IBD Flashcards
What is IBD?
a spectrum of remitting and relapsing chronic inflammatory conditions of the intestine
What is the difference between CD and UC?
CD
- patchy and transmural inflammation anywhere in the GI tract from mouth to anus
UC
- continious superfifical inflammation starting from the anus and works its way up
Does living in rurual/being exposed to greenspaces or urban areas reduce the risk of IBD? Which age group is this important for?
growing up in a rurual environment or being exposed to greenspaces during the first five years of life was associated with a reduced risk of IBD
What kind of countries have higher prevelances of IBD?
industrialized countries – especially western socieity
How does immigration affect the risk of IBD? What does this suggest?
- younger age at time of immigration association with highest risk
- next generation assumes risk of general population
- suggests some environmental exposure during early period of life can predispose individual to developing IBD
How can microplastics be ingested during infant formula prep?
formula prep promotes the release of microplastics from polypropylene bottles
What is IBD characterized by?
a dysregulated immune response – more pro- than anti-inflammatory
What kind of genes are associated with risk of IBD?
- microbial sensing
- microbial clearance
- epithelial barrier
- integration of antimicrobial adaptive responses
How deos the microbiota regulate human health?
- educates the IS
- aids in digestion of plant material
- produces energy substrate for HCs (SCFA)
- produces vitamins and antimicrobials
- produces signalling molecules to interact with immune and epithelial cells
- communicates with brain
what phyla of bacteria promotes health vs disease? In a low biodiversity microbiome which kind of bacteria is there more of?
health = bacteriodetes, firmicutes
disease = proteobacteria, fusobacteria (e.g. E coli)
less biodiveristy –> more proteobacteria and fusobacteria
What factors affect gut microbiota composition and function?
- exercise
- stress
- antibiotics
- age – biodiversity decreases when aging
- diet – breast milk vs. formula
- mode of birth delivery
Does your small intestine or large intestine have more bacteria?
large intestine
Why does the mucosal IS have to be balances between immune activation and suppression?
- immune activation for protection from pathogens (e.g. has to protect against salmonella)
- immune suppression (tolerance) to allow for peaceful co-existence with commensal microbes
What are microbial bar codes?
each microbe has its unique set of Ags which will activate different sets of TLRs which will lead to different responses
What are the five barriers of the gut against pathogens?
- microbial layer (commensal bacteria)
- chemical barrier (mucus layer)
- physical barrier (the epithelium + tight junctions)
- immunological barrier
- muscle layer
Describe the polarized expression of TLRs on intestinal epithelial cells (IECs), why is this important?
no TLR4/5 on the apical (lumen) side, expressed on the basolateral surface
activated by bacterial flagellin – if bacteria are in the lumen, thats fine; if bacteria on the basolateral side, that bad so need to trigger an immune response
What cytokines do epithelial cells release when activated? What do they do?
IL-6, IL-1B –> polarizes T cells into Th1 phenotype – proinflammatory response
During homeostasis of the gut, what signals do IECs release to DCs to maintain tolerance, and what signals do DCs release to Tregs cells to maintain tolerance to microbes?
IEC –> DC
- TSLP
- IL-10
- TGFB
- RA
DC –> Treg
- RA
- TGFB
A dysfunctional mucosal immune response is the central driver of IBD, what is it characterized by?
- altered innate immunity
- activated effector T cells
- large presence of B cells and Ab production
- large recruitment of ICs from circulation
- large production of pro-inflammatory mediators
What is the GEM study?
international study that started in 2008 that is following 5000 subjects that are”at-risk” of developing CD (1st degree relatives of those with IBD)
What kind of microbial changes are commonly seen in IBD patients?
- less microbial diversity
- less commensal bacteria
- more bacteria that break down the mucus layer
- less bacteria that produce butyrate and propinoate (SCFA)
Why are SCFAs important?
- energy source of coloncytes
- stimulate mucus production
- induce Treg cells
- enhance CD8 T cell responses
- stimulate sIgA production
- enhance epithelial barrier function
- more AMPs
Why are ROS bad for the gut?
ROS kills butryate producing microbes and E.coli loves oxygen
What happens if you transfer dysbiotic microbiota to healthy mice?
certain strains of bacteria can transfer the colitis phenotype
What (4) host deficiencies can prevent containment of commensal bacteria?
- less mucus secretion (less expression of the MUC1 gene)
- increase gut permeability (altered expression of tight junction proteins; driven by dietary factors)
- decreased AMP secretion
- worser ability to kill bacteria
How does the LOF NOD2 gene affect chronic inflammation?
NOD2 fails to recognize and properly deal with commensal bacteria –> intestinal inflammation (NOD1/2 detect peptidigylcan)
What are the treaments for IBD?
- surgery
- biologic agents
- immunomodulators
- antibiotics
What is the cascade effect?
cytokines can stimulate production of other cytokines
What are biologic drug targets?
- cytokine blockade (block cytokine receptors)
- intracellular signaling pathway blockade
- cytokine targeting
- lymphocyte trafficking blockade
What would personalized treatment take into consideration to determine an appropriate treatment?
- genome
- transcriptosome
- microbiome
- cellular measurements
