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gi ii > Immuno-Patho of IBD > Flashcards

Immuno-Patho of IBD Flashcards

1
Q

IBD

A

Inflammatory Bowel Disease

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2
Q

Disorders of IBD

A

Ulcerative Colitis and Crohn’s Disease

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3
Q

Ulcerative Colitis

A

chronic inflammation and ulcers in innermost lining of colon and/or rectum

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4
Q

Crohn’s Disease

A

inflammation of lining of GI which often spreads deep and may occur in any part of the GI

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5
Q

How does the epithelial barrier of the GI tract change in patients with IBD?

A

increase in permeability caused by impaired formation of tight junctions

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6
Q

How are inflammatory responses induced in patients with IBD?

A

bacterial components cross the mucosal barrier and induce innate and adaptive immune responses

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7
Q

IBD develops as a result of…

A

persistent and inappropriate pertubation of the immune system and commensal bacteria resulting in dysbiosis and mucosal inflammation

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8
Q

Aberrant responses in UC

A

disruption of barrier function and changes in immunoregulation

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9
Q

Aberrant responses in CD

A

dysfunction of microbe sensing, changes in immunoregulation

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10
Q

Signs and Sxs of CD

A

abd pain, obstruction, fever

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11
Q

Lab test for CD

A

ASCA-positive, Anti-Saccharomyces Cerevisiae Abs

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12
Q

Signs and Sxs of UC

A

bloody diarrhea, urgency

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13
Q

Lab test for UC

A

pANCA-positive, perinuclear Anti-Neutrophil Cytoplasmic Abs

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14
Q

Causes of IBD

A

genetic susceptibility, luminal microbial antigens and adjuvants, immune response, environmental triggers

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15
Q

Environmental factors that trigger IBD

A

smoking, diet, drugs, geography, stress, microbes and enteric flora, permeability, appy

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16
Q

Functional roles of gut microbiota

A

protection, facilitation, provision of immunologic surveillance signals

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17
Q

Where does IBD develop?

A

areas of high bacterial concentration, terminal ileum and colon

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18
Q

Lymphocytes from IBD patients show reactivity against what antigens?

A

fecal antigens

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19
Q

Classification of bacteria found in proximal GI tract

A

aerobic and facultative anaerobic bacteria

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20
Q

Classification of bacteria found in distal GI tract

A

obligate anaerobic bacteria

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21
Q

Gut microbiome is primarily composed of what species

A

Firmicutes, bacteroidetes

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22
Q

Major Firmicutes Spp. in microbiota

A

Clostridium, Lactobacillus, Eubacterium

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23
Q

Major Bacteroidetes Spp. in microbiota

A

Bacteroides, Prevotella

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24
Q

Major bacteria present in UC

A

proteobacteria

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25
Q

Major bacteria present in CD

A

actinobacteria, firmicutes

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26
Q

How is the microbiota of babies born from IBD women different from those not?

A

lower bacterial diversity and altered bacterial comp

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27
Q

What factors control the microflora composition?

A

host genetics, maternal transfer, abx, infection, inflammation, age, diet, obesity

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28
Q

How does a high fiber diet impact microbiota?

A

increases levels of bacteroidetes, firmicutes and actinobacteria, decreases proteobacteria

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29
Q

How does a high protein diet impact microbiota?

A

increases bacteroidetes, firmicutes, and proteobacteria

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30
Q

How does a high fat diet impact microbiota?

A

decreases bacteroidetes, firmicutes, and proteobacteria

31
Q

How does a carb diet impact microbiota?

A

increases bacteroidetes, firmicutes, and actinobacteria

32
Q

Acute infections thought to play a role in IBD development

A

gastroenteritis (Shigella and Campylobacter), inversely associated with helminth colonization

33
Q

IBD is uncommon in what populations?

A

Asian and African populations

34
Q

Genes involved in CD/UC development encode for what?

A

Immuno-inflammatory components

35
Q

Susceptibility locus for IBD

A

chromsome 16

36
Q

IBD-1 locus contains what genes?

A

CARD15/NOD2

37
Q

CARD15 is expressed in what cells?

A

macrophages and dendritic cells

38
Q

Percentage of CD cases associated with defects in CARD15/NOD2

A

17-27%

39
Q

CARD15 triggers activation of what?

A

NF-kB

40
Q

Mechanisms of CD caused by NOD 2 mutation

A

defective macrophage function, defective epithelial cell responses, defective APC conditioning

41
Q

Colonization of the GI with beneficial bacteria induces the development of…

A

GALT

42
Q

Microbiota maintains basal activity level of what cells in the lamina propria

A

Th1 and Th17 cells

43
Q

How are pathobionts suppressed by beneficial bacteria?

A

comensal bacteria induce Treg cells and IL-10 production

44
Q

Comensal bacteria ferment …. to produce ….

A

nondigestible polysaccharides, SCFAs

45
Q

SCFAs have anti-inflammatory properties in what cells?

A

macrophage, dendritic cell, CD4 T cell and intestinal epithelial cell

46
Q

Receptor on Treg cells for SCFAs

A

GPR43

47
Q

T cells important for integrity of epithelial barrier

A

Th17

48
Q

Bacteria associated with induction of Treg cells in lamina propria

A

Bacteroides fragilis, Clostridium ssp., segmented filamentous bacteria

49
Q

How is host immune tolerance to comensal bacteria induced?

A

MAMPs, polysaccharide signaling, SCFA production, expression of epithelial intestinal alkaline

50
Q

Functions of SCFA

A

induce IgA, mucus secretion, promote epithelial barrier integrity, prevent pathogen colonization

51
Q

Commensal bacteria effect on NF-kB

A

Bacteroides attenuates inflammatory response by inducing peroxisome proliferation activated receptor

52
Q

Dysbiosis/Chronic inflammation involves hyperactivation of what cells and inhibition of what cells?

A

Increased activation of Th1 and Th17, inhibition of Treg

53
Q

Genetic and environmental factors induce what phase of IBD

A

impaired barrier function

54
Q

Complications of chronic GI inflammation

A

fibrosis, stenosis, abscess, fistula, cancer

55
Q

T cell paradigm in CD

A

activation of Th1 and Th17 cells driven by IL-12, IL-6, and IL-23 by DC and macophages

56
Q

Th1 cells secrete…

A

IL-2, IFN-g, TNF

57
Q

Th17 cells secrete….

A

IL-17

58
Q

T cell paradigm in UC

A

atypical activation of Th2 and NKT cells which cause the production of IL-5, IL-4, and IL-13

59
Q

IL-12 causes differentiation to what T cell

A

Th1

60
Q

IL-4 causes differentiation to what T cell

A

Th2

61
Q

IL-6, IL-23, TGFb cause differentiation to what T cell

A

Th17

62
Q

IL-23 is produced by what cells?

A

APCs, macrophages and DC

63
Q

LOF SNP in IL-10 and TGF-B would — to IBD

A

predispose

64
Q

GOF SNP in IL-10 and TGF-B would — from IBD

A

protect

65
Q

LOF SNP in TNFa, IFN-g, IL-17 would — from CD

A

protect

66
Q

GOF SNP in TNFa, IFN-g, IL-17 would — to CD

A

predispose

67
Q

LOF SNP in IL-4, IL-5, and IL-13 would — from UC

A

protect

68
Q

GOF SNP in IL-4, IL-5, and IL-13 would — to UC

A

predispose

69
Q

What do Treg cells secrete to inhibit Th17 formation

A

retinoic acid, vitamin A

70
Q

Excess of TGFB and limited expression of proinflammatory cytokines from APCs causes differentiation of what T cells

A

Treg

71
Q

Functions of Treg cells

A

activated by APC, express CTLA-4 and CD25 (binds IL-2), suppress APCs, suppress activated T cells

72
Q

TNF blocker MOA

A

mAb that binds TNF, reserved for UC and CD; reduce inflammation associated with IBD

73
Q

Potential treatments of interest for IBD patients

A

fecal microbiota transplant, anti-TNF

gi ii (8 decks)

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