Tuberculosis Flashcards
Mycobacterium tuberculosis is a facultative intracellular pathogen that causes chronic pneumonia; it is transmitted via _
Mycobacterium tuberculosis is a facultative intracellular pathogen that causes chronic pneumonia; it is transmitted via aerosols
(T/F) Of individuals exposed, about 70% of individuals will be able to eliminate the pathogen
True; Of individuals exposed, about 70% of individuals will be able to eliminate the pathogen
* It is an opportunistic pathogen
The 30% of individuals exposed to TB will have a primary infection characterized by _
The 30% of individuals exposed to TB will have a primary infection characterized by mild symptoms, ghon complex
Primary TB involves caseating necrosis in the _ lobe and _ lymph node
Primary TB involves caseating necrosis in the lower lung lobe and hilar lymph nodes
Most individuals with primary TB will next go into a _ phase
Most individuals with primary TB will next go into a latent infection phase
* Primary phase: macrophages have phagocytosed the bacteria; bacteria grew intracellularly
* Latent phase: granuloma formation walls off infection
TB has a virulence factor called _ that inhibits _ and allows the bacteria to replicate inside the phagosome of the macrophages
TB has a virulence factor called sulfatides that inhibit phagosome-lysosomal fusion and allow the bacteria to replicate inside the phagosome of the macrophages
Macrophages recognize the PAMPs and release cytokines such as _
Macrophages recognize the PAMPs and release cytokines such as IL-1, IL-6, TNF-alpha
_ is the cytokine responsible for causing aggregation of macrophages and walling off the infection
TNF-alpha is the cytokine responsible for causing aggregation of macrophages and walling off the infection
Both _ cells and cord factor are releasing TNF-alpha
Both macrophages and cord factor are releasing TNF-alpha
Fibrocaseous cavitary lesions are associated with _ stage of TB
Fibrocaseous cavitary lesions are associated with reactivated TB
In a minority of patients, they are not able to wall of the primary infection and go into _
In a minority of patients, they are not able to wall of the primary infection and go into progressive primary TB
* Immune system fails to control
* Bateria replicating in the macrophage burst out and release the bacteria
* Granulomas enlarg and bacteria is draining into hilar lymph (ghon complex)
If progressive primary TB travels into the blood, we can see _ stage
If progressive primary TB travels into the blood, we can see miliary TB
Classic symtoms of TB are those seen in reactivation like _
Classic symtoms of TB are those seen in reactivation like fever, night sweats, fatigue, productive cough, blood-tinged sputum
During reactivation, the enlarged granulomas can liquefy in the center (central necrosis) causing _
During reactivation, the enlarged granulomas can liquefy in the center (central necrosis) causing lung cavities with replicating bacteria –> highly infectious
Explain the steps of the initial MTB immune response
- Macrophages have TLR that recognize the PAMPs
- Macrophages secrete IL-12
- IL-12 activates Th1 cells
- The T cells secrete IFN-gamma that activate the macrophages
- Macrophages secrete TNF-alpha
- Granuloma formation controls the infection
Granulomas are formed by macrophages, T cells, and multi-nucleated _ cells
Granulomas are formed by macrophages, T cells, and multi-nucleated Langhan cells
_ and _ are TB virulence factors that detoxify oxygen radicals and hydrogen peroxide to stay alive
Catalase and Peroxidase are TB virulence factors that detoxify oxygen radicals and hydrogen peroxide to stay alive
* We actually rely on the action of catalase to activate the drug isoniazid from its prodrug form
TB that carries mutations in _ or _ gene may be resistant to isoniazid
TB that carries mutations in KatG or InhA gene may be resistant to isoniazid
The Tuberculin Skin Test works by looking for a _
The Tuberculin Skin Test works by looking for a delayed-type hypersensitivity response to antigens from M.bovis
* May get a falsely positive test if previously vaccinated against TB
Quantiferon-Gold TB test measures _
Quantiferon-Gold TB test measures interferon gamma produced by T cells
* Does not cross react with the BCG vaccine (those vaccinated should not have false positives)
Isoniazid works by inhibiting _
Isoniazid works by inhibiting mycolic acid synthesis
* Specifically targeting the InhA enzyme
Isoniazid is ineffective against strains of TB with mutated _ or _ genes
Isoniazid is ineffective against strains of TB with mutated KatG or InhA genes
* KatG is required to activate the prodrug
* InhA is the enzyme that is targeted so altering it makes the drug ineffective
Rifampin is a TB drug that works by inhibiting _
Rifampin is a TB drug that works by inhibiting mRNA synthesis
* Blocks RNA polymerase
The P drug in RIPE stands for _ ; its mechanism is unknown
The P drug in RIPE stands for pyrazinamide ; its mechanism is unknown
Ethambutol is a TB drug that works by inhibiting _ enzyme
Ethambutol is a TB drug that works by inhibiting arabinosyl transferase
* It inhibits arabinoglycan synthesis
* This is a component of the cell wall
The most classic drug regimen for treating latent TB is the combination of _ + _
The most classic drug regimen for treating latent TB is the combination of rifampin + isoniazid
When treating latent TB, rifampin and isoniazid must be combined for _ months or Rifampin alone for _ months, isoniazid alone for _ months
When treating latent TB, rifampin and isoniazid must be combined for 3 months or Rifampin alone for 4 months or Isoniazid alone for 9 months
For active TB we most commonly use _ drugs for the first 2 months, followed by _ for 6 months
For active TB we most commonly use all 4 RIPE drugs for the first 2 months, followed by 2-3 RIPE drugs for 6 months
* Alternatively we can use 9 months of Rifampin + Isoniazid
To treat drug resistant TB we must use _ drugs for the first 8 months followed by _ for the following months
To treat drug resistant TB we must use 5 drugs for the first 8 months followed by 3-4 drugs for the following 12 months
Amikacin is a common second line drug used against TB that _ (MOA)
Amikacin is a common second line drug used against TB that binds 30S ribosomal subunit (aminoglycoside)
_ is a second line drug for TB that works by inhibiting topoisomerase/gyrase
Ciprofloxacin is a second line drug for TB that works by inhibiting topoisomerase/gyrase
Ethionamide is a second line drug for TB that works via _
Ethionamide is a second line drug for TB that works via inhibition of mycolic acid synthesis
Cycloserine is a second line TB drug that works by inhibiting _
Cycloserine is a second line TB drug that works by inhibiting cell wall synthesis
Multidrug resistant TB has resistance against _
Multidrug resistant TB has resistance against Isoniazid + Rifampin
XDR TB means _
XDR TB means extensively resistant TB
* Resistant to isoniazid, rifampin, any fluoroquinolone, and at least one aminoglycoside
_ is a TB drug that can turn the skin, urine, feces, saliva, or tears orange/yellow
Rifampin is a TB drug that can turn the skin, urine, feces, saliva, or tears orange/yellow
Rifampin has _ effect on CYP 450 enzymes
Rifampin induces CYP450
* Means that it will make other drugs less effective
* Specifically problematic for HIV patients because RT inhibitors and protease inhibitors will be less effective
Many individuals have polymorphisms in the host _ enzyme that causes variable response to isoniazid
Many individuals have polymorphisms in the host NAT2 enzyme that causes variable response to isoniazid
* If N-acetyltransferase does not function properly, we can get a build up of toxic metabolites that lead to increased toxicities
* Lots of Americans are “slow acetylators”
A patient on Isoniazid should be given _ supplements due to the risk of _ side effects
A patient on Isoniazid should be given B6 supplements due to the risk of neurological side effects
* Isoniazid inhibits the synthesis of B6 which can lead to peripheral neuropathy
_ is a TB drug that is known to cause Red/Green colorblindness
Ethambutol is a TB drug that is known to cause Red/Green colorblindness
