immunopathogenic mechanisms of IBD

Question 1

ulcerative colitis is characterized by ulcers in _____ of the ______

Answer 1

innermost lining

colon or rectum

Question 2

crohn ds is characterized by inflammation which often ____ into affected tissues and may occur in _____

Answer 2

spreads deep

in any part of the GI system

Question 3

in IBD, the ____ bacterial of the cause inflammation, leading to ______ mucosal irritation. bacterial components cross _____to induce a __&___ immune response

Answer 3

commensal bacteria of the normal intestine

self sustained

mucosal barrier,
innate and adaptive

Question 4

IBD develops as a result of ___ and ____

Answer 4

dysbiosis (inappropriate perturbation commensal bactera to immune system)
mucosal inflammation

Question 5

aberrant immune responses in IBD include ____(both), ____ (UC), _____(Crohn)

Answer 5

changes in Treg immune regulation

disruption of barrier function

dysfunction of microbe sensing

Question 6

a combination (+)___ and (-)__ test has the highest specificity

Answer 6

ASCA

pANCA

Question 7

IBD is complex combination of

____intestinal inflammation, genetic susceptibility influenced by _____, ____ that act as adjuvants to stimulate other immune responses, and _____ triggers

Answer 7

chronic
luminal microbiota
microbial Ags
environmental triggers

Question 8

what environmental factors can lead to IBD

Answer 8

NSAIDs, abx
diet
smoking
stress
epigenetics (microbes, enteric flora, permeability)
appendectomy

Question 9

what are the functional roles of gut microbiota in our beautiful symbiotic relationship

Answer 9

protection against invasion or colonization (outcompete)

facilitation of difestion and absorption

provide immunological surveillance signals

Question 10

main players in normal gut microbiome

Answer 10

bacteriodetes (bacteriodes/provetella)

firmicutes (C. dif, lactobacillus)

Question 11

describe the state of dysbiosis in ulcerative colitis

Answer 11

way more proteobacteria

E. Coli, desulfovibrio

Question 12

describe the state of dysbiosis in crohn

Answer 12

way more firmicutes (C. dif, lactobacillus)
and actinobacteria (bifidobacterium, collinsella)

Question 13

what is the main predictor of diversity of infant microbiota

Answer 13

maternal IBD

–> lower diversity

Question 14

what features control host microflora composition

Answer 14

host genetics
maternal transfer
abx/meds
infection, inflammation
stress, hygeine, age

Question 15

while no specific organism has been proven to cause IBD, ___ (3) have shown to be related, as well as acute gastroenteritis caused by _____(2). prevalence of IBD is inversely associated with the prevalence of ___

Answer 15

M. paratuberculosis, persistent paramyxovirus (measles), listeria monocytogenes

salmonella, campylobacter

helminth colonization

Question 16

genes related to IBD

a susceptibility locus ____ is found on chr __

___, primarily expressed in Mø/DCs and lost in Crohn, is an intracellular ___ that recognizes ___ and triggers acitvation of ___

Answer 16

IBD1, 16

CARD15, PPR, MDP, NF-kB

Question 17

how does CARD15 mutation increase risk for IBD

Answer 17

mutation in CARD15 stops it from activating NFKB= no inflammation

–> defective Mø= persistent intracellular infection and chronic T cell stimulation

–> defective epithelial cell response –> LOF of barrier and increased exposure to mucosal microflora

–> inappropriate activation of APCs

Question 18

speak to how gut microbiota maintains homeostasis

Answer 18

GALT development
maintain basal activation levels of Th17+Th1
increase barrier function by maintaining permeability
increase Treg and IL-10 formation,
suppress pathbionts

ferment non-digestible polysachs into SCFAs which have an ant-inflammatory properties in Mø, DCs, CD4 T cells, intestinal epithelial cells

Question 19

describe the pathway of SCFA function

Answer 19

released by microbiota after fatty acid metabolites

GP43 receptor on Treg cells –> release IL-10 -> block inflammatory response

Question 20

the ___ represents the primary barrier limiting contact between the microbiota and host tissue. epithelial cells can produce ____ to limit exposure, and any translocating commensal bacteria are rapidly eliminated by ____. capture of Ags by DC leads to differentiation of ___(3)

Answer 20

mucus
antimicrobial peptides
tissue resident macrophages
Treg cells, Th17 cells, and IgA producing B cells

Question 21

__+ __ + __ + __ = mucosal firewall

Answer 21

epithelial barrier + IgA + DCs + T cells

Question 22

commensal microbiota suppresses the ___ pathway, so in IBD ___ is lost

Answer 22

NF-kB

tolerance to commensal bacteria

Question 23

when pathogenic bacteria reach colon, they activate ___ on epithelium which starts a chain that activates pro-inflammatory genes? but normal commensal bacteria will ___ that inflammation

Answer 23

TLR5

attenuate

Question 24

dysbiosis results in hyper-activation of ___(2) and inhibition of ___(2)

Answer 24

Th1 and Th17

Treg and IL-10

Question 25

Th1/Th17 paradigm in crohn

Answer 25

IL-6, IL-12--> Th1 --> IL-2, IFN-y (--> Mø -->TNF) IL-23 --> Th17 --> IL-17

Question 26

UC characterized by activation of ___ (2) which produce (3)__ which will cause ____ of colonic epithelium

Answer 26

Th2, NKT IL-5, IL-4, IL-13 --> increased permeability

Question 27

salt and pepper nucleus = stippling of the nucleus = ?

Answer 27

carcinoid tumor

Question 28

secretory products and sx of esophageal carcinoid tumor

Answer 28

unknown dysphagia, weight loss, reflux

Question 29

substance P released in carcinoid syndrome will cause ___ due to increased __

Answer 29

diarrhea | peristalsis

Question 30

CCK causes

Answer 30

gallbladder release

Question 31

secretory products, sx, disease associations of carcinoid tumors of the stomach

Answer 31

histamine, somatostatin, serotonin gastritis, ulcer, asx atrophic gastritis, MEN-1

Question 32

secretory products, sx, disease associations of carcinoid tumors of the proximal duodenum

Answer 32

gastrin, somatostatin, cholecystokinin sx=peptic ulcer, biliary obstruction, abd pain ds= zollinger-ellison syndrome, NF-1, sporadic

Question 33

secretory products, sx, of carcinoid tumors of the jejunum and ileum

Answer 33

serotonin, substance P, polypeptide YY sx= asx, obstruction, metastatic ds

Question 34

secretory products, sx, of carcinoid tumors of the appendix

Answer 34

serotonin, polypeptide YY sx= asx

Question 35

secretory products, sx, of carcinoid tumors of the colorectum

Answer 35

serotonin, peptide YY abd pain, weight loss, incidental

Question 36

Treg cells are activated by ___ presenting ___. They constituitively express __ and ___, and can directly act on either ___ or _____

Answer 36

APCs, autoAg CTLA-4 and IL-2R APCs or activated T cells

Question 37

current trx for IBD

Answer 37

TNF blockers, for moderate to severe risk for worsening HF, reactivation of infection and malignancy