Mtb

• Mycolic acid - alpha and beta hydroxy fatty acids - form the inner leaflet of Mtb cell wall - resists antimicrobials and antibiotics - low permeability and makes Mtb hydrophobic
• Lipoarabinomannan - a glycoprotein forming centre of Mtb cell wall - inhibits phagosome-lysosome fusion - suppresses O2 burst
• Phenolic glycolipid - outer layer of Mtb - inhibit phagosome maturation and acidification
• Mtb uses ESX-1 (type vii secretion) to release ESAT-6 and CFP-10 into host cells
• ESAT-6 and CFP-10 - inhibit TLR signal, preventing activation of NF-kB and MAPK
• ESAT-6 and CFP-10 - aids with phagosome escape
• Post-escape, Mtb can neutralise cytosolic enzymes
• ESAT-6 and CFP-10 - cause necrosis in host macrophages
• Mtb downregulates MHC II
• Mtb exploits autophagy using Eis
• In hypoxic and nutrient-deficient granulomas, Mtb can become persister cells, changing their metabolism and becoming even more resistant to antimicrobials and antibiotics
• SapM - phosphatase - dephosphorylates host proteins to prevent maturation
• LipY - lipase - disrupts membrane trafficking for phagosome maturation, and prevents phagosome fusion
• Mtb uses RPFs to reactivate persister cells in latent infection
• Pre-exposure - use BCG vaccination

  Limitation - wanes over time, efficacy is varied
• Latent - isoniazid

  Limitation - Treatment adherence is poor, need better diagnostics to help identify highest-risk patients
• Active - rifampicin

  Limitation - Resistant strains, treatment adherence sometimes poor
• Social work in TB - limited resources for affected regions
• What happens to infected macrophages during caseous granuloma formation?

  Necrosis of infected macrophages, with excessive macrophage activation and microbial persistence.
• What are the long-term consequences of caseous granuloma formation in TB?


  Chronic inflammation, scarring, respiratory complications, increased risk of TB reactivation, and sequelae such as pneumothorax and bronchiectasis.
• What is a long-term complication of caseous granuloma formation?

  Chronic lung disease and fibrosis, leading to permanent lung scarring and respiratory failure.
• What can occur due to chronic inflammation in TB?

  Pneumothorax, bronchiectasis, and respiratory failure due to prolonged inflammation and fibrosis.