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

Question 1

What is IBD?

Answer 1

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

Question 2

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

Answer 2

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

Question 3

what is ulcerative colitis (UC) characterized by?

Answer 3

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

Question 4

what is crohn’s disease characterized by?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

what two things play an important role in IBD?

Answer 6

genetics and immune mechanisms

Question 7

patients with IBD have been shown to have increased what?

Answer 7

intestinal permeability

Question 8

IBD often results in what?

Answer 8

in irreversible impairment of gastrointestinal structure and function

Question 9

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

Answer 9

hygiene hypothesis of allergic and autoimmune diseases

Question 10

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

Answer 10

increased permeability of the epithelial barrier

Question 11

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

Answer 11

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

Question 12

what happens when bacterial components cross the mucosal barrier?

Answer 12

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

Question 13

what immune responses have been described in cases of IBD?

Answer 13

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

Question 14

IBD develops as a result of what?

Answer 14

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

Question 15

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

Answer 15

genetically determined

Question 16

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

Answer 16

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)

Question 17

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

Answer 17

positive ASCA and negative pANCA test

Question 18

which test is positive for CD?

Answer 18

ASCA-positive

Question 19

which test is positive for UC?

Answer 19

pANCA-positive

Question 20

genetic susceptibility to IBD is influenced by what?

Answer 20

the luminal microbiota

Question 21

microbial antigens act as what?

Answer 21

adjuvants that stimulate either pathogenic or protective immune responses

Question 22

what is necessary to initiate or reactivate IBD?

Answer 22

environmental triggers

Question 23

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

Answer 23

low concordance rate in identical twins

Question 24

what is the human GI colonized by?

Answer 24

a vast, complex, and dynamic bacterial community

Question 25

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

Answer 25

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

Question 26

what are the three functional roles of the gut microbiota?

Answer 26

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

Question 27

where does IBD develop?

Answer 27

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

Question 28

what prevents intestinal inflammation?

Answer 28

surgical diversion of the fecal stream

Question 29

what leads to recurrence of IBD?

Answer 29

reestablishment of the flow

Question 30

what has been shown to have beneficial effects on IBD?

Answer 30

the use of antibiotics and probiotics

Question 31

what is detected in IBD?

Answer 31

circulating Abs against fecal bacterial antigens

Question 32

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

Answer 32

lymphocytes

Question 33

the gut microbiome is primarily composed of what two phyla?

Answer 33

Bacteroidetes and Firmicutes

Question 34

what 2 species majorly make up the Bacteroidetes phyla?

Answer 34

Bacteroides and Prevotella

Question 35

what 2 species majorly make up the Firmicutes phyla?

Answer 35

Clostridium and Lactobacillus species

Question 36

what is the dysbiosis in UC IBD?

Answer 36

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

Question 37

what is the dysbiosis in CD IBD?

Answer 37

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

Question 38

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

Answer 38

these mice are colonized by commensal bacteria

Question 39

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

Answer 39

they showed exacerbated disease in an experimental model of colitis

Question 40

what did babies born from IBD women present with?

Answer 40

lower bacterial diversity and altered bacterial composition

Question 41

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

Answer 41

maternal IBD

Question 42

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

Answer 42

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

Question 43

what things have a major effect on gut microbiota composition?

Answer 43

diet and other environmental factors and host genetics

Question 44

what is symbiosis and what is its role?

Answer 44

it is a balanced microbial composition that maintains the homeostasis

Question 45

what does a dysbiosis lead to?

Answer 45

dysregulation of the immune system and inflammation in genetically susceptible host

Question 46

what could cause dysbiosis?

Answer 46

may be caused by environmental factors

Question 47

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

Answer 47

increased Bacteroidetes, increased firmicutes, decreased proteobacteria, increased actinobacteria

Question 48

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

Answer 48

increased Bacteroidetes, increased firmicutes, increased proteobacteria

Question 49

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

Answer 49

decreased Bacteroidetes, decreased firmicutes, decreased proteobacteria

Question 50

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

Answer 50

increased bacteroidetes, increased firmicutes, increased actinobacteria

Question 51

Can an acute infection trigger the development of IBD?

Answer 51

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

Question 52

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

Answer 52

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

Question 53

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

Answer 53

gastroenteritis (such as salmonella and campylobacter)

Question 54

what is the relationship between IBD and helminth colonization?

Answer 54

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