Immunology of the gut Flashcards

1
Q

What is microbiota?

A

Mixture of microorganisms that makes up a community within an anatomical niche

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2
Q

What is a microbiome?

A

Collective genomes of all microbiota in all the different anatomical niches

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3
Q

What is immune tolerance?

A

Body does not react to something that would usually cause a response

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4
Q

What is active immune response?

A

Body is actively reacting to a substance

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5
Q

What is the state of restrained activation?

A

Tolerance vs active immune response
Early has tolerance but if too much activation goes to the active phase
Dual immunological role

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6
Q

Why is germ-free mice experiments good?

A

-Have a lot of immunological defects so do not have a an active immune response

-Can see progression of pathogen with no interference of immune response

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7
Q

What are the 4 major phyla of bacteria in the gut?

A

-Bacteroidetes
-Firmicutes
-Actinobacteria
-Proteobacteria

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8
Q

What roles do viruses and fungi have in our gut?

A

-Essential nutrients
-Metabolism indigestible compounds
-Defence against colonisation by opportunistic pathogens
-Contribute to intestinal architecture

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9
Q

What is a dysbiosis?

A

Altered microbiota composiiton

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10
Q

What are the 3 types of microbiota?

A

-Symbionts
-Commensals
-Pathobionts

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11
Q

What are symbionts?

A

Microbiota that live with humans but do not benefit or harm each other (they just live)

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12
Q

What are commensals?

A

Microorganisms that benefit from hist but has no effect on the host

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13
Q

What are pathobionts?

A

Symbionts that doesn’t normally cause an inflammatory response but under specific conditions can cause dysregulated inflammatory disease

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14
Q

What are causes of dysbiosis?

A

-Infection and inflammation
-Diet
-Xenobiotics
-Hygiene
-Genetics

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15
Q

What are xenobiotics?

A

Substances that enter the body unnaturally (drugs, pollutants)

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16
Q

How can dysbiosis negatively impact the body?

A

By producing bacterial metabolites and toxins

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17
Q

What are examples of bacterial metabolites and toxins?

A
  • Trimethylamine N-oxide (TMAO)
  • 4-EPS
    -Short chain fatty acids (SCFs)
    -AHR ligands
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18
Q

What is TMAO associated with?

A

Atherosclerosis

Increased cholesterol deposition in artery walls

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19
Q

What is 4-EPS associated with?

A

Autism

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20
Q

What are SCFAs associated with?

A
  • Decreased SCFAs→ IBD
  • Increased SCFAs → neuropsychiatric disorders (stress)
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21
Q

What are AHR ligands associated with?

A
  • Multiple sclerosis
  • Rheumatoid arthritis
  • Asthma
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22
Q

What is the mucosal defence?

A

The first line of defence the body has against pathogens

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23
Q

What are the 2 types of physical barriers in mucosal defence?

A

-Anatomical
-Chemical

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24
Q

What are examples of anatomical physical barriers in mucosal defence?

A

-Epithelial barriers
-Peristalsis

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25
Q

What are examples of chemical physical barriers in mucosal defence?

A

-Enzymes
-Acidic pH

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26
Q

What does the epithelial barrier consist of?

A

1) Goblet cells= Mucus layer
2) Epithelial monolayer= tight junctions
3) Paneth of cells (small intestine)= base of crypts that secrete peptides for digestion

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27
Q

Where are the commensal bacteria found?

A

Microvilli

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28
Q

What types of lymphoid tissue are there?

A

-Mucosa associated lymphoid tissue (MALT)
-Gut associated lymphoid tissue (GALT)

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29
Q

Where is MALT found?

A

Submucosa below the epithelium

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30
Q

How is MALT found as?

A

Lymphoid mass containing lymphoid follicles

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31
Q

What allows lymphocytes to easily move in and out of MALT?

A

Follicles surrounded by HEV postcapillary venules

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32
Q

What part of the body is particularly rich in immunological/lymphoid tissue?

A

Oral cavity

Esp pharyngeal, palatine and lingual tonsils

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33
Q

What is MALT responsible for?

A

Short term, immediate immune response

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34
Q

What is GALT responsible for?

A

Both adaptive and innate immune responses through generations of lymphoid cells and antibodies

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35
Q

What is the biggest mass of lymphoid tissue in the body?

A

GALT

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36
Q

What are the 2 types of GALT?

A
  • Non-organised
  • Organised
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37
Q

What are non-organised GALT?

A
  • Intra-epithelial lymphocytes
  • Lamina propria lymphocytes
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38
Q

What are intra-epithelial lymphocytes?

A
  • Found between enterocytes
  • Make up 1/5 of intestinal epithelium
  • Contain T cells and NK cells
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39
Q

As you go further down the small bowel, how does it change?

A

-Lymphocytes decrease
-Goblet cells increase

40
Q

What are examples of organised GALT?

A
  • Peyer’s patches (small intestine)= lumps of lymphoid tissue
  • Caecal patches (large intestine)
  • Isolated lymphoid follicles
  • Mesenteric lymph nodes
  • Mesenteric lymph nodes (encapsulated)= lymph nodes with mesentery
41
Q

What can enlarged mesenteric lymph nodes be mistaken for?

A

Pathological

42
Q

Where are Peyer’s patches mainly found?

A

-Distal ileum

43
Q

What are Peyer’s patches?

A

Aggregated lymphoid follicles with follicle associated epithelium

44
Q

What is follicle associated epithelium?

A

-Made up of specialised enterocytes
-Role of transferring things to Peyer’s patches
-Eg= Bacteria

45
Q

What cells do FAE lack?

A

-Goblet cells
-Secretory IgA
-Microvilli

46
Q

What cells make up Peyer’s patches?

A

-Naive T cells
-Naive B cells

47
Q

What does Peyer’s patches development require?

A

-Bacterial exposure

48
Q

How many fold does Peyer’s patches increase by from last trimester to teens?

A

4 fold

49
Q

What are M cells?

A

Microfold cells

50
Q

How does antigen uptake occur in Peyer’s patches?

A

-Via M cells within FAE
-M cells express IgA receptors which facilitate transfer of IgA-bacteria complex into the Peyer’s patches

51
Q

Where are transepithelial dendritic cells found?

A

Underneath mucosal epithelial cells

52
Q

What is an alternative route of bacteria uptake than M cells?

A

-Transepithelial dendritic cells can open up tight junctions

-This can allow dendrites to enter lumen of GI tract and directly sample bacteria

-Brings bacteria back

-Transports bacteria to mesenteric lymph nodes

53
Q

How does the B cell adaptive response work?

A

1) M cells take up pathogens
2) Pathogens excreted into pockets formed in inner surface of enterocyte
3) Pockets contain APCs (dendritic cells)
4) APC migrates to Peyer’s patch where T and B cells are
5) Mature naive b cells class switch from IgM to IgA upon antigen presentation in Peyer’s patch
6) Some APCs escape into lymph to activate even more B and T cells in mesenteric lymph nodes
7) Some of these activated cells return to gut tissue to produce antibodies back into the lumen
8) IgA secreting B cells populate lamina propria

54
Q

How do IgA get into the lumen?

A

-IgA goes into a vesicle in enterocyte
-Enzymatic cleavage occurs to produce secretory IgA (sIgA) which goes in the lumen

55
Q

What does sIgA do?

A

Binds luminal antigen to prevent its adhesion and consequent invasion

56
Q

How does lymphocyte homing and circulation work?

A

1) Peyer’s patch presentation and activation occurs
2) Lymphocytes travel to mesenteric lymph nodes where lymphocyte proliferation occurs
3) Return to circulation through thoracic duct
4) It can either go to the peripheral immune system or return to mucosa via vessels in lamina propria

57
Q

What is the thoracic duct?

A

The main lymphatic vessel for return of lymph from GI tract to venous system

58
Q

What are high endothelial venules?

A

Specialised blood vessels found mainly in lymphoid tissue and facilitate the migration of lymphocytes from bloodstream into the lymphoid tissue

59
Q

What is α4β7 integrin?

A

Expressed by lymphocytes to bind to high endothelial venules

60
Q

What is MAdCAM1?

A

-Mucosal addressin cell adhesion molecule 1
-Expressed on epithelial cells of HEVs which allows migration of lymphocytes through

61
Q

How does lymphocyte move from blood vessel into lamina propria?

A

1) Lymphocytes roll along HEV wall
2) Rolling chemo tactically activates T cell which means the α4β7 integrin and MAdCAM1 interact
3) The cell then gets pulled into lamina propria

62
Q

Why do enterocytes have such a short lifespan?

A

-First line defence against GI pathogens
-May be directly affected by agents interfering with cell function or metabolism
-Lesions short lived

63
Q

What happens if escalator like transit of enterocytes is interrupted?

A

Severe intestinal dysfunction

64
Q

What is cholera?

A

Acute bacterial disease

65
Q

What is cholera caused by?

A

Vibrio cholerae serogroups O1 and O139

66
Q

What is the mechanism of action of cholera?

A

1) Bacteria reach small intestine and get into contact with epithelium to release cholera enterotoxin
2) Enterotoxin gets internalised by retrograde endocytosis
3) Increases adenylyl cyclase activity and cAMP levels
4) Increases active secretion of salts (Na+,K+,Cl-,HCO3-) via cystic fibrosis transmembrane conducts regulators (CFTR)
5) Water follows and leads to diarrhoea

67
Q

How is cholera transmitted?

A

Faecal-oral transmission
(contaminated water and food)

68
Q

What are the 2 main symptoms of cholera?

A

-Severe dehydration
-Watery diarrhoea

69
Q

What are 3 other symptoms of cholera?

A

-Vomiting
-Nausea
-Abdominal pain

70
Q

How do you diagnose cholera?

A

-Bacterial culture from stool sample on selective agar (gold standard)
-Rapid dipstick tests also available

71
Q

How do we treat cholera?

A

Oral rehydration

72
Q

What are the vaccine for cholera?

A

-Dukoral
-Given orally
-Inactivated form of pathogen

73
Q

What are viral causes of gastroenteritis?

A

-Rotavirus (children)
-Norovirus (winter vomiting bug)

74
Q

What is rotavirus?

A

-RNA virus which replicates in enterocytes
-5 types (A-E)
-Type A the most common in humans

75
Q

How do you treat rotavirus?

A

-Oral rehydration therapy

76
Q

What is the vaccine for rotavirus?

A

-Rotarix
-Live attenuated oral vaccine
-Against type A rotarix

77
Q

What is norovirus?

A

-RNA virus
-Incubation period is 24-48 hours

78
Q

How is norovirus transmitted?

A

-Faecal oral transmission
-Individuals may shed infectious virus for up to 2 weeks
-Outbreaks occur in closed community

79
Q

What are symptoms of norovirus?

A

Acute gastroenteritis

80
Q

How long does acute gastroenteritis last for norovirus?

A

Recovery 1-3 days

81
Q

How do you diagnose norovirus?

A

Sample PCR

82
Q

What parasites cause gastroenteritis?

A

-Giardia lamblia
-Entamoeba histolytica

83
Q

What bacteria causes gastroenteritis?

A

-Campylobacter jejuni/coli (curved bacteria)
-Escherichia coli
-Salmonella
-Shigella
-Clostridium difficile

84
Q

How can campylobacter jejuni be transmitted?

A

-Undercooked meat, untreated water and unpasteurised milk

85
Q

What is the infective dose for campylobacter jejuni?

A

Low infective dose

86
Q

How is campylobacter treated?

A

-Not usually required
-Azithromycin (macrolide) is standard antibiotic
-Resistance to fluoroquinolones is bad

87
Q

What is escherichia coli?

A

-Diverse group of gram negative intestinal bacteria
-Most harmless

88
Q

What are the 6 types of escherichia coli associated with diarrhoea?

A

1) Enterotoxigenic E.Coli (ETEC)
2) Enteroinvasive E.Coli (EIEC)
3) Enterohaemorrhagic E.Coli/Shiga toxin producing E.Coli (EHEC/STEC)
4) Enteropathogenic E.Coli (EPEC)
5) Enteroaggressive E.Coli (EAEC)
6) Diffusely adherent E.Coli (DAEC)

89
Q

What does enterotoxigenic E.Coli cause?

A

-Cholera like toxin
-Watery diarrhoea

90
Q

What does enteroinvasive E.Coli cause?

A

-Shigella like illness
-Bloody diarrhoea

91
Q

What does enterohaemorrhagic E.Coli cause?

A

-Haemolytic uraemic syndrome

92
Q

What can haemolytic uraemic syndrome cause?

A

Loss of kidney function

93
Q

How does clostridium difficile cause problems?

A

Dysbiosis causes intermediate dysbiotic state

94
Q

How do you manage C.Diff?

A

-Isolate patient
-Stop current antibiotics
-Give vancomycin/metronidazole

95
Q

Why is metronidazole an odd treatment for C.Diff?

A

Can cause C.Diff as well as treating it too

96
Q

How do you cure C.Diff?

A

Faecal microbiota transplantation

97
Q

What is faecal microbiota transplantation?

A

Replace decal matter from a healthy donor is transplanted into the recipient