Chronic Frustrated Flashcards

1
Q

Describe the normal situation in the gut. Talk about Peyer’s Patches, TGF-beta, and Tregs

A
  • A lot of TGF-beta in Peyer’s Patches —» differentiation of Th0 to Treg
  • DCs in PPs make IL-10 —» favors Treg development
  • Large Treg presence is desirable b/c of constant exposure to bacteria/food (aka Ags) coming through gut epithelium
  • Tfh also in PPs —» cause B cells to produce IgA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the situation in the gut when there is stress or damage. Talk about Il-6, Th1, Th2, Th17, and Tregs

A
  • IL-6 produced as a response to stress/damage

- Combo of TGF-beta and IL-6 downregulates Treg and upregulate Th1/2/17

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe IBD

A
  • Includes Crohn Disease and ulcerative colitis
  • Both thought to involve dysregulated immune responses to bacteria
    CD: affects large/small intestine, especially terminal ileum — microabcesses –» generalized inflammation
    UC: usually more superficial in large intestine - can erode surface —» bleeding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Discuss the relative influence of environment and genetics on the risk of IBD

A
  • GWAS have identified 163 loci associated for increased risk of IBD —» strong genetic component
  • HOWEVER, concordance in monozygotic twins is only 30-35% for CD and 10-15% for UC —» environmental factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is tissue transglutaminase 2?

A

TG2

  • The autoAg in celiac disease
  • Normally makes protein crosslinks through glutamines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the pathogenesis of celiac disease

A
  • TG2 couples to but can’t release wheat peptides —» becomes an autoAg —» B cell presents it via foreign + self hybrid to Tfh
  • Tfh w/ HLA DQ2/8 recognize autoAg and stimulate Ab production in B cells
  • Leads to: inflammation, gut becomes battleground —» flattening of villi and decreased absorption
    OVERALL: Ab doesn’t cause the disease, but Ab is caused by disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Discuss the importance of HLA alleles in celiac disease

A
  • 90% of those w/ celiac have HLA-DQ2, the rest DQ8 (but most of the people w/ these don’t get celiac)
  • Only people w/ these surface receptors can respond to the autoAg presented by B cell
  • Therefore autoAg can be presented, but w/o stimulation disease does not occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the mechanism of chronic beryllium disease

A
  • A pulmonary inflammatory and fibrotic disease – caused by inhaling beryllium dust
  • Be become covalently linked to peptides —»> creates novel epitopes
  • Th1/17 respond to these epitopes, and late Th2 responds w/ scarring
  • Be can’t be removed by macros —» therefore disease is established and chronic after one exposure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the Hygiene hypothesis? Which observations support it?

A
  • Theorized that exposure to environmental dirt/infections helped immune system mature normally (Th2 dominated —> balanced btwn Th1 and Th2)
  • Evidence: Poor/equatorial countries, large families all head less of an increase in asthma/allergies
    BUT — rich, clean peeps have increased risk for Th1 disease like IBD, DM Type 1 (should be more susceptible to Th2)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the Old Friends hypothesis? Which observations support it?

A
  • Says certain harmless microorgs have been in humans so long that we rely on their presence to instruct our immune systems
  • Adequate exposure to these “old friends” —» develop balance btwn activation (Th1/2/17) and regulation (Treg)
  • W/o these “old friends”, there are too few Tregs and too many Th1/2/17 when there isn’t anything threatening to respond to —» attacks normal gut flora or pollen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How might it be possible to switch the Th1/2/17 responses to Treg?

A
  • Based on an experiment w/ persons w/ severe CD and UC
  • Ingesting whipworms (only live a few days in gut, safe)
  • Increased Treg production in gut —» suppresses Th1/2/17 responses
  • But remember too much Treg —»> immunosuppression also (can’t have any responses via Th1/2/17)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly