iMmUnOloGy oF tHe gUt Flashcards
What is the difference between microbiome and microbiota?
microbiota = all the microorganisms in an environment
microbiome = all the bacteria and their genes
What are gnotobiotic studies?
relating to study where every microorganism present is known and defined which can inform immunological defects etc
How much gut bacteria is there?
10 to the power of 14
What are the major phyla of bacteria in the gut?
bacteroidetes
firmicutes
actinobacteria
proteobacteria
as well as viruses and fungus
How does the stomach fight against pathogens?
HCL, so pH is low
pepsin production
gastric lipase
How does bacteria content changed down through the gastrointestinal system?
the bacterial content increases from the stomach to colon and the amount of host digestive factors and immunological defence mechanisms decreases
What is dysbiosis?
an altered microbiota composition
What are symbionts?
organism lives with the host, but does not provide harm or benefit
What are commensals?
organism that lives in the host and provides benefit to the host
What are pathobionts?
symbionts with the potential to cause harm to the host by causing dysregulated inflammation for example, in dysbiosis
What can cause dysbiosis?
diet, infection, xenobiotics, hygeine, genetics can encourage dysbiosis
What is the bacterial metabolite TMAO associated with?
an increase in cholesterol deposition, resulting in atherosclerosis
What is the bacterial metabolite 4-EPS associated with?
autism
What is the bacterial metabolite SCFA associated ?
short chain fatty acids - decreased numbers associated with inflammatory bowel disease and increased numbers associated with stress
What is the bacterial metabolite AHR ligands associated with?
asthma, rheumatoid arthritis, athersclerosis
What are immunological related physical mucosal defence barriers?
anatomical - epithelial barrier consisting of mucus layer, tight junctions, paneth cells that secrete lysosymes and antimicrobial peptides
chemical - enzymes, hcl secretion causing acidic ph
How do commensals provide immunological related mucosal defense?
by occupying the ecological niche - preventing proliferation of other bacteria
What does MALT stand for?
mucosa associated lymphoid tissue
What does GALT stand for ?
gut associated lymphoid tissue
What are Peyers patches?
aggregated lymphoid follicles covered with follicle associated epithelium with an organised collection of naive T cells and B cells with only become sensitised after exposure to microbiota
Where are peyers patches found?
in the submucosa of the small intestine particularly the distal ileum
What is follicle associated epithelium?
they have no goblet cells, no microvilli (microfolds instead) no secretory IgA (M cells express IgA receptors)
How is antigen taken up into the peyers patch?
via M cells within the follicle associated epithelium
they express IgA receptors and facilitate the transfer of IgA-bacteria complex into the peyers patch
How can dendritic cells in the peyers patch sample antigen?
extension of dendrites through the tight junctions between M cells and phagocytosis of the antigen which is then transported to the mesenteric lymph node
Outline the b cell adaptive response
- pathogens taken up by M cells and secreted into the inner surface of an enterocyte
- the enterocyte inner surface contains antigen presenting cells such as dendritic cells
- dendrities present antigen in the context of MHC class 2
- dendritic cells migrate to the peyers patches through lymph system
- formation of an organised lymph follicle consisting of the dendrites, t cells and b cells
- the antigen activates T cells and B cells mature, which will return to GALT and secrete dimeric IgA antibody against the antigen
- the dimeric IgA antibody binds to a poly-Ig receptors and undergoes enzymatic cleavage in its vesicle
- the epithelial cells secrete the IgA as secretory IgA through the basolateral membrane to the lumen
What is the function of secretory IgA?
sIgA binds luminal antigen to prevent its adhesion and consequent invasion
Outline how lymphocytes circulate from the peyers patch
- lymphocytes activated in peyers patch
- migrate to the mesenteric lymph node through lymphatic system and undergo lymphocyte proliferation
- the lymphocytes return to circulation from thoracic duct
- it can enter the skin, bronchus associated lymphoid tissue, and tonsils, or it can return to intestinal lymphoid tissue via lamina propria
How do lymphocytes travel through high endothelial venules?
through alpha 4 beta 7 integrin MAdCAM-1 adhesion
What is life span of enterocytes and goblet cells?
36 hours
Why is the life span short for enterocytes and goblet cells?
they are the first line of immunological defence in the gastrointestinal system
the effect of agents which interfere with cell function and metabolic rate are diminished by the cell death
any lesions will be short lived as effects are reduced
How does cholera infection cause disease?
- bacteria reaches the small intestine, makes contact with epithelium and release cholera enterotoxin
- increased adenylate cyclase activity and increase in cAMP
- causing active secretions of salts by activating CFTR, causing water to enter the lumen, resulting in watery diarrhoea
What pathogen causes cholera?
vibrio cholera serogroup O1 and O139
How is cholera transmitted?
faecal oral route via contaminated water and food
What are the main symptoms of cholera?
severe dehydration and watery diarrhoea
What are the other symptoms of cholera?
vomiting, nausea, abdominal pain
How is cholera diagnosed?
bacterial culture from stool
How do we treat cholera?
oral rehydration
What preventative cholera treatments are there?
vaccines
What are other causes of infectious diarrhoea?
rotavirus norovirus salmonella clostridium difficile giardia lamblia
What is rotavirus?
often Type A rotavirus infection, an RNA virus that replicates in enterocytes
What is the treatment for rotavirus?
oral rehydration therapy
What is norovirus?
rna virus
What are the symptoms of norovirus?
acute gastroenteritis
How do we diagnose norovirus?
PCR
What is campylobacter?
infection caused by undercooked meat, untreated water, unpasteurised milk
What are treatment options for campylobacter?
azithromycin
What is campylobacter resistant to?
fluoroquinolones
Which type of e coli causes haemolytic uraemic syndrome?
ecoli O157 serogroup - shigatoxin/ verotoxin that results in loss of kidney function
What is the mechanism of action of c diff?
dysbiotic state -> more proliferation of c diff leading to toxin production and inflammation causing symptoms
How do we manage C diff?
isolate the patient and stop antibiotics
could consider starting metronidazole or vancomycin
faecal microbiota transplantation
