Gut Immunology Flashcards
1
Q
What is the surface area of the GI tract?
A
200m^2
2
Q
What is the state of the GI tract?
A
State of “restrained activation”
3
Q
Why is bacterial microbiota important?
A
Immune homeostasis of gut & development of healthy immune system requires presence of bacterial microbiota
4
Q
What is tolerance?
A
- food antigens
- commensal bacteria
5
Q
What is the massive antigen load that the GI tract needs to deal with?
A
- Resident microbiota 1014 bacteria
- Dietary antigens
- Exposure to pathogens
6
Q
What is immunoreactivity?
A
pathogens
7
Q
What is involved in GI tract immunology?
A
– Tolerance vs active immune response
– Dual immunological role
8
Q
How many gut bacteria and cells are there?
A
10^14 gut bacteria and 10^13 cells in the body
9
Q
What are the 4 major phyla of bacteria?
A
- Bacteriodetes
- Firmicutes
- Actinobacteria
- Proteobacteria
- also viruses and fungi
10
Q
Why do we need the gut microbiota?
A
provide traits we have not had to evolve on our own, genes in. gut flora 100 times our own genome
11
Q
What is dysbiosis?
A
altered microbiota composition
12
Q
What is all balanced in immunological equilibrium?
A
- Symbionts (regulation): live with host no benefits/harm
- Commensals: benefits from host but no affect on host
- Pathobionts (inflammation): can cause inflammation and disease in certain circumstance but usually symbionts
13
Q
Which bacterial metabolites and toxins can be produced by pathobiomes in dysbiosis?
A
- TMAO
- 4-EPS
- SCFAs
- bile acids
- AHR ligand
14
Q
What are the brain diseases that can develop from dysbiosis?
A
- Stress
- Autism
- Multiple sclerosis
15
Q
What are the lung diseases that can develop from dysbiosis?
A
asthma
16
Q
What are the liver diseases that can develop from dysbiosis?
A
- NAFLD
2. NASH
17
Q
What are the adipose tissue diseases that can develop from dysbiosis?
A
- Obesity
2. Metabolic disease
18
Q
What are the intestine diseases that can develop from dysbiosis?
A
- IBD
2. Coeliac disease
19
Q
What are the systemic diseases that can develop from dysbiosis?
A
- T1 diabetes
- Atheroscelerosis
- Rhematoid arthritis
20
Q
What aspects can contribute to both healthy microbiota and dysbiosis?
A
- Infection or inflammation
- Diet
- Xenobiotics
- Hygiene
- Genetics
21
Q
What are the anatomical physcial barriers to muscosal defence?
A
- Epithelial barrier
* Peristalsis
22
Q
What are the chemical physcial barriers to muscosal defence?
A
- Enzymes
* Acidic pH
23
Q
What are commensal bacteria?
A
occupy “ecological niche”
24
Q
What is an immunological response to invasion?
A
following invasion
•MALT (Mucosa Associated Lymphoid Tissue)
•GALT (Gut Associated Lymphoid Tissue)
25
What is the epithelial barrier made up of?
1. Mucus layer - Goblet cells
2. Epithelial monolayer - Tight junctions
3. Paneth Cells (small intestine)
26
What are Paneth Cells? Where are they?
-small intestine
•Bases of crypts of Lieberkühn
•Secrete antimicrobial peptides (defensins) & lysozyme
27
Where is MALT found?
in the submucosa below the epithelium, as lymphoid mass containing lymphoid follicles
28
What are the follicles in MALT surrounded by?
surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes
29
What is the oral cavity rich in?
immunological tissue
30
What is GALT responsible for?
adaptive and innate immune system
31
What does GALT consist of?
1. B and T lymphocytes
2. Macrophages
3. APC (dendritic cells)
4. Specific epithelial and intra epithelial lymphocytes
32
What is the non organised section of GALT?
1. Intra-epithelial lymphocytes
•Make up 1/5th of intestinal epithelium, e.g. T-cells, NK cells
2. Lamina propria lymphocytes
33
What is the organised section of GALT?
1. Peyer’s patches (small intestine)
2. Caecal patches (large intestine)
3. Isolated lymphoid follicles
4. Mesenteric lymph nodes (encapsulated)
34
Where are peyer's patches found?
in submucosa small intestine – mainly distal ileum
35
What are stimulatory factors for microbiota?
1. Ingested nutrients
2. Secreted nutrients
- lead to bacterial growth
36
What are inhibitory factors for microbiota?
1. Chemical digestive factors (bacterial lysis)
| 2. Peristalsis, contractions and defecation (bacterial elimination)
37
What is dysbiosis?
- immunological dysequilbrium
| - Altered microbiota composition
38
What are the aggregated lymphoid follicles covered with in peyers patches?
with follicle associated epithelium (FAE)
39
What is FAE?
no goblet cells, no secretory IgA, no microvilli
40
What is Peyer's Patches?
Organised collection of naïve T cells & B-cells
41
What is needed for the development of Peyer's Patches?
-requires exposure to bacterial microbiota
| •50 in last trimester foetus, 250 by teens
42
What are M cells in Peyer's patches?
* Antigen uptake via M (microfold) cells within FAE
| * M cells express IgA receptors, facilitating transfer of IgA-bacteria complex into the Peyer's patches.
43
What do mature naive B cells express in Peyer's patches?
IgM
44
What happens to the IgM on antigen presentation?
class switches to IgA
45
What influences B cell maturation? What do they populate?
1. T-cells & epithelial cells influence B cell maturation via cytokine production
2. B cells further mature to become IgA secreting plasma cells.
3. Populate lamina propria
46
What is the formation of IgA?
Up to 90% of gut B-cells secrete IgA
47
Where does sIgA bind (secretory IgA)?
* sIgA binds luminal antigen
| * → preventing its adhesion and consequent invasion.
48
Why if enterocytes & goblet cells of small bowel have a short life span (about 36 hrs)
and rapid turnover contrasts with lifespan of weeks/months for other epithelial cell types (e.g. lung, blood vessels)?
1. Enterocytes are first line of defense against GI pathogens & may be directly affected by toxic substances in diet
2. Effects of agents which interfere with cell function, metabolic rate etc will be diminished.
3. Any lesions will be short-lived.
49
What is the mechanism of cholera infection?
1. Cholera -acute bacterial disease caused by Vibrio cholerae serogroups O1 & O139
2. Bacteria reaches small intestine → contact with epithelium & releases cholera enterotoxin
50
How is cholera transmitted?
* Transmitted through faecal-oral route
| * Spreads via contaminated water & food
51
What are the symptoms of cholera?
1. Main symptoms
•Severe dehydration & watery diarrhoea
2. Other symptoms
Vomiting, nausea & abdominal pain
52
What does the diagnosis of cholera involve?
bacterial culture from stool sample on selective agar is the gold standard, rapid dipstick tests also available
53
What does the treatment of cholera involve?
oral-rehydration is the main management ; up to 80% of cases can be successfully treated
54
Is there a vaccine for cholera?
Dukoral, oral, inactivated
55
What is the epidemiology of cholera?
Globally 1.3 - 4 million cases, avg. 95,000 deaths/year (last indigenous UK case 1893: 2017 - 13 cases)
56
What are the viral causes of infectious diarrhoea?
* Rotavirus (children)
| * Norovirus “winter vomiting bug”
57
What are the protozoal parasitic causes of infectious diarrhoea?
- Giardia lamblia
| - Entamoeba histolytica
58
What are the bacterial causes of infectious diarrhoea?
1. Campylobacter jejuni
2. Escherichia coli
3. Salmonella
4. Shigella
5. Clostridium difficile
59
What is rotavirus?
* RNA virus, replicates in enterocytes.
| * 5 types A – E, type A most common in human infections.
60
What is the epidemiology of rotaviruses?
Most common cause of diarrhoea in infants & young children worldwide
61
What is the treatment of rotaviruses?
1. Oral rehydration therapy
2. Still causes ~ 200,000 deaths/year.
3. Before vaccine, most individuals had an infection by age 5, repeated infections develop immunity.
62
Is there a vaccination for rotaviruses?
Live attenuated oral vaccine (Rotarix) against type A introduced in UK July 2013
63
What is norovirus?
* RNA virus
| * Incubation period 24-48 hours
64
What is the transmisstion of norovirus?
1. Faecal-oral transmission.
2. Individuals may shed infectious virus for up to 2 weeks
3. Outbreaks often occur in closed communities
65
What are the symptoms of norovirus?
•Acute gastroenteritis, recovery 1 – 3 days
66
What is the treatment of norovirus?
•Not usually required
67
What is the diagnosis of norovirus?
•Sample PCR.
68
What is the epideimiology of norovirus?
•Estimated 685 million cases per year.
69
What is the most common species of campylobacter?
•Campylobacter jejuni, Campylobacter coli
70
What is the transmission of campylobacter?
* Undercooked meat (especially poultry), untreated water & unpasteurised milk
* Low infective dose, a few bacteria (<500) can cause illness
71
What is the treatment of campylobacter?
1. Not usually required
2. Azithromycin (macrolide) is standard antibiotic
3. Resistance to fluoroquinolones is problematic
72
What is the epidemiology of campylobacter?
* Estimated 280,000 cases per year in UK, 65,000 confirmed
| * Commonest cause of food poisoning in the UK
73
What is E.Coli?
•Diverse group of Gram-negative intestinal bacteria
•Most harmless
6 ”pathotypes” associated with diarrhoea (diarrhoeagenic)
74
What is Enterotoxigenic E. coli (ETEC)?
* Cholera like toxin
| * Watery diarrhoea
75
What is Enterohaemorrhagic or Shiga toxin-producing E. coli (EHEC/STEC)?
* E. coli O157 serogroup, Shigatoxin/verotoxin
| * 5-10% get haemolytic uraemic syndrome: loss of kidney function
76
What is Enteroinvasive E. coli (EIEC)?
* Shigella like illness
| * Bloody diarrhea
77
What are other pathotypes of E coli?
•Enteropathogenic E. coli (EPEC)
•Enteroaggregative E. coli (EAEC)
-Diffusely adherent E. coli (DAEC
78
What is the management of Clostridium Difficile?
1. Isolate patient (very contagious)
2. Stop current antibiotics
3. Metronidazole, Vancomycin
4. Recurrence rate 15-35% after initial infection, increasingly difficult to treat.
5. Faecal Microbiota Transplantation (FMT) – 98% cure rate
