Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Gastrointestinal II Exam #1 > Immuno-pathogenic Mechanisms of IBD > Flashcards

Immuno-pathogenic Mechanisms of IBD Flashcards

1
Q

UC =

CD =

What feature is key to both diseases?

A

Chronic inflammation and ulcers in the innermost lining of the colon and/or rectum

Inflammation of the lining of the GI tract, which often spreads deep into affected tissues - may happen in any part of the GI tract

Chronic relapsing idiopathic inflammation of the GI tract

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

Patients with IBD are known to have what 2 major defects of the colon?

A

Increased intestinal permeability (impaired tight junctions) + irreversible impairment of GI structure/function

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

What is the mechanism for sustained mucosal inflammation in IBD?

A

Commensal bacteria of normal intestinal microbiota causes the self-sustained inflammation of the mucosa.

They cross the mucosal barrier and induces both an innate and an adaptive response

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

IBD develops as a result of: (2)

A

Dysbiosis + mucosal inflammation

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

Disruption of barrier function occurs mainly in which form of IBD?

A

UC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Dysfunction of microbe sensing occurs mainly in which form of IBD?

A

CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which Ab tests are positive in CD vs. UC?

The combo of what outcomes is a 96% predictive value for CD?

A

ASCA-positive - CD

pANCA-positive - UC

Positive ASCA and a negative pANCA = 96% predictive value for CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the concordance rates in CD vs UC?

What does it mean?

A

50% for CD
10% for UC

Means that environmental factors are huge (moreso in UC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where does IBD tend to develop?

The use of what drugs have beneficial effects on IBD?

What circulating Abs are detected in IBD?

A

High bacterial concentration

Abx and probiotics

Circulating Abs against fecal bacterial Ags

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which 2 phyla are predominant in the gut microbiome?

A

Bacteriodes (Bacteriodes and Prevotella) - majority (approx. 70%)

Firmicutes (Clostridium and Lactobacillus)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which microbe becomes overwhelming in UC?

A

Proteobacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which microbes become overwhleming in CD?

A

Firmicutes and Actinobacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the evidence for importance of GI microbiota in IBD pathogenesis? (2)

A

The rat study: rats kept in a sterile environment were then introduced into the world (now infected with commensal bacteria) showed an *exaggerated response.

The baby study: babies to IBD women (low microbial diversity and altered composition) were at a greater risk for developing IBD. Mom’s microbiome is the main predictor of the diversity of the infant’s microbiome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

No specific microbes have been linked to the development of IBD.

However, what are 3 implicated agents?

What kind of infection may also play a role?

What infection is inversely associated with IBD prevalence?

A

M. paratuberculosis, Paramyxovirus (measles), Listeria

Gastroenteritis - Salmonella and Campylobacter

Helminth colonization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which populations are unlikely to develop IBD?

A

Asian and African populations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What locus on what chromosome causes susceptibility toward IBD?

Which 2 genes are contained within the locus?

A

IBD-1 gene on chr. 16

CARD and NOD2 genes

17
Q

CARD15 is primarily expressed in which cells?

What can cause a 20x increased risk for developing CD?

What is the function of CARD15 normally?

What pathway does it trigger?

A

Mo and DCs

Homozygous pts. for SNPs of CARD15

Intracellular PPR that recognizes MDP (on both G+ or G- bacteria)

Activates NK-kB

18
Q

What are 3 possible mechanisms of CD caused by mutations in NOD2?

A
  1. Defective function of Mo
  2. Defective epithelial-cell responses - loss of function of barrier and increased exposure to microflora
  3. Defective “conditioning” of APCs - inappropriate activation
19
Q

How does normal GI flora maintain homeostasis? (3)

A

Colonization of GI tract induces GALT development.
+
Microbiota maintains the basal level of Th17 and Th1 cell activity in the lamina propria.
+
Pathobionts are directly suppressed by commensal bacteria partly through induction of Tregs and IL-10.

All of these improve barrier function.

20
Q

What is produced by commensal bacteria frmo non-digestable polysaccharides?

What is their effect?

A

SCFAs

Anti-inflammatory properties in Mo, DCs, CD4+ and intestinal epithelial cells.

21
Q

Intestinal colonization of which bacteria results in induction of Treg cells in the lamina propria?

SFB also plays a role in the basal activation level of what cells?

A

Segmented filamentous bacteria (SFB), Bacteriodes fragilis and Clostridium spp.

Th17 cells, which are important for integrity of the epithelial barrier.

22
Q

What is the mucosal firewall composed of? (5)

What is its function?

A 
Epithelial barrier
Mucous layer
IgA
DCs
T cells

It prevents passage/exposure of commensals to the GALT and unnecessary activation/pathology.

23
Q

What pathway is suppressed by commensal microbiota?

A

NF-kB

24
Q

In the absence of commensal Bacteriodes, what happens with Salmonella?

A

Its flagellin binds to TLR5 intestinal epithelial cells (IECs), which activate NF-kB which mediated transcription of pro-inflammatory genes

25
Q

Chronic inflammation of the gut involves hyperactivation of which cells?

Which cells are inhibited?

A

+ Th1 and Th17

  • Treg cells producing IL-10
26
Q

What are the 4 overall major phases of development of IBD?

A
  1. Genetics/environment induce impaired barrier function in the intestinal mucosa.
  2. Altered barrier function induces translocation of commensal bacteria which activate immune cells and cytokines.
  3. If an acute inflammation cannot be resolved by anti-inflammatory mechanisms and leads to chronic intestinal inflammation.
  4. Chronic inflammation may lead to complications like fibrosis, stenosis, fistula and cancer.
27
Q

Which cells and cytokines are involved mostly in CD?

What cytokines induce activation of these cells?

A

Th1 (IFN-y and TNF) and Th17 (IL-17 and TNF)

Th1 and Th17 are driven by IL-12, IL-6 and IL-23 produced by DCs

28
Q

Which cells and cytokines are involved mostly in UC?

A

Th2 (IL-4, IL-5, IL-13)

29
Q

Which cytokines activate Th1?

Which cytokines activate Th2?

Which cytokines activate Th17?

What cells produce IL-23?

A

Th1: IL-12

Th2: IL-4

Th17: IL-6, IL-23, TGF-beta

Mo and DCs

30
Q

Which 2 cytokines activate Treg cells? What do they do once activated?

A

IL-2 and TGF-beta activate Tregs which inhibit Th17 cells via retinoic acid.

31
Q

What 2 receptors are constitutively expressed on Tregs?

What do the Tregs do once activated?

A

CTLA-4 and an alpha subunit of IL-2 receptor (CD25)

They can suppress APCs directly via cell-to-cell interactions or indirectly through inhibitory cytokines

32
Q

What drug is used for IBD?

A

TNF blockers

Gastrointestinal II Exam #1 (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions