GI Mucosal Immunology - Treatment of IBD

Question 1

Challenges the immune system faces when developing immune responses in the gut tract?

Answer 1

Develop self tolerance
Develop tolerance of normal gut microbiota
Develop effective immune response

Question 2

Levels of immune protection in the colon?

Answer 2

1. Mucous layer - physical barrier
2. Tight junctions in epithelial lining
3. Innate immunity - TLRs, anti-microbial peptides & IgA
4. Antigen presenting cells (macrophages)
5. Adaptive immune response (T-Cells)
6. Soluble mediators - chemokines and cytokines

Question 3

How do cytokines influence T cells?

Answer 3

Important regulators of whether they develop to Th1, Th2 or Treg cells

Question 4

What are Peyer’s Patches?

Answer 4

Masses of lymphatic tissue in the ileum of the SI - large numbers of immune cells
Monitor bacterial populations in intestines

Also called aggregated lymphoid nodules

Question 5

Macrophage function in mucosal immunity?

Answer 5

First line fo defence - sample antigens and ingest and kill foreign micro-organisms

Question 6

Dendritic cell function in mucosal immunity?

Answer 6

Mature into APCs
Sample antigens and present to naive T cells to trigger response
Important in tolerance of self and microbiota

Question 7

Main cells of the innate immune system?

Answer 7

Macrophages
Monocytes
Neutrophils
Dendritic cells

Question 8

Main cells of the adaptive immune system?

Answer 8

T & B cells

Question 9

Immunological treatment strategies for IBD?

Answer 9

Target lymphocytes (suppress)
Inhibit single/multiple cytokines
Target migration of immune cells to GI mucosa
Modify microbiota

Question 10

How do drugs block migration of immune cells to mucosa?

Examples of such drugs?

Answer 10

target transmembrane trafficking proteins such as integrins - prevents adhesion of immune cells

Vedolizumab

Question 11

Drugs that block cytokines and their method of doing so?

Answer 11

Ustekinumab - blocks cytokines within the cell

Tofacitinib - blocks intracellular pathways that activate cytokines

Question 12

What is FMT?

Answer 12

Full microbiota transplantation
Transplantation of a healthy microbiota from a donor stool into a patient with dysbiosis of gut microbes

Likely effective in some UC cases

Question 13

What is coeliac disease?

Answer 13

Inflammation of the small intestine which results in malabsorption - can induce diarrhoea
Caused by intolerance to gluten

Question 14

What part of the small intestine is damaged by coeliac inflammation?

Answer 14

Loss of villi due to improper immune responses