Immunology of the Gut Flashcards
What does the antigen load in the gut consist of?
Resident microbiota
Dietary antigens
Exposure to pathogens
What does homeostasis of the gut involve?
Bacterial microbiota
What are the 4 major phyla of the gut microbiota?
Bacteroidetes
Firmicutes
Actinobacteria
Proteobacteria
Define dysbiosis
Altered microbiota composition
What are symbionts?
Microorganisms that live inside us with no effect, they aren’t gaining anything
What are commensals?
Microorganism that live in us and benefit from the host but don’t help the host
What are pathobionts?
Microorganisms that have potential to cause dysregulated inflammation
What affects the immunological equilibrium?
Symbiont, pathobionts and commensals
What are the 2 states in the immunological balance?
Regulation and inflammation
What are some causes of dysbiosis?
Infection Inflammation Diet Xenobiotics Hygiene Genetics
Why is dysbiosis significant?
It can have many effects on the rest of the body
What are the physical barriers in the mucosal defence?
Epithelial barrier
Peristalsis
What are the chemical barriers in the mucosal defence?
Enzymes
Acidic pH
What does the epithelial barrier consist of?
Mucus layer - Goblet cells
Epithelial monolayer - tight junctions
Paneth Cells
Where are paneth cells found?
Small intestine, bases of crypts of Lieberkühn
What do paneth cells secrete?
Antimicrobial peptides (defensins) & lysozyme.
Where is mucosa associated lymphoid tissue (MALT) found?
In the submucosa below the epithelium
What is the role of gut associated lymphoid tissue (GALT)?
Responsible for both adaptive & innate immune responses
What are non organised aspects of GALT?
Intra-epithelial lymphocytes
Lamina propria lymphocytes
What are organised aspects of GALT?
Peyer’s patches (small intestine)
Caecal patches (large intestine)
Isolated lymphoid follicles
Mesenteric lymph nodes (encapsulated)
Where are Peyer’s patches mostly found?
Submucosa of the small intestine, mainly distal ileum
What are the characteristics of follicle associated epithelium (FAE)?
No goblet cells
No secretory IgA
No microvilli
What cells are involved in antigen uptake in FAE?
M cells
How do M cells in FAE allow antigen/bacteria uptake?
They express IgA receptors, facilitating transfer of IgA-bacteria complex into the Peyer’s patches
What do mature naive B cells express in Peyer’s patches? What happens after antigen exposure
IgM After antigen exposure the class switches to IgA
What class of antibodies do gut B cells secrete?
IgA
What is the role of IgA secreted by gut B cells?
They bind to luminal antigens preventing adhesion and consequent invasion
In the gut where does antigen presentation and activation occur?
Peyer’s patches
How does antigen presentation in Peyer’s patches lead to eventual lymphocyte honing and circulation?
After antigen presentation in Peyer’s patches they are - transferred to mesenteric lymph nodes where lymphocytes proliferate
Lymphocytes then go into circulation via thoracic duct
They can then enter the peripheral immune system and go to skin, tonsils etc via honing cascades
What is the lifespan of gut enterocytes and goblet cells?
36 hours
Why is the lifespan of gut enterocytes and goblet cells so short?
They are the first line of defense against GI pathogens & may be directly affected by toxic substances in diet
Whats the mechanism of cholera infection?
Bacteria reaches small intestine and comes into contact with epithelium & releases cholera enterotoxin
This leads to eventual loss of Na+, K+, Cl-, Hco3- and water and diarrhoea
How is cholera transmitted?
Faecal-oral (via contaminated water and food)
What are the main symptoms of cholera?
Severe dehydration & watery diarrhoea
How is cholera diagnosed?
Bacterial culture from stool sample
How is cholera treated?
Oral rehydration
What are some other causes of infectious diarrhoea besides cholera?
Viral (rotavirus/norovirus)
Protozoal parasitic
Bacterial (E coli, salmonella, shigella, c diff)
What type of virus is rotavirus?
RNA
Where does rotavirus replicate?
In enterocytes
How is infection by rotavirus treated?
Oral rehydration
Is there a vaccine for cholera?
Yes
Is there a vaccine for rotavirus?
Yes
What type of virus is novovirus?
RNA
What is the incubation period for novovirus?
24-48 hours
What are symptoms of infection by novovirus?
Acute gastroenteritis with recovery in 1 – 3 days
How is infection by novovirus treated?
Treatment isn’t usually required
How is infection by novovirus diagnosed?
Sample PCR
Is E coli gram positive or negative?
Negative
How may pathotypes of of E coli are associated with diarrhoea?
6
How is c diff managed?
Isolate patient (very contagious)
Stop current antibiotics
Faecal Microbiota Transplantation (FMT) has a 98% cure rate
Why is recurrent infection by c diff possible?
Even in intermediate recovery stages it doesn’t produce toxins but it is still invading so you can return to the previous state
