lecture 14- coeliac disease Flashcards Preview

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Flashcards in lecture 14- coeliac disease Deck (27):
1

What is coeliac disease?

It is chronic inflammation of the small intestine, due to an unnecessary immune response to the harmless gluten protein found in wheat and grains.

2

Where does coeliac disease occur, on a micro scale within the intestinal lumen?

It occurs at the individual villi and involves the IEL's (Immune lymphocytes).

3

What type of lymphocytes are found in the intestinal villi with regards to coeliac disease?

The CD3+ and CD8+ lymphocytes.

4

How do Intraepithelial lymphocytes (IEL's) act as a marker of coeliac disease?

Normally, there are only a small number IEL's in the villi. They proliferate and infiltrate the villi, with heaps more found during coeliac disease.

5

How are enterocytes affected during coeliac disease?

Enterocytes are stunted and distorted in coeliac disease patients.

6

How does coeliac disease affect the crypts and villi of the small intestine brushborder?

The crypts are little grooves that produce new enterocytes and cover the villi. In coeliac disease, the crypts get bigger (hyperplasia) because of increased demand for new enterocytes from the villi.

7

What are the clinical manifestations of coeliac disease?

Gastrointestinal problems; flatulence, bloating, diarrhoea, abdominal cramps.
Vitamin deficiency: Anaemia, vitamin deficiencies.

8

What are the 2 genes that are present in all coeliac disease sufferers?

HLA-DQ2 or HLA-DQ8. Note that a small population do have this gene, but don't have coeliac disease.

9

What is the role of early infant environment in preventing coeliac disease?

Breastfeeding is protecting because it exposes the infant to gluten via breastmilk. Too much early exposure though can end up promoting coeliac disease.

10

What are the names of the two gluten proteins that cause coeliac disease?

Gliadins and Glutenins

11

Where does coeliac disease occur, on a micro scale within the intestinal lumen?

It occurs at the individual villi and involves the IEL's (Immune lymphocytes).

12

What type of lymphocytes are found in the intestinal villi with regards to coeliac disease?

The CD3+ and CD8+ lymphocytes.

13

How do Intraepithelial lymphocytes (IEL's) act as a marker of coeliac disease?

Normally, there are only a small number IEL's in the villi. They proliferate and infiltrate the villi, with heaps more found during coeliac disease.

14

How are enterocytes affected during coeliac disease?

Enterocytes are stunted and distorted in coeliac disease patients.

15

How does coeliac disease affect the crypts and villi of the small intestine brushborder?

The crypts are little grooves that produce new enterocytes and cover the villi. In coeliac disease, the crypts get bigger (hyperplasia) because of increased demand for new enterocytes from the villi.

16

What are the clinical manifestations of coeliac disease?

Gastrointestinal problems; flatulence, bloating, diarrhoea, abdominal cramps.
Vitamin deficiency: Anaemia, vitamin deficiencies.

17

What are the 2 genes that are present in all coeliac disease sufferers?

HLA-DQ2 or HLA-DQ8. Note that a small population do have this gene, but don't have coeliac disease.

18

What is the role of early infant environment in preventing coeliac disease?

Breastfeeding is protecting because it exposes the infant to gluten via breastmilk. Too much early exposure though can end up promoting coeliac disease.

19

What are the names of the two gluten proteins that cause coeliac disease?

Gliadins and Glutenins

20

what is it about the Gliadin and Glutenin polypeptides as proteins that makes them uneasy to digest?

They have high Proline and Glutamine content. They are resistant to digestion proteases and they pass through the intestinal epithelium intact.

21

What happens to the undigested gluten polypeptides when they pass through the intestinal epithelium?

They are deanimated by an enzyme called 'tissue transglutaminase' (tTG). This enzyme converts glutamine to -ve glutamate.

22

What occurs during the interaction of the deamidated gluten peptides and the antigen presenting cells of the immune system?

The negatively charged glutamate will bind to the antigen presenting cell, which are the HLA-DQ2 or HLA-DQ8 molecules.

23

How is the immune response triggered once the gluten peptides have bound to the antigen presenting cells?

The CD4+ cells recognise the deamidated peptides when they bind to the MHC-11 molecules as dangerous. Thus it triggers cytokine release.

24

How do the enterocytes of the small intestine respond to the inflammation from the gluten peptides?

The cells start to synthesise stress proteins (MIC-A and MIC-B). The t-cells bind to these two molecules within the cell and this induces apoptosis of the enterocyte.

25

How does the inflammation caused by the gluten peptides alter behaviour of the intraepithelial lymphocytes?

The IEL's have a reduced activation threshold and they become self-reactive and proliferate uncontrollably. They also kill enterocytes via apoptosis.

26

How is coeliac disease tested for?

HLA-DQ haplotyping, or checking for the presence of HLA-DQ2/DQ8 and searching for gluten peptide or transglutaminase antibodies.

27

What is the major health risk for undiagnosed sufferers of coeliac disease?

small bowel lymphoma or other gastrointestinal tract cancers.