Mycobacteria (TB and Leprosy) Flashcards
Describe the 4 species of mycobacteria and their diseases
-
M. tuberculosis - tuberculosis in humans
- Often called “TB” for tubercle bacilli
- Bacilli = shape
- Tubercle = lesions they cause in the lungs
- Often called “TB” for tubercle bacilli
-
M. bovis - tuberculosis in cows
- We can get infected by consuming unpasteurised milk from infected cow
- Important for vaccine for tuberculosis (BCG)
- M. avium - tuberculosis-like illness in humans, particularly AIDS patients (functioning T cells = usually not a problem)
- M. leprae - leprosy in humans
What does it mean for TB to be latent or active?
How many people have latent?
- Infection is latent (immune response present but asymptomatic) or active (infection symptoms)
- 2 billion people have latent TB –> 10% with latent develop active
Describe Mycobacterium tuberculosis
Is it Gram negative or positive?
- Intracellular pathogen, lives in macrophages
- Slow generation time, level 3
- It is impermeable to stains and dyes due to the mycolic acid layer (hydrophobic layer)
- Tree of life = Gram positive
- Acid fast
Describe the cell envelope of mycobacteria
What properties does it incur?
- Has mycolic acid (wax layer) link to the cell wall by the arabinoglycan structure
- Incurs 4 properties:
- Resistance to ABx; cannot penetrate envelope
- Resistance to acids and bases in phag
- Resistance to osmotic lysis (influx fluid) from complement deposition
- Resistant to oxidative stress - key for phag survival

Describe the acid fast stain test
- Stain sample on slide with carbol-fuchsin dye
- Melts max layer
- Wash with EtOH, HCl
- Dye can now penetrate
- Counter stain with methylene blue
- Acid fast = red
- Non-acid fast = blue
Describe stage 1 of tuberculosis
- Inhalation of organisms into lungs (via droplet nuclei - 1 droplet contains 3 bacteria); does this to be immediately take up by lung macrophages
- 1 bacteria = TB!
- Droplets stay airborne
Describe stage 2 of tuberculosis
- 7-21 days after exposure, TB inhibits fusion of lysosome to phagosome, survives and mulitples within (key virulence factor)
- TB lyses macrophages, escape and infect more
Describe stage 3 of tuberculosis
- Infected macrophages become surrounded by lymphocytes and form granulomas (tubercles)
- T cells activate macrophages by secreting IFN-gamma, but it is hard to activate ones in the centre
- Latent infection - TB can’t escape but can’t be killed
- Chronic inflammation = cheesy nodules in lungs
Describe stage 4 of tuberculosis
- Granuloma grows
- At some point, tubercle erodes into airways –> transmission
- Deterioration of host immunity (breakdown in T) –> active tuberculosis
- Ex., HIV/AIDS, age, undernourishment, etc.
- Caseous center liquefies = cavities in lung
Describe the 2 types of tuberculosis
- Pulmonary (most cases)
- Progressive, irreversible lung destruction
- Bacteremia
- Extra pulmonary/miliary (immunocompromised individuals)
Describe the general symptoms of TB
- >2 weeks cough with thick/bloody mucus
- Flu like symptoms
- Chest pain, shortness of breath, weight loss (consumption). pallor/pale skin (the white death)
- Extra pulmonary symptoms vary depending on where TB has spread systemically
How is TB diagnosed?
- PPD: purified protein derivate taken from M. tuberculosis is injected
- Positive = red/swollen at 48 h indicating latent/active, BCG, previously treated but still have T response
- Negative = not infected, immunocompromised, not infected long enough
- Chest x-ray looks for shadowing = lesions, granulomas
- Staining of sputum (coughed mucous) for acid fast test, culturing
How is TB treated?
Active TB kills 2/3 people untreated
- 6 months of antibiotics = short treatments
- Slow growth = longer treatments
- Cocktail to prevent complete resistance
- Rifampin: inhibits RNA polymerase
- Isoniazid: inhibits mycolic acid synthesis
- others
Define the terms MDR, XDR, and TDR-TB
- MDR-TB = multi-drug resistant: TB does not respond to first-line drugs (rifampin and isoniazid)
- XDR-TB = extensively drug resistant: TB resistant to first and second line drugs used to treat MDR-TB
- TDR-TB = total drug resistant: nothing can be done for treatment
What is the BCG (TB vaccine?)
- “bacille Calmette-Guerin”; living vaccine prepared from attenuated M. bovis
- It is controversial due to variable efficacy (how well it works - probably varies due to different strains) for pulmonary TB
- Effective against miliary TB
- Vaccine leaves scar and gives false positive for TB test
- Recommended for individuals with high risk to exposure
What is leprosy (Hansen’s disease) caused by?
What are the symptoms?
Who is affected by it?
- Mycrobacterium leprae
- Incudbation of 5 years but less infectious than TB
- Symptoms: damage to skin, nerves, limbs, eyes
- Developing countries; 2 mil permanently disabled (low estimate due to stigma)
- Stigma = rejected by family, friends; murdered
Describe the tuberculoid form of leprosy (1 of 2 forms)
- Occurs if cell-mediated immunity is good; macrophages kill bacteria
- Lesions appear from nerve damage (anesthetic areas)
- Bacteria not recovered from lesion
- TB positive
- Self limiting (immune system success)
Describe the lepromatous form of leprosy (2 of 2 forms)
- Occurs when cell-mediated immunity is absent; inactive macrophages
- M. leprae survives, multiples in macrophages and Schwann cells = nerve damage, prone to serious injury (macrophages cause the damage)
- Lion-like appearence
- Lesions become secondarily infected = bone breakdown, disfigurements, mutilation
Is it true that most incidents of M. leprae are cleared without incident?
Yes; most people clear, some get tuberculoid, others progress to lepromatous

Describe the pathogen M. leprae
- “Gram positive” (tree), acid fast, rod shaped, mycolic acid wax envelope
- Can be grown in foot pads of mice or armadillo, not in vitro
How is leprosy treated?
- Leprosy is treatable with antibiotics
- Multiple drugs must be used just like TB
- Dapsone, rifampin, clofazime
- 1 dose of this MDT (multidrug therapy) = not infectious anymore
What is spectinamide?
A novel antibiotic with the potential to treat drug resistant tuberculosis infections