GI Mucosal Immunology – Treatment of IBD

Question 1

true or false:

The gastrointestinal tract represents a major site of host-environment (luminal contents) interaction

Answer 1

true

Question 2

what type of immunity does the colonic mucosa exert?

Answer 2

physiological

Question 3

apart from immunity, what other function does colonic mucosa do?

Answer 3

Detect luminal contents and recognize commensal microbiome ‘good bacteria’ (tolerance) from pathogens that require robust immune response

Question 4

what are the challenges of antigen processing in the GI tract

Answer 4

develop self tolerance

develop exogenous tolerance

develop an effective immune response

Question 5

whats the function of the epithelial layer of the antigen?

Answer 5

specialized tight junctions that regulate permeability

Question 6

whats the function of the mucus layer of the antigen?

Answer 6

physical barrier keeping microbes from host cells

Question 7

whats the function of the innate immune responses of the antigen?

Answer 7

sensing of bacteria (eg TLRs) + anti-microbial peptides + IgA

Question 8

whats the function of the antigen presenting cells of the antigen?

Answer 8

– dendritic cells and macrophage

Question 9

whats the function of the soluble mediators of immunity of the antigen?

Answer 9

chemokines and cytokines

Question 10

what are the immune cell responses of the granulocytes?

Answer 10

CD4+ T cells

Question 11

what are the immune responses to mast cells?

Answer 11

CD8+ T cells

Question 12

what are the immune responses to monocytes?

Answer 12

B cells

Question 13

what is the cytokine milieu a key determinant of?

Answer 13

T cell differentiation. i.e. wether a T cell becomes Th1 or Th2

Question 14

cytokines and chemokines are what type of mediators of immune response?

Answer 14

soluble

Question 15

whats the function of peyers patches?

Answer 15

major organised lymphoid structure in the gut

Important for immune responses to commensal bacteria (tolerance) and pathogens (active immunity)

Allow efficient sampling of particulate antigens and deliver to APC

Question 16

function of macrophages

Answer 16

first line defence system in the gut
sampling of particulate antigens
phagocytic
secrete cytokines eg IL-10 required for the survival of FoxP3+ Treg cells
Professional APCs to modulate adaptive immune response

Question 17

function of dendritic cells

Answer 17

Lamina propria and PP
DCs are important for mucosal immune responses
Efficient sampling of antigen
Different DC subsets give rise to distinct T cell responses
(eg. Tolerance versus Immunity)
Different DC subsets distinguished by cell markers
DC present antigen to naïve T cells

Question 18

importance of dendritic cells in mucosal immunity?

Answer 18

Lamina propria and PP DCs are important for directing the function of T cells

Question 19

how is the innate immune system induced?

Answer 19

upon infection with microbes

Question 20

how is the adaptive immune system induced?

Answer 20

upon infection by specialised pathogens

Question 21

what cells carry out the innate immune system?

Answer 21

macrophages, monocytes, neutrophils and dendritic cells

Question 22

what cells carry out the adaptive immune system

Answer 22

T and B cells

Question 23

what fundamental role does the innate immune system play?

Answer 23

induction and regulation of the adaptive immune response

Question 24

why are Th1 cells required?

Answer 24

clearance of intracellular pathogens

Question 25

what happens when normal immune homeostasis goes wrong?

Answer 25

Inflammatory bowel disease (IBD)

Coeliac disease

Question 26

what are the types of inflammatory bowel disease?

Answer 26

Chronic, relapsing, remitting inflammation of gastrointestinal tract
Crohn’s disease and ulcerative colitis

Question 27

treatment strategies for IBD

Answer 27

Target lymphocytes directly
Target single cytokines
Target migration of immune cells to GI mucosa
Target multiple cytokines
Target cytokine intracellular signalling pathways
Modulation of microbiota

Question 28

what are integrins?

Answer 28

are transmembrane proteins – lymphocyte trafficking, cell adhesion

Question 29

dysbiosis of bacteria in IBD

Answer 29

Bacteria……virome, fungal

Change in metabolome – diverse effects on host

Question 30

what part of the body does coeliac disease effect?

Answer 30

small bowell

Question 31

signs of coeliac disease

Answer 31

Malabsorption – failure to thrive as a child; iron deficiency anaemia, fatigue, GI symptoms – loose stool, abdominal pain or asymptomatic

Question 32

what does a damaged lining of the intenstine look liked from celiac disease?

Answer 32

Results in changes in the gut mucosa –

Loss of villi – loss of absorptive capacity

Increase in intra-epithelial lymphocytes