Gut Immunology Flashcards
Describe GI tract immunology
Has a massive antigen load (resident microbiota, dietary antigen and exposure to pathogens). In a state of restrained activation as dual immunological role (tolerance vs active immune response) as immune homeostasis of gut & development of healthy immune system requires presence of bacterial microbiota.
Describe the microbiota of the gut
4 major phyla of bacteria (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria), also viruses & fungi. These provide traits we have not evolved ourselves - genes in gut flora 100 times our own.
Describe immunological equilibrium
Symbionts responsible for regulation, commensals balance and pathobionts lead to inflammation.
What is dysbiosis and what are its causes?
When there is an altered microbiota composition in the gut leading to adverse effects. Infection or inflammation, diet, xenobiotics, hygiene and genetics can all influence the balance between healthy microbiota and dysbiosis.
What are the consequences of dysbiosis?
Brain (Stress, Autism, Multiple Sclerosis), Lung (Asthma), Liver (NAFLD, NASH), Adipose tissue (Obesity, Metabolic disease), Intestine (IBD, Coeliac disease) and Systemic diseases (T1 diabetes, Atherosclerosis, Rheumatoid Arthritis).
What bacterial metabolites and toxins induce the adverse effects of dysbiosis?
TMAO, 4-EPS, SCFAs, bile acids and AHR ligands.
Describe mucosal defense
Anatomical: Epithelial barriers and peristalsis
Chemical: Enzymes and acidic pH
Immunological: MALT (mucosal-associated lymphoid tissue) and GALT (gut-associated lymphoid tissue)
Epithelial barrier: Mucus layer (goblet cell), epithelial monolayer (tight junctions), Paneth cells (small intestine)
Where are Paneth cells found and what is their role?
Bases of crypts of Lieberkühn.
Secrete antimicrobial peptides (defensins) & lysozyme.
Where is MALT found?
Found in the submucosa below the epithelium, as lymphoid mass containing lymphoid follicles. Follicles are surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes.
What is GALT responsible for?
Responsible for both adaptive & innate immune responses. Consists of B & T lymphocytes, macrophages, APC (dendritic cells), and specific epithelial & intra-epithelial lymphocytes.
What are organised and non-organised GALT?
Non-organised
Intra-epithelial lymphocytes - Make up 1/5th of intestinal epithelium, e.g. T-cells, NK cells
Lamina propria lymphocytes
Organised Peyer’s patches (small intestine) Caecal patches (large intestine) Isolated lymphoid follicles Mesenteric lymph nodes (encapsulated)
Where are Peyer’s patches found?
Found in submucosa small intestine – mainly distal ileum. Aggregatedlymphoid follicles covered with follicle associated epithelium (FAE). FAE has no goblet cells, no secretory IgA, no microvilli.
What are Peyer’s patches?
Organised collection of naïve T cells & B-cells. Development requires exposure to bacterial microbiota. Antigen uptake via M (microfold) cells within FAE. M cells expressIgA receptors, facilitating transfer of IgA-bacteria complexinto the Peyer’s patches.
Describe B cell adaptive response
Mature naïve B-cells express IgM in Peyer’s Patches. On antigen presentation class switches to IgA. T-cells & epithelial cells influence B cell maturation via cytokine production. B cells further mature to become IgA secreting plasma cells. Populate lamina propria.
What is the mechanism of cholera infection?
Cholera -acute bacterial disease caused by Vibrio cholerae serogroups O1 & O139. Bacteria reaches small intestine, contactswith epithelium & releasescholera enterotoxin.
