gut infection Flashcards
what is meant by state of ‘retrained activation’?
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.
How many gut bacteria?
And what are they major phyla of bacteria?
10^14 gut bacteria and 4 major phyla of bacteria (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria), also viruses & fungi.
Define the following:
Microbiota – Microbiome – Metagenomics – Metataxonomics – Metabonomics –
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.
what is dysbiosis
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
causes of dysbiosis
infection or inflammation diet xenobiotics hygiene genetics
mucosal defences 3 types
physical barriers (anatomical such as epithelial barrier and chemical such as enzymes)
commensal bacteria (occupy ecological niche)
immunological: following invasion (MALT and GALT)
epithelial barrier
Mucus layer - Goblet cells Epithelial monolayer - Tight junctions Paneth Cells (small intestine) Bases of crypts of Lieberkühn. Secrete Antimicrobial peptides (defensins) and lysozyme.
MALT
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
GALT
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)
Peyer’s patches- immune sensors
-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.
FAE characteristics
no goblet cells, no secretory IgA, lack microvilli.
M cells express what?
M cells expressIgA receptors, facilitating transfer of IgA-bacteria complexinto the peyer’s patches.
particulate antigen sampling uses?
Microfold cells
antigen sampling: trans-epithelial dendritic cells
B cell adaptive response
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
secretory IgA (sIgA)
Up to 90% of gut B-cells secrete IgA.
sIgA binds luminal antigen, thereby preventing its adhesion and consequent invasion.
GALT- T cell Homing
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.
cholera infection
-mechanism
- 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
cholera
-diagnosis & treatment
symptoms
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).
cholera
-transmission & symptoms
Transmitted through faecal-oral route, and spreads through contaminated water & food.
Main symptoms – Severe dehydration and diarrhoea (watery).
Other symptoms - vomiting, nausea & abdominal pain.
other causes of infectious diarrhea
viral (rotavirus)
protozoal parasitic (giardia lamblia)
bacterial (E coli, salmonella)
rotavirus
RNA virus
most common cause of diarrhoea in infants
oral rehydration therapy
live attenuated oral vaccine- rotarix
norovirus
RNA virus
sample PCR
acute gastroenteritis
faecal-oral transmission
campylobacter
Campylobacter jejuni, Campylobacter coli undercooked meat untreated water and unpasteurised milk low infective dose most common cause of food poisoning no treatment usually required
E coli
diverse group of gram negative intestinal bacteria, most harmless but ‘pathotypes’ associated with diarrhea
