Mycobacteria Flashcards
What do mycobacteria stain as?
Ziehl-Neelsen positive
What disease does M. tuberculosis cause?
Tuberculosis
What disease does M. avium complex (MAC) cause?
Disseminated infection in AIDS, chronic lung infection
What disease does M. kansasii cause?
Chronic lung infection
What disease does M. marinum cause?
Fish tank granuloma
What disease does M. ulcerans cause?
Buruli ulcer
What disease does rapidly growing mycobacteria (M. fortuitum complex) cause?
Skin and soft tissue infections
What disease does M. leprae cause?
Leprosy
What is the shape of mycobacteria?
- Rod shaped
- Slightly curved, bacillus
Why doesn’t mycobacteria stain with gram stains?
- High lipid content with mycolic acids in cell wall makes mycobacteria resistant to Gram stain
What are the properties of the cell wall of mycobacteria?
- High molecular weight lipids
- Weakly gram-positive or
colourless - Survive inside macrophages,
even in low pH environment
- Weakly gram-positive or
What are the properties of mycobacteria?
Aerobic, non-spore forming, non motile bacillus
What are the challenges of diagnosing tuberculosis?
- Slow growing
- Slow reproduction
- Slow response to treatment
What is the growth rate of tuberculosis?
M. tuberculosis generation time 15-20h vs. 1h for common bacterial pathogens
What makes using drugs difficult for TB?
Thick lipid rich cell wall making immune cell killing and penetration of drugs challenging
How is TB spread?
- Transmission through sputum
- Air droplets
Describe what happens in primary TB
- Initial infection
- Remains contained
- Initial contact made by alveolar macrophages
- Bacilli taken in lymphatics to hilar lymph nodes
Describe what happens in latent TB
- In immunocompromised people
- Cell mediated immune (CMI) response from T-cells
- Macrophages bring into apex of lung → triggers T cell response causing localised infection
- Could stay in state for decades
- Primary infection contained but CMI persists
- No clinical disease
- Detectable CMI to TB on tuberculin skin test
What happens in pulmonary TB?
- Latent TB can develop into
- Infection in the apex of the lung
- Granulomas form around bacilli that have settled in apex
- In apex of lung, more air less blood so less WBCs
- TB may spread in lung causing other lesions
- Could occur immediately following primary or months later
- Necrosis results in abscess forming and caseous material being coughed up
Where could TB spread to and cause?
- TB meningitis
- Miliary TB (all around the place)
- Pleural TB
- Bone and joint TB
What do macrophages do to mycobacteria?
- Mycobacteria are phagocytosed by macrophages and traffic to a phagolysosomes
- The bacterium has adapted to the intracellular environment and aims to withstand phagolysosomal killing and escape to the cytosol
- May not do every time but has the machinary to do so
What do CD4 T cells do to mycobacteria?
- Effective immunity requires CD4 T-cells which generate interferon gamma and this helps activate intracellular killing by macrophage
- Generate pro-inflammatory cytokines (interferon gamma)
- Need cooperation between macrophages and T cells to control mycobacteria
What leads to granuloma formation?
- TB uses macrophages as Trojan Horses
- To drag mycobacteria out of alveoli in lungs to tissues
- Leads to granuloma formation
- Signals to immune cells to form granulomas
What is important for keeping granulomas stable?
CD4
If depleted, granulomas become unstable → disease
What disease is CD4 depleted in?
HIV
- 20x more likely get TB
- Leading cause of death in TB
What pro-inflammatory cytokine is also responsible for keeping granulomas stable?
tumour necrosis factor alpha (TNFa)
- TNF therapy, or anti-TNF for rheumatoid arthritis or organ transplant or immunocompromised can cause latent TB to cause systemic disease
What is nucleic acid detection?
- More rapid diagnosis
- Nucleic acid amplification test using PCR
- Sensitivity 88%, specificity 98%
- Recommended for rapid diagnosis in TB endemic countries
What is acid fast bacilli test?
stain used to identify organisms with wax-like, thick cell walls e.g.
mycobacteria (resistant to gram stain)
