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GI 2 Exam 1 > Immuno of IBD > Flashcards

Immuno of IBD Flashcards

1
Q

chronic inflammation and ulcers in the innermost (superficial) lining of the colon and/or rectum

A

ulcerative colitis

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2
Q

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

A

Crohn’s disease

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3
Q

What is spared in 40% of patients with CD?

A

the rectum

- in contrast to universal rectal involvement in UC

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4
Q

what causes increased permeability of the epithelial barrier?

A

impaired formation of tight junctions

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5
Q

is disruption of barrier function a response seen mainly in UC or CD?

A

UC

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6
Q

immune system sensing foreign/aberrant microbes, seen more in UC or CD?

A

CD

  • main factor is TLR’s in Chron’s, failure of Treg cells in both
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7
Q

ASCA-positive more likely in UC or CD?

A

CD
- combination of positive ASCA and negative pANCA has a positive predictive value of 96% and specificity of 97% for CD

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8
Q

pANCA-positive more likely in UC or CD?

A

UC

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9
Q

what are the two most important environmental factors leading to IBD?

A
  • microbes/enteric flora (CD)

- membrane permeability (UC)

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10
Q

where does IBD develop?

A

the terminal ileum and colon (areas of high bacterial concentration)

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11
Q

circulating Abs against what, are detected in IBD?

A

fecal bacterial antigens

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12
Q

what show reactivity against fecal antigens?

A

lymphocytes

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13
Q

where do the majority of our gut flora reside?

A

the colon and cecum 10^9-10^12 (compared to 10^3-10^7 in the small intestine)

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14
Q

the gut microbiome is composed primarily of which phyla?

A

90% belong to Bacteroidetes (largest percentage) and Firmicutes phyla

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15
Q

which disease is more likely if there is an increase in Proteobacteria in the gut flora?

A

UC

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16
Q

which disease is more likely if there if a significant increase in Firmicutes and Actinobacteria (with a decrease in the amount of Bacteroidetes)

A

CD

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17
Q

what is the main predictor of diversity of infant microbiota?

A

maternal IBD

- infant stool of mothers with IBD showed significantly altered adaptive immune system response of the intestines

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18
Q

dysbiosis leads to what, of the immune system?

A

dysregulation and inflammation (in a genetically susceptible host)

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19
Q

what effect does a high fiber diet have on gut flora?

A

increases bacteroidetes, firmicutes, and actinobacteria

- decreases proteobacteria

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20
Q

what effect does high protein (or high carb) diet have on gut flora?

A

increases bacteroidetes, firmicutes, and proteobacteria

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21
Q

what effect does a high fat diet have on gut flora?

A

decreases bacteroidetes, firmicutes, and proteobacteria

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22
Q

individuals diagnosed with what, have been shown to subsequently have an increased risk of developing IBD?

A

gastroenteritis

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23
Q

the prevalence of what, is inversely associated with the prevalence of IBD?

A
  • *HELMINTH COLONIZATION**

- thought to play important immunoregulatory role with intestinal flora

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24
Q

where is UC 10-fold less common, and CD very uncommon?

A

Asia and Africa

25
Q

what LOF mutations are associated with CD?

A

CARD15/NOD2 (IBD-1 locus on xsome 16)
- defects found in 17-27% of CD cases

NOTE: homozygous individuals of CARD15 variant have 20-fold risk of developing CD

26
Q

what interleukens are associated with CD?

A

IL3, IL4, IL5, IL13, and TNF

27
Q

what is CARD15?

A

intracellular pathogen recognition receptor (PPR)
- recognizes molecules containing specific structure called muramyl dipeptide (MDP) -> triggers activation of NF-kb -> adaptive immune response

28
Q

where is CARD15 primarily expressed?

A

monocytes/macrophages

29
Q

what does a mutation in CARD15 lead to?

A

reduces activation of NF-kb -> inhibiting adaptive immune response

  • increases susceptibility to chronic intracellular infection
  • disrupts CARD15-mediated effects on APC, leading to less effector and Treg cell activation
30
Q

colonizaton of the GI with beneficial bacteria induces what?

A
  • development of GALT
  • increased Treg cells
  • increased IL10
31
Q

microbiota maintains the basal level of what types of T cells?

A

Th17 and Th1 (important for membrane integrity)

32
Q

what are directly suppressed by beneficial commensal bacteria via induction of Treg cells and stimulation of IL10 production?

A

pathobionts

33
Q

short chain fatty acids tend to have what?

A

anti-inflammatory properties

34
Q

SCFAs -> FA metabolites -> GPR43 -> what?

A

Treg cells -> IL10 –> BLOCKING inflammatory response

35
Q

segmented filamentous bactera (SFB) colonization results in what?

A

induction of Treg cell populations in the lamina propria

- also plays a role in Th17 levels (important for epithelial integrity)

36
Q

microbiota participate in the formation of active what?

A

secondary forms of bile acids

37
Q

what makes up the mucosal firewall?

A

epithelial barrier, mucus layer IgA, DC’s, and T cells

38
Q

Where does IgA class switching occur?

A

in Peyer’s patches

39
Q

which pathway does commensal mirobiota suppress?

A

NF-kb pathway

40
Q

what triggers UC?

A
  • *epithelial antigens and altered AEROBIC bacteria**

- Salmonella enteritidis -> binds TLR5 -> activates NF-kb -> PRO-inflammatory genes

41
Q

what triggers CD?

A
  • *ANAEROBIC bacteria**

- bacteroides thetaiotaomicron -> stimulates transcription factor PPAR -> exports activated NF-kb from nucleus

42
Q

chronic inflammation leads to hyperactivation of what?

- and inhibition of what?

A

hyperactivation of Th1 and Th17

- inhibition of Treg cells and IL10

43
Q

which disease is characterized as a Th1 and Th17-type disease?
(Th1 and Th17 cooperation!)

A

CD

  • Th1 secretes IL2, IFNy, TNF
  • Th17 secretes IL17, IL22
44
Q

which disease is characterizes as a Th2-type disease?

A
  • *UC**
  • Th2 cells secrete IL5
  • NK cells secrete IL13

leads to B cell and WBC recruitment (humoral response)

45
Q

what activates Th17 cells?

A

IL6, IL23, TGFb

46
Q

what activates Th1 cells?

A

IL12

47
Q

what activates Th2 cells?

A

IL4

48
Q

what produces IL6 and IL23?

A

APC’s

49
Q

IL23 is closely related to what, and regulates Th1 cell responses?

A

IL12

NOTE: IL23 also regulates macrophage and DC resposes

50
Q

what is the most important inducer or macrophages and DC’s?

A

IFN-y

51
Q

what is the most powerful inducer of Th17?

A

IL23

52
Q

GOF SNP’s of:
- TNFa, IFNy, IL1, IL6, IL2, IL17, IL22

predispose you to what?

A

cell-mediated inflammation and CD

53
Q

GOF SNP’s of:
- IL4, IL5, IL13

predispose you to what?

A

Ab-mediated inflammation and UC

54
Q

IBD is believed to be the result of a breakdown of tolerance to what?

A

resident enteric bacteria

55
Q

Treg cells suppress APC’s directly through what

- and indirectly via what?

A
  • directly: cell-cell interaction

- indirectly: cytokines or chemokines

56
Q

inadequate suppression of effector T cells leads to what?

A

inflammation and IBD

- normally, Treg cells suppress activation of effector T cells and prevent IBD

57
Q

what are the current treatment options for IBD?

A
  • TNF blockers (administered IV, for moderate-severe UC or CD, risk for worsening HF, infection and malignancy)
  • leukocyte adhesion inhibitors (recommended in pts who failed previous TNF therapy, risk of life-treatening progressive multifocal leukoencephalopathy)
58
Q

what is on the horizon for IBD treatment?

A

fecal microbiota transplantation (FMT)

GI 2 Exam 1 (22 decks)

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