). M. tuberculosis hominis is responsible for most cases of tuberculosis; the reservoir of infection typically is found in individuals with active pulmonary disease. Transmission usually is direct, by inhalation of airborne organisms in aerosols generated by expectoration or by exposure to contaminated secretions of infected individuals. Oropharyngeal and intestinal tuberculosis contracted by drinking milk contaminated with Mycobacterium bovis infection is now rare except in those countries with tuberculous dairy cows and sales of unpasteurized milk. Other mycobacteria, particularly Mycobacterium avium complex, are much less virulent than M. tuberculosis and rarely cause disease in immunocompetent individuals. However, they cause disease in 10% to 30% of patients with AIDS.
The pathogenesis of tuberculosis in the previously unexposed immunocompetent individual is centered on the development of cell-mediated immunity, which confers resistance to the organism and results in development of tissue hypersensitivity to tubercular antigens. The pathologic features of tuberculosis, such as caseating granulomas and cavitation, are the result of the destructive tissue hypersensitivity that is part and parcel of the host immune response. Because the effector cells for both protective http://ebooksmedicine.net
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Lack of acid pH
Bacteremia with seeding of multiple sites
TNF, ˜-IFN chemokines
Production of nitric oxide
Production of reactive oxygen species