Immuno-Pathogenic Mechanisms of Inflammatory Bowel Disease (IBD) (part 1 of 2) Flashcards
What is IBD?
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
what are the two disorders that IBD is used to describe?
ulcerative colitis (UC) and Crohn’s disease (CD)
what is ulcerative colitis (UC) characterized by?
chronic inflammation and ulcers in the innermost lining of the colon and/or rectum
what is crohn’s disease characterized by?
inflammation of the lining of the GI which often spreads deep into affected tissues and may occur in any part of the GI
what is a major difference to note between CD and UC?
in ~40% of patients with CD, the rectum is spared from inflammation in contrast to the universal rectal involvement in UC
what two things play an important role in IBD?
genetics and immune mechanisms
patients with IBD have been shown to have increased what?
intestinal permeability
IBD often results in what?
in irreversible impairment of gastrointestinal structure and function
what has been invoked to explain an increased incidence of IBD?
hygiene hypothesis of allergic and autoimmune diseases
what does IBD associated impaired function of tight junctions lead to?
increased permeability of the epithelial barrier
what exactly causes the inflammatory reactions that are seen in IBD?
the commensal bacteria of the normal intestinal microbiota cause inflammatory reactions leading to self-sustained mucosal inflammation
what happens when bacterial components cross the mucosal barrier?
they contact with immune cells, and induce innate and adaptive responses of the immune system
what immune responses have been described in cases of IBD?
both cellular and humoral immune responses to a variety of antigens of the commensal bacteria
IBD develops as a result of what?
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
the aberrant responses seen in cases of IBD are to a large degrees _________ determined?
genetically determined
the aberrant responses seen in cases of IBD are to a large degree genetically determined and many include what 3 things?
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)
The combination of what two tests has a positive predictive value and specificity for CD?
positive ASCA and negative pANCA test
which test is positive for CD?
ASCA-positive
which test is positive for UC?
pANCA-positive
genetic susceptibility to IBD is influenced by what?
the luminal microbiota
microbial antigens act as what?
adjuvants that stimulate either pathogenic or protective immune responses
what is necessary to initiate or reactivate IBD?
environmental triggers
what suggests the importance of environmental factors in cases of IBD?
low concordance rate in identical twins
what is the human GI colonized by?
a vast, complex, and dynamic bacterial community
what type of interaction is the gut microbiota in with host cells? and what does this compose?
symbiotic and reciprocal–> composes an extremely complex and highly regulated ecosystem
what are the three functional roles of the gut microbiota?
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
where does IBD develop?
in areas of high bacterial concentration (terminal ileum and colon)
what prevents intestinal inflammation?
surgical diversion of the fecal stream
what leads to recurrence of IBD?
reestablishment of the flow
what has been shown to have beneficial effects on IBD?
the use of antibiotics and probiotics
what is detected in IBD?
circulating Abs against fecal bacterial antigens
what has been isolated from IBD patients to show reactivity against FECAL Ags?
lymphocytes
the gut microbiome is primarily composed of what two phyla?
Bacteroidetes and Firmicutes
what 2 species majorly make up the Bacteroidetes phyla?
Bacteroides and Prevotella
what 2 species majorly make up the Firmicutes phyla?
Clostridium and Lactobacillus species
what is the dysbiosis in UC IBD?
there is much more proteobacteria than in normal healthy large intestine microbiota
what is the dysbiosis in CD IBD?
there is much more Firmicutes and Actinobacteria than in normal healthy large intestine microbiota
spontaneous colitis does not occur in mutant mouse strains when they are maintained in a germ-free environment; however, it develops rapidly when?
these mice are colonized by commensal bacteria
what happened when germ free mice were colonized with intestinal microbiotas from IBD donors?
they showed exacerbated disease in an experimental model of colitis
what did babies born from IBD women present with?
lower bacterial diversity and altered bacterial composition
what is the main predictor of the diversity of infant microbiota?
maternal IBD
what happens if a germ free mother is inoculated with IBD mother and infant stools?
there is a significantly altered adaptive immune system of the intestines in the germ free mother
what things have a major effect on gut microbiota composition?
diet and other environmental factors and host genetics
what is symbiosis and what is its role?
it is a balanced microbial composition that maintains the homeostasis
what does a dysbiosis lead to?
dysregulation of the immune system and inflammation in genetically susceptible host
what could cause dysbiosis?
may be caused by environmental factors
how does a high fiber diet affect the microbiota diversity and composition?
increased Bacteroidetes, increased firmicutes, decreased proteobacteria, increased actinobacteria
how does a high protein diet affect the microbiota diversity and composition?
increased Bacteroidetes, increased firmicutes, increased proteobacteria
how does a high fat diet affect the microbiota diversity and composition?
decreased Bacteroidetes, decreased firmicutes, decreased proteobacteria
how does a high carb diet affect the microbiota diversity and composition?
increased bacteroidetes, increased firmicutes, increased actinobacteria
Can an acute infection trigger the development of IBD?
to date, no specific microbial organisms have been conclusively linked to the development of IBD
the implicated agents (not yet definitively proven) in humans are:
M. paratuberculosis; persistent measles virus infection (paramyxovirus); listeria monocytogenes
what infection may play a role in the etiology of IBD?
gastroenteritis (such as salmonella and campylobacter)
what is the relationship between IBD and helminth colonization?
the prevalence of IBD is inversely associated with the prevalence of helminth colonization
