mycobacterial dz Flashcards
- Describe the unique properties of mycobacteria and how they create special problems for the isolation and identification of these organisms.
Aerobic rod shaped. Slow growing (require 3-6 weeks for primary isolation). Resistant to desiccation (M. tuberculosis is viable after 6-8months in dried sputum) and resistant to disinfectants, but can be killed by UV.
Why is mycobacteria resistant to disinfectants
high lipid content of their cell wall. Clinical samples containing M. tuberculosis are often treated with alkali, which kills most normal flora but not the mycobacteria, prior to culturing.
mycobacterial cell wall
Attached to the peptidoglycan matrix is a polysaccharide (arabinogalactan) that anchors the long chain mycolic acids. Also associated with this basic structure are lipoproteins and glycoproteins. Cell wall is rich in lipids (made of mycolic acids)
What does the tuberculin skin test test for
lipoproteins and glycoproteins attached to the cell wall of TB
What is acid fastness
Hallmark of mycobacteria- The mycolic acids of mycobacteria are long chain lipids of 60-90 carbons, that make the bacteria hardy and very difficult to stain, but once stained resist de-staining with acidified alcohol. Ziehl-Neelson stain stains mycobacteria red and others do not retain the stain.
Which mycobacterial strains can cause human TB
M. tuberculosis, M. africanum, M. bovis, M. pinnipedii, M. microti, and M. canettii. They are all from a common ancestor
What proportion of the world population is infected with TB
1/3 of the world. Most persons infected with M. tuberculosis become tuberculin skin test positive and harbor viable bacteria but show no signs of active disease and are considered latently infected
- Describe how M. tuberculosis is transmitted and the odds of developing disease.
airborne droplet nuclei (size 1-5 mm) expelled when a person coughs, sneezes, or speaks who has infectious (not latent) TB. Rarely from ingestion. Infected contacts develop a positive delayed-type hypersensitivity reaction to the tuberculin test between 2-10 weeks after initial infection. 5-10% progress to active TB within the first 2 years of infection, another 5% develop active TB within their lifetime.
Who is at increased risk of developing active TB
HIV infected persons with a latent TB infection have a 7-10% chance of developing active TB disease each year. Persons with other medical conditions such as diabetes, end-stage renal disease, and immunosuppressive therapy are also at an increased chance for developing active TB.
forms of TB
Pulmonary, lymphatic, pleural, miliary (disseminated). Infants, HIV positive and immunosuppressed are more likely to get extrapulmonary and miliary forms
- Describe the development of immunity to M. tuberculosis.
Cell mediated immunity develops at 2-6weeks (TH1). Cell mediated immunity controls infection. Th cells activate macrophages which kill intracellular bacteria. When the macrophages die, bacilli are released and spread to lymph nodes and other tissues/organs. Also IFNgamma and alpha control TB infection.
TB symptoms/ signs
During the initial infection symptoms are absent or produce a mild influenza-like disease. In healthy people, TB lesions will heal and become fibrotic or calcified (visible on CXR). Some mycobacteria may persist within granulomas for decades causing continued antigenic stimulation and possible reactivation later in life. Latent TB can not be spread
- List the immune factors known to control M. tuberculosis.
Th1 cells (and macrophages), IFNg and IFNa.
TB histology
The bacteria are confined in “tubercles”, granulomas (see figure) consisting of epithelioid cells, giant cells, and lymphocytes. With time the tubercles grow and their centers may become necrotic (caseous necrosis).
Ghon complex
The combination of a (usually single)TB lesion in the lung and in the draining bronchial lymph node
- Differentiate between primary, latent, and reactivation tuberculosis.
Primary: 5-10% chance in first 2 years post infection. In immunocompromised often spreads to all organs leading to potentially fatal miliary TB. Secondary: aka reactivation. Often associated with impaired immune function (AIDs, measles, corticosteroids, chemo, anti-TNFalpha therapy). Disease manifestations are in large part the result of hypersensitivity to tubercular antigens and are not the result of a specific bacterial toxin
Most common site of TB reactivation and pathogenesis
Apex of the lung (most highly oxygenated), ), but can occur in any tissue harboring latent bacteria from a primary infection. Lesions slowly become necrotic, caseous, and eventually liquefy. Adjacent lesions may coalesce to form larger lesions and eventually break through to the bronchi. Organisms actively grow both intra- and extracellularly, and may reach very high densities in these lesions. The bacteria-laden material is discharged into the bronchi resulting coughing and transmission the bacilli to other susceptible individuals.
- Describe M. tuberculosis pathogenesis
Intracellular survival- inhaled bacilli are phagocytosed and multiply in alveolar macrophages. M. tuberculosis interferes with membrane controlled trafficking and arrests phagosome maturation at a stage when no harm can be done to the pathogen (marked by prevention of phagosome acidification), while delivery of nutrients by membrane bound vesicles is unimpeded.
