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GI II > Immuno-Pathogenic Mechanisms of Inflammatory Bowel Disease (IBD) (part 1 of 2) > Flashcards

Immuno-Pathogenic Mechanisms of Inflammatory Bowel Disease (IBD) (part 1 of 2) Flashcards

1
Q

What is IBD?

A

a term used to describe two disorders that involve chronic inflammation of the GI tract; it is a chronic relapsing idiopathic inflammation of the GI tract

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2
Q

what are the two disorders that IBD is used to describe?

A

ulcerative colitis (UC) and Crohn’s disease (CD)

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3
Q

what is ulcerative colitis (UC) characterized by?

A

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

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4
Q

what is crohn’s disease characterized by?

A

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

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5
Q

what is a major difference to note between CD and UC?

A

in ~40% of patients with CD, the rectum is spared from inflammation in contrast to the universal rectal involvement in UC

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6
Q

what two things play an important role in IBD?

A

genetics and immune mechanisms

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7
Q

patients with IBD have been shown to have increased what?

A

intestinal permeability

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8
Q

IBD often results in what?

A

in irreversible impairment of gastrointestinal structure and function

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9
Q

what has been invoked to explain an increased incidence of IBD?

A

hygiene hypothesis of allergic and autoimmune diseases

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10
Q

what does IBD associated impaired function of tight junctions lead to?

A

increased permeability of the epithelial barrier

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11
Q

what exactly causes the inflammatory reactions that are seen in IBD?

A

the commensal bacteria of the normal intestinal microbiota cause inflammatory reactions leading to self-sustained mucosal inflammation

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12
Q

what happens when bacterial components cross the mucosal barrier?

A

they contact with immune cells, and induce innate and adaptive responses of the immune system

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13
Q

what immune responses have been described in cases of IBD?

A

both cellular and humoral immune responses to a variety of antigens of the commensal bacteria

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14
Q

IBD develops as a result of what?

A

a persistent and inappropriate perturbation of highly regulated interaction between the immune system and commensal bacteria of the normal microbiome resulting in: dysbiosis and mucosal inflammation

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15
Q

the aberrant responses seen in cases of IBD are to a large degrees _________ determined?

A

genetically determined

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16
Q

the aberrant responses seen in cases of IBD are to a large degree genetically determined and many include what 3 things?

A

disruption of the barrier function (mainly in UC); dysfunction of microbe sensing (mainly in CD); and changes in immunoregulation of innate and adaptive immune responses (in both disorders)

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17
Q

The combination of what two tests has a positive predictive value and specificity for CD?

A

positive ASCA and negative pANCA test

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18
Q

which test is positive for CD?

A

ASCA-positive

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19
Q

which test is positive for UC?

A

pANCA-positive

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20
Q

genetic susceptibility to IBD is influenced by what?

A

the luminal microbiota

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21
Q

microbial antigens act as what?

A

adjuvants that stimulate either pathogenic or protective immune responses

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22
Q

what is necessary to initiate or reactivate IBD?

A

environmental triggers

23
Q

what suggests the importance of environmental factors in cases of IBD?

A

low concordance rate in identical twins

24
Q

what is the human GI colonized by?

A

a vast, complex, and dynamic bacterial community

25
Q

what type of interaction is the gut microbiota in with host cells? and what does this compose?

A

symbiotic and reciprocal–> composes an extremely complex and highly regulated ecosystem

26
Q

what are the three functional roles of the gut microbiota?

A

protection of the host against invasion or colonization by pathogens; facilitation of nutrient digestion and absorption in humans; providing the immunological surveillance signals at the gut mucosa-lumen interface

27
Q

where does IBD develop?

A

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

28
Q

what prevents intestinal inflammation?

A

surgical diversion of the fecal stream

29
Q

what leads to recurrence of IBD?

A

reestablishment of the flow

30
Q

what has been shown to have beneficial effects on IBD?

A

the use of antibiotics and probiotics

31
Q

what is detected in IBD?

A

circulating Abs against fecal bacterial antigens

32
Q

what has been isolated from IBD patients to show reactivity against FECAL Ags?

A

lymphocytes

33
Q

the gut microbiome is primarily composed of what two phyla?

A

Bacteroidetes and Firmicutes

34
Q

what 2 species majorly make up the Bacteroidetes phyla?

A

Bacteroides and Prevotella

35
Q

what 2 species majorly make up the Firmicutes phyla?

A

Clostridium and Lactobacillus species

36
Q

what is the dysbiosis in UC IBD?

A

there is much more proteobacteria than in normal healthy large intestine microbiota

37
Q

what is the dysbiosis in CD IBD?

A

there is much more Firmicutes and Actinobacteria than in normal healthy large intestine microbiota

38
Q

spontaneous colitis does not occur in mutant mouse strains when they are maintained in a germ-free environment; however, it develops rapidly when?

A

these mice are colonized by commensal bacteria

39
Q

what happened when germ free mice were colonized with intestinal microbiotas from IBD donors?

A

they showed exacerbated disease in an experimental model of colitis

40
Q

what did babies born from IBD women present with?

A

lower bacterial diversity and altered bacterial composition

41
Q

what is the main predictor of the diversity of infant microbiota?

A

maternal IBD

42
Q

what happens if a germ free mother is inoculated with IBD mother and infant stools?

A

there is a significantly altered adaptive immune system of the intestines in the germ free mother

43
Q

what things have a major effect on gut microbiota composition?

A

diet and other environmental factors and host genetics

44
Q

what is symbiosis and what is its role?

A

it is a balanced microbial composition that maintains the homeostasis

45
Q

what does a dysbiosis lead to?

A

dysregulation of the immune system and inflammation in genetically susceptible host

46
Q

what could cause dysbiosis?

A

may be caused by environmental factors

47
Q

how does a high fiber diet affect the microbiota diversity and composition?

A

increased Bacteroidetes, increased firmicutes, decreased proteobacteria, increased actinobacteria

48
Q

how does a high protein diet affect the microbiota diversity and composition?

A

increased Bacteroidetes, increased firmicutes, increased proteobacteria

49
Q

how does a high fat diet affect the microbiota diversity and composition?

A

decreased Bacteroidetes, decreased firmicutes, decreased proteobacteria

50
Q

how does a high carb diet affect the microbiota diversity and composition?

A

increased bacteroidetes, increased firmicutes, increased actinobacteria

51
Q

Can an acute infection trigger the development of IBD?

A

to date, no specific microbial organisms have been conclusively linked to the development of IBD

52
Q

the implicated agents (not yet definitively proven) in humans are:

A

M. paratuberculosis; persistent measles virus infection (paramyxovirus); listeria monocytogenes

53
Q

what infection may play a role in the etiology of IBD?

A

gastroenteritis (such as salmonella and campylobacter)

54
Q

what is the relationship between IBD and helminth colonization?

A

the prevalence of IBD is inversely associated with the prevalence of helminth colonization

GI II (20 decks)

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