Tuberculosis I & II PDF

TUBERCULOSIS I&II Prof Thidar Aung Learning Objectives The students will be able to 1. List the various socioeconomic and immune factors that predispose to pulmonary tuberculosis. (C1) 2. Explain the pathogenesis and the role of host resistance to tuberculosis (C2) 3. Describe the clini...

TUBERCULOSIS I&II Prof Thidar Aung Learning Objectives The students will be able to 1. List the various socioeconomic and immune factors that predispose to pulmonary tuberculosis. (C1) 2. Explain the pathogenesis and the role of host resistance to tuberculosis (C2) 3. Describe the clinical presentation of pulmonary tuberculosis (C2) 4. Describe primary tuberculosis, secondary tuberculosis and miliary tuberculosis (C1) 5. Compare primary tuberculosis and secondary tuberculosis on the basis of lung involvement, morphology and their sequelae (C6) 6. Explain the complications of pulmonary tuberculosis including miliary tuberculosis (C2) 7. Describe the sites and pathogenesis of extrapulmonary tuberculosis Manipal University College Malaysia 2  Tuberculosis Tuberculosis is a communicable chronic granulomatous disease and the leading infectious cause of death worldwide Causative organisms Typical organisms for immunocompetent hosts Mycobacterium tuberculosis Mycobacterium bovis Atypical organisms in immunocompromised hosts Mycobacterium Avium Intracellulae Mycobacterium kansasii Manipal University College Malaysia 3 Factors That Predispose to Pulmonary Tuberculosis Medically & economically deprived persons Poverty, crowding, chronic debilitating illness Elderly persons Patients with AIDS, Diabetes Mellitus, Hodgkin Disease, chronic lung disease, chronic renal failure, malnutrition, alcoholism, immunosuppression HIV infection single most important risk factor for development of TB in HIV prevalent area Manipal University College Malaysia 4  Pathogenesis The outcome of infection in a previously unexposed, immunocompetent person depends on the development of antimycobacterial T cell–mediated immunity. T cells control the host response to the bacteria and development of pathologic lesions (caseating granulomas and cavitation) Infection by M. tuberculosis proceeds in steps; 1. Entry into macrophage 2. Replication in macrophage 3. Innate immunity 4. The Th1 response 5. Th1-mediated macrophage activation and killing of bacteria 6. Granulomatous inflammation and tissue damage 7.Manipal HostUniversity College Malaysia susceptibility to disease 5  Pathogenesis M. tuberculosis enters macrophages by endocytosis mediated by several macrophage receptors; (mannose receptors bind lipoarabinomannan & complement receptor) Once inside the macrophage, M. tuberculosis organism replicate within the phagosome by blocking fusion of the phagosome & lysosome. Multiple pathogen associated molecular patterns made by M. tuberculosis are recognized by innate immune receptors and initiate and the innate and adaptive immune responses. 6  Pathogenesis Contd 3 weeks after infection, the tubercle bacilli within the macrophages are transported via lymphatic pathway to the regional tracheobronchial lymph nodes and presented to T lymphocytes. This induces T cell mediated delayed hypersensitivity. TH1 cells produce IFN . IFN  activate macrophages into epithelioid cells that aggregate to form granulomas. This halts the infection before significant tissue destruction. In others, infection progress results in caseation necrosis. Activated mφ also produce TNF recruit more monocytes Host susceptibility: AIDS, immunosuppression and rare inherited mutation of IL-12 receptor  more prone for severe infection. In persons with polymorphisms in the NRAMP 1 gene, the disease may progress due to absence of an effective immune response. Manipal University College Malaysia 7 1. Entry into macrophages. M. tuberculosis enters macrophages by phagocytosis mediated by several receptors expressed on the phagocyte, including mannose- binding lectin and the type 3 complement receptor (CR3). Manipal University College Malaysia 8 2. Replication in macrophages. blocks formation of the Replicate unchecked phagolysosome M. tuberculosis inhibits maturation of bacteria the phagosome Protected from Lysosomal killing inhibition of phagosome- lysosome fusion During the earliest stage of primary tuberculosis (