GI mucosal immunology treatment Flashcards
what role does the colonic mucosa play in physiological immunity?
it detects luminal contents and recognises commensal bacteria from pathogens that require a robust immune response
What do we want our immune system to do? (3)
develop self tolerance - recognise self antigens as non-threat
develop exogenous tolerance - not reacting to the vast array of newly encountered environmental antigens - food and microbes
develop an effective immune response - eliminate or control infections, allergic and noxious agents
How does the epithelial layer in the gut help with immunity
single cell thick – tightly packed – tight control of permeability - prevents microbes getting through
What are the 2 antigen presenting cells
dendritic cells and macrophages
What are the soluble mediators of immunity called? what do they do
chemokines
cytokines
soluble mediators of the immune response - control functional cells and migration of cells to area if immune response is required
Adaptive immunity: cell types
CD4+ T cell CD8+ T cell B cell (memory cells) plasma cell
Innate immunity: cell type
granulocyte mast cell monocyte dendritic cell macrophage natural killer cell
What type of responses can cytokines provoke?
Pro inflammatory and anti inflammatory response
most cytokines have a specific response but some can be both
What does it mean to maintain immune homeostasis?
can have a proinflammatory or anti-inflammatory/regulatory (which dampens down inflammation) - need to have a balance of these responses to maintain gut health
What are peyer’s patches?
small masses of lymphatic tissue found in the small intestine - they lie underneath the epithelial barrier - have special cells called M cells that transport antigens from the lumen to cells of the immune system, thereby initiating an immune response or tolerance - antigen presentation
important role in tolerance and active immunity
what is the 1st line defence system in the gut?
Macrophages
phagocytosis of foreign microorganisms
they secrete cytokines - pro and anti inflammatory
what role do dendritic cells play in immunity?
important for mucosal immune responses - they direct the function of T cells
they present antigen to naive T cell - one that hasn’t decided which subset it is yet
where are dendritic cells found?
lamina propria and peyer’s patches
what do dendritic cells become when they undergo maturation?
Potent antigen presenting cells
What 3 signals are involved in the interaction between dendritic cells and T cells
MHC/peptide-TCR
CD80-CD28
Cytokine
name 3 T regulatory cells
Th3
Tr1
Treg
What can happen when normal immune homeostasis goes wrong?
Inflammatory bowel disease (IBD)
Coeliac disease
what is dysbosis
microbial imbalance
- damaged epithelial barrier, increased bacterial adherence and translocation (leaky gut) - chronic inflammation
Pathogenesis of IBD
barrier defect
increased mucus
microbial dysbosis
what is NOD2
a protein that senses bacteria that has managed to pass through the epithelial cell
treatment strategies for IBD (5)
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
How does anti-TNF therapy work for IBD? what are the mechanisms?
works to reduce inflammation
they neutralise the cytokine - cell doesn’t get the signal and doesn’t work as they should normally
cause cell death or apoptosis
what are some bad side effects of anti-TNF drugs
More susceptible to infection
increased risk of malignancy
toxic effect on nerves
what happens if a patient doesn’t respond to TNF
use vedolizumab instead - blocks integrin on cell surface of lymphocytes (the signal that tells cells where they are going)
Tofacitinib drug
blocks JAK pathway - no matter if the cytokine binds - proinflammatory signal can’t get through
there isn’t just one JAK pathway - there are many
Faecal microbiota transplant/ stool transplant
stool from healthy patient put into diseased patient - to encourage positive microflora to thrive – usually administered using colonoscopy
what is coeliac disease
inflammatory disorder of the small bowel
intolerance to dietary gluten in wheat and similar proteins
can cause:- Malabsorption – failure to thrive as a child; iron deficiency anaemia, fatigue, GI symptoms – loose stool, abdominal pain or asymptomatic
some people have an inappropriate response to gluten after it has been modified by zonalin
Detection of which receptors is a good indication of coeliac disease?
HLA-DQ2 and HLA-DQ8
