Immunopathogenic Mechanisms of IBD Flashcards
What is a chronic relapsing idiopathic inflammation of the GI tract?
IBD
IBD is a term used to describe what two disorders that involve chronic inflammation of the gastrointestinal tract?
1) Ulcerative colitis
2) Crohn’s disease
Ulcerative colitis is characterized by chronic inflammation and?
Ulcers in the innermost lining of the colon and/or rectum
Crohn’s disease is characterized by inflammation of?
Where may it occur?
However, in 40% of patients with CD, what is spared from inflammation in contrast to its universal
involvement in UC?
1) The lining of GI
2) Any part of GI
3) The rectum
Patients with IBD have been shown to have increased permeability of?
This is caused by impaired formation of?
1) Epithelial barrier
2) Tight junctions
What has been invoked to explain an increased incidence of IBD?
Hygiene hypothesis
What does the increased intestinal barrier seen in IBD cause?
Commensal bacteria to cross mucosal barrier and induce both innate and adaptive immunity
Disruption of the barrier function is seen with what form of IBD?
Dysfunction of microbe sensing is seen with what form of IBD?
Changes in immune regulation of innate and adaptive immune response is seen with what form of IBD?
1) UC
2) CD
3) Both
Abdominal pain, obstruction, and fever are signs and symptoms of what IBD condition?
Bloody diarrhea urgency are signs and symptoms of what IBD condition?
1) CD
2) UC
Pseudopolyps, toxic megacolon, and mucosal/submucosal inflammation describes the pathology of what IBD condition?
Abscesses, fistulas, stictures, granulomas, and transmural inflammation describes the pathology of what IBD condition?
1) UC
2) CD
Which form of IBD shows string sign on barium x-ray and cobblestone appearance on endoscopy?
Which shows lead-pipe colon?
1) CD
2) UC
A patient with CD will be positive for what Ab?
A patient with UC will be positive for what Ab?
1) ASCA
2) pANCA
A patient that is positive for ASCA and negative for pANCA test have what condition?
CD
With IBD, the low concordance rate in identical twins (~50% for CD, and ~10% for UC) suggests the importance of?
Environmental factors
IBD develops in areas of?
High bacterial concentration such as terminal ileum and colon
What class of drugs have beneficial effects on IBD?
Antibiotics and probiotics
Circulating Abs against what antigens are detected in IBD?
What cells show reactivity against these Ags?
1) Fecal bacterial Ags
2) Lymphocytes
What component of gut microbiome dominants in UC?
What component dominants in CD?
1) Proteobacteria
2) Firmicutes and Actinobacteria
How do infants born from IBD women present in terms of their intestinal microbiota?
Low bacterial diversity and altered bacterial composition
In terms of diet, what is important for maintenance of normal microflora?
Fiber intake
If there is disruption in microflora composition, what takes place?
Dysbiosis which leads to immune dysregulation and inflammation of lamina propria (IBD)
What effect does a high fiber diet have on bacteroidetes, firmicutes, proteobacteria, and actinobacteria?
1) Increase bacteroidetes
2) Increase firmicutes
3) Decrease proteobacteria
4) Increase actinobacteria
What effect does a high protein diet have on bacteroidetes, firmicutes, and proteobacteria?
1) Increase bacteroidetes
2) Increase firmicutes
3) Increase proteobacteria
What effect does a high fat diet have on bacteroidetes, firmicutes, and proteobacteria?
1) Decrease bacteroidetes
2) Decrease firmicutes
3) Decrease proteobacteria
What effect does a high carb diet have on bacteroidetes, firmicutes, and actinobacteria?
1) Increase bacteroidetes
2) Increase firmicutes
3) Increase Actinobacteria
Individuals diagnosed with what have condition have been shown to subsequently have an increased risk of
developing IBD?
Acute gastroenteritis such as salmonella and campylobacter
The prevalence of IBD is inversely associated with the prevalence of?
Helminth colonization
UC and CD are uncommon in what populations?
Asian and African populations
What genetic factor increases the risk for IBD?
First-degree relatives
Defects in what gene is associated with CD?
What is this gene also known as?
What chromosome is it found on?
1) IBD-1
2) CARD15 or NOD2
3) 16
CARD15 is primarily expressed in?
What type of PPR is CARD15?
What does it recognize that is a constituent of both gram positive and negative bacteria?
What does it trigger activation of?
1) Macrophages and DCs
2) Intracellular
3) MDP (muramyl dipeptide - a peptidoglycan)
4) NF-kB
What are possible mechanisms of CD caused by CARD15 mutations?
1) Defective function of macrophages
2) Defective epithelial cell barrier
3) Defective conditioning of APCs
Colonization of the GI with beneficial bacteria induces the development of?
It maintains activity of what cells in the lamina propria?
1) Gut-associated lymphoid tissue (GALT)
2) Th17 and Th1
Commensal bacteria suppressed pathobionts (Any potentially pathological organism) through the induction of?
1) Treg cells
2) IL-10
Commensal bacteria ferment non digestible polysaccharides ingested in the diet (for example, cellulose) to produce?
Short-chain fatty acids (SCFAs)
SCFAs have anti-inflammatory properties in what cells?
1) Macrophages
2) DCs
3) CD4+ T cells
4) Intestinal epithelial cells
Colonization of the intestine with the segmented filamentous bacteria (SFB) Bacteroides fragilis and
Clostridium spp. results in?
SFB also play a role in the maintenance of the basal
activation level of what cells that are important
for the integrity of the epithelial barrier?
1) Induction of Treg cells in the lamina propria
2) Th17 cells
What does SCFA also induce into the lumen in order to promote epithelial barrier integrity and prevent pathogen colonization?
1) IgA
2) Mucus secretion
Translocation commensal bacteria are rapidly eliminated by?
Tissue resident macrophages
Presentation of commensal Ags by DCs leads to the differentiation of what cells?
1) Treg cells
2) Th17 cells
3) IgA producing B cells
What comprises the “mucosal firewall” which limits the passage and exposure of commensals to the GALT?
1) Epithelial barrier
2) Mucus layer
3) IgA
4) DCs
5) T cells
Commensal microbiota suppress what pathway?
NF-kB
In the absence of commensal bacteroides, salmonella flagellin binds to?
This causes the activation of?
1) TLR5 intestinal epithelial cells
2) NF-kB
Dysbiosis leads to chronic inflammation which has what effect on Th1, Th17, Treg cells, and IL-10?
1) Hyperactivation of Th1 and Th17 cells
2) Inhibition of Treg cells producing IL-10
CD is characterized by activation of what cells?
What ILs that are produced by DCs and macrophages drive this activation?
1) Th1 and Th17
2) IL-12 (Th1) and IL-6, IL-23 (Th17)
What do Th1 cells secrete?
What do Th17 cells secrete?
1) IL-2, IFN-γ, TNF
2) IL-17
UC is characterized by an atypical activation of what cells?
What do each of theses cells produce?
1) Th2 cell -> IL-4, IL-5, IL-13
2) NK T cells -> IL-13
Loss of function SNPs in IL-10 and TGF-β causes?
Gain of function SNPs in these genes causes?
1) Predisposition to IBD
2) Protection from IBD
Loss of function SNPs in TNF-α, IFN-γ, IL-1, IL-6, IL-2, IL-17, and IL-22 causes?
Gain of function SNPs in these genes causes?
1) Protection from CD
2) Predisposition to CD
Loss of function SNPs in IL-4, IL-5, and IL-13 causes?
Gain of function SNPs in these genes causes?
1) Protection from UC
2) Predisposition to UC
What cells suppress activation of effector T cells and prevent IBD?
Treg cells
What is the current treatment for moderate to severe UC and CD?
TNF blockers
What may become the first line treatment for UC and CD in the future?
Fecal Microbiota Transplantation
