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GI II Midterm > Immunologic Mechanisms Of IBD > Flashcards

Immunologic Mechanisms Of IBD Flashcards

1
Q

What is IBD?

A

A term used to describe two disorders that involve chronic inflammation of the GI tract
Includes ulcerative colitis and Crohn’s disease

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2
Q

What is ulcerative colitis characterized by?

A

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

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3
Q

What is Crohn’s disease characterized by?

A

Inflammation of the lining of the GI tract which often spreads deep into affected tissues and may occur in any part of the GI tract
Rectum is usually spared

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4
Q

IBD is associated with an increased permeability of what?

A

The epithelial barrier caused by impaired formation of tight junctions

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5
Q

IBD develops as a result of what?

A

A persistent inappropriate perturbation of highly regulated interaction between the immune ssytem and commensal bacteria of the normal micro biome resulting in dysbiosis and mucosal inflammation

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6
Q

The aberrant responses in IBD are to a large degree genetically determined and may include what?

A

Disruption of the barrier function (mainly in UC)
Dysfunction of microbe sensing (mainly in CD)
Changes in immunoregulation of innate and adaptive immune responses (both)

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7
Q

A low concordance rate in identical twins suggests what?

A

Imporatnace of environmental factors

50% for CD and 10% for UC

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8
Q

What are the functional roles of gut microbiota?

A

Protection of the host against invasion or colonization by pathogens
Facilitation of nutrient digestion and absorption in humans
Providing the immunological surveillance signals at the gut mucosa lumen interface

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9
Q

IBD develops in areas with high concentrations of what?

A

Bacteria (terminal ileum and the colon)

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10
Q

Surgical diversion of the fecal stream prevents what?

A

Intestinal inflammation

Reestablishment of the flow leads to recurrence of IBD

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11
Q

What has beneficial effects on IBD?

A

Use of abx and probiotics

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12
Q

Circulating Abs against what are detected in IBD?

A

Fecal bacterial antigens

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13
Q

What is the gut micro biome primarily comprised of?

A

The phyla bacteroidetes (largely bacteroides or Prevotella species) or Firmicutes (largely clostridium and Lactobacillus species)

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14
Q

Which factors have a major effect on gut microbiota?

A

Diet and other environmental factors + host genetics

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15
Q

What maintains gut homeostasis?

A

Symbiosis (a balanced microbial composition)

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16
Q

What does dysbiosis lead to?

A

Dysregulation of the immune system and to inflammation in a genetically susceptible host
May be caused by various environmental factors

17
Q

True or false: no specific microbial organisms have been conclusively linked to the development of IBD

A

True

18
Q

Which disease may play a role in the etiology of IBD?

A

Gastroenteritis (such as salmonella and campylobacter)

Individuals diagnosed with an acute gastroenteritis have been shown to have an increased risk of developing IBD

19
Q

The prevalence of IBD is inversely associated with the prevalence of what?

A

Helminth colonization

Helminths are thought to play an important immunoregulatory role with the intestinal flora

20
Q

Describe the prevalence of UC and CD in Asian and African populations

A

UC is 10 fold less common in Asian and African populations

CD seems very uncommon in Asia and Africa

21
Q

If a first degree relative has IBD are the changes increased or decreased in an individual with that relative?

A

Increased

22
Q

There is a greater concordance rate in which types of twins?

A

Monozygotic vs dizygotic twins

23
Q

Describe the IBD1 gene

A

Found on chromosome 16

Contains CARD15/NOD2 genes

24
Q

Describe CARD15?

A

Primarily expressed in macrophages and DCs
It’s an intracellular PPR
Recognizes MDP (a peptidoglycan constituent of both gram + and - bacteria)
Triggers activation of NF-kB

25
Q

Individuals homozygous for susceptible variant (SNPs) of CARD15 have more than a 20 fold increased risk of developing what?

A

Crohn’s disease

26
Q

What are the 3 possible mechanisms that CARD15/NOD2 mutations can lead to Corin’s disease?

A

Defective function of macrophages
Defective epithelial cell responses
Defective conditioning of APCs

27
Q

Commensal bacteria ferment non-digestible polysaccharides ingested in the deity to produce what?

A

SCFAs which have anti inflammatory properties in macrophages, DCs, CD4 T cells, and intestinal epithelial cells

28
Q

The microbiota induces host immune tolerance to commensal bacteria directly via what?

A

A microbe associated molecular pattern (MAMP)
Polysaccharide (PSA) signaling
Indirectly through the production of SCFAs
Potentially through expression of epithelial intestinal alkaline phosphatase (IAP) which detoxifies luminal LPS

29
Q

What comprises the mucosal firewall of the GI tract?

A

The combination of the epithelial barrier, mucus layer, IgA, DCs and T cells

30
Q

What is the function of the mucosal firewall?

A

Limits the passage and exposure of commensal pts to the GALT preventing untoward activation and pathology

31
Q

Which pathway do commensal microbiota suppress?

A

NF-kB

32
Q

Describe immune tolerance in the GI tract

A

The tolerance is related to DCs and macrophages which do not sense the presence of microflora and thus dont secrete pro-inflammatory cytokines
In IBD the tolerance is lost

33
Q

What happens in the absence of commensal bacteroides?

A

Salmonella flagellin binds to TLR5 intestinal epithelial cells (IECs)
Activates IkB kinase (IKK) —> activation and nuclear translocation NF-kB

34
Q

What happens in the presence of commensal bacteroides?

A

Proinflammatory response caused by S enteritidis is attenuated
Induction of peroxisome proliferation activated receptor (PPAR) which exports the activated NFkB from the nucleus

35
Q

Crohn’s disease is characterized by the activation of which types of T cells?

A

Th1 and Th17 cell responses driven by IL-12, IL-6 and IL-12 produced by DCs and macrophages

36
Q

Which cytokines do Th1 cells secrete?

A

IL-2, IFN-gamma, TNF

37
Q

Which cytokines do Th17 cells secrete?

A

IL-17

38
Q

Ulcerative colitis is characterized by an atypical activation of which cell?

A

Th2 cell and natural killer T cell (NKT) which produce IL-5 and IL-4 (Th2) and IL-13 (Th2 and NKT cells)

GI II Midterm (8 decks)

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