iMmUnOloGy oF tHe gUt Flashcards

1
Q

What is the difference between microbiome and microbiota?

A

microbiota = all the microorganisms in an environment

microbiome = all the bacteria and their genes

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2
Q

What are gnotobiotic studies?

A

relating to study where every microorganism present is known and defined which can inform immunological defects etc

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3
Q

How much gut bacteria is there?

A

10 to the power of 14

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4
Q

What are the major phyla of bacteria in the gut?

A

bacteroidetes
firmicutes
actinobacteria
proteobacteria

as well as viruses and fungus

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5
Q

How does the stomach fight against pathogens?

A

HCL, so pH is low
pepsin production
gastric lipase

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6
Q

How does bacteria content changed down through the gastrointestinal system?

A

the bacterial content increases from the stomach to colon and the amount of host digestive factors and immunological defence mechanisms decreases

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7
Q

What is dysbiosis?

A

an altered microbiota composition

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8
Q

What are symbionts?

A

organism lives with the host, but does not provide harm or benefit

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9
Q

What are commensals?

A

organism that lives in the host and provides benefit to the host

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10
Q

What are pathobionts?

A

symbionts with the potential to cause harm to the host by causing dysregulated inflammation for example, in dysbiosis

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11
Q

What can cause dysbiosis?

A

diet, infection, xenobiotics, hygeine, genetics can encourage dysbiosis

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12
Q

What is the bacterial metabolite TMAO associated with?

A

an increase in cholesterol deposition, resulting in atherosclerosis

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13
Q

What is the bacterial metabolite 4-EPS associated with?

A

autism

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14
Q

What is the bacterial metabolite SCFA associated ?

A

short chain fatty acids - decreased numbers associated with inflammatory bowel disease and increased numbers associated with stress

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15
Q

What is the bacterial metabolite AHR ligands associated with?

A

asthma, rheumatoid arthritis, athersclerosis

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16
Q

What are immunological related physical mucosal defence barriers?

A

anatomical - epithelial barrier consisting of mucus layer, tight junctions, paneth cells that secrete lysosymes and antimicrobial peptides

chemical - enzymes, hcl secretion causing acidic ph

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17
Q

How do commensals provide immunological related mucosal defense?

A

by occupying the ecological niche - preventing proliferation of other bacteria

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18
Q

What does MALT stand for?

A

mucosa associated lymphoid tissue

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19
Q

What does GALT stand for ?

A

gut associated lymphoid tissue

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20
Q

What are Peyers patches?

A

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

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21
Q

Where are peyers patches found?

A

in the submucosa of the small intestine particularly the distal ileum

22
Q

What is follicle associated epithelium?

A

they have no goblet cells, no microvilli (microfolds instead) no secretory IgA (M cells express IgA receptors)

23
Q

How is antigen taken up into the peyers patch?

A

via M cells within the follicle associated epithelium

they express IgA receptors and facilitate the transfer of IgA-bacteria complex into the peyers patch

24
Q

How can dendritic cells in the peyers patch sample antigen?

A

extension of dendrites through the tight junctions between M cells and phagocytosis of the antigen which is then transported to the mesenteric lymph node

25
Q

Outline the b cell adaptive response

A
  1. pathogens taken up by M cells and secreted into the inner surface of an enterocyte
  2. the enterocyte inner surface contains antigen presenting cells such as dendritic cells
  3. dendrities present antigen in the context of MHC class 2
  4. dendritic cells migrate to the peyers patches through lymph system
  5. formation of an organised lymph follicle consisting of the dendrites, t cells and b cells
  6. the antigen activates T cells and B cells mature, which will return to GALT and secrete dimeric IgA antibody against the antigen
  7. the dimeric IgA antibody binds to a poly-Ig receptors and undergoes enzymatic cleavage in its vesicle
  8. the epithelial cells secrete the IgA as secretory IgA through the basolateral membrane to the lumen
26
Q

What is the function of secretory IgA?

A

sIgA binds luminal antigen to prevent its adhesion and consequent invasion

27
Q

Outline how lymphocytes circulate from the peyers patch

A
  1. lymphocytes activated in peyers patch
  2. migrate to the mesenteric lymph node through lymphatic system and undergo lymphocyte proliferation
  3. the lymphocytes return to circulation from thoracic duct
  4. it can enter the skin, bronchus associated lymphoid tissue, and tonsils, or it can return to intestinal lymphoid tissue via lamina propria
28
Q

How do lymphocytes travel through high endothelial venules?

A

through alpha 4 beta 7 integrin MAdCAM-1 adhesion

29
Q

What is life span of enterocytes and goblet cells?

A

36 hours

30
Q

Why is the life span short for enterocytes and goblet cells?

A

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

31
Q

How does cholera infection cause disease?

A
  1. bacteria reaches the small intestine, makes contact with epithelium and release cholera enterotoxin
  2. increased adenylate cyclase activity and increase in cAMP
  3. causing active secretions of salts by activating CFTR, causing water to enter the lumen, resulting in watery diarrhoea
32
Q

What pathogen causes cholera?

A

vibrio cholera serogroup O1 and O139

33
Q

How is cholera transmitted?

A

faecal oral route via contaminated water and food

34
Q

What are the main symptoms of cholera?

A

severe dehydration and watery diarrhoea

35
Q

What are the other symptoms of cholera?

A

vomiting, nausea, abdominal pain

36
Q

How is cholera diagnosed?

A

bacterial culture from stool

37
Q

How do we treat cholera?

A

oral rehydration

38
Q

What preventative cholera treatments are there?

A

vaccines

39
Q

What are other causes of infectious diarrhoea?

A
rotavirus
norovirus 
salmonella 
clostridium difficile 
giardia lamblia
40
Q

What is rotavirus?

A

often Type A rotavirus infection, an RNA virus that replicates in enterocytes

41
Q

What is the treatment for rotavirus?

A

oral rehydration therapy

42
Q

What is norovirus?

A

rna virus

43
Q

What are the symptoms of norovirus?

A

acute gastroenteritis

44
Q

How do we diagnose norovirus?

A

PCR

45
Q

What is campylobacter?

A

infection caused by undercooked meat, untreated water, unpasteurised milk

46
Q

What are treatment options for campylobacter?

A

azithromycin

47
Q

What is campylobacter resistant to?

A

fluoroquinolones

48
Q

Which type of e coli causes haemolytic uraemic syndrome?

A

ecoli O157 serogroup - shigatoxin/ verotoxin that results in loss of kidney function

49
Q

What is the mechanism of action of c diff?

A

dysbiotic state -> more proliferation of c diff leading to toxin production and inflammation causing symptoms

50
Q

How do we manage C diff?

A

isolate the patient and stop antibiotics

could consider starting metronidazole or vancomycin

faecal microbiota transplantation