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GI II Exam 1. > IBD Immuno > Flashcards

IBD Immuno Flashcards

1
Q

Why is there increased permeability in IBD of the epithelial barrier?

A

impaired formation of tight junctions

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2
Q

What causes the inflammation in IBD?

A

commensal bacteria cause inflammatory rxn leading to self sustained mucosal inflammation

loose tight junctions –> bacteria cross barrier –> immune adaptive and innate response

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3
Q

Aberrant responses is due to:

A

genetically determined

disruption of barrier function (UC)

dysfunction of microbe sensing (CD)

changes in immunoregulation (both)

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4
Q

What is necessary to initiate or reactive IBD?

A

environmental triggers

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5
Q

What are the functional roles of the gut microbiota?

A
  1. protection of host against invasion or colonization by pathogens
  2. facilitation of nutrient digest and absorption
  3. providing immunological surveillance signals at gut mucosa-lumen interface
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6
Q

What effect do ABs and probiotics have on IBD?

A

beneficial (kills microbiota)

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7
Q

Where are aerobic and faculative anaerobics found?

A

almost exlusively in the proximal GI tract

obligate anaerobes are found in the distal GI tract

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8
Q

What are the four major phyla of gut microbiome?

A

Firmicutes

Bacteroidetes

Actinobacteria

Proteobacteria

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9
Q

What phyla are majority in UC? CD?

A

UC - Proteobacteria

CD - Firmicutes, Actinobacteria

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10
Q

What controls microbiota composition?

A

diet

genetics

environmental factors

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11
Q

What specific microbial organisms are linked to IBD?

A

none have been found yet

M. paratuberculosis, paramyxovirus, listeria have been implicated

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12
Q

What illness has been linked to increased risk of developing IBD?

A

gastroenteritis (ex. salmonella, campylobacter)

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13
Q

What infection is protective against IBD?

A

helminth (why IBD rates are low in Asia and Africa)

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14
Q

The genes linked to IBD all do what?

A

encode immuno inflammatory components

NOT mutations, but SNPs

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15
Q

What chromo is IBD 1 on?

A

16

contains CARD15/NOD2 - linked to CD

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16
Q

What is the role of CARD15?

A

intracellular pathogen recognition receptor (PPR)

recognizes molecules containing MDPs (murmyl dipeptide)

triggers NFkB

mainly expressed in monocytes and macrophages

17
Q

Mutation in CARD15 does what to NFkB pathway?

A

reduces activation

CARD15 mutation may increase susceptibility to chronic intracellular infection or prevent the development of tolerance to commensal microflora

18
Q

What maintains Th17 and Th1 cell basal level in the LP?

A

microbiota

19
Q

What contributes to suppressing pathobionts?

A

commensal bacteria thu inductino of Treg cells and stimulation of IL-10

20
Q

How do commensal bacteria make SCFAs?

A

by fermenting nondigestible polysaccharides from the diet

SCFAs have anti inflammatory properties

  1. induce IgA and mucus secretion into lumen
  2. promote epithelial barrier integrity
  3. prevent pathogen colonization
21
Q

Segmented filamentous bacteria have what role?

A

induction of Treg cells in LP

maintenance/development of basal level of Th17 cells

22
Q

The microbiota induce host immune tolerance to commensal bacteria how?

A
  1. MAMP
  2. PSA signaling
  3. indirectly through SCFA production
  4. expression of epithelial intestinal alkaline phosphatase
23
Q

What is required for proper GALT development?

A

microbiota

24
Q

How does mucus layer help?

A

separates commensal bacteria from host tissue

epi cells also make antimicrobial peptides to limit exposure

and commensals that get thru are taken out by Macrophages or taken up by DCs –> Treg, Th17, and IgA producing B cells

25
Q

What is the mucosal firewall?

A

epi barrier

mucus layer

IgA

DCs

T cells

26
Q

What do commensal microbiota do to NFkB pathway?

A

suppress it

27
Q

What type of bacteria trigger IBD?

A

aerobic (and epi Ags) - UC

anaerobic - CD

28
Q

With salmonella infection, what happens with and without Bacteroides?

A

with - proinflamm response is attenuated, inductin of PPAR exports activated NFkB from nuclues

without - salmonella flagellin bind TLR5, which activates IkB –> activation and nuclear translocation of NFkB –> proinflam genes

29
Q

What are the major phases in IBD development?

A

genetic/env factors impair barrier –>

translocation of commensal bacteria which activate immune cells and cytokine production –>

chronic intestinal inflammation –>

complications of IBD (fibrosis, stenosis, fistula, cancer)

30
Q

What T cells go with what?

A

Th2, NKT - UC

Th17, Th1 - CD

31
Q

What is the role of IL 23?

A

regulate responses of Th1 cell

regulate activity of Macrophages and DCs

stimulates T cells to produce IL 17 (NOT IFNy (Th1) or IL 4 (Th2))

32
Q

Th1 and Th17 role in CD

A
33
Q

What are in charge in inhibition of IBD and maintenance of tolerance?

A

IL 10 and TGF-b

loss of function of SNPS: inc IBD

gain of function of SNPS: protection

34
Q

What is in charge of cell mediated inflammation and CD?

A

TNF-a, IFNy, IL 1, IL 6, IL 17, IL 22

loss of function of SNPS: protection

gain of function of SNPS: inc CD

35
Q

What is in charge of Ab mediated inflammation and UC?

A

IL 4, IL 5, IL 13

loss of function of SNPS: protection

gain of function of SNPS: inc UC

36
Q

IBD is believed to be the _____ to _____?

A

IBD is believed to be the breakdown of tolerance to resident enteric bacteria (microflora).

37
Q

How do Treg cells prevent IBD?

A

suppress activation of effector T cells

GI II Exam 1. (25 decks)

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