Mycobacterium TB Flashcards
What type of bacteria is mycobacterium tb?
Obligate aerobe. It is an acid fast bacilli (somewhere between Gram +tve and -tve)
What are the different types of TB?
Primary TB
Latent TB
Post primary TB
Milliary TB
What is primary TB?
Usually symptomless- possible cough or wheeze
Small transcient pleural effusion may occur
What is post-primary TB?
Onset of symptoms over weeks/months
Symptoms include weight loss, fever, blood-stained spit, plueral effusion
What is miliary TB?
Wide dissemination of TB from the lymph nodes via hematogenous dissemination (the blood) Spreads throughout entire body, fatal without treatment
1.5% of cases are miliary
Where does TB first enter in its pathogenesis?
TB enters via the airways into the alveolar sacs, in which it will be engulfed by alveolar macrophages
What happens after TB is engulfed by macrophages?
It will reside in macrophage and replicate intracellularly by inhibiting the fusion of phagosomes with lysosomes
What will happen to the infected macrophages in primary (latent) TB?
Pro-inflammatory responses (recruitment of additional monocytes and lymphocytes) will causes wbcs to assemble around the macrophage, forming a granuloma
What is a granuloma wrt TB?
Granuloma is the hallmark of TB, and can arrest TB growth (causing it to be latent TB)
What can happen to infected macrophages in post-primary/miliary TB?
Infected cells will migrate to local draining lympth nodes, allowing TB to infect other regions of the lung (or body in miliary TB)
What can happen to the granulomas over time?
If the immune system weakens, necrosis of macrophages in granuloma may allow TB to grow and spread
What is a calcified granuloma?
Over time calcium deposits can build up in granulomas, causing them to harden; this may result in the eradication of TB from the body
What are 3 important virulence factors for TB?
ESX-1 secretion system
LAM glycolipid
Mycolic acids
How does ESX-1 secretion system act as a virulence factor?
Crucial for secretion of proteins like ESAT-6, which is known to (sometimes in conjunction with CFP-10) modulate host immune response to help survival and proliferation of TB
How do LAM glycolipids act as a virulence factor?
It is found in the cell wall of M. tb, and inhibits the fusion of phagosomes with lysosomes in macrophages, preventing destruction of TB
How do mycolic acids act as a virulence factor?
Major component of TB cell wall. They provide a barrier that grants protection to bacteria from host immunomodulatory molecules and antibiotics.
What are two tests for TB?
Mantoux tuberculin skin test
Interferon gamma release assay
What is cord factor?
Cord factor consists of two mycolic acid molecules, and has been shown to induce formation of granulomas, which helps TB persist in host
What are the symptoms associated with primary TB?
- Often asymptomatic
Some may experience: - Low-grade fever
- Cough
- Fatigue
How is ghon focus?
A primary lesion that is visible under chest X-ray at the site of infection. Can be used to indicate primary TB
What are the symptoms associated with latent TB infection?
There are no symptoms, and the individual is not infectious
How can latent TB be diagnosed?
Using a tuberculin skin test or and IGRA blood test
What are the symptoms associated with post-primary TB?
- Persistent cough (often bloody)
- Fever
- Weight loss
- Chest pain
Highly infectious at this stage
What is the pathogen progression associated with post-primary TB?
Bacteria escape granulomas and continue spread and replication
They can cause necrosis and cavitation, particularly of lung tissue
What are some general diagnostic methods for TB?
Sputum AFB smear
GeneXpert MTB/RIF
Chest x-rays
What is sputum AFB?
Thick mucus coughed up from the lower respiratory tract.
AFB refers to acid-fast bacteria
What is an issue with sputum diagnostics?
- Positive smear could be due to other mycobacteria (other than TB)
- Bacteria may have spread elsewhere in the body (e.g. miliary), so is no longer found in sputum
What is the best diagnostic method for TB and why?
Culture followed by molecular diagnostics like GeneXpert MTB/RIF
What is GeneXpert MTB/RIF?
A molecular assay that simultaneously detects TB DNA and rifampicin resistance with high sensitivity in under 2 hours
How can x-rays diagnose TB?
They can be used to view damage like cavitary lesions and fibrotic scars.
However, X-rays cannot alone diagnose TB, as other issues like lung cancer can cause the same symptoms
