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04. GI > Immuno pathogenic mechanisms of IBD > Flashcards

Immuno pathogenic mechanisms of IBD Flashcards

1
Q

ulcerative colitis

A

characterized by chronic inflammation and ulcers in the innermost lining of the colon and/or rectum

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2
Q

crohn’s disease

A

characterized by inflammation of the lining of the GI which often spreads deep into affected tissues and may occur in any part of the GI tract

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3
Q

IBD

A

an inappropriate and exaggerated mucosal immunity to normal flora

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4
Q

UC/ CD is the rectum spared?

A 
UC = not spared
CD = spared 40% of the time
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5
Q

dysbiosis

A

condition in which there is disequilibrium of the microbial communities that constitute the microbiota at a given body site

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6
Q

What type of IBD shows string sign on barium x-ray?

A

crohn’s disease

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7
Q

what type of IBD shows lead pipe sign on barium x-ray?

A

ulcerative colitis

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8
Q

What type of IBD has a positive ASCA test?

A

Crohn’s disease

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9
Q

what type of IBD has a positive pANCA test?

A

ulcerative colitis

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10
Q

what type of IBD has cobblestone appearance on endoscopy?

A

Crohn’s disease

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11
Q

What type of gene editing is associated with IBD?

A

Single nucleotide polymorphisms (SNPs): loci variants with alleles that differ at a single base

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12
Q

Susceptibility locus for IBD and where is it found?

A

IBD-1 on chromosome 16

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13
Q

What does susceptibility gene for IBD contain?

A

CARD15/NOD2 genes

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14
Q

where is CARD15 expressed? What does it do?

A

in macrophages and dendritic cells; it is a pattern recognition receptor that triggers NF-kB

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15
Q

Mechanism for IBD susceptibility with CARD15/NOD2

A

1) defective macrophage function (chronic T cell activation)
2) defective epithelial cell responses (loss of barrier function)
3) defective conditioning of APCs (inappropriate activation)

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16
Q

What phyla is the gut microbiome mainly composed of?

A

Bacteroides (bacteroides or prevotella) and Firmicutes (clostridium and lactobacillus)

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17
Q

What bacteria is increased in UC patients?

A

proteobacteria

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18
Q

what bacteria is increased in CD patients?

A

firmicutes and actinobacteria

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19
Q

What happens when mice raised in a germ free environment are colonized with commensal bacteria?

A

spontaneous colitis develops rapidly

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20
Q

Explain the microbiota of babies born to women with IBD

A

lower bacterial diversity and altered bacterial composition

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21
Q

What happens to the microbiota with a high fat diet?

A

dysbiosis with a decrease in bacteriodetes, firmicutes, proteobacteria

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22
Q

infections (3) implicated in the development of IBD

A

1) M. paratuberculosis
2) Measles virus (paramyxovirus)
3) listeria monocytogenes

23
Q

Populations where IBD is uncommon

A

Asia, Africa

24
Q

role of anti-inflammatory microbiota (bacteroides) in homeostasis

A

beneficial bacteria upregulates Treg cells and IL-10 which, along with commensal bacteria, suppress pathobionts

25
Q

important commensal bacteria product (from fiber)

A
  • commensal bacteria ferment nondigestable polysaccharides to produce SCFAs
26
Q

Roles (2) of SCFAs

A
  • anti-inflammatory properties in macrophages, dendritic cells, CD4+ T cells and intestinal epithelial cells
  • induction of IgA and mucus secretion into the lumen
27
Q

what happens when intestine is colonized with Bacteroides fragilis and clostridium species?

A

induction of Treg cells in the lamina propria

28
Q

What type of bacteria are bacteroides fragilis and clostridium species?

A

segmented filamentous bacteria (SFB)

29
Q

What type of maintenance are segmented filamentous bacteria (SFB) involved in?

A

maintenance of the basal activation level of Th17 cells –> which is important for the integrity of the epithelial barrier

30
Q

How is GALT developed properly?

A

Microbiota is required for GALT to develop properly.

31
Q

What helps to form active secondary forms of bile acids?

A

microbiota

32
Q

NF-kB relationship to commensal microbiota

A

commensal microbiota suppresses NF-kB pathway (tolerance to microflora)

33
Q

How does bacteroides inactivate NF-kB directly?

A

induction of Peroxisome Proliferation Activated Receptor (PPAR) exports activated NF-kB from nucleus

34
Q

General immune response in IBD dysbiosis

A
  • increased Th17 and Th1 response

- decreased Treg and IL-10 response

35
Q

What immune responses are up regulated in Crohn’s disease?

A

Th1 and Th17

36
Q

cytokine(s) activating Th1 cells

A

IL-12

37
Q

cytokine(s) produced by Th1 cells

A

IFN-gamma

38
Q

cytokine(s) activating Th17 cells

A

IL-6
IL-23
TGF-beta

39
Q

cytokine(s) produced by Th17 cells

A

IL-17

40
Q

immune response upregulated in ulcerative colitis

A

Th2

41
Q

cytokine(s) activating Th2

A

IL-4

42
Q

cytokine(s) produced by Th2 cells

A

IL-4
IL-5
IL-13

43
Q

What cytokine is produced by antigen presenting cells and is closely related to IL-12, but activates Th17 response?

A

IL-23

44
Q

Result LOSS OF FUNCTION SNP in IL-10 and TGF-beta?

A

predisposition to IBD

45
Q

Result LOSS OF FUNCTION SNP in TNF, IFN, IL-1, IL-6, IL-17, IL-22 (cell mediated inflammation)?

A

protection from Crohns

46
Q

Result LOSS OF FUNCTION sNP in IL-4, IL-5, and IL-13 (Ab mediated inflammation) ?

A

protect from UC

47
Q

Theory: IBD is a result of…

A

breakdown of tolerance to resident enteric bacteria (loss of Treg function)

48
Q

Cytokines for maintenance of tolerance

A

IL-10 and TGF-beta

49
Q

How are Treg cells activated?

A

APCs presenting auto-Ag

50
Q

Receptors Tregs express (2)

A

CTLA-4 and CD25 (IL-2 receptor)

51
Q

How do Treg cells suppress APCs?

A

cell-to-cell interactions and inhibitory cytokines

52
Q

How do Treg cells act on activated T cells?

A

CTLA-4 and IL-2 deprivation

** deprive through their high affinity IL-2R receptor

53
Q

Immuno-therapeutic treatment option for IBD

A

TNF-blockers for moderate to severe UC and CD

54
Q

Future therapy IBD

A

fecal microbiota transplantation

04. GI (7 decks)

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