Mycobacterium Tuberculosis

Question 1

Mycobacterium bovis reservoir? how can humans be infected?

Answer 1

cow; humans can get infected by consuming unpasteurized milk and lead to extrapulmonary TB => bone infections => hunchbacks!

Question 2

Mycobacterium avium prevalent in what patients?

Answer 2

AIDS

Question 3

M. leprae causative agent of what?

Answer 3

leprosy

Question 4

M. tuberculosis reservoir?

Answer 4

humans - called white plague, leading cause of death in the world from a bacterial infectious disease

Question 5

What are some general characteristics of M. Tuberculosis?

Answer 5

large, nonmotile, rod shaped, obligate aerobe, facultative IC pathogen, can form serpentine cords, slow growing (takes 4 weeks to culture)

Question 6

What is M. Tuberculosis classified as?

Answer 6

Acid fast but it does have a peptidoglycan.

Question 7

What staining method is used?

Answer 7

Ziehl-Neelsen stain. appear pink in a contrasting background

Question 8

What makes up the cell wall of M. Tuberculosis?

Answer 8

The peptidoglycan is composed of complex lipids made up of mycolic acid, cord factor, and Wax-D

Question 9

What are mycolic acids?

Answer 9

alpha-branched lipids that make up 50% of dry wt. They are strong hydrophobic molecules that form a lipid shell around the organism and affect permeability properties at the cell surface.

Question 10

How do mycolic acids help with virulence?

Answer 10

prevent attack of mycobacteria by cationic proteins, lysozymes, and oxygen radicals. also protect from complement deposition in serum

Question 11

What is cord factor?

Answer 11

responsible for serpentine cording. Toxic to mammalian cells and an inhibitor of PMN migrations

Question 12

What is Wax-D?

Answer 12

major component of Freud’s complete adjuvant

Question 13

Does MTB have classic bacterial virulence factors?

Answer 13

no

Question 14

What does MTB do for cell entry?

Answer 14

binds direcrly to mannose receptors on macrophages via cell wall associated LAM or indirectly via Fc receptors

Question 15

How does MTB effectively evade the immune system?

Answer 15

grows intracellularly and can inhibit phagosome-lysosome fusion

Question 16

How does MTB interfere w/ toxic effects of ROS?

Answer 16

1. uses compounds that down regulate oxidative cytotoci mechanism
2. macrophage uptake via complement receptors may bypass the activation of a respiratory burst

Question 17

What is the Antigen 85 complex?

Answer 17

binds fibronectin and aids in walling off the bacteria from the immune system and may facilitate tubercle formation

Question 18

What does the high lipid concentration in cell wall help MTB with?

Answer 18

impermeability and resistance to antimicrobial agents, resistance to killing by acidic and alkaline compounds in both the IC and EC environment, and resistance to osmotic lysis via complement deposition and attack by lysozyme

Question 19

What is TB infection?

Answer 19

When MTB is in the body but the immune system is keeping the bacteria under control by producing macrophages that surround the tubercle bacilli

Question 20

Are people who have infection infectious?

Answer 20

NO! and they usually have a normal CXR

Question 21

What are predisposing factors to TB?

Answer 21

HIV!, close contact, poor nutrition, iv drug use, EtOH, etc

Question 22

how many infected individuals will develop active disease?

Answer 22

3-4% upon initial infection, 5-10% within a year

Question 23

TB disease progression depends on what?

Answer 23

strain of MTB, prior exposure, vaccination, infectious dose, immune status of host

Question 24

What happens in stage 1 of MTB?

Answer 24

1. droplet nuclei inhaled (most effectives ones are 5 micrometers in diameter)
2. bacteria nonspecifically taken up by alveolar macrophages but since not activated; unable to destroy bacteria

Question 25

What happens in stage 2 of MTB?

Answer 25

begins 7-21 days after infection, MTB multiples unrestricted until macrophages burst and continue to grow in other macrophages

Question 26

What happens in stage 3?

Answer 26

- Lymphyocytes begin to infiltrate and T cells are activated which causes cytokines to be released. IFN gamma activated macrophages and now they can destroy MTB. - Pt becomes tuberculin positive now. - Cell mediated immune response must be mounted to control a MTB infection - most cytokines are released (IL1, TNF) - tubercle forms - caseous necrosis

Question 27

Why can't MTB multiply w/in the tubercles?

Answer 27

b/c of low pH and anoxic environment but it can persist for extended periods

Question 28

What happens in stage 4?

Answer 28

-MTB uses unactivated macrophages to grow the tubercle and can even lead to milliary TB. Secondary lesions caused by miliary TB involve the GU system, bones, joints, lymph nodes, and peritoneum

Question 29

What are the 2 types of secondary lesions caused by miliary TB?

Answer 29

1. exudative lesion - PMN accumulation around MTB --> soft tubercle 2. productive or granulomatous lesion --> hard tubercle

Question 30

What happens in stage 5?

Answer 30

caseous centers liquefy and this is very conducive to MTB growth. Large antigen load causes walls of nearby bronchi to become necrotic and rupture and cavity forms.

Question 31

What is a Ghon Complex?

Answer 31

when primary lesion heals and become fibrotic and calcifies

Question 32

What is a Simon foci?

Answer 32

When small metastatic foci containing low numbers of MTB calcify. often sites of reactivation

Question 33

What is MDR TB?

Answer 33

TB that is resistant to at least two fo the best anti-TB drugs, isoniazid and rifampicin

Question 34

What is XDR TB?

Answer 34

Tb resistant to isoniazid and rifampin plus resistant to any fluoroquinolone and at least one of the three injectable second line drugs

Question 35

How does one Dx TB?

Answer 35

medical history, PE, and TB skin text (PPD)

Question 36

What is the Rx for TB?

Answer 36

use multiple drugs for an effective regimen. Most commonly used drugs - rifampin - isoniazid - pyrazinamide - stretomycin

Question 37

What is the vaccine for MTB?

Answer 37

BCG - live attenuated strain derived from bovis