Immunoevasion strategies by M.tuberculosis

Question 1

What is the main outcome of Mtb infection

Answer 1

95% experience latency, 5% gets primary extra pulmonary diseases

Question 2

Why isn’t the BCG vaccine so effective

Answer 2

• The bacteria isn’t Mtb its M.bovis, live attenuated whole bacteria.
• Host genetics matter
• Also BCG vaccination can interfere with other mycobacterial infections, during immunization other bacterial infections can compete and the BCG doesn’t propagate an effective immunity

Question 3

How do Mtb survive in the body

Answer 3

Mtb mainly infect Macrophages, where it can survive the acidification by avoiding the phagosome, The bacteria can also survive NO and ONOO by degrading them with its own enzyme.
Mycobacteria can recruit and infect permissive macrophages but still evade the microbicidal active ones. causing granuloma formation.

Question 4

What is granuloma formation, in regard to Mtb infection

Answer 4

Granuloma is a collection of immune cells known as granulocytes, these form when the immune system attempts to wall off substances when they are unable to eliminate these. The granulomas of tuberculosis tend to contain necrosis. As the number of immunecells increase in the granuloma the adaptive immune cells cause recrution of fibrotic cells creating a fibrous cap. Further the center is consisting of necrotic cells

• Solid granulomas is a sign of latent TB
• necrotic granulomas exist in early stages of active TB

Question 5

Other than granuloma formation, how do the Mtb evade the immune system

Answer 5

Other than the fact that Mtb can block macrophage acidity

Mtb downregulate T cell response by inhibiting TNFg signaling, a proper antigen-specific CD4 response is essential for protection against Mtb

Mtb also blocks the adaptive immunity by blocking MCH 2 antigen presentation, and block migration of DCs into the LN

Question 6

Which types of antibiotic resistance is there

Answer 6

MDR - multi drug resistance, ca 2
XDR - Extensively drug resistance, MDR + 2
TDR - totally dig resistant, all drugs are tested ineffective
untreatable TB - clinical TB form that cannot be treated

Question 7

new drugs to overcome antibiotic resistance has come, how do they work and what can be de side effects

Answer 7

Better anti-TB drugs, have been successful in MDR, these inhibit ATP- synthase in the bacteria and thereby starve it

Since these drugs will be used during a long time there is chance of side effect such as killing of the microflora