🍔Gastro🍔 - Immunology of the Gut Flashcards
Why must the GI tract have “restrained activation” of the immune response?
Massive antigen load
Resident microbiota 1014 bacteria
Dietary antigens
Exposure to pathogens
Tolerance vs active immune response – Dual immunological role
Immune homeostasis of gut & development of healthy immune system requires presence of bacterial microbiota
What must the immune system of the GI tract show tolerance and immunoreactivity to?
Tolerance - food antigens, commensal bacteria
Immunoreactivity - pathogens
What 4 major phyla of bacteria exist in the gut?
Bacteroidetes
Firmicutes
Actinobacteria
Proteobacteria
What host actions lead to increased cell numbers in the gut microbiota?
Ingested nutrients
Secreted nutrients
Both lead to bacterial growth
What host actions lead to decreased cell numbers in the gut microbiota?
Chemical digestive factors - bacterial lysis
Peristalsis, contractions, defecation - bacterial elimination (i.e. removal)
What functions does the gut microbiota perform?
Production of essential nutrients
Metabolism of indigestible compounds
Defence against colonisation of pathogens
What is symbiosis?
living together, doesn’t imply either partner benefits
What are symbionts?
organism that lives with a host without benefit or harm to either
What are commensals?
a microorganism which benefits from association but has no known effects on host
What are pathobionts?
symbionts that don’t normally elicit an inflammatory response BUT under particular conditions (usually environmental) has the POTENTIAL to cause dysregulated inflammation & disease
What is dysbiosis?
Unhealthy (for whatever reason) gut microbiota
What can cause dysbiosis?
Infection/inflammation
Diet
Xenobiotics - small chemical compounds that enter the gut unnaturally e.g. drugs, pollutants etc…
Hygiene
Genetics
What is gnotobiology?
selective colonisation of germ-free animals
What are the physical barriers of the mucosa?
Anatomical - epithelial barrier, peristalsis
Chemical - enzymes, acidic pH
What role do commensal bacteria play in immune defence of the gut?
They occupy an ecological niche
They compete with potential pathogens for space and nutrients
What are the immunological tissues present in the GI tract?
MALT (Mucosa Associated Lymphoid Tissue)
GALT (Gut Associated Lymphoid Tissue)
What are the components of the epithelial barrier?
Mucus layer - goblet cells
Epithelial monolayer - tight junctions
Paneth cells (small intestine)
What are paneth cells?
Found in the bases of crypts of Lieberkühn
Secrete antimicrobial peptides (defensins) and lysozymes
What is MALT?
Mucosa Associated Lymphoid Tissue
Present in the submucosa below epithelial layers as lymphoid masses (e.g., follicles surrounded by HEVs)
What are HEVs?
high endothelial venules (HEV) postcapillary venules
help lymphocytes migrate from bloodstream
Outline the importance of HEVs
Immune surveillance: identify foreign invaders and changes in the body’s own cells, such as neoantigens in cancer
Lymphocyte recirculation: support high levels of lymphocyte extravasation from the blood.
Immune responses: help initiate and maintain immune responses in lymph nodes
What are the key MALTs in the oral cavity?
Palatine tonsils
Lingual tonsils
Pharyngeal tonsils
What is GALT?
Gut Associated Lymphoid Tissue (GALT)
Responsible for both adaptive & innate immune responses through generations of lymphoid cells & antibodies
What are the non-organised components of GALT?
Intra-epithelial lymphocytes
-Make up 1/5th intestinal epithelium, e.g. T-cells, NK cells
Lamina propria lymphocytes
What are the organised components of GALT?
Peyer’s patches (small intestine)
Caecal patches (large intestine)
Isolated lymphoid follicles
Mesenteric lymph nodes (encapsulated)
Outline the non-organised GALT in the small intestine
Epithelium - goblet cells and intraepithelial lymphocytes
Crypts contain paneth cells
Lamina propria contains T cells, IgA B cells, macrophages, DCs
How does the non-organised GALT in the large intestine compare to that of the small intestine?
No paneth cells in the crypts
Increased number of goblet cells
What are Peyer’s patches?
Found in submucosa small intestine – mainly distal ileum
Aggregatedlymphoid follicles covered with follicle associated epithelium (FAE)
Organised collection of naïve T cells and B-cells