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Gastro > Immunology of the gut > Flashcards

Immunology of the gut Flashcards

1
Q

What are the reasons for the massive antigen load in the GI tract?

A

Large microbiome
Dietary antigens
Pathogen exposure

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2
Q

What is the dual immunological state of the GI tract

A

State of restrained activation
balance between tolerance (food antigens/commensal bacteria) and an active immune response (against pathogens)

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3
Q

Why is bacterial microbiota important

A

Gut immune homeostasis and the development of a healthy immune system rq microbiota

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4
Q

Key discoveries in germ-free mice

A

Defect in the development of Peyer’s patches in the SI

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5
Q

What are the 4 major phyla of bacteria in the gut microbiota?
(Bacteria Are Fucking Painful)

A

Bacteroidetes, Actinobacteria, Firmicutes, Proteobacteria

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6
Q

Benefits provided by gut flora

A

Essential nutrients
Metabolism of indigestible compounds
Defence against pathogen colonisation

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7
Q

What are the factors that stimulate gut bacteria growth?

A

Ingested and secreted nutrients

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8
Q

What are the factors that stimulate gut bacteria lysis and elimination?

A

Chemical digestive factors
peristalsis & defecation

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9
Q

What are the three ‘types’ of bacteria in the gut microbiota?

A

Symbionts, Commensals, Pathobionts

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10
Q

What are symbionts?

A

Bacteria living in GI tract and get benefit from doing so

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11
Q

What are commensals?

A

Bacteria living in GI tract with no harm to host

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12
Q

What are pathobionts?

A

Bacteria living in GI tract and are no harm but can become pathological

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13
Q

What is altered microbiota composition called?

A

Dysbiosis
Changes in gut bacterial distribution

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14
Q

What are some causes of dysbiosis?

A

Infection, Diet, Xenobiotics, Hygiene, Genetics

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15
Q

Xenobiotics definition

A

Chemical compound that is foreign to host metabolism
e.g. drugs/pollutants

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16
Q

What conditions can be caused by dysbiosis

A

due to bacterial metabolites/toxins
- Autism, MS
- Asthma
- Obesity
- IBD, Coeliac
- T1DM, Atherosclerosis

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17
Q

What are the GI physical barriers against pathogens?

A

Anatomical (epithelial barrier, peristalsis)
Chemical (pH, enzymes)

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18
Q

What are some examples of epithelial barriers?

A

Goblet cells (in the mucus layer)
Tight junction epithelium (in epithelial monolayer)
Paneth cells (small intestine crypt base)

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19
Q

What do paneth cells secrete?

A

Antimicrobial peptides (defensins) and lysozymes

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20
Q

What are the immunological defences against pathogens?

A

MALT (mucosa associated lymphoid tissue),
GALT (gut associated lymphoid tissue)

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21
Q

What are MALTs?

A

mucosa associated lymphoid tissue
Lymphoid masses containing lymphoid follicles

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22
Q

Where are MALTs found relative to epithelium?

A

Submucosa below the epithelium

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23
Q

What are MALT follicles surrounded by and why?

A

HEV Postcapillary Venules - allowing easy passage of lymphocytes

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24
Q

Where in the body are MALTs found in abundance?

A

Oral Cavity - Palatine, Lingual, Pharyngeal Tonsils

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25
Q

What is the function of GALTs?

A

gut associated lymphoid tissue)
Adaptive and Innate immunity in the gut
Longer term immunity than MALTs

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26
Q

What cells do GALTs contain?

A

B & T lymphocytes, macrophages, dendritic cells, intra-epithelial lymphocytes

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27
Q

What are the two classifications of GALTs?

A

Non-organised and Organised

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28
Q

What are two examples of lymphocytes in non-organised GALTs?

A

Intra-epithelial Lymphocytes,
Lamina Propria Lymphocytes

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29
Q

What are four examples of organised GALTs?
(Prokaryotes Can Infect Mice)

A

Peyer’s Patches, SI
Caecal Patches, LI
Isolated Lymphoid Follicles,
Mesenteric Lymph Nodes

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30
Q

At which part of the bowel are there more lymphocytes and why?

A

More in small bowel than large
Site of majority absorption, encounters most antigens. igA in large to combat lack of cells

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31
Q

Where are Peyer’s patches found?

A

Small Intestine - distal ileum

32
Q

What are Peyer’s patches

A

Aggregated lymphoid follicles covered by follicle associated epithelium (FAE)
organised collection of naive B/T cells

33
Q

What are the lymphoid follicles in Peyer’s patches covered with and what is their function?

A

Follicle Associated Epithelium (FAE) - provide barrier between Peyer’s patches and antigens

34
Q

Characteristics of FAE

A

No goblet cells, no secretory igA, lack microvilli

35
Q

How is antigen uptake controlled in the FAE?

A

Microfold (M) cells express IgA receptors, facilitate transfer of IgA bacteria into Peyer’s patches. This allows activation of naive lymphocytes

36
Q

What lymphocytes are found in Peyer’s patches?

A

Naive T cells and B cells

37
Q

What is another method of antigen sampling?

A

Trans-epithelial Dendritic Cells

38
Q

How do Trans-epithelial Dendritic Cells sample antigens

A

Independent of M cells
Squeeze through tight jcts and collect antigens on the other side of the barrier, before transporting them to the mesenteric lymph nodes

39
Q

What immunoglobulin is expressed by mature B cells

A

igM
on contact with APC class switch to igA

40
Q

Influencers on B cell maturation

A

Cytokine production by T cells and epithelial cells

41
Q

Describe how B cells become activated in Peyer’s patches

A

Antigens pass through M cells, present to MHC II Dendritic Cells. DCs take antigens to organised lymphoid follicles in Peyer’s patch to activate B cells

42
Q

Describe the actions of B cells in the gut after becoming activated

A

B cells migrate to lymphatic circulation for maturation, return to populate lamina propria, where they release secretory IgA into the gut lumen

43
Q

What is the function of secretory IgA?

A

Binds to luminal antigen - preventing pathogenic adhesion and invasion into enterocytes

44
Q

Describe lymphocyte homing and circulation

A

Antigen presentation activates naive T and B cells in PP. Lymphocytes migrate to mesenteric lymph node for proliferation. Enter thoracic duct for circulation to: lamina propria or peripheral tissue

45
Q

What peripheral tissues do these lymphocytes migrate to?

A

Skin, Tonsils, Bronchial-Associated Lymphoid Tissue (BALT)

46
Q

Explain how T cells re-enter the lamina propria

A

T cells transported in High Endothelial Venule (HEV). T cells express (alpha-4, beta-7) integrin, to allow rolling on endothelial wall. This binds to MAdCAM-1 on GALT lining, which allows diffusion into the lamina propria

47
Q

What is L selectin

A

Cell adhesion molecule
signalling molecule in the PP

48
Q

Why do enterocytes and goblet cells have a high turnover

A

36hrs
First line of defence, exposed to toxins which may affect function e.g. metabolic rate
Ensures any lesions are short lived, replaces damage quickly

49
Q

When can severe intestinal dysfunction occur?

A

Disruption to rapid turnover and migration of enterocytes from the base of crypts - e.g from radiation

50
Q

How does cholera release its toxins?

A

Vibrio cholerae serogroups on surface bind to small intestine epithelium and release cholera enterotoxin

51
Q

How is cholera transmitted?

A

Faecal-oral route, from contaminated water and food

52
Q

What are the main symptoms of cholera and infectious diarrhoea in general?

A

Severe dehydration, Watery diarrhoea

53
Q

What are other symptoms associated with cholera?

A

Vomiting, nausea and abdominal pain

54
Q

What is the main action of the cholera enterotoxin

A

Opens up ion channels
Causes luminal water retention

55
Q

How do you diagnose cholera?

A

Stool sample in selective agar
rapid dipstick test

56
Q

What is the main treatment for cholera and infectious diarrhoea in general?

A

Oral Rehydration

57
Q

What vaccine can you give for cholera?

A

Oral inactivated vaccine

58
Q

What are other viral causes of infectious diarrhoea?

A

Rotavirus, Norovirus

59
Q

What are other bacterial causes of infectious diarrhoea?

A

Campylobacter,
E.Coli,
Salmonella,
Shigella,
C. Diff

60
Q

What are rotaviruses?

A

RNA viruses, replicate in enterocytes
5 types (A most common)

61
Q

What is the treatment for rotavirus?

A

Oral rehydration therapy

62
Q

What is the vaccine for rotavirus?

A

Live attenuated oral vaccine - Rotarix

63
Q

What is norovirus?

A

RNA virus, species: Norwalk Virus

64
Q

What is the transmission for norovirus?

A

Faecal-oral transmission, often in closed communities (cruise ships)

65
Q

What are the symptoms for norovirus?

A

Acute gastroenteritis - watery diarrhoea, vomiting
recovery in 1-3d

66
Q

How can you identify campylobacter on electron microscopy?

A

Curved bacteria shape

67
Q

What is the transmission of campylobacter?

A

undercooked poultry, untreated water, unpasteurised milk

68
Q

What is the treatment of campylobacter?

A

Don’t really need treatment
azithromycin can be used

69
Q

What is E.coli

A

group of gram -ve intestinal bacteria
dif pathotypes associated with diarrhoea

70
Q

What are 3 examples of diarrhoeagenic E Coli species?

A

Enterotoxigenic E Coli (ETEC)
Enterohaemorrhagic E Coli (EHEC)
Enteroinvasive E Coli (EIEC)

71
Q

What is the symptom of ETEC?

A

Cholera-like, watery diarrhoea

72
Q

What is the symptom of EIEC?

A

Shigella-like, bloody diarrhoea

73
Q

What is the symptom of EHEC?

A

Haemolytic Uraemic Syndrome - small renal blood vessels inflamed and damaged
leads to loss of kidney fct

74
Q

How do you manage C. Diff?

A

Isolate patient to prevent contamination, stop current antibiotics. Prescribe metronidazole or vancomycin

75
Q

How can you “cure” C. Diff?

A

Faecal Microbiota Transplant
AB clear host microbiota then transplant a new population to eliminate C.diff

76
Q

Clinical assessment for GI conditions

A

Symptom onset - post ingestion?
Amount, consistency, frq - watery stools, blood, pus, mucus
Associated symptoms - pain, bloating, nausea, fever
Travel, diet, lifestyle - pets, vacay, hospitals, social

Gastro (10 decks)

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