(B) Lecture 14: Tuberculosis and Leprosy Flashcards
Mycobacteria
- M. tuberculosis
- M. leprae
- M. bovis
- M. avium
M. tuberculosis is the agent for…
- causative agent of Tuberculosis in humans
- often called TB for tubercle bacilli
M. leprae is the agent for…
causative agent of Leprosy in humans
M. bovis is the agent for…
- causes tuberculosis in cows, rarely in humans
- humans can be infected by consumption of unpasteurized milk leading to extrapulmonary TB
M. avium
can cause TB-like illness in humans, especially in patients w/ AIDS
- usually in immunocompromised patients
Tuberculosis
- infection by M. tuberculosis
- can be latent (not transmissible) or active (transmissible)
- approx. 2 billion ppl (1/4 of world’s population) likely have latent TB
- TB is contagious + spreads through air by ppl w/ ACTIVE TB
- about 10% of ppl infected w/ latent TB develop active TB in their lifetime
Order of mortality of pathogens
- COVID
- TB
- HIV/AIDS
- Malaria
Mycobacterium tuberculosis
- INTRACELLULAR pathogen (lives within macrophages)
- SLOW generation time
- M. tuberculosis can be grown in the lab on specialized media
M. tuberculosis cell envelope
- have an unusual cell envelope w/ high conc of mycolic acid = WAXY
- impermeable to stains and dyes (gram POSITIVE ACID FAST STAIN) - hallmark
- lipid rich/waxy envelope is very hydrophobic and resists common stains
- mycolic acid causes “acid-fastness”
Unusual cell envelope is associated w/ resistance to:
- some antibiotics
- osmotic lysis via complement deposition
- lethal oxidative stress = survival inside of macrophages
Acid fast stain
- stained w/ carbol-fuschin dye w/ slow heating to melt wax
- washed w/ ethanol and HCl
- counter stained w/ methylene blue
- acid-fast organisms (like TB) appear red while non-acid fast organisms appear blue
Spread of TB
Stage 1
- transmission thru inhalation of droplets from infected host (coughing/sneezing)
- small droplets can stay airborne for extended periods of time
Spread and Progression of TB
Stage 2
- lung macrophages phagocytose TB cells
- TB blocks acidification of phagosome
- TB inhibits fusion of lysosome to phagosome
- TB multiplies in macrophages
- macrophages lyse + release TB cells to infect more macrophages
- TB delays dendritic cell migration to lymph nodes
ESX secretion systems
- 5 ESX systems exist in M. TB
- enables transport of select bacterial molecules across thick Mtb cell envelope
- multiple functions like damage to phagosome membrane
- also inhibits immune responses
Spread and progression of TB
Stage 3
- infected macrophages form GRANULOMAS
- TB granulomas are TUBERCLES of immune cells that try to destroy invading pathogens
granuloma represents a balance btwn pathogen and host = LATETNT INFECTION
- T-cell activated macrophage can kill TB
- activated T cells secrete cytokines (IFN-gamma) to activate macrophage
- macrophages at centre of granuloma are harder to activate by T cells
- chronic inflammation causes cheese-like necrosis = CASEOUS NECROSIS
Spread and progression of TB
Stage 4
- some macrophages remain unactivated and infected
- tubercle grows
- granuloma erodes into airway = route of transmission
- deterioration of host immunity = active TB
- caseous centre/lesions can liquefy and cause CAVITATION