1. What is TB missing?
    toxins and/or hydrolytic enzymes
  2. How does TB cause disease?
    multiply in normal unactivated macrophages but killed by activated form (require IFN-α & Th-CD4 cells)

    cmpds are produced that suppress T cell proliferation (cell wall bound) and block transcription f interferon-inducible genes that trigger macrophage activation.

    T-helper (CD4+) stimulate antibodies against TB but CANNOT act on intracellular organism (serum resistant)
  3. What are the factors that affect host susceptibility and severity of symptoms?
    size of inoculum, length & # of exposures all have an affect 

    (varies from no infection--latent infection--active/chronic infection)
  4. Are there genetic predispositions that render some people more susceptible to infection?
    • yes, mouse model 
    • Bcg - genetic locus involved in susceptibility of diff strains of mice to TB
    • Codes for natural resistance-associated macrophage protein
  5. How do you control the spread of TB?
    • isolation in (-) pressure hepa-filtered room
    • face masks w/ high efficiency filters
  6. What is the TB test also known as? and what is it?
    • aka Mantoux tuberculin skin test (TST)
    • performed by injecting 0.1 mL of tuberculin purified protein derivative (PPD) protein extracts 4rm M. tuberculosis into inner surface of forearm.
  7. What goes to the site of injection ?
    • Pre-primed T CD4 cells (which secrete cytokines)
    • -poly mono nucleocyte, monocytes, and macrophages are recruited to the injection site leading to immune rxn
  8. How can you tell is a TB test is positive ?
    redness and swelling btwn 48-72 hrs and 5-15 mm
  9. How long does it take after exposure to give positive results in TB?
    4-8 wks 

    • possible false positives / cross-reactivity 
    • (infection w/ non-TB mycobacteria//previous BCC vaccination)
  10. What's a better test for TB?
    IGRA (Interferon Gamma Release Assay)
  11. What is IGRA?
    • Interferon Gamma Release Assay 
    • WBC's blood cells 4rm most person infected w/ TB will release interferon-gamma (IFN-g) when mixed w/ antigens derived 4rm M.tuberculosis
  12. BCG (bacille Calmette-Guerin) does not do what?
    cause false (+) IGRA test result
  13. What does DOT mean? Why did it occur?
    DOT (Direct Observation of Therapy) means that a trained health care worker / other designated individual (excluding a family member) provides prescribed TB drugs and watches patient swallow every dose

    because patients were not completing course of drugs!
  14. What is Rifampin? (1963)
    an inhibitor of tubercle bacillus RNA 

  15. MDT (multiple-drug-therapy) was developed for what?
  16. What does Isoniazid do?
    blocks synthesis of mycolic acids
  17. Which antibiotics are used for TB?
    • Isoniazid (inhibits mycolic acid synthesis)
    • Rifampin (inhibit processing of RNA and shuts down protein synthesis)
    • Pyrazinamide (disrupts TB)
  18. What's the issue with W strain of TB?
    • worst bc MDR-TB (multiple drug resistant TB) 
    • resistant to 2/more of anti-TB drugs (isoniazid & rifampin)
    • highly virulent and infectious
  19. what is XDR-TB?
    • Extremely Drug Resistant TB 
    • -resistant to isoniazid, rifampin, and at least 3 second line drugs
  20. What is TDR-TB?
    totally drug resistant TB
  21. What is an attenuated vaccine ?
    vaccine created by reducing virulence of a pathogen, but still keeping t viable (or "live")

    attenuation takes an infectious agent and alters it so it becomes harmless/less virulent
  22. What does attenuation (attenuated vaccine) do?
    takes an infectious agent and alters it so it becomes harmless/less virulent
  23. What is a future vaccine for TB?
    use of psoralen and UV treatment; cross-links DNA and prevents DNA synthesis while allowing protein synthesis and metabolism. Organism do not multiply but remain alive and produce antigens.
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