1b Immunology of the Gut Flashcards
Describe the antigen load in the gut?
Massive antigen load
- resident microbiota
- dietary antigens
- exposure to pathogens
Why is the GI Tract immune system in a state of ‘restrained activation’?
It balances tolerance of food antigens and commensal bacteria vs immunoreactivity against pathogens
What are gnotobiotic mice?
These are mice which have been colonized to be germ-free
They are used in experiments to derive the relationship between microbiota and immune system’s response to them
What are the four major phyla of bacteria found in the gut microbiota?
Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, as well as viruses and fungi
What factors which the host does leads to bacterial growth?
Ingested nutrients
Secreted nutrients
Which factors leads to bacterial lysis and bacterial elimination?
Chemical digestive factors
peristalsis, contractions and defecations
In general, explain why bacterial content varies as you pass down the GI tract
The chemical digestive factors produced by the host impact viability of the bacteria to survive in different parts of the GI tract
The bacterial content increases as you pass down the GI tract because the factors produced are less hostile to bacterial growth.
List the chemical digestive factors produced by the stomach, liver, pancreas, small intestine and colon respectively
Stomach - Pepsin, gastric lipase
Liver - bile salts
Pancreas - trypsin, amylase and carboxypeptidase
Small Intestine - Brush border enzymes
Colon - nothing
What is Dysbiosis?
Altered microbiota composition
What is the balance of dysbiosis between?
Symbionts = regulation
Commensals
Pathobionts = inflammation
Define the term ‘Symbiont’
Lives with a host but no benefit/harm to either
Define commensals?
Organism which livs or or in a host and benefits from living there, but does not cause any harm to the host
Define pathobiont?
Symbiont that doesn’t naturally produce an immune response but under certain environmental conditions can produce dysregulated inflammation/disease.
Give 5 factors that can either contribute to the maintenance of healthy microbiota or towards dysbiosis
1) Infection or inflammation
2) Diet
3) Xenobiotics
4) Hygiene
5) Genetics
Give 5 examples of metabolites and toxins which bacteria produce that can cause damage to body systems
TMAO
4-EPS
SCFAs
Bile acids
AHR Ligands
What are the anatomical barriers which contribute to mucosal defense?
Epithelial barrier
Peristalsis
What are the chemical barriers which contribute to mucosal defense?
Enzymes
Acidic pH
What dysfunction can TMAO cause in the body?
TMAO = Trimethylamine N-oxide
Can cause atherosclerosis due to increased cholesterol deposition
What has 4-EPS been associated with?
Increased levels of autism
What are decreased numbers of SCFA’s associated with?
SCFAs = Short-chained fatty acids
Decreased numbers of SCFAs are associated with Inflammatory bowel disease
What are increased numbers of SCFAs associated with?
Neuropsychiatric disorders like stress
What are AHR ligands associated with?
cancer
What are the two immunological defense mechanisms following an invasion?
MALT (Mucous associated lymphoid tissue)
GALT (Gut associated lymphoid tissue)
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Where is MALT tissue particularly rich?
MALT is particularly rich within the oral cavity ( the three tonsils - palatine, lingual and adenoid)
It is found in the submucosa below the epithelium as a lymphoid mass containing lymphoid follicles
What cells make up the mucus layer?
Goblet cells
What are paneth cells and how are they used in mucosal defense?
They are cells of the small intestine, found at the bases of the cypts of lieberkuhn and they secrete anti-microbial peptides (defensins) and lysozyme
What is found in the epithelial monolayer?
Tight junctions
Where is MALT found?
Found in the submucosa below the epithelium, as lymphoid mass containing lymphoid follicles