IBD Immunology Flashcards
what factors are highly associated with IBD?
increased permeability of the epithelial barrier
mucosal inflammation
bacterial dysbiosis
what does ASCA-positive serology indicate?
CD
what does pANCA-positive serology indicate?
UC
what phyla of bacteria predominate in a healthy colon?
- Bacteroidetes
2. Firmicutes
what phyla of bacteria predominate in a UC colon?
Proteobacteria
what microbiota changes occur in high fiber diet?
increased bacteroidetes, firmicutes and actinobacteria
decreased proteobacteria
what microbiota changes occur in high protein diet?
increased bacteriodetes, firmicutes and proteobacteria
what microbiota changes occur in high fat diet?
decrease bacteroidetes, firmicutes and proteobacteria
what microbiota changes occur with high carb diet?
increased bacteroidetes, firmicutes, and actinobacteria
what infective agents may contribute to development of IBD?
M. paratuberculosis measles listeria monocytogenes salmonella campylobacter
what infective agents decrease the risk of developing IBD?
helmenth colonization
what populations have the lowest risk of developing IBD?
Asian and African descent
which gene mutation puts you at increased risk of developing CD?
IBD-1 locus on chromosome 16
CARD15/NOD2 genes
where is CARD15 primarily expressed?
macrophages
dentritic cells
what is the role of CARD15?
recognizes MDP - peptidoglycan constituent of gram + and gram - bacteria
what is the downstream effect of CARD15?
activation of NF-kB
what is the downstream effect of a NOD2 mutation?
defective function of macrophages
defective epithelial cell responses
defective conditioning of APCs
how does the gut microbiota maintain homeostasis?
induces development of GALT
maintains basal level of Th17 and Th1
directly and indirectly suppresses pathogenic bacteria via Tregs and IL-10
how does commensal bacteria contribute anti-inflammatory properties in the gut?
they ferment indigestible polysaccharides (cellulose) to produce short chain fatty acids (SCFAs)
SCFAs have anti-inflammatory properties in macrophages, DCs, CD4 cells an epithelial cells
SCFA also induce IgA and mucus secretion into the lumen
what is the role of segmented filamentous bacteria (SFB) in gut tolerance?
induce Tregs
maintaince of Th17 cells within the epithelial barrier
what occurs in the absence of commensal bacteria?
Salmonella flagellin binds to TLR5 which activates NF-kB and promotes inflammation
what occurs in the presence of commensal bacteria?
salmonella response is attenuated by commensal bacteria
induction of PPAR occurs to export the activated NF-kB from the nucelus (no inflammatory response)
what is primarily activated in CD that results in inflammation?
Th1 and Th17 cells driven by IL-12, IL-6 and IL-23 produced by macrophages and DCs
what cytokines are produced in CD?
IL-2
IFN-y
TNF
IL17
what is primarily activated in UC that results in inflammation?
Th2 cells and NK T cells by IL-4 produced by macrophages and DCs
what cytokines are produced in UC?
IL-4
IL-5
IL-13
what cytokines are produced in a healthy gut to maintain tolerance?
IL-10
TGF-B
what is the primary role of Treg cells in suppression of IBD?
suppress effector T cells via cell-to-cell interactions and IL-2 deprivation
what are the current treatment options for IBD?
TNF blockers
fecal microbiota transplantation (FMT)
loss of function SNP to IL-10 and TGF-B genes would result in…
predisposition to IBD
gain of function SNP to IL-10 and TGF-B genes would result in…
protection from IBD
loss of function SNP to TNF-a, IFN-y, IL-1, IL-6, IL-2, IL-17 and IL-22 genes would result in…
protection from IBD
gain of function SNP to TNF-a, IFN-y, IL-1, IL-6, IL-2, IL-17 and IL-22 genes would result in…
predisposition to IBD
loss of function SNP in IL-4, IL-5 and IL-13 genes would result in…
protection from IBD
gain of function SNP in IL-4, IL-5 and IL-13 genes would result in…
predisposition to IBD
what phyla of bacteria predominate in CD?
Firmicutes
Actinobacteria
