Mucosal immunology of the GI tract

Question 1

What is the physiological function of the GI tract?

Answer 1

Food digestion and absorption

Immune regulation

Question 2

Describe the cellular structure of the small intestine

Answer 2

Villi and crypts

Goblet cells, paneth cells and Peyer’s patches

Question 3

Describe the cellular structure of the epithelium of the large intestine?

Answer 3

Crypts, no villi
No paneth cells 
Lots of goblet cells and mucus 
No Peyer's patches
Enterocyctes do defence

Question 4

What does the mucosal immune system of the GI tract have to do?

Answer 4

Capture the antigen
Initiate the local immune response
Carryout effector functions to clear any infection

Question 5

Where does antigen capture occur?

Answer 5

In Peyer’s patches and directly across the epithelium by dendritic cells

Question 6

What are the specialized epithelial cells in Peyer’s patched called?

Answer 6

M cells

Question 7

What happens to antigens when they meet M cells?

Answer 7

M cells take up the antigen by endocytosis and phagocytosis
Antigen is transported across the M cells in the vesicles and released at the basal surface
Antigen is bound by dendritic cells, which activate T cell

Question 8

Where does initiation of the intestinal immune response occur?

Answer 8

In the mesenteric lymph nodes

Question 9

What are lymph nodes a hub for?

Answer 9

Maximising T lymphocyte exposure to antigens

Question 10

What two types of cell drain to the lymph nodes with antigens?

Answer 10

Dendritic cells and B cells

Question 11

What happens to T lymphcytes when they are activated?

Answer 11

The loose CCR7 meaning they can no longer re-circulate

Question 12

Where do activated T cells drain to?

Answer 12

They drain via the mesenteric lymph nodes to the thoracic duct and return to the gut via the bloodstream

Question 13

What is the most important antibody in the gut/

Answer 13

IgA (80% of immunoglobin in the gut)

IgM 15% and IgG 5%

Question 14

How is IgA produced and released?

Answer 14

Produced by a IgA-secreting cell
Binds to receptor on basolateral face of epithelial cell
Endocytosis
Transcytosis to apical face of epithelial cell
Release of IgA dimer at apical face of epithelial cell

Question 15

What does secreted IgA do?

Answer 15

Secreted IgA binds to pathogens and toxins and neutralizes them
While being secreted, IgA can bind to toxins that have entered epithelial cells and export them

Question 16

What are intraepithelial lymphocytes?

Answer 16

Cells that sit within the epithelial barrier

90% are T cells, 80% of which are CD8+ (effector T cells) that do not need activated

Question 17

What are the two recognition mechanisms for intraepithelial lymphocytes?

Answer 17

Virus specific recognition (TCR/CD8 cells)

Stress specific recognition (NK cells)

Question 18

What is the default state of the gut immune system?

Answer 18

Systemic hyporesponsiveness

Question 19

What immunoglobin causes an aggressive response?

Answer 19

IgE

Question 20

What are the distinctive anatomical features of the mucosal immune system?

Answer 20

The tissues sit in a very intimate relationship between mucosal epithelial and lymphoid tissue
There are organised lymphoid structures unique to mucosal sites
Specialized antigen uptake mechanisms

Question 21

What is the hygiene hypothesis?

Answer 21

A theory that suggests a young child’s environment can be “too clean” to effectively stimulate or challenge the child’s immune system to respond to various threats during the time their immune system is maturing

Question 22

What mechanism eliminates most intestinal infections?

Answer 22

Innate mechanisms

Question 23

What are the innate receptors?

Answer 23

Pattern recognition receptors (PRR)

Question 24

What happens when pattern recognition receptors are activated?

Answer 24

Gene transcription and production of cytokines, chemokines and defensins

Question 25

What is coeliac disease?

Answer 25

Damage to the small intestine due to an abnormal reaction to the gluten antigen It has a T cell component Results in malnutirion (not an allergy)

Question 26

What is the score to measure the scale of coeliac disease?

Answer 26

MARSH score

Question 27

How does the antigen cause villi destruction?

Answer 27

The gluten peptides activate mucosal epithelial cells to express MIC molecules Intraepithelial lymphocytes are activated by MIC molecules binding to the expressed NKG2D They kill the epithelial cells by programmed cells death through the recognition of the stress receptor

Question 28

What is a second killing mechanism in coelic disease?

Answer 28

Enzyme modifies peptides so they can bind to MHC class II molecules Bound peptide activates gluten-specific CD4-T cells Activated T cells kill mucosal epithelial cells

Question 29

How is coeliac disease diagnosed?

Answer 29

Serology and genetics in most children

Question 30

What other tests are down when diagnosis coeliac disease to avoid a false negative?

Answer 30

IgA deficiency tests | also if they are have IgA deficiency they go for biopsy as 10x more likely to have the disease

Question 31

What is inflammatory bowel disease?

Answer 31

Altered function and imbalance of the relationship between prevention of invasion by pathogens and tolerance to innocuous foods and commensal microorganisms

Question 32

What are the two subtypes of inflammatory bowel disease?

Answer 32

Crohn's and ulcerative colitis.

Question 33

Which inflammatory bowel disease has the deepest inflammation?

Answer 33

Crohn's disesae

Question 34

Which inflammatory bowel disease has the greatest genetic influence?

Answer 34

Crohn's disease

Question 35

Where does Crohn's disease affect?

Answer 35

Any part of the GI tract, commonly the distal ileum and colon

Question 36

Where does ulcerative colitis affect?

Answer 36

Restricted to the rectum and colon

Question 37

What is the difference between CD and UC?

Answer 37

In CD there are healthy parts of the intestine mixed in between inflammed areas In UC it is continuous inflammation of the colon UC only occurs in the inner most lining of the colon whereas CD can occur in all the layers of the bowel walls

Question 38

What is the treatment for inflammatory bowel disease?

Answer 38

Non-specific anti-inflammatory and immunosuppresive drugs

Question 39

What causes a food allergy?

Answer 39

Type I hypersensitivity reaction initiated by crosslinking of allergen specific IgE on the surface of mast cells with the specific allergen