Role of mucosal immunity in disease Flashcards
What is the mucosal response to infection?
Innate mechanisms eliminate most intestinal infections rapidly
There is activation through ligation of pattern recognition receptors (PRR)
PRR in epithelial cells activate the NFkB pathway ( a protein complex that controls DNA transcription).
There is gene transcription and production of cytokines, chemokines and defensins.
There is also activation of the underlying immune response.
Briefly describe what coeliac disease is.
A genetically linked, autoimmune disorder which causes damage to the small intestine which leads to malnutrition. It is life long and incurable.
Is coeliac disease an allergy?
No
What is the antigen responsible for the response in coeliac disease?
Gluten, which comes from wheat, rye and barley
What triggers coeliac disease?
There is a genetic susceptibility, but the trigger is unknown.
What mediates the immunopathology of coeliac disease?
T cell and intra epithelial lymphocyte (IEL).
How can you cure the symptoms of coeliac disease?
By removing the antigen (gluten).
what happens to the intestine in coeliac disease?
The mucosa becomes “scalloped” and there is villous atrophy.
Describe the immunology of coeliac disease.
Gliadin peptides pass through the epithelium, either para or intracellularly and are deaminated by tissue transglutaminase (tTG), which increases their immunogenicity. Gliadin peptides then bind to dendritic cells which interact with CD4+ T cells in the lamina propria via HLA class II molecules, DQ2 or DQ8. These T cells produce proinflammatory cytokines, particularly interferon-gamma. CD4+ T cells also interact with B cells to produce endomysial and tissue transglutaminase antibodies. Gliadin peptides also cause release of IL-15 from enterocytes, activating intraepithelial lymphocytes with a natural killer cell marker. This inflammatory cascade releases metalloproteinases and other mediators that contribute to the villous atrophy and crypt hyperplasia which are typical of the disease.
How is coeliac disease diagnosed?
Biopsy is the gold standard
Serology is useful as a screening test (IgA anti-tissue transglutaminase autoantibodies)
What must you take into account when doing serology for tTG antibodies?
If the patient has an IgA deficiency you could get a false negative.
If the patient is not consuming gluten there will not be any antibodies, so the usefulness of the test is dependent on the dietary state of the patient.
As well as screening, what is IgA anti-TTG serology used for?
Dietary compliance monitoring
What is the main cause of persistent coeliac symptoms?
Lack of dietary compliance
What may lead to inflammatory bowel disease?
Altered function and balance of the relationship between the intestinal immune system and the specific microbiota of the intestine.
What parts of the GI tract are affected by a) UC and b) Crohn’s disease?
a) The colon is affected by UC
b) Any part of the GI tract can be affected by CD
What is the inflammation in a)UC and b) Crohn’s disease?
a) The inflammation is mucosal
b) The inflammation is transmural and granulomatous
What is the cytokine profile of a) UC and b) CD?
a) Th2, IL 5/13
b) Th1, IL23, gamma IFN
Is there higher concordance of UC or CD in monozygotic twins?
CD- 45% compared to 6-14%
What is the risk of a first degree relative having a) UC and b) CD?
a) x10
b) x30
What is the effect of smoking on a) UC and b) CD?
a) It is protective
b) It is harmful
What part of the GI tract is most commonly affected by Crohn’s disease?
The distal ileum and the colon
Describe the inflammation in Crohn’s disease
Focal and discontinuous inflammation with deep and eroding fissures with out without granulomas
Which parts of the GI tract are affected by UC?
How does the disease spread?
The rectum and the colon only.
The disease starts in the rectum and moves proximally and continuously.
Which parts of the world are mostly affected by IBD?
Urbanised westernised societies, although they are now emerging in India and China.
What is the treatment for IBD?
Non specific anti-inflammatory and immunosuppressive drugs:
steroids, azathioprine, cyclosporin, methotrexate, anti TNF, anti0IL6, anti-alpha4beta7
