Pathogenesis of TB Flashcards
Give the list of mTB symptoms
A persistent cough- initially mild but then productive w haemoptysis
Weight loss, chronic fatigue
Loss of appetite
Fever – low grade
Night sweats
Dyspnoea
Multi-organ dysfunction or adrenal insufficiency
Draw a diagram to explain the natural history of TB
What is the difference between latent and active TB?
Give the risk factors for tb reactivation
Poverty
Immunosuppression
Diabetes
Old age
HIV!!!- accounts for ~20% of HIV-related deaths.
Primary and reactivation TB is more progressive
Where can there be sites of infection from tb?
Initial mTB infection in immunocomp occurs in lower lung lobe, producing a Ghon focus lesion.
Lymphangitic spread from the Ghon focus in primary tb often leads to Granulomatous peribronchial and hilar lymph nodes
Ghon focus+lymph node lesion=Ghon complex. These lesions heal–>fibro-calcific nodules.
What do these xrays show?
What does this pathology show? Label and explain
Miliary tb: occurs in poor resistance to infection.
Hay enlarged lung lymph nodes (part of og Ghon complex), plus miliary tubercles in lung parenchyma
1-3% of all TB cases, generally <5yr or >65yr old
What is intestinal TB?
Intestinal tb can be 2º to pulmonary TB from swallowed infected sputum
1º intestinal TB develops in ppl who drink M. bovis-infected milk
Large tuberculoma in the mesentery which can also occur in the gut wall itself (image)
What are we looking at here?
Antes era common complication in children with post-1˚ miliary TB. Rarely seen in ppl who’ve had BCG
Can TB occur in our bones and lymph nodes?
TB in bones and spine= Potts disease.
The necrosis due to the tb can destroy the spine and pinch on the spinal cord=paralysis
TB in the lymph nodes= scrofula.
How is the immune system a “double edged sword” when dealing with tb?
Excessive immune response leads to TNF-alpha overproduction
Hay healthy tissue damage by macrophages (immunopathology of TB - granuloma).
How can TB survive inside macrophages?
Inhibits Phagolysosome fusion
Maintains early endosome: tb secretes a protein which blocks acidification of the endosome.
It escapes this early endosome into cytoplasm, where it evades macrophage killing mechanisms
Controls Ag presentation: stops CTL recruitment and blocks macrophage activation
Describe the pathogenesis cascade of tb
-Inhaled mTB enters alveolar macrophages
-Spread to other parts of lung via lymphatics and capillaries
-A brief acute inflammatory response:neutrophils, cytokine storms, macrophage activation
-Recruitment of CD4, CD8, NK w IFNy, causes chronic inflammation
-Immune containment forms granuloma and tissue damage
Describe granulomas- what is it formed from and what happens to the TB inside it?
Formed from infiltrating cells surrounding the infected cells to contain the infection.
Provides a milieu for cell-cell interactions that may facilitate bacterial removal.
TB survives inside the granuloma, the i.system cannot kill mTB–> granuloma is calcified as a defense- seen on CXR
What happens to the granuloma?
The granuloma undergoes liquefaction and coagulative necrosis producing caseous necrosis.
This=UNIQUE to TB, causes mucho host tissue destruction
Liquefaction leads to cavitation and TB release, which causes transmission
One of the immunological tests for TB inclue the Elispot test. Describe the advantages and disadvantages of this
Outline the drug treatment for TB
- Rifampicin, Isoniazid, Pyrazinamide, Ethambutol
- important contraindication: interacts w the pill
Typically how do we expect the recovery from TB to go once treatment has began?
