Mycobacterium Tuberculosis Flashcards
Mycobacterium bovis reservoir? how can humans be infected?
cow; humans can get infected by consuming unpasteurized milk and lead to extrapulmonary TB => bone infections => hunchbacks!
Mycobacterium avium prevalent in what patients?
AIDS
M. leprae causative agent of what?
leprosy
M. tuberculosis reservoir?
humans - called white plague, leading cause of death in the world from a bacterial infectious disease
What are some general characteristics of M. Tuberculosis?
large, nonmotile, rod shaped, obligate aerobe, facultative IC pathogen, can form serpentine cords, slow growing (takes 4 weeks to culture)
What is M. Tuberculosis classified as?
Acid fast but it does have a peptidoglycan.
What staining method is used?
Ziehl-Neelsen stain. appear pink in a contrasting background
What makes up the cell wall of M. Tuberculosis?
The peptidoglycan is composed of complex lipids made up of mycolic acid, cord factor, and Wax-D
What are mycolic acids?
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.
How do mycolic acids help with virulence?
prevent attack of mycobacteria by cationic proteins, lysozymes, and oxygen radicals. also protect from complement deposition in serum
What is cord factor?
responsible for serpentine cording. Toxic to mammalian cells and an inhibitor of PMN migrations
What is Wax-D?
major component of Freud’s complete adjuvant
Does MTB have classic bacterial virulence factors?
no
What does MTB do for cell entry?
binds direcrly to mannose receptors on macrophages via cell wall associated LAM or indirectly via Fc receptors
How does MTB effectively evade the immune system?
grows intracellularly and can inhibit phagosome-lysosome fusion
How does MTB interfere w/ toxic effects of ROS?
- uses compounds that down regulate oxidative cytotoci mechanism
- macrophage uptake via complement receptors may bypass the activation of a respiratory burst
What is the Antigen 85 complex?
binds fibronectin and aids in walling off the bacteria from the immune system and may facilitate tubercle formation
What does the high lipid concentration in cell wall help MTB with?
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
What is TB infection?
When MTB is in the body but the immune system is keeping the bacteria under control by producing macrophages that surround the tubercle bacilli
Are people who have infection infectious?
NO! and they usually have a normal CXR
What are predisposing factors to TB?
HIV!, close contact, poor nutrition, iv drug use, EtOH, etc
how many infected individuals will develop active disease?
3-4% upon initial infection, 5-10% within a year
TB disease progression depends on what?
strain of MTB, prior exposure, vaccination, infectious dose, immune status of host
What happens in stage 1 of MTB?
- droplet nuclei inhaled (most effectives ones are 5 micrometers in diameter)
- bacteria nonspecifically taken up by alveolar macrophages but since not activated; unable to destroy bacteria
What happens in stage 2 of MTB?
begins 7-21 days after infection, MTB multiples unrestricted until macrophages burst and continue to grow in other macrophages
What happens in stage 3?
- 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
Why can’t MTB multiply w/in the tubercles?
b/c of low pH and anoxic environment but it can persist for extended periods
What happens in stage 4?
-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
What are the 2 types of secondary lesions caused by miliary TB?
- exudative lesion - PMN accumulation around MTB –> soft tubercle
- productive or granulomatous lesion –> hard tubercle
What happens in stage 5?
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.
What is a Ghon Complex?
when primary lesion heals and become fibrotic and calcifies
What is a Simon foci?
When small metastatic foci containing low numbers of MTB calcify. often sites of reactivation
What is MDR TB?
TB that is resistant to at least two fo the best anti-TB drugs, isoniazid and rifampicin
What is XDR TB?
Tb resistant to isoniazid and rifampin plus resistant to any fluoroquinolone and at least one of the three injectable second line drugs
How does one Dx TB?
medical history, PE, and TB skin text (PPD)
What is the Rx for TB?
use multiple drugs for an effective regimen. Most commonly used drugs
- rifampin
- isoniazid
- pyrazinamide
- stretomycin
What is the vaccine for MTB?
BCG - live attenuated strain derived from bovis
