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HDID Block 2 > L43 > Flashcards

L43 Flashcards

1
Q

Where is TB epidemic in the world?

A

Asia

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2
Q

How is TB transmitted?

A

Haling infectious droplets from someone who is actively infected
Droplets can persist in air for hours

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3
Q

Which patient populations are at high risk for developing TB?

A 
Anyone in close contact with infected person
Immigrants
*HIV 
* Diabetics 
Homeless 
Incarcerated
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4
Q

What are 4 risk factors for getting TB?

A
  1. Being around a TB infected person
  2. Infectiousness of the TB case
  3. Proximity
    Duration
    Frequency of exposure
  4. [M.TB] due to environmental factors
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5
Q

What are the 3 layers of the mycobacterial cell wall?

A 
Inner = peptidoglycan 
Middle = arabinoglactan
Outer = mycolic acid layer
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6
Q

What is unique about the mycobacterium peptidoglycan layer vs other GP organism?

A

3-3 cross linked (vs 4-3)

Glycolylation of NAM residues

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7
Q

Describe the composition of the mycolic acid layer.

A 
Free lipids ("waxy") + lipoglycans 
Why acid fast
Where microbe interacts w/ phagocytic cells
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8
Q

Which of the cell layers is targeted by TB drugs?

A

Mycolic acid layer (b/c most unique distinguisher)

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9
Q

Describe the infection path of TB once inhaled.

A

Wk 1 = Form bacilli - ingested by alveolar macrophages & dendritic cells
Wk 2 = Bacilli multiple in the macrophages - while APCs migrate to lymph node
Wk 3 = Th1 cytokines activate macrophages
Wk 4 = granuloma formation

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10
Q

What are the M.TB virulence factors?

A

LAM & manLAM
PIM
Trehalose dimycolate = cord factor

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11
Q

Explain the normal macrophage autophagy rxn.

A

Phagosome uses activated vitamin D3 (1,25(OH2)D3)
Creates CATHELICIDIN
Tags phagosome for autophagy = intracell bacterial elimination

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12
Q

How does M.TB stop normal phagocytic destruction in macrophages?

A
  1. ManLAM & cord factor = X phago-lysosome fusion
  2. Escape the phagosome via ESX1
  3. Detox normally produced ROS/RNS
  4. Inhibit lipoxane A4 mediated apoptotic pathway
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13
Q

Why does M.TB want to push a macrophage toward necrosis instead of apoptosis?

A

NECROSIS:

  • Less controlled
  • More bacterial release from intracell contents
  • Less effective antigen presentation to other immune cells = persistent infection
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14
Q

Which M.TB virulence factor helps to recruit uninfected macrophages to the primary site of infection?

A

ESX1

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15
Q

Describe granuloma formation.

A

Form multi-nucleated giant cells
1. = sanctuary for bacterial growth
2. Best site for interaction between infected APCs & effector T cells
See shift from favroable to bacteria growth –> favorable for immune response

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16
Q

Why are granulomas able to contain infection?

A

Restrict O2 & nutrients

Keep bacteria in acidic pH

17
Q

What is the role of TNFalpha in the immune response to M.TB?

A

Released by infected APCs & effector T cells
Activates macrophages
Maintains granumolas!

18
Q

What is the role of IFNg in the immune response to M.TB?

A
  1. Released by infected APCs & effector T cells
  2. Activates macrophages
  3. Autophagy
  4. Maintain granuloma
19
Q

What is the role of IL12 in the immune response to M.TB?

A

Secreted by infected APCs only!

Th –> Th1 maturation

20
Q

What is the relationship between Th1 & Th2 immune responses in TB?

A

If increased Th2 response (ongoing parasite infection) - decreased Th1 response
- Impaired autophagy

21
Q

What are TB lesions called? How do these heal?

A

@ lung = Ghon focus
@ LN = Ghon complex
Heal via calcification

22
Q

How do you detect latent TB?

A

CANNOT culture bacteria in granulomas
Must do PPD or IGRA
- May or may not see granulomas on CXR

23
Q

Describe the tuberculin skin test.

A

= PPD
Acellular protein of inactivated M.TB
Type 4 delayed HST rxn
Will get cross rxn w/ environmental mycobacteria & BCG vaccine

24
Q

What do you give with PPD if you think someone might be anergic? (yielding a false negative)

A

+ Candida
Rx to neither = anergy
Rx to candida only = true negative

25
Q

What is the size for a positive PPD?

A

15 mm = normal people
10 mm = high risk people
5 mm = recent contacts, HIV, immune suppressed, h/o lung lesions

26
Q

Describe an IGRA.

A

= measurement of much IFNg is released in response to MtB antigen stimulation
Quantiferon-gold assay
- 1 time visit
- Blood draw (don’t infect someone with Mtb)
- More reliable b/c less variable

27
Q

What do you do if a PPD or IGRA is positve?

A

CXR - to rule in/out ACTIVE TB

28
Q

How do you treat latent TB?

A

Isoniazid for 9 mo

Other options require LFT

29
Q

What are the side effects of isoniazid? When would to stop treatment early?

A 
N/V
RUQ pain
Dark urine
Rash
Fever
STOP
- 5x increase transaminases 
- 3x increase + symptoms

HDID Block 2 (39 decks)

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