IBD Immuno Flashcards
Why is there increased permeability in IBD of the epithelial barrier?
impaired formation of tight junctions
What causes the inflammation in IBD?
commensal bacteria cause inflammatory rxn leading to self sustained mucosal inflammation
loose tight junctions –> bacteria cross barrier –> immune adaptive and innate response
Aberrant responses is due to:
genetically determined
disruption of barrier function (UC)
dysfunction of microbe sensing (CD)
changes in immunoregulation (both)
What is necessary to initiate or reactive IBD?
environmental triggers
What are the functional roles of the gut microbiota?
- protection of host against invasion or colonization by pathogens
- facilitation of nutrient digest and absorption
- providing immunological surveillance signals at gut mucosa-lumen interface
What effect do ABs and probiotics have on IBD?
beneficial (kills microbiota)
Where are aerobic and faculative anaerobics found?
almost exlusively in the proximal GI tract
obligate anaerobes are found in the distal GI tract
What are the four major phyla of gut microbiome?
Firmicutes
Bacteroidetes
Actinobacteria
Proteobacteria
What phyla are majority in UC? CD?
UC - Proteobacteria
CD - Firmicutes, Actinobacteria
What controls microbiota composition?
diet
genetics
environmental factors
What specific microbial organisms are linked to IBD?
none have been found yet
M. paratuberculosis, paramyxovirus, listeria have been implicated
What illness has been linked to increased risk of developing IBD?
gastroenteritis (ex. salmonella, campylobacter)
What infection is protective against IBD?
helminth (why IBD rates are low in Asia and Africa)
The genes linked to IBD all do what?
encode immuno inflammatory components
NOT mutations, but SNPs
What chromo is IBD 1 on?
16
contains CARD15/NOD2 - linked to CD
What is the role of CARD15?
intracellular pathogen recognition receptor (PPR)
recognizes molecules containing MDPs (murmyl dipeptide)
triggers NFkB
mainly expressed in monocytes and macrophages
Mutation in CARD15 does what to NFkB pathway?
reduces activation
CARD15 mutation may increase susceptibility to chronic intracellular infection or prevent the development of tolerance to commensal microflora
What maintains Th17 and Th1 cell basal level in the LP?
microbiota
What contributes to suppressing pathobionts?
commensal bacteria thu inductino of Treg cells and stimulation of IL-10
How do commensal bacteria make SCFAs?
by fermenting nondigestible polysaccharides from the diet
SCFAs have anti inflammatory properties
- induce IgA and mucus secretion into lumen
- promote epithelial barrier integrity
- prevent pathogen colonization
Segmented filamentous bacteria have what role?
induction of Treg cells in LP
maintenance/development of basal level of Th17 cells
The microbiota induce host immune tolerance to commensal bacteria how?
- MAMP
- PSA signaling
- indirectly through SCFA production
- expression of epithelial intestinal alkaline phosphatase
What is required for proper GALT development?
microbiota
How does mucus layer help?
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
What is the mucosal firewall?
epi barrier
mucus layer
IgA
DCs
T cells
What do commensal microbiota do to NFkB pathway?
suppress it
What type of bacteria trigger IBD?
aerobic (and epi Ags) - UC
anaerobic - CD
With salmonella infection, what happens with and without Bacteroides?
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
What are the major phases in IBD development?
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)
What T cells go with what?
Th2, NKT - UC
Th17, Th1 - CD
What is the role of IL 23?
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))
Th1 and Th17 role in CD
What are in charge in inhibition of IBD and maintenance of tolerance?
IL 10 and TGF-b
loss of function of SNPS: inc IBD
gain of function of SNPS: protection
What is in charge of cell mediated inflammation and CD?
TNF-a, IFNy, IL 1, IL 6, IL 17, IL 22
loss of function of SNPS: protection
gain of function of SNPS: inc CD
What is in charge of Ab mediated inflammation and UC?
IL 4, IL 5, IL 13
loss of function of SNPS: protection
gain of function of SNPS: inc UC
IBD is believed to be the _____ to _____?
IBD is believed to be the breakdown of tolerance to resident enteric bacteria (microflora).
How do Treg cells prevent IBD?
suppress activation of effector T cells
