gut infection

Question 1

what is meant by state of ‘retrained activation’?

Answer 1

State of “restrained activation” - Tolerance vs. active immune response – Dual immunological role.
Immune homeostasis of gut & development of healthy immune system requires presence of bacterial microbiota.

Question 2

How many gut bacteria?

And what are they major phyla of bacteria?

Answer 2

10^14 gut bacteria and 4 major phyla of bacteria (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria), also viruses & fungi.

Question 3

Define the following: 

Microbiota –  Microbiome –  Metagenomics –  Metataxonomics –  Metabonomics –

Answer 3

 Microbiota – Information about different microbes present in a system (who and how abundant).
 Microbiome – The functions the microbiota has, i.e. bile metabolism (a function catalogue).
 Metagenomics – The genetic analysis of genomes contained within a sample to inspect the microbiome/function.
 Metataxonomics – Creation of 16S rRNA gene inventories, used to define the microbiota.
 Metabonomics – A catalogue of metabolites in a sample.

Question 4

what is dysbiosis

Answer 4

an imbalance between the types of organism present in a person’s natural microflora, especially that of the gut, thought to contribute to a range of conditions of ill health.
Relies on symbionts; regulation
and pathobionts: inflammation

Question 5

causes of dysbiosis

Answer 5

infection or inflammation 
diet 
xenobiotics 
hygiene 
genetics

Question 6

mucosal defences 3 types

Answer 6

physical barriers (anatomical such as epithelial barrier and chemical such as enzymes)

commensal bacteria (occupy ecological niche)

immunological: following invasion (MALT and GALT)

Question 7

epithelial barrier

Answer 7

Mucus layer - Goblet cells
Epithelial monolayer - Tight junctions
Paneth Cells (small intestine)
Bases of crypts of Lieberkühn.
Secrete Antimicrobial peptides (defensins) and lysozyme.

Question 8

MALT

Answer 8

found in the submucosa below the epithelium, as lymphoid mass containing lymphoid follicles
follicles are surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes
the oral cavity is rich in immunological tissue

Question 9

GALT

Answer 9

Responsible for both adaptive & innate immune responses through generation of lymphoid cells & Abs.
CONSISTS OF NOT ORGANISED AND ORGANISED
Not organised:
-intra-epithelial lymphocytes and lamina propria (lies just beneath the basement membrane) lymphocytes

Organised 
peyer's patches (small intestine) 
caecal patches (large intestine) 
isolated lymphoid follicles 
mesenteric lymph nodes (encapsulated)

Question 10

Peyer’s patches- immune sensors

Answer 10

-small intestine, mainly distal ileum -Aggregatedlymphoid follicles covered with follicle associated epithelium (FAE).
Organised collection of naïve T cells and B-cells.
Development requires exposure to bacterial microbiota (50 in last trimester foetus, 250 by teens).
Antigen uptake via M (microfold) cells within FAE.

Question 11

FAE characteristics

Answer 11

no goblet cells, no secretory IgA, lack microvilli.

Question 12

M cells express what?

Answer 12

M cells expressIgA receptors, facilitating transfer of IgA-bacteria complexinto the peyer’s patches.

Question 13

particulate antigen sampling uses?

Answer 13

Microfold cells

antigen sampling: trans-epithelial dendritic cells

Question 14

B cell adaptive response

Answer 14

mature naïve b cells express IgM in PPs
upon antigen presentation class switch to IgA
T cells and epithelial cells influence B cell maturation via cytokine production
B cells further mature to become IgA secreting plasma cells
Populate lamina propria

Question 15

secretory IgA (sIgA)

Answer 15

Up to 90% of gut B-cells secrete IgA.

sIgA binds luminal antigen, thereby preventing its adhesion and consequent invasion.

Question 16

GALT- T cell Homing

Answer 16

GALT – T-Cell Homing 
§ The homing system is regulated by: 
o The T-cell exhibits a4b7-Integrin. 
o The gut epithelium exhibits MAdCAM-1. 
§ The receptor interaction means the t-cell is specific to the gut.

Question 17

cholera infection

-mechanism

Answer 17

• caused by vibrio cholerae aerogroups O1 and O139
• bacteria reaches small intestine
• makes close contact with epithelium releases cholera toxin
• starts a series of biochemical reactions resulting in exit of ions such as Na+, K+ and Cl- and water from the epithelial cells

Question 18

cholera
-diagnosis & treatment
symptoms

Answer 18

Diagnosis: bacterial culture from stool sample on selective agar is the gold standard, rapid dipstick tests also available.
Treatment: oral-rehydration is the main management; up to 80% of cases can be successfully treated.
Vaccine: Dukoral, oral, inactivated.
Globally 1.3 - 4 million cases, avg. 95,000deaths/year (last indigenous UK case 1893: 2017 - 13 cases).

Question 19

cholera

-transmission & symptoms

Answer 19

Transmitted through faecal-oral route, and spreads through contaminated water & food.
Main symptoms – Severe dehydration and diarrhoea (watery).
Other symptoms - vomiting, nausea & abdominal pain.

Question 20

other causes of infectious diarrhea

Answer 20

viral (rotavirus)
protozoal parasitic (giardia lamblia)
bacterial (E coli, salmonella)

Question 21

rotavirus

Answer 21

RNA virus
most common cause of diarrhoea in infants
oral rehydration therapy
live attenuated oral vaccine- rotarix

Question 22

norovirus

Answer 22

RNA virus
sample PCR
acute gastroenteritis
faecal-oral transmission

Question 23

campylobacter

Answer 23

Campylobacter jejuni, Campylobacter coli
undercooked meat 
untreated water and unpasteurised milk 
low infective dose 
most common cause of food poisoning 
no treatment usually required

Question 24

E coli

Answer 24

diverse group of gram negative intestinal bacteria, most harmless but ‘pathotypes’ associated with diarrhea

Question 25

clostridium difficile- management

Answer 25

isolate patient 
stop current antibiotics 
metronidazole 
recurrence rate 
faecal microbiota transplantation

Question 26

coeliac disease- autoimmune disease

Answer 26

Gliadin (33aa peptide component of gluten) is not broken down in the stomach, reaches small intestine, binds to sIgA and is transferred to the lamina propria.

• abdominal pain
• diarrhoea
• Ab blood tests
• biopsy test of duodenum
• diet-management- gluten free diet

Question 27

irritable bowel syndrome

Answer 27

Visceral hypersensitivity
Triggered by diet / stress
Recurrent abdominal pain
Abnormal bowel motility
Constipation and/or Diarrhoea
Diet modification - Avoiding certain foods such as apples, beans, cauliflowers.
Treatment of constipation - soluble fiber, stool softeners and osmotic laxatives.
Treatment of spasms and pain - anti-diarrheals, anti-muscarinic.
Management of stress, anxiety, depression

Question 28

Inflammatory bowel disease (IBD)

Answer 28

see slide