L43 Flashcards
Where is TB epidemic in the world?
Asia
How is TB transmitted?
Haling infectious droplets from someone who is actively infected
Droplets can persist in air for hours
Which patient populations are at high risk for developing TB?
Anyone in close contact with infected person Immigrants *HIV * Diabetics Homeless Incarcerated
What are 4 risk factors for getting TB?
- Being around a TB infected person
- Infectiousness of the TB case
- Proximity
Duration
Frequency of exposure - [M.TB] due to environmental factors
What are the 3 layers of the mycobacterial cell wall?
Inner = peptidoglycan Middle = arabinoglactan Outer = mycolic acid layer
What is unique about the mycobacterium peptidoglycan layer vs other GP organism?
3-3 cross linked (vs 4-3)
Glycolylation of NAM residues
Describe the composition of the mycolic acid layer.
Free lipids ("waxy") + lipoglycans
Why acid fast
Where microbe interacts w/ phagocytic cellsWhich of the cell layers is targeted by TB drugs?
Mycolic acid layer (b/c most unique distinguisher)
Describe the infection path of TB once inhaled.
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
What are the M.TB virulence factors?
LAM & manLAM
PIM
Trehalose dimycolate = cord factor
Explain the normal macrophage autophagy rxn.
Phagosome uses activated vitamin D3 (1,25(OH2)D3)
Creates CATHELICIDIN
Tags phagosome for autophagy = intracell bacterial elimination
How does M.TB stop normal phagocytic destruction in macrophages?
- ManLAM & cord factor = X phago-lysosome fusion
- Escape the phagosome via ESX1
- Detox normally produced ROS/RNS
- Inhibit lipoxane A4 mediated apoptotic pathway
Why does M.TB want to push a macrophage toward necrosis instead of apoptosis?
NECROSIS:
- Less controlled
- More bacterial release from intracell contents
- Less effective antigen presentation to other immune cells = persistent infection
Which M.TB virulence factor helps to recruit uninfected macrophages to the primary site of infection?
ESX1
Describe granuloma formation.
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
Why are granulomas able to contain infection?
Restrict O2 & nutrients
Keep bacteria in acidic pH
What is the role of TNFalpha in the immune response to M.TB?
Released by infected APCs & effector T cells
Activates macrophages
Maintains granumolas!
What is the role of IFNg in the immune response to M.TB?
- Released by infected APCs & effector T cells
- Activates macrophages
- Autophagy
- Maintain granuloma
What is the role of IL12 in the immune response to M.TB?
Secreted by infected APCs only!
Th –> Th1 maturation
What is the relationship between Th1 & Th2 immune responses in TB?
If increased Th2 response (ongoing parasite infection) - decreased Th1 response
- Impaired autophagy
What are TB lesions called? How do these heal?
@ lung = Ghon focus
@ LN = Ghon complex
Heal via calcification
How do you detect latent TB?
CANNOT culture bacteria in granulomas
Must do PPD or IGRA
- May or may not see granulomas on CXR
Describe the tuberculin skin test.
= PPD
Acellular protein of inactivated M.TB
Type 4 delayed HST rxn
Will get cross rxn w/ environmental mycobacteria & BCG vaccine
What do you give with PPD if you think someone might be anergic? (yielding a false negative)
+ Candida
Rx to neither = anergy
Rx to candida only = true negative
What is the size for a positive PPD?
15 mm = normal people
10 mm = high risk people
5 mm = recent contacts, HIV, immune suppressed, h/o lung lesions
Describe an IGRA.
= 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
What do you do if a PPD or IGRA is positve?
CXR - to rule in/out ACTIVE TB
How do you treat latent TB?
Isoniazid for 9 mo
Other options require LFT
What are the side effects of isoniazid? When would to stop treatment early?
N/V RUQ pain Dark urine Rash Fever STOP - 5x increase transaminases - 3x increase + symptoms
