[Immuno] Imuno Path Mechanisms of IBD Flashcards
What is IBD?
IBD is a term used to describe TWO DISORDERS that involve chronic inflammation of the GI
- Ulcerative colitis (UC)
- Crohn’s disease (CD)
What is ulcerative colitis?
Chronic inflammation and ulcers in the innermost lining of the COLON and/or RECTUM
What is crohn disease (CD)?
Inflammation of the lining of the GI which SPREADS DEEP into affected tissues ane may OCCUR IN ANY PART of GI
In 40% of pts with CD, which portion of the GI is spared?
Rectum
Patients with IBD have been shown to have INCREASED intestinal _____________
Patients with IBD have been shown to have INCREASED intestinal permeability
IBD often results in __________of GI structure and function
IBD often results in IRREVERSIBLE IMPAIRMENT of GI structure and function
What hypothesis may explain the increased incidence of IBD?
Hygeiene hypothesis
Describe how the increased permeability that results from IBD relates to the eitiology of IBD
The increased permeability of the epithelial layer from impaired tight junctions leads to commensal bacteria of normal intestinal microbiota to cause inflammatory reactions leading to self sustained mucosal inflammation.
The bacterial components cross the mucosal barrier and induce innate and adaptive responses of the immune system
IBD develops as a result of…
A persistent and inappropriate pertubation of highly regulated interaction between the IMMUNE SYSTEM and COMMENSAL BACTERIA of the normal microbiome
The ABBERANT RESPONSES of IBD are largely due to…
Genetic factors
Which is more related to UC and CD?
Dysfunction in microbe sensing:
Dysfunction in barrier function:
Dysfunction in microbe sensing: CD
Dysfunction in barrier function: UC
Describe the difference in pathology b/w CD and UC
CD = Absesses, Fistulas, Strictures, Granuloma formation, Transmural inflammation
UC = Pseudopolyps, Toxic megacolon, Mucosal/submucosal inflammation
Describe the difference in GI involvement b/w CD and UC
CD: Mouth to anus (rectum spared)
UC: Colon and/or rectum
Describe the X-ray appearance of CD vs UC
CD: “String sign” on barium X-ray, “Cobblestone” on endoscopy
UC: “Lead pipe” colon
What is the lab test associated with CD vs UC?
***What is the problem with isolated tests?
CD = ASCA-positive
UC = pANCA positive
***Problem is that only 80% of CD pts are positive for ASCA. Also, only 50-70% of UC pts are pANCA positive. Therefore, could get a negative result and miss catching IBD!!!
What is the best laboratory standard to follow when screening for CD?
Combination of a positive ASCA test with a negative pANCA test has a positive predictive value of 96% and specificity of 97% for CD
What causes IBD?
Combination of:
- Genetics
- Microbial Ags
- Enviornmental triggers
- Immune response
What does the low concordance rate in identical twin studies for CD and UC suggest?
In identical twins, if one twin had CD…other twin had 50% chance of CD
In identical twins, if one twin had UC…other twin had 10% chance of UC
This suggests the importance of ENVIORNMENTAL FACTORS
What is a very strange protective eniornmental factor for UC?
Smoking
What are the three major roles of the gut microbiota?
- PROTECTION of host against invasion or colonization by pathogens
- FACILITATION of nutrient digestion and absorption
- PROVIDING the immunological surveillance signals at the gut mucosa-lumen interface
Where does IBD typically develop within the GI system?
Areas of HIGH BACTERIAL CONCENTRATION
(Terminal ileum and colon)
Use of what drugs can have benificial effects on IBD?
Antibiotics and Probiotics
What is the predominant phyla associated with healthy GI?
Bacteroidetes
Firmicutes
What are the predominant phyla of UC?
Proteobacteria
What is the predominant phyla of CD?
Firmicutes
Role Infections in IBD
____________ may play a role in the etiology of IBD
GASTROENTERITIS (salmonella and campylobacter) may play a role in the etiology of IBD
Role infections in IBD
The prevalence of IBD is inversely associated with the prevalence of ________________
The prevalence of IBD is inversely associated with the prevalence of HELMINTH COLONIZATION
UC is 10 fold less common in which populations?
Asian and African
CD is very uncommon in which populations?
Asia and Africa
Role of Genetic Factors in IBD
What are primarily responsible for IBD?
SNPs
All of the IBD related genes with contained SNPs all code for….
IMMUNO-INFLAMMATORY components
What is the primary gene involved in the IBD-1 locus?
CARD15
(CAspase Recruitment Domain family member 15)
What is CARD15?
What does it do?
Intracellular PPR
Triggers activation of NF-kappaB
Microbiota maintains the BASAL LEVEL of _____ and _____ cell activity in the lamina propria
Microbiota maintains the BASAL LEVEL of Th17** and **Th1 cell activity in the lamina propria
What is an important product produced by commensal bacteria that have anti-inflammatory properties?
Short chain fatty acids (SCFAs)
Review this image for the microbial effects on the host
Overall, in IBD…. _________ is lost
Tolerance
In IBD, what immunologic factors are HYPERACTIVE and what is INHIBITED?
HYPERACTIVE = TH1, TH17
INHIBITED = Treg cells, IL-10
What Th and ILs are involved in CD?
Th1, Th17
IL-12, IL-6, IL-23
What Th and ILs are involved in UC?
Th2
IL-5, IL-4, IL-13
