Micro - TB Flashcards
4 mycobacteria strains and their reservoirs
- M. bovis - cows
- M. avium - AIDS pts
- M. tuberculosis - humans
- M. leprae - humans?
Presentation of M. bovis
Extrapulmonary TB in someone exposed to unpasteurized milk
Presentation of M. avium
TB-like dz in AIDS pt
M. tuberculosis is the leading cause of:
Death by bacterial infectious disease
How many people affected by TB worldwide?
1/3 of population
White plague v. black plague
White plague - TB
Black plague - Yersinia pestis (subcutaneous hemorrhage)
MTB is (aerobic, anaerobic) (intracellular, extracellular) (shape)
Aerobic, facultative aerobe, large rod
Where do mycobacteria normally reside in body?
Dry, oily areas
Virulence factors of MTB
- Facultative intracellular parasite
- Obligate aerobe
- Peptidoglycan + lots of lipoproteins
- Binds to mannose, complement, and Fc receptors of macrophages
- Inhibit phagosome-lysosome fusion
- Decreased oxidative toxicity of macrophages
- Antigen 85
- Slow generating
How does being a facultative intracellular parasite contribute to MTB virulence?
Avoids Ab/complement toxicity
How does being an obligate aerobe contribute to MTB virulence?
Can live in upper lobes of lungs
How does having peptidoglycan + lots of lipoproteins contribute to MTB virulence?
Antibiotic resistance Resistance to complement lysis Resistance to stains Resistance to acid or base compounds Can live in macrophages
How does binding to mannose, complement, and Fc receptors of macrophages contribute to MTB virulence?
Allows cell entry
What is antigen 85 and how does it contribute to MTB virulence?
Group of proteins secreted by MTB that bind fibronectin and wall off the bacteria from immune cells + facilitate tubercle formation
How does the slow generation of TB contribute to virulence of MTB?
Can grow under the radar of immune cells
Characteristic of MTB culture
Serpentine cord colonies due to cord factor
Only virulent strains of MTB produce:
Cord factor
Characteristic of MTB gram stain
Ghost cells - mycolic acid repels the stain, causing cleared areas that resemble empty cells/ghosts
Name of acid-fast technique? How does it work?
Ziehl-Neelsen stain
Stain with carbolfuschin (pink dye) then decolorized with acid; holds “fast” to the pink stain
3 lipid proteins of MTB cell wall
- Mycolic acid
- Wax D
- Cord factor
To which MTB lipoprotein does carbolfuschin bind?
Mycolic acid
What is the function of mycolic acid?
Reduces permeability of MTB to ROS of macrophages
What is the function of cord factor?
2 mycolic acids + disaccharide that allows parallel growth of MTB (serpentine colonies) and inhibits PMN migration and complement deposition
What is the function of wax D?
Part of lipid envelope; major component of Freund’s complete adjuvant (solution used to boost immunity)
TB infection vs. disease
Infection = immune system controlling MTB Disease = immune system unable to control MTB
When is MTB contagious?
During disease!!
How does immune system control MTB?
Surrounds tubercles with macrophages, forming a hard shell that keeps MTB from spreading
1 predisposing factor for MTB
HIV
___% of people exposed with TB get infected
___% of people infected with TB get disease
25%
10%
___% of AIDS patients have TB
10% (400x general population)
(T/F): Most people infected with TB progress through stage 5 of the disease
False - only 10% infected develop disease, and only a small % of those will progress to stage 5
Stage 1
Inhaled MTB taken up by alveolar macrophages
Most infective droplet nuclei?
5 micrometers
Nuclei droplet contain ~ ___ TB
3
What happens to large droplet nuclei?
Deposit in URT where they do not cause infection
Stage 2
MTB replicates in alveolar macrophages but they’re inactive so they can’t kill MTB; additional inactive macrophages recruited; can spread to lymph nodes via macrophages
Time course of stage 2
Begins 7-21 days after infection
Stage 3
Cell-mediated response
T cells release IFy –> activate macrophages –> destroy TB –> macrophages release lytic factors that cause tissue damage and tubercle formation
Time course of stage 3? Significance?
6-10 weeks post infection
This is when skin test will be +; must re-test pt 2 months later if skin test -
What is a tubercle?
Caseating granuloma lined by macrophages; MTB can’t multiply within these granulomas due to low pH and anoxic environment but they persist there
Stage 4
Inactivated macrophages recruited by MTB for replication –> tubercle grows –> can spread to bronchus or blood vessel –> miliary TB
Two types of lesions in milliary TB
- Exudative - PMNs surround MTB and they replicate without restriction = soft tubercle
- Productive or granulomatous - host becomes hypersensitive to tuberculoproteins = hard tubercle
Stage 5
Center of tubercle caseates/liquifies which is conducive to MTB growth –> MTB grows extracellularly –> invades bronchus –> bronchus necrosis –> cavity and spread of MTB
Two routes cavity can take:
- Heals and undergoes calcified fibrosis –> Gohn complex
2. Small metastatic foci heal and undergo calcified fibrosis –> Simon foci
How do Gohn complex/Simon foci lead to reactivation?
Contain viable MTB
When is TB considered MDR TB?
Resistant to 2+ Abx
Typical regimen for TB and duration of tx?
RIPE (rifampin, isoniazid, pyrazinamide, ethambutol)
6-9 months
Who would you expect to see XDR TB in?
HIV
Foreign-born
Reactivation TB
Ways to diagnose TB
- PPD skin test
- Acid-fast stain
- CXR
- Culture
How does PPD skin test work?
Inject pt with purified protein derivative (PPD; usually tuberculin); if macrophages have been activated, you will get a red welt
How long do you wait before reading TB skin test?
72 hours
What would you see on CXR of primary TB?
Pleural effusion of any lobe + lymphadenopathy
What would you see on CXR of reactivated TB?
Consolidation in upper lobe only + cavitations
What would you see on CXR of milliary TB?
Caseating granulomas
What is difficult about culture of MTB from sputum?
Slow growing so takes up to 4 weeks for dx; Abx resistance testing can take additional time
Why might someone born outside US have + PPD?
Vaccinated or exposed to TB
Could someone have a true + PPD without having MTB?
Yes - could have another strain of mycobacterium
Why must you never give only a single agent in tx of TB?
Development of resistance; must give at least 4
Name of TB vaccine? Type?
BCG
Live attenuated M. bovis
Why don’t we give BCG in US?
- Makes PPD ineffective
- Can’t circumvent disease reactivation
- It can’t prevent infection, only disease