Gut Immunology Flashcards
What is the massive antigen load in the gut formed of?
-Resident microbiota 10^14 bacteria
-Dietary antigens
-Exposure to antigens
How big is the GI tract?
200m2
What is restrained activation
-Tolerance (food antigens and commensal bacteria) vs active immune response (immunoreactivity - pathogens)
-Dual immunological role
What is bacterial microbiota required for?
Immune homeostasis of gut and development of healthy immune system
What is bacterial microbiota required for?
Immune homeostasis of gut and development of healthy immune system
What are the 4 major phyla of bacteria ?
Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria
-Also viruses and fungi
What do bacteria provide that we don’t have?
Traits that we have no had to evolve on or our own - genes in gut flora 100 times our own genome
-Essential nutrients
-Metabolism of indigestible compounds
-Defence against colonisation of pathogens
How does the host increase cell numbers
How does the host decrease cell numbers
What chemical digestive factors are produced by the host and what is the bacterial content ?
Host digestive factors decrease down the gut and the bacterial content therefore increases
What are symbionts?
Bacteria that live in the gut and cause no harm
What are commensals?
Live with the host but get an advantage by getting nutrients
What are pathobionts?
Can be tipped over to start harming the host
What is dysbiosis?
What can cause it?
Imbalance in the gut microbes
What does dysbiosis lead to?
What are microbiota?
Combination of organisms within a distinct anatomical niche
What are microbiomes
Composed of microbiota - all the genomes put together
What the types of physical mucosal defences in the gut?
What is commensal bacteria?
It occupies an ecological niche
Is a type of mucosal defence
What are immunological mucosal defences?
How does the epithelial barrier work?
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
-The oral cavity is rich in immunological tissue
E.g. tonsils, adenoids
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 is non-organised GALT made of?
Intra-epithelial lymphocytes
—–Make up 1/5th of intestinal epithelium, e.g. T-cells, NK cells
Lamina propria lymphocytes
What is organised GALT made of?
Peyer’s patches (small intestine)
Caecal patches (large intestine)
Isolated lymphoid follicles
Mesenteric lymph nodes (encapsulated)
How do Peyers patches work?
What are the two ways in which Antigens can be taken up by the Peyers patch?
Via M cells or dendritic cells
How do dendritic cells take up antigens?
By squeezing through tight junctions
How does the B Cell Adaptive Response occur?
How does the B Cell Adaptive Response occur?
How is sIgA formed?
What does it do?
What is lymphocyte homing and circulation?
How does homing cascade direct circulating Naive T cells to PP’s Patches?
Why do Enterocytes & goblet cells of the small bowel have a short life span (about 36 hrs) in comparison to the lifespan of weeks/months for other epithelial cell types (e.g. lung, blood vessels)
-Enterocytes are first line of defense against GI pathogens and may be directly affected by toxic substances in diet
-Effect of agents which interfere with cell function, metabolic rate etc will be diminished
-Any lesions will be short-lived
-If escalator-like transit of enterocytes is interrupted through impaired production of new cells (e.g. radiation) severe intestinal dysfunction will occur
What was cholera caused by?
What is the mechanism for cholera?
How is cholera trasmmitted?
Transmitted through faecal-oral route
—Spreads via contaminated water & food.
What are the symptoms for cholera?
Main symptoms
—Severe dehydration & watery diarrhoea
Other symptoms
—Vomiting, nausea & abdominal pain.
How is cholera diagnosed and treated?
Diagnosis: bacterial culture from stool sample on selective agar is the gold standard, rapid dipstick tests also available.
Treatment: oral-rehydration is the main management ; up to 80% of cases can be successfully treated.
Vaccine: Dukoral, oral, inactivated.
Globally 1.3 - 4 million cases, avg. 95,000 deaths/year (last indigenous UK case 1893: 2017 - 13 cases).
What are Other Causes of Infectious Diarrhoea - Gastroenteritis
What are rotaviruses?
Epidemiology?
Treatment?
Vaccinations?
What are noroviruses?
Transmission?
Symptoms?
Diagnosis?
Epidemiology?
What is campylobacter?
Transmission?
Treatment?
Epidemiology
What are Escherichia coli (E. coli)?
What is Enteroinvasive E. coli (EIEC)
-Shigella like illness
-Bloody diarrhea
What is Enterotoxigenic E. coli (ETEC)
-Cholera like toxin
-Watery diarrhoea
What is Enterohaemorrhagic or Shiga toxin-producing E. coli (EHEC/STEC)
-E. coli O157 serogroup, Shigatoxin/verotoxin
-5-10% get haemolytic uraemic syndrome: loss of kidney function
Name 3 other E.coli?
Enteropathogenic E. coli (EPEC)
Enteroaggregative E. coli (EAEC)
Diffusely adherent E. coli (DAEC)
What is the management of Clostridium difficile (C. Diff.)