GI Mucosal Immunology – Treatment of IBD Flashcards
true or false:
The gastrointestinal tract represents a major site of host-environment (luminal contents) interaction
true
what type of immunity does the colonic mucosa exert?
physiological
apart from immunity, what other function does colonic mucosa do?
Detect luminal contents and recognize commensal microbiome ‘good bacteria’ (tolerance) from pathogens that require robust immune response
what are the challenges of antigen processing in the GI tract
develop self tolerance
develop exogenous tolerance
develop an effective immune response
whats the function of the epithelial layer of the antigen?
specialized tight junctions that regulate permeability
whats the function of the mucus layer of the antigen?
physical barrier keeping microbes from host cells
whats the function of the innate immune responses of the antigen?
sensing of bacteria (eg TLRs) + anti-microbial peptides + IgA
whats the function of the antigen presenting cells of the antigen?
– dendritic cells and macrophage
whats the function of the soluble mediators of immunity of the antigen?
chemokines and cytokines
what are the immune cell responses of the granulocytes?
CD4+ T cells
what are the immune responses to mast cells?
CD8+ T cells
what are the immune responses to monocytes?
B cells
what is the cytokine milieu a key determinant of?
T cell differentiation. i.e. wether a T cell becomes Th1 or Th2
cytokines and chemokines are what type of mediators of immune response?
soluble
whats the function of peyers patches?
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
function of macrophages
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
function of dendritic cells
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
importance of dendritic cells in mucosal immunity?
Lamina propria and PP DCs are important for directing the function of T cells
how is the innate immune system induced?
upon infection with microbes
how is the adaptive immune system induced?
upon infection by specialised pathogens
what cells carry out the innate immune system?
macrophages, monocytes, neutrophils and dendritic cells
what cells carry out the adaptive immune system
T and B cells
what fundamental role does the innate immune system play?
induction and regulation of the adaptive immune response
why are Th1 cells required?
clearance of intracellular pathogens
what happens when normal immune homeostasis goes wrong?
Inflammatory bowel disease (IBD)
Coeliac disease
what are the types of inflammatory bowel disease?
Chronic, relapsing, remitting inflammation of gastrointestinal tract
Crohn’s disease and ulcerative colitis
treatment strategies for IBD
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
what are integrins?
are transmembrane proteins – lymphocyte trafficking, cell adhesion
dysbiosis of bacteria in IBD
Bacteria……virome, fungal
Change in metabolome – diverse effects on host
what part of the body does coeliac disease effect?
small bowell
signs of coeliac disease
Malabsorption – failure to thrive as a child; iron deficiency anaemia, fatigue, GI symptoms – loose stool, abdominal pain or asymptomatic
what does a damaged lining of the intenstine look liked from celiac disease?
Results in changes in the gut mucosa –
Loss of villi – loss of absorptive capacity
Increase in intra-epithelial lymphocytes
