Tuberculosis Flashcards
where does mycobacterium tuberculosis live
in macrophages
what is mycobacterium TB generation time
15 hours
what is the waxy cell envelope associated with
1- resistance to antibiotics
2- osmotic lysis via complement deposition
3- lethal oxidation stress promotes survival in macrophages
acid fast stain
1- stained with carbol-fuchsin dye with slow heating (to melt the wax)
2- washed with ethanol and HCl
3- counter stained with methylene blue
4- acid-fast organisms appear red whereas non-acid fast organisms appear blue
transmission of TB stage 1
from inhalation of droplets from infected host, cough can produce 3000 droplets each droplet nuclei <10 bacteria
small diameter means they stay airborne for a long time
progression of TB stage 2
-lung macrophages phagocytose TB cells
-TB blocks acidification of the phagosome
-TB inhibits the fusion of the lysosome to the phagosome
-TB multiplies in macrophages
-macrophages lyse and release TB cells to infect more macrophages
-TB delays dendritic cell migration to lymph nodes
ESX secretion system in MTB
-5 systems
-enable the transport
of select bacterial molecules across the thick Mtb cell envelope
-multiple functions including damage to the phagosome membrane
-inhibit the immune responses
progression of TB stage 3
-infected macrophages may form granulomas
– TB granulomas are “tubercles” of immune cells that try to destroy invading pathogens (typically formed by macrophages)
-the granuloma represents a “balance” between the pathogen and the host —> latent infection (no symptoms)
– T cell activated macrophages can kill TB
– activated T cells can secrete cytokines (IFN-gamma) to activate the macrophages
– macrophages at the center of the granuloma are harder to activate by T cells
– chronic inflammation cause
“cheese-like” necrosis —> caseous necrosis
progression of TB stage 4
-some macrophages remain unactivated and infected
-the tubercle grows
-erosion of the granuloma into the airway provides the route of transmission
-deterioration of host immunity can result in a life-threatening infection. —> active tuberculosis
-the caseous center can liquefy leading to cavitation
Extrapulmonary Tuberculosis
- Infection outside the lungs
- Can infect multiple organ systems (bone, joints, liver, spleen, gastrointestinal tract and brain)
- More likely to occur in immunocompromised (e.g. HIV- infected patients) individuals and young children
- Widespread dissemination, called miliary tuberculosis, is almost always fatal
tb testing
- Tuberculin test (PPD = purified protein derivative from M. tuberculosis)
- T cell-mediated response
- a positive result is a red and swollen circle at 48h
- a positive result could mean: latent or active TB, BCG vaccinated, previously infected
- a negative result could mean:
not infected, immune compromised (e.g.AIDS), not infected long enough
if TB positive what do we do
careful history and a chest X-ray
X-ray: typical upper lobe “shadowing” = lesions
calcified granulomas may be seen on an X-ray
staining of sputum for acid fast bacilli and culturing
Interferon-gamma response assay
What are the types of tuberculosis?
Pulmonary tuberculosis: infection in the lungs
Extrapulmonary tuberculosis: infection outside of the lungs that can affect bone, joints, liver, spleen, gastrointestinal tract, and brain. It is more likely to occur in immunocompromised individuals and young children.
Miliary tuberculosis: widespread dissemination of tuberculosis that is almost always fatal.
What are the treatments for tuberculosis?
active TB can kill ~2 out of 3 people if untreated
six months of antibiotics for the short treatment – slow growth means long treatments
generally, multiple types of antibiotics are used: – Rifampin (inhibits RNA polymerase)
– Isoniazid (inhibits mycolic acid synthesis)
What are the types of drug resistant tuberculosis?
Multi-drug resistant TB (MDR-TB): resistant to the two most effective first-line drugs: isoniazid and rifampin.
Extensively-drug resistant TB (XDR-TB): resistant to the most effective second-line drugs used to treat MDR-TB. XDR-TB has been found in all regions of the world.
What is the BCG vaccine?
A live vaccine prepared from attenuated M. bovis that lacks the ESX-1 secretion system.
Shares antigenicity with TB.
Controversial due to variable efficacy for pulmonary TB but effective against miliary TB.
Can cause a false positive tuberculin test.
Vaccination leaves large scars.
Recommended for individuals at high risk of exposure.
Characteristics of Leprosy
- a chronic disease caused by Mycobacterium leprae
- very slow progression – incubation period of ~5 years
- can cause permanent damage to skin, nerves, limbs and eyes
- Leprosy is very rare in high-income countries
- ~ 2 million people are permanently disabled by leprosy, mainly in tropical developing countries
Mycobacterium leprae
- “Gram-positive” acid fast, rod shaped, waxy cell envelope (mycolic acid)
- cannot be cultivated in vitro
- M. leprae infects macrophages of skin and Schwann cells in nerves
What is the historical and social significance of Leprosy?
Historically victims were ostracized, rejected by family and friends, and driven out of communities.
Lesions in tuberculosis are “hidden” while lesions in leprosy are “visible” leading to stigma.
Leprosy is much less infectious than tuberculosis.
What are the two major forms of Leprosy?
Tuberculoid and Lepromatous
Tuberculoid leprosy
Cell-mediated immunity is present
Macrophages can contain the bacteria
Presents as light-colored lesions
Sometimes causes loss of hair and pigmentation
Patients become tuberculin positive because of the active T cell-mediated responses
Bacterial cells are generally not recoverable from lesions
Can be self-limiting
Lepromatous Leprosy
Cell-mediated immune responses are absent
Macrophages are not activated
M. leprae survives and multiplies in macrophages and Schwann cells
Nerve damage leads to lesions on the face and extremities due to damage of Schwann cells
Can cause a “lion-like” appearance
Lesions can become secondarily infected, eventually resulting in bone disfigurements, and mutilation.
Spread and progression of leprosy
- transmission is not well understood
- probably close and direct contact is required for extended periods of time - inhaled droplets?
- most exposed individuals do not develop disease – host genetics likely plays an important role
What are the treatments for Leprosy?
Treatable with multidrug therapy (MDT) using 3 antibiotics. These treatments have remained the same since the 1980s.
Treatment lasts 6 months to one year.
Patients are no longer thought to transmit the disease after one dose of MDT.
