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GI2 E1 > immunopathogenic mechanisms of IBD > Flashcards

immunopathogenic mechanisms of IBD Flashcards

1
Q

ulcerative colitis is characterized by ulcers in _____ of the ______

A

innermost lining

colon or rectum

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2
Q

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

A

spreads deep

in any part of the GI system

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3
Q

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

A

commensal bacteria of the normal intestine

self sustained

mucosal barrier,
innate and adaptive

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4
Q

IBD develops as a result of ___ and ____

A

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

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5
Q

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

A

changes in Treg immune regulation

disruption of barrier function

dysfunction of microbe sensing

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6
Q

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

A

ASCA

pANCA

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7
Q

IBD is complex combination of

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

A

chronic
luminal microbiota
microbial Ags
environmental triggers

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8
Q

what environmental factors can lead to IBD

A 
NSAIDs, abx
diet
smoking
stress
epigenetics (microbes, enteric flora, permeability)
appendectomy
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9
Q

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

A

protection against invasion or colonization (outcompete)

facilitation of difestion and absorption

provide immunological surveillance signals

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10
Q

main players in normal gut microbiome

A

bacteriodetes (bacteriodes/provetella)

firmicutes (C. dif, lactobacillus)

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11
Q

describe the state of dysbiosis in ulcerative colitis

A

way more proteobacteria

E. Coli, desulfovibrio

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12
Q

describe the state of dysbiosis in crohn

A 
way more firmicutes (C. dif, lactobacillus)
and actinobacteria (bifidobacterium, collinsella)
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13
Q

what is the main predictor of diversity of infant microbiota

A

maternal IBD

–> lower diversity

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14
Q

what features control host microflora composition

A 
host genetics
maternal transfer
abx/meds
infection, inflammation
stress, hygeine, age
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15
Q

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 ___

A

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

salmonella, campylobacter

helminth colonization

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16
Q

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 ___

A

IBD1, 16

CARD15, PPR, MDP, NF-kB

17
Q

how does CARD15 mutation increase risk for IBD

A

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

18
Q

speak to how gut microbiota maintains homeostasis

A

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

19
Q

describe the pathway of SCFA function

A

released by microbiota after fatty acid metabolites

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

20
Q

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)

A

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

21
Q

__+ __ + __ + __ = mucosal firewall

A

epithelial barrier + IgA + DCs + T cells

22
Q

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

A

NF-kB

tolerance to commensal bacteria

23
Q

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

A

TLR5

attenuate

24
Q

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

A

Th1 and Th17

Treg and IL-10

25
Q

Th1/Th17 paradigm in crohn

A

IL-6,

IL-12–> Th1 –> IL-2, IFN-y (–> Mø –>TNF)

IL-23 –> Th17 –> IL-17

26
Q

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

A

Th2, NKT

IL-5, IL-4, IL-13 –> increased permeability

27
Q

salt and pepper nucleus = stippling of the nucleus = ?

A

carcinoid tumor

28
Q

secretory products and sx of esophageal carcinoid tumor

A

unknown

dysphagia, weight loss, reflux

29
Q

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

A

diarrhea

peristalsis

30
Q

CCK causes

A

gallbladder release

31
Q

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

A

histamine, somatostatin, serotonin

gastritis, ulcer, asx

atrophic gastritis, MEN-1

32
Q

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

A

gastrin, somatostatin, cholecystokinin

sx=peptic ulcer, biliary obstruction, abd pain

ds= zollinger-ellison syndrome, NF-1, sporadic

33
Q

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

A

serotonin, substance P, polypeptide YY

sx= asx, obstruction, metastatic ds

34
Q

secretory products, sx, of carcinoid tumors of the appendix

A

serotonin, polypeptide YY

sx= asx

35
Q

secretory products, sx, of carcinoid tumors of the colorectum

A

serotonin, peptide YY

abd pain, weight loss, incidental

36
Q

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

A

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

37
Q

current trx for IBD

A

TNF blockers, for moderate to severe

risk for worsening HF, reactivation of infection and malignancy

GI2 E1 (19 decks)

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