Tuberculosis

Question 1

Mycobacterium tuberculosis is a facultative intracellular pathogen that causes chronic pneumonia; it is transmitted via _

Answer 1

Mycobacterium tuberculosis is a facultative intracellular pathogen that causes chronic pneumonia; it is transmitted via aerosols

Question 2

(T/F) Of individuals exposed, about 70% of individuals will be able to eliminate the pathogen

Answer 2

True; Of individuals exposed, about 70% of individuals will be able to eliminate the pathogen
* It is an opportunistic pathogen

Question 3

The 30% of individuals exposed to TB will have a primary infection characterized by _

Answer 3

The 30% of individuals exposed to TB will have a primary infection characterized by mild symptoms, ghon complex

Question 4

Primary TB involves caseating necrosis in the _ lobe and _ lymph node

Answer 4

Primary TB involves caseating necrosis in the lower lung lobe and hilar lymph nodes

Question 5

Most individuals with primary TB will next go into a _ phase

Answer 5

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

Question 6

TB has a virulence factor called _ that inhibits _ and allows the bacteria to replicate inside the phagosome of the macrophages

Answer 6

TB has a virulence factor called sulfatides that inhibit phagosome-lysosomal fusion and allow the bacteria to replicate inside the phagosome of the macrophages

Question 7

Macrophages recognize the PAMPs and release cytokines such as _

Answer 7

Macrophages recognize the PAMPs and release cytokines such as IL-1, IL-6, TNF-alpha

Question 8

_ is the cytokine responsible for causing aggregation of macrophages and walling off the infection

Answer 8

TNF-alpha is the cytokine responsible for causing aggregation of macrophages and walling off the infection

Question 9

Both _ cells and cord factor are releasing TNF-alpha

Answer 9

Both macrophages and cord factor are releasing TNF-alpha

Question 10

Fibrocaseous cavitary lesions are associated with _ stage of TB

Answer 10

Fibrocaseous cavitary lesions are associated with reactivated TB

Question 11

In a minority of patients, they are not able to wall of the primary infection and go into _

Answer 11

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)

Question 12

If progressive primary TB travels into the blood, we can see _ stage

Answer 12

If progressive primary TB travels into the blood, we can see miliary TB

Question 13

Classic symtoms of TB are those seen in reactivation like _

Answer 13

Classic symtoms of TB are those seen in reactivation like fever, night sweats, fatigue, productive cough, blood-tinged sputum

Question 14

During reactivation, the enlarged granulomas can liquefy in the center (central necrosis) causing _

Answer 14

During reactivation, the enlarged granulomas can liquefy in the center (central necrosis) causing lung cavities with replicating bacteria –> highly infectious

Question 15

Explain the steps of the initial MTB immune response

Answer 15

1. Macrophages have TLR that recognize the PAMPs
2. Macrophages secrete IL-12
3. IL-12 activates Th1 cells
4. The T cells secrete IFN-gamma that activate the macrophages
5. Macrophages secrete TNF-alpha
6. Granuloma formation controls the infection

Question 16

Granulomas are formed by macrophages, T cells, and multi-nucleated _ cells

Answer 16

Granulomas are formed by macrophages, T cells, and multi-nucleated Langhan cells

Question 17

_ and _ are TB virulence factors that detoxify oxygen radicals and hydrogen peroxide to stay alive

Answer 17

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

Question 18

TB that carries mutations in _ or _ gene may be resistant to isoniazid

Answer 18

TB that carries mutations in KatG or InhA gene may be resistant to isoniazid

Question 19

The Tuberculin Skin Test works by looking for a _

Answer 19

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

Question 20

Quantiferon-Gold TB test measures _

Answer 20

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)

Question 21

Isoniazid works by inhibiting _

Answer 21

Isoniazid works by inhibiting mycolic acid synthesis
* Specifically targeting the InhA enzyme

Question 22

Isoniazid is ineffective against strains of TB with mutated _ or _ genes

Answer 22

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

Question 23

Rifampin is a TB drug that works by inhibiting _

Answer 23

Rifampin is a TB drug that works by inhibiting mRNA synthesis
* Blocks RNA polymerase

Question 24

The P drug in RIPE stands for _ ; its mechanism is unknown

Answer 24

The P drug in RIPE stands for pyrazinamide ; its mechanism is unknown

Question 25

Ethambutol is a TB drug that works by inhibiting _ enzyme

Answer 25

Ethambutol is a TB drug that works by inhibiting **arabinosyl transferase** * It inhibits arabinoglycan synthesis * This is a component of the cell wall

Question 26

The most classic drug regimen for treating latent TB is the combination of _ + _

Answer 26

The most classic drug regimen for treating latent TB is the combination of **rifampin** + **isoniazid**

Question 27

When treating latent TB, rifampin and isoniazid must be combined for _ months or Rifampin alone for _ months, isoniazid alone for _ months

Answer 27

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**

Question 28

For active TB we most commonly use _ drugs for the first 2 months, followed by _ for 6 months

Answer 28

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

Question 29

To treat drug resistant TB we must use _ drugs for the first 8 months followed by _ for the following months

Answer 29

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

Question 30

Amikacin is a common second line drug used against TB that _ (MOA)

Answer 30

Amikacin is a common second line drug used against TB that **binds 30S ribosomal subunit** (aminoglycoside)

Question 31

_ is a second line drug for TB that works by inhibiting topoisomerase/gyrase

Answer 31

**Ciprofloxacin** is a second line drug for TB that works by inhibiting topoisomerase/gyrase

Question 32

Ethionamide is a second line drug for TB that works via _

Answer 32

Ethionamide is a second line drug for TB that works via **inhibition of mycolic acid synthesis**

Question 33

Cycloserine is a second line TB drug that works by inhibiting _

Answer 33

Cycloserine is a second line TB drug that works by inhibiting **cell wall synthesis**

Question 34

Multidrug resistant TB has resistance against _

Answer 34

Multidrug resistant TB has resistance against **Isoniazid + Rifampin**

Question 35

XDR TB means _

Answer 35

XDR TB means *extensively resistant TB* * Resistant to isoniazid, rifampin, any fluoroquinolone, and at least one aminoglycoside

Question 36

_ is a TB drug that can turn the skin, urine, feces, saliva, or tears orange/yellow

Answer 36

**Rifampin** is a TB drug that can turn the skin, urine, feces, saliva, or tears orange/yellow

Question 37

Rifampin has _ effect on CYP 450 enzymes

Answer 37

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

Question 38

Many individuals have polymorphisms in the host _ enzyme that causes variable response to isoniazid

Answer 38

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"

Question 39

A patient on Isoniazid should be given _ supplements due to the risk of _ side effects

Answer 39

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*

Question 40

_ is a TB drug that is known to cause Red/Green colorblindness

Answer 40

**Ethambutol** is a TB drug that is known to cause Red/Green colorblindness