Mycobacterium tuberculosis

Categorization
Cell Wall: Acid-fast	Shape: Rod
Metabolism: Obligate Aerobe	Life Cycle: Facultative Intracellular

Transmission

Transmission of M. tuberculosis in most cases is due to inhalation of contaminated respiratory droplets.

Immune Response

Although most inhaled droplets deposit in the upper respiratory tract, a small percentage deposit in alveoli and are then phagocytosed by alveolar macrophages. Like many facultative intracellular organisms, M. tuberculosis evades death within the macrophage phagosome, begins to replicate, and eventually lyses the cell to facilitate spread. Over time, either infected macrophages or recruited Dendritic Cells travel to local lymph nodes and display tubercular antigens on MHC II molecules, thus initiating cell-mediated immunity to the organism. Cell-mediated immunity generates antigen-specific CD4+ T-cells of the Th1 subtype as well as cytotoxic CD8+ T-cells which bring the growing infection under control using distinct mechanisms. Antigen-specific Th1 cells return to infected areas and stimulate infected alveolar macrophages with Interferon-gamma which improves their capacity to kill phagocytosed bacteria. In contrast, antigen-specific cytotoxic CD8+ T-cells return to infected areas and directly kill infected alveolar macrophages. In addition, through cryptic mechanisms, antigen-specific CD4+ T-cells likely coordinate the development of granulomas around infected foci which physically isolates organisms from the uninfected respiratory parenchyma. On going cell death within the center of the granuloma causes caseous necrosis which over time may calcify, leaving a "Ghon Complex".

Clinical Consequences

The clinical consequences of M. tuberculosis infection are in large part dependent on the strength of the host's cell-mediated immunity. The initial inoculating event in a previously un-exposed individual is called "Primary Tuberculosis". When cell-mediated immunity is strong, as in most normal adults, Primary Tuberculosis is rapidly brought under control at the foci of infection and beyond some pathological changes in the lung, clinical consequences are never seen. In those with reduced cell-mediated immunity such as AIDS patients, children, the elderly, or immunocompromised patients, primary tuberculosis can lead to substantial pulmonary disease and may disseminate widely throughout the body, affecting multiple organ systems. However, even a healthy immune system can never fully eliminate the organism and substantial pulmonary or disseminated disease can appear in an individual years after uneventful primary disease in what is termed "Reactivation" of primary tuberculosis.

Because the clinical and morphological consequences of tuberculosis are so wide and varied we have divided its discussion into several subsections.
Primary Pulmonary Tuberculosis: Discusses pulmonary sequelae of initial infection
Reactivation Pulmonary Tuberculosis: Discusses pulmonary sequelae of reactivated infection
Extrapulmonary Tuberculosis: This page has not yet been written but will discuss the multifarious extrapulmonary manifestations of M. tuberculosis

Diagnosis

Detection of Acid-Fast bacilli on a sputum smear or biopsied tissue indicates active infection; however, this test has low sensitivity and thus results in a substantial false negative rate.

Culture of M. tuberculosis from sputum or biopsied tissue is often performed for diagnostic purposes but also to determine the drug sensitivity profile of the infecting strain; however, cultures can take 1-2months to grow.

Latent disease may appear as calcified "Ghon Complexes" as discussed in Primary Pulmonary Tuberculosis. Alternatively, active disease may be observed as cavitations as discussed in Reactivation Pulmonary Tuberculosis.

The PPD test involves subcutaneous injection of M. tuberculosis antigens. In individuals who have been previously exposed to the organism a Delayed-type Hypersensitivity (DTH) response develops by means of previously-generated antigen-specific CD4+ T-cells (See Delayed-type Hypersensitivity). This manifests as an erythematous induration of the skin at the site of injection. Although this cannot differentiate between latent and active infection, PPDs are typically used to screen for latenty infected individuals. False-negatives can occur in those with severely reduced cell-mediated immunity such as immunocompromised patients, specifically AIDS Patients. False-positives can occur in those exposed to other species of Mycobacteria, which often share similar antigens, or those vaccinated with the ineffective BCG Tuberculosis vaccine.

Treatment

Drug regimens are usually combinations of Rifampin, Isoniazid, Pyrazinamide, Ethambutol, or Streptomycin. Antibiotics must be taken for several months to ensure elimination of slow-growing M. tuberculosis.

Related Topics: Will take you to Respiratory Medicine

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