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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
What is the function of GALTs?
gut associated lymphoid tissue) Adaptive and Innate immunity in the gut Longer term immunity than MALTs
26
What cells do GALTs contain?
B & T lymphocytes, macrophages, dendritic cells, intra-epithelial lymphocytes
27
What are the two classifications of GALTs?
Non-organised and Organised
28
What are two examples of lymphocytes in non-organised GALTs?
Intra-epithelial Lymphocytes, Lamina Propria Lymphocytes
29
What are four examples of organised GALTs? (Prokaryotes Can Infect Mice)
Peyer's Patches, SI Caecal Patches, LI Isolated Lymphoid Follicles, Mesenteric Lymph Nodes
30
At which part of the bowel are there more lymphocytes and why?
More in small bowel than large Site of majority absorption, encounters most antigens. igA in large to combat lack of cells
31
Where are Peyer's patches found?
Small Intestine - distal ileum
32
What are Peyer's patches
Aggregated lymphoid follicles covered by follicle associated epithelium (FAE) organised collection of naive B/T cells
33
What are the lymphoid follicles in Peyer's patches covered with and what is their function?
Follicle Associated Epithelium (FAE) - provide barrier between Peyer's patches and antigens
34
Characteristics of FAE
No goblet cells, no secretory igA, lack microvilli
35
How is antigen uptake controlled in the FAE?
Microfold (M) cells express IgA receptors, facilitate transfer of IgA bacteria into Peyer's patches. This allows activation of naive lymphocytes
36
What lymphocytes are found in Peyer's patches?
Naive T cells and B cells
37
What is another method of antigen sampling?
Trans-epithelial Dendritic Cells
38
How do Trans-epithelial Dendritic Cells sample antigens
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
What immunoglobulin is expressed by mature B cells
igM on contact with APC class switch to igA
40
Influencers on B cell maturation
Cytokine production by T cells and epithelial cells
41
Describe how B cells become activated in Peyer's patches
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
Describe the actions of B cells in the gut after becoming activated
B cells migrate to lymphatic circulation for maturation, return to populate lamina propria, where they release secretory IgA into the gut lumen
43
What is the function of secretory IgA?
Binds to luminal antigen - preventing pathogenic adhesion and invasion into enterocytes
44
Describe lymphocyte homing and circulation
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
What peripheral tissues do these lymphocytes migrate to?
Skin, Tonsils, Bronchial-Associated Lymphoid Tissue (BALT)
46
Explain how T cells re-enter the lamina propria
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
What is L selectin
Cell adhesion molecule signalling molecule in the PP
48
Why do enterocytes and goblet cells have a high turnover
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
When can severe intestinal dysfunction occur?
Disruption to rapid turnover and migration of enterocytes from the base of crypts - e.g from radiation
50
How does cholera release its toxins?
Vibrio cholerae serogroups on surface bind to small intestine epithelium and release cholera enterotoxin
51
How is cholera transmitted?
Faecal-oral route, from contaminated water and food
52
What are the main symptoms of cholera and infectious diarrhoea in general?
Severe dehydration, Watery diarrhoea
53
What are other symptoms associated with cholera?
Vomiting, nausea and abdominal pain
54
What is the main action of the cholera enterotoxin
Opens up ion channels Causes luminal water retention
55
How do you diagnose cholera?
Stool sample in selective agar rapid dipstick test
56
What is the main treatment for cholera and infectious diarrhoea in general?
Oral Rehydration
57
What vaccine can you give for cholera?
Oral inactivated vaccine
58
What are other viral causes of infectious diarrhoea?
Rotavirus, Norovirus
59
What are other bacterial causes of infectious diarrhoea?
Campylobacter, E.Coli, Salmonella, Shigella, C. Diff
60
What are rotaviruses?
RNA viruses, replicate in enterocytes 5 types (A most common)
61
What is the treatment for rotavirus?
Oral rehydration therapy
62
What is the vaccine for rotavirus?
Live attenuated oral vaccine - Rotarix
63
What is norovirus?
RNA virus, species: Norwalk Virus
64
What is the transmission for norovirus?
Faecal-oral transmission, often in closed communities (cruise ships)
65
What are the symptoms for norovirus?
Acute gastroenteritis - watery diarrhoea, vomiting recovery in 1-3d
66
How can you identify campylobacter on electron microscopy?
Curved bacteria shape
67
What is the transmission of campylobacter?
undercooked poultry, untreated water, unpasteurised milk
68
What is the treatment of campylobacter?
Don't really need treatment azithromycin can be used
69
What is E.coli
group of gram -ve intestinal bacteria dif pathotypes associated with diarrhoea
70
What are 3 examples of diarrhoeagenic E Coli species?
Enterotoxigenic E Coli (ETEC) Enterohaemorrhagic E Coli (EHEC) Enteroinvasive E Coli (EIEC)
71
What is the symptom of ETEC?
Cholera-like, watery diarrhoea
72
What is the symptom of EIEC?
Shigella-like, bloody diarrhoea
73
What is the symptom of EHEC?
Haemolytic Uraemic Syndrome - small renal blood vessels inflamed and damaged leads to loss of kidney fct
74
How do you manage C. Diff?
Isolate patient to prevent contamination, stop current antibiotics. Prescribe metronidazole or vancomycin
75
How can you "cure" C. Diff?
Faecal Microbiota Transplant AB clear host microbiota then transplant a new population to eliminate C.diff
76
Clinical assessment for GI conditions
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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