Tuberculosis

Question 1

Stages of infection of TB

Answer 1

infection: latent, where the immune system controls the disease
disease: where bacterium escapes the immune response

Question 2

features of Mycobacterium tuberculosis

Answer 2

• Aerobic (obligate)
  
  • Acid-fast
  • Resistant to drying
  • Resistant to common antimicrobials
  • Very slow growing
    ○ Requirement for diagnostic methods other than culture
    ○ Management implications: takes a long time to determine antimicrobial susceptibility
    Survives in host macrophages

Question 3

cell wall of TB

Answer 3

• very thick fatty cell wall
• has extra components such as mycolic acids (for a waxy coat), arabino-galactan, glycolipids, lipoarabinomannan
• very immunogenic components

Question 4

Ziel-Nielsan stain

Answer 4

Step 1: carbolfuchsin stain
2: heat fixation
3: decolorization with acid alcohol
4: counter stain is methylene blue
acid fast positive is pink
acid fast negative is blue

Question 5

Parthenogenesis of TB

Answer 5

• Hides in macrophages
• produces protein that interferes with fusion of lysosome to phagosome = reduction of reactive oxygen intermediates and other enzymes
• pH held at 6.2 for replication

Question 6

Granuloma induction

Answer 6

Antigens are presented on MHC class II
drives strong CD4+ T cells that produce interferon gamma which helps control infection and help produce granuloma structure
activated macrophages fuse -> multinucleate giant cell
+ lymphocytes + epithelioid cells = granuloma

Question 7

Latent, primary, latent TB

Answer 7

Latent: delayed type hypersensitivity response controls symptoms, individuals are not infectious

Primary TB: bacteria causes infection in initial infection

Secondary TB: reactivation of latent infection
- Most common when bacteria in the tubercles replicate
- Macrophages and bacterial product induce caseous necrosis -> liquification that forms a cavity
Granulomas enlarge, increased immune response, excess cytokines and tissue damage cause symptoms

Question 8

Tuberculin skin test (Mantoux test)

Answer 8

Purified proteins derivatives that are taken from the organisms (tuberculin) that is injected into the skin
Inflammation at site is evidence of Mtb specific CD4+ T cell response
delayed hyper-sensitive reaction
x vaccinated individuals

Question 9

IGRA

Answer 9

• collect blood, add purified proteins derivatives that have a different preparation so that it is specific to bacteria but is not present in vaccine
  Test for IFNg production from Mtb specific CD4+ cells that has been secreted into media
• Doesn’t say whether you have an active infection
  Preferred for children over the age of 2 (T cell reaction not easily measured)

Question 10

Diagnosing active TB

Answer 10

chest X ray: look for tubercles

microscopy: find acid fast bacilli in sputum samples
- Culturing with enriched medium that takes weeks
- Antibody detection unreliable
- Nucleic acid tests -> combine with tests for antibiotic resistance

Question 11

Treatment of active TB

Answer 11

• 6 months of 3 anti-tuberculosis agents (INH, PZA, RIPE)
• hard to get into granulomas
• Rely on processing by micro bacterial enzymes -> need active bacteria for compounds to work
• Organisms require resistance through mutations in these enzymes
  Directly observed treatment essential to avoid resistance -> taking frequent samples during treatment

Question 12

Treatment for latent TB

Answer 12

• Used for those with a positive result without active infection or vulnerable contacts
• Use isoniazid for 6 months to prevent reactivation
  Single drug is used because number of organisms is small

Question 13

TB Vaccine

Answer 13

BCG vaccine
produced attenuated strain of M bovis
used in areas of high incidence

Question 14

What are the major immune responses for TB?

Answer 14

Secretion of IFN-g by CD4+ cells that produces granulomas