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GII Exam 1 [Path, Pharm, Immuno, CLMD] > [Immuno] Imuno Path Mechanisms of IBD > Flashcards

[Immuno] Imuno Path Mechanisms of IBD Flashcards

1
Q

What is IBD?

A

IBD is a term used to describe TWO DISORDERS that involve chronic inflammation of the GI

  • Ulcerative colitis (UC)
  • Crohn’s disease (CD)
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2
Q

What is ulcerative colitis?

A

Chronic inflammation and ulcers in the innermost lining of the COLON and/or RECTUM

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3
Q

What is crohn disease (CD)?

A

Inflammation of the lining of the GI which SPREADS DEEP into affected tissues ane may OCCUR IN ANY PART of GI

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4
Q

In 40% of pts with CD, which portion of the GI is spared?

A

Rectum

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5
Q

Patients with IBD have been shown to have INCREASED intestinal _____________

A

Patients with IBD have been shown to have INCREASED intestinal permeability

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6
Q

IBD often results in __________of GI structure and function

A

IBD often results in IRREVERSIBLE IMPAIRMENT of GI structure and function

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7
Q

What hypothesis may explain the increased incidence of IBD?

A

Hygeiene hypothesis

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8
Q

Describe how the increased permeability that results from IBD relates to the eitiology of IBD

A

The increased permeability of the epithelial layer from impaired tight junctions leads to commensal bacteria of normal intestinal microbiota to cause inflammatory reactions leading to self sustained mucosal inflammation.

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

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9
Q

IBD develops as a result of…

A

A persistent and inappropriate pertubation of highly regulated interaction between the IMMUNE SYSTEM and COMMENSAL BACTERIA of the normal microbiome

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10
Q

The ABBERANT RESPONSES of IBD are largely due to…

A

Genetic factors

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11
Q

Which is more related to UC and CD?

Dysfunction in microbe sensing:

Dysfunction in barrier function:

A

Dysfunction in microbe sensing: CD

Dysfunction in barrier function: UC

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12
Q

Describe the difference in pathology b/w CD and UC

A

CD = Absesses, Fistulas, Strictures, Granuloma formation, Transmural inflammation

UC = Pseudopolyps, Toxic megacolon, Mucosal/submucosal inflammation

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13
Q

Describe the difference in GI involvement b/w CD and UC

A

CD: Mouth to anus (rectum spared)

UC: Colon and/or rectum

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14
Q

Describe the X-ray appearance of CD vs UC

A

CD: “String sign” on barium X-ray, “Cobblestone” on endoscopy

UC: “Lead pipe” colon

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15
Q

What is the lab test associated with CD vs UC?

***What is the problem with isolated tests?

A

CD = ASCA-positive

UC = pANCA positive

***Problem is that only 80% of CD pts are positive for ASCA. Also, only 50-70% of UC pts are pANCA positive. Therefore, could get a negative result and miss catching IBD!!!

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16
Q

What is the best laboratory standard to follow when screening for CD?

A

Combination of a positive ASCA test with a negative pANCA test has a positive predictive value of 96% and specificity of 97% for CD

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17
Q

What causes IBD?

A

Combination of:

  • Genetics
  • Microbial Ags
  • Enviornmental triggers
  • Immune response
18
Q

What does the low concordance rate in identical twin studies for CD and UC suggest?

A

In identical twins, if one twin had CD…other twin had 50% chance of CD

In identical twins, if one twin had UC…other twin had 10% chance of UC

This suggests the importance of ENVIORNMENTAL FACTORS

19
Q

What is a very strange protective eniornmental factor for UC?

A

Smoking

20
Q

What are the three major roles of the gut microbiota?

A
  1. PROTECTION of host against invasion or colonization by pathogens
  2. FACILITATION of nutrient digestion and absorption
  3. PROVIDING the immunological surveillance signals at the gut mucosa-lumen interface
21
Q

Where does IBD typically develop within the GI system?

A

Areas of HIGH BACTERIAL CONCENTRATION

(Terminal ileum and colon)

22
Q

Use of what drugs can have benificial effects on IBD?

A

Antibiotics and Probiotics

23
Q

What is the predominant phyla associated with healthy GI?

A

Bacteroidetes

Firmicutes

24
Q

What are the predominant phyla of UC?

A

Proteobacteria

25
Q

What is the predominant phyla of CD?

A

Firmicutes

26
Q

Role Infections in IBD

____________ may play a role in the etiology of IBD

A

GASTROENTERITIS (salmonella and campylobacter) may play a role in the etiology of IBD

27
Q

Role infections in IBD

The prevalence of IBD is inversely associated with the prevalence of ________________

A

The prevalence of IBD is inversely associated with the prevalence of HELMINTH COLONIZATION

28
Q

UC is 10 fold less common in which populations?

A

Asian and African

29
Q

CD is very uncommon in which populations?

A

Asia and Africa

30
Q

Role of Genetic Factors in IBD

What are primarily responsible for IBD?

A

SNPs

31
Q

All of the IBD related genes with contained SNPs all code for….

A

IMMUNO-INFLAMMATORY components

32
Q

What is the primary gene involved in the IBD-1 locus?

A

CARD15

(CAspase Recruitment Domain family member 15)

33
Q

What is CARD15?

What does it do?

A

Intracellular PPR

Triggers activation of NF-kappaB

34
Q

Microbiota maintains the BASAL LEVEL of _____ and _____ cell activity in the lamina propria

A

Microbiota maintains the BASAL LEVEL of Th17** and **Th1 cell activity in the lamina propria

35
Q

What is an important product produced by commensal bacteria that have anti-inflammatory properties?

A

Short chain fatty acids (SCFAs)

36
Q

Review this image for the microbial effects on the host

A
37
Q

Overall, in IBD…. _________ is lost

A

Tolerance

38
Q

In IBD, what immunologic factors are HYPERACTIVE and what is INHIBITED?

A

HYPERACTIVE = TH1, TH17

INHIBITED = Treg cells, IL-10

39
Q

What Th and ILs are involved in CD?

A

Th1, Th17

IL-12, IL-6, IL-23

40
Q

What Th and ILs are involved in UC?

A

Th2

IL-5, IL-4, IL-13

41
Q
A

GII Exam 1 [Path, Pharm, Immuno, CLMD] (16 decks)

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