Flashcards in Lecture 16 Deck (18)
Tuberculosis is the disease caused by
either Mycobacterium tuberculosis
or Mycobacterium bovis.
They cause slowly progressive chronic
How do you test for TB?
M. tuberculosis and M. bovis are bacilli that
do not stain with Gram’s stain.
They can be grown on agar or in broth.
• Organisms seen in sputum (or other
samples) with ZN stain (or other stains). • Carbol fuchsin (red) in phenol driven into bacilli with heat. Background decolourised with acid/alcohol (doesn't decolourise so AFB). Background counter-stained with methylene
• Colonies grown on solid or in liquid media. Growth cycle = 18 hrs. Detection of colonies usually takes 2-6
• M. tuberculosis DNA detected by PCR
• Mantoux and Quantiferon tests
What are the two main sites of tubercolosis?
• Pneumonia (85%)
• Lymph node (5-10%)
What are the properties of TB?
• Usually one organ involved
• Occasionally disease in many organs
• Gradual onset and slow progression
What is the Epidemiology of tuberculosis?
• Tuberculosis was responsible for
approximately 1/3 of all adult deaths in
Europe in 1800s
• 1/3 world population (= 2 billion) infected
• 16 million (= 0.8%) active tuberculosis
• 8 million new cases per year
• 2 million deaths per year
• Increasing again in wealthy countries
- due to : immigration from 3rd world
immunosuppression due to HIV
What is mycobacterium tuberculosis pathogenesis?
• Exposure to infection
• From a patient with pulmonary tuberculosis
• Inhalation of droplet nuclei
containing 1-3 bacilli
A macrophage is always present between alveolar cells to ingest the bacteria
What happens once TB is ingested?
• Blockage of fusion of
phagosome with lysosomes. Multiplication of M. tuberculosis within
phagosome. Escape of M. tuberculosis into cytoplasm. Multiplication
within cytoplasm. Death of infected macrophage once about 8 bacilli present in cell. Ingestion of released bacilli by other macrophages. Dissemination of infected macrophages
through body. Recruitment of T helper
(CD4) lymphocytes to sites of infection. Release of inﬂammatory
cytokines by T helper lymphocytes. Activation of macrophages to increase ingestion and
intracellular killing of bacilli.
How does a granuloma form due to TB?
- a central region containing necrotic material from dead cells and bacilli. Surrounding macrophages with ingested bacilli and some giant cells. T helper lymphocytes at the edges.
What happens after a granuloma forms in TB?
• Establishment of an equilibrium:
- multiplication of bacilli
- ingestion and killing of bacilli
• Leads to formation and maintenance
of many small, stable granulomata
• In about 1% infected patients per year
the granulomas in some tissue (usually lung)
due to the equilibrium shifting in favour of
What are the consequences of a granuloma?
• In about 1% infected patients per year
the granulomas in some tissue (usually lung) enlarge due to the equilibrium shifting in favour of the bacilli. If the enlarging granuloma in the lung erodes into a bronchiole then the increased oxygen supply to the bacilli shifts the equilibrium markedly in their favour. The bacteria multiply more quickly
in the liquiﬁed caseous necrosis. The bacilli can be more readily dispersed by coughing.
What are the consequences of TB treatment?
• Prevention of infection progressing to
disease is dependent on activation of
macrophages by T helper lymphocytes
• Any process that impairs T helper
lymphocyte function will favour progression of infection to disease
Mantoux and Quantiferon tests
Both detect release of Interferon by lymphocytes in response to mycobacterial antigens.
A positive result to either indicates the presence in blood of lymphocytes previously sensitised to mycobacterial antigens.
Neither distinguishes between latent infection and disease
Mantoux test = Tuberculin Skin Test
1. Inject into dermis 0.1ml tuberculin (puriﬁed protein derivative= PPD)
= cell wall extract of M. tuberculosis
2. In a person whose lymphocytes have previously been exposed to similar
mycobacterial antigens they will migrate to the injection site and release Interferon and other cytokines that will result in capillary permeability and ﬂuid extravasation.
A palpable swelling will develop over 2- 3 days.
3. Measure the diameter of induration at 2-3 days > 5mm = positive.
Quantiferon Gold Test
Quantiferon Gold blood test tubes have M. tuberculosis speciﬁc antigens (not shared with M. bovis like the PPD antigens ) attached to the inside of the tube.
Lymphocytes sensitised by prior exposure to M tuberculosis release interferon
Interferon levels are measured after 3 days incubation of the blood tube.
What are the differences between Mantoux and Quantiferon?
The PPD antigen used in the Mantoux test
is present in M. tuberculosis and in M. bovis.
The antigen used in the Quantiferon Gold test
is present only in M. tuberculosis.
What is the live organism present in BCG vaccine?
People who have been vaccinated with BCG
will have a positive Mantoux test but a negative Quantiferon test
How would you treat tuberculosis?
Use multiple drugs.
• Routine situation where resistance of all
infecting bacilli is thought unlikely
eg. no prior treatment for Tb
• isoniazid for months