Immunology of the Gut Flashcards
What is the surface area of the GI tract?
200m^2
Size of tennis court
What does the gut have to deal with?
Massive antigen load
What comprises the massive antigen load of the gut?
Resident microbiota 1014 bacteria
Dietary antigens
Exposure to pathogens
What is the permanent state of the gut?
“restrained activation”
– Tolerance vs active immune response
– Dual immunological role.
What must the gut develop tolerance towards?
Food antigens
Commensal bacteria
What is Gnotobiology?
Gnotobiology
Take germ free animals and you selectively colonise them with selective bateria
Observe differences in these mice to conventioanlly housed mice
e.g. development of peyer’s patches, paneth cells
How many gut bacteria are there?
10^14 gut bacteria and 10^13 cells in body - most densely populated “ecosystem” on Earth
What are the 4 major phyla of bacteria?
Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria
Why is the gut microbiota important?
Provide traits we have not had to evolve on our own - Genes in gut flora 100 times our own genome
Give example of functions of the gut microbiota?
Provide essential nutrients that cannot be manufactures
Metabolise indigestible compounds
Defence against opportunistic pathogens
Contribute to architecture of the gut
What is the microbiome?
Collective genome of all microbiota
What can increase numbers of microbiota?
Ingested nutrients
Secreted nutrients
What can decrease the numbers of microbiota?
Chemical digestive factors leading to bacterial lysis
Peristalsis and defecation
What is the bacterial content of the stomach?
10^1
HCL, Pepsin and Gastic Lipase
What is the bacterial content of the duodenum?
10^3
Bile acids from liver
What is the bacterial content of the jejunum?
10^4
Trypsin, amylase, carboxypeptidase from pancreas
What is the bacterial content of the ileum?
10^7
Brush border enzymes
What is the bacterial content of the colon?
10^12
No host digestive factors
What is dysbiosis?
Altered microbota compsition
What are symbionts?
Organisms that live with the host without harm or benefit to host or organism
What are commnesals?
Benefits from host but does not benefit or harm host
What are pathobionts?
Symbionts that do not normally illicit an inflammatory response
But in certain environments have the potential to cause disregualted inflammation and disease
What causes dysbiosis?
Infection or inflammation
Xenobiotics
Hygiene
Genetics
What is TMAO?
Increased deposition of cholesterol in artery walls
What is 4-EPS?
Associated with Autism
What are SCFAs?
Short chain fatty acids
Decrease associated with IBS
Increase associated with stress
What are AHR ligands?
Associated with MS, rheumatoid arthritis and asthma
What is NAFLD?
alcoholic fatty liver disease
What is NASH?
alcoholic steatohepatitis
inflammation from fat
What comprises the bodies mucosal defence?
Anatomical Epithelial barrier Peristalsis Chemical Enzymes Acidic pH
What forms the epithelial barrier?
Mucus layer - Goblet cells
Epithelial monolayer - Tight junctions
Paneth Cells (small intestine)
What are the main features of paneth cells?
Bases of crypts of Lieberkühn.
Secrete antimicrobial peptides (defensins) & lysozyme
What are the different types of immunological tissue?
MALT (Mucosa Associated Lymphoid Tissue)
GALT (Gut Associated Lymphoid Tissue)
Where is MALT found?
Found in the submucosa below the epithelium, as lymphoid mass containing lymphoid follicles
What are they surrounded by?
Follicles are surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes
Where is rich in MALT?
Oral cavity
Palatine and lingual tonsils
Pharyngeal tonsisl (Adenoids)