Immunology of the gut

Question 1

Why is mucosal immunology important?

Answer 1

Because the vast majority of infections occur via mucosal tissues.

Question 2

Name two diseases associated with gut immunology dysfunction.

Answer 2

Inflammatory bowel disease (Crohn’s disease, ulcerative colitis) and coeliac disease.

Question 3

What proportion of the UK population is affected by inflammatory bowel disease?

Answer 3

Estimated to affect more than 1 in 123 people.

Question 4

What proportion of the UK population is affected by coeliac disease?

Answer 4

Estimated to affect 1 in 100 people.

Question 5

What is a unique feature of mucosal tissues?

Answer 5

They are thin, permeable barriers facilitating entry of non-pathogenic antigens.

Question 6

What is the main physiological function of the gut’s mucosal tissue?

Answer 6

Food absorption.

Question 7

What is the approximate mucosal surface area of the digestive tract?

Answer 7

~32 m² (equivalent to half a badminton court).

Question 8

How does bacterial concentration change along the gastrointestinal tract?

Answer 8

It increases further down the gastrointestinal tract.

Question 9

How much of body weight do gut bacteria constitute?

Answer 9

Approximately 1 kg.

Question 10

What is the primary role of the mucosal immune system?

Answer 10

To mount protective responses to pathogens and ignore harmless antigens.

Question 11

What happens when mucosal immune regulation fails?

Answer 11

Diseases like coeliac disease and inflammatory bowel disease occur.

Question 12

Name three key cell types in the intestinal epithelial barrier.

Answer 12

Enterocytes/colonocytes, Paneth cells, Goblet cells.

Question 13

What do Paneth cells secrete?

Answer 13

Antimicrobial peptides.

Question 14

What do Goblet cells secrete?

Answer 14

Mucins.

Question 15

What does MALT stand for?

Answer 15

Mucosa-Associated Lymphoid Tissue.

Question 16

What are the three components of MALT?

Answer 16

NALT, BALT, GALT.

Question 17

What percentage of lymphocytes are found in the mucosal immune system?

Answer 17

Approximately ¾ of all lymphocytes.

Question 18

What type of antibody is predominantly produced in mucosal tissues?

Answer 18

Secretory IgA (sIgA).

Question 19

How much IgA is produced daily in mucosal tissues?

Answer 19

About 5 grams.

Question 20

How do antigens reach immune cells in the GALT?

Answer 20

They must be transported across the epithelial barrier.

Question 21

What is the function of M cells in the gut?

Answer 21

To uptake and transport antigens across the epithelium.

Question 22

Name a pathogen that targets M cells.

Answer 22

Salmonella (also Shigella, Yersinia, Poliovirus, Reovirus).

Question 23

Where do antigen-loaded dendritic cells migrate?

Answer 23

To T-cell areas of Peyer’s patches and mesenteric lymph nodes.

Question 24

What do macrophages in the healthy intestine secrete?

Answer 24

Anti-inflammatory IL-10.

Question 25

What do dendritic cells in the healthy intestine secrete?

Answer 25

Anti-inflammatory TGF-β.

Question 26

What effect do Clostridia species have on Tregs?

Answer 26

Promote proliferation and de novo induction of Tregs in the colonic lamina propria.

Question 27

What is the main function of secretory IgA?

Answer 27

To limit access of pathogens to mucosal surfaces without causing inflammation.

Question 28

Why doesn’t secretory IgA induce inflammation?

Answer 28

It has little capacity to activate complement or act as an opsonin.

Question 29

What replaces secretory IgA in IgA-deficient patients?

Answer 29

Secretory IgM.

Question 30

What is oral tolerance?

Answer 30

The default immune response to oral protein antigens resulting in specific peripheral unresponsiveness.

Question 31

What cells are generated in oral tolerance?

Answer 31

Antigen-specific Treg cells.

Question 32

How do commensals influence the immune system?

Answer 32

They induce IgA and Tregs in the intestine and are ignored by the systemic immune system.

Question 33

Where is TLR4 expressed in the gut?

Answer 33

In intestinal epithelial cells at the base of crypts.

Question 34

Where is TLR5 expressed in the gut?

Answer 34

On the basolateral side of the intestinal epithelium.

Question 35

What is the function of bacterial virulence factors like Salmonella’s type III secretion system?

Answer 35

To activate intracellular inflammasomes via flagellin.

Question 36

How do some commensals avoid immune detection?

Answer 36

By altering their flagellin to make TLR5 hyporesponsive.

Question 37

What is the role of IL-23 in Crohn’s disease?

Answer 37

Produced by innate cells after PRR activation, associated with inflammation.

Question 38

What gene mutation is associated with Crohn’s disease?

Answer 38

Mutations in NOD2.

Question 39

What does NOD2 recognize?

Answer 39

Muramyl dipeptide in bacterial peptidoglycans.

Question 40

Name two anti-TNF-α monoclonal antibodies used in IBD treatment.

Answer 40

Infliximab and Adalimumab.

Question 41

What is Ustekinumab?

Answer 41

An anti-IL-12/IL-23 monoclonal antibody used in IBD treatment.

Question 42

Name two corticosteroids used in IBD treatment.

Answer 42

Prednisolone and hydrocortisone.

Question 43

What is helminth therapy?

Answer 43

Treatment involving ingestion of live Trichuris suis eggs.

Question 44

What is the goal of fecal microbiota transplantation (FMT)?

Answer 44

To restore healthy gut microbiota.

Question 45

What is the main challenge for the mucosal immune system?

Answer 45

To ignore harmless antigens while defending against pathogens.

Question 46

What maintains intestinal homeostasis?

Answer 46

A balance between effector and regulatory T-cell responses.