Gut Immunology Flashcards
Describe GI tract immunology
Has a massive antigen load (resident microbiota, dietary antigen and exposure to pathogens). In a state of restrained activation as dual immunological role (tolerance vs active immune response) as immune homeostasis of gut & development of healthy immune system requires presence of bacterial microbiota.
Describe the microbiota of the gut
4 major phyla of bacteria (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria), also viruses & fungi. These provide traits we have not evolved ourselves - genes in gut flora 100 times our own.
Describe immunological equilibrium
Symbionts responsible for regulation, commensals balance and pathobionts lead to inflammation.
What is dysbiosis and what are its causes?
When there is an altered microbiota composition in the gut leading to adverse effects. Infection or inflammation, diet, xenobiotics, hygiene and genetics can all influence the balance between healthy microbiota and dysbiosis.
What are the consequences of dysbiosis?
Brain (Stress, Autism, Multiple Sclerosis), Lung (Asthma), Liver (NAFLD, NASH), Adipose tissue (Obesity, Metabolic disease), Intestine (IBD, Coeliac disease) and Systemic diseases (T1 diabetes, Atherosclerosis, Rheumatoid Arthritis).
What bacterial metabolites and toxins induce the adverse effects of dysbiosis?
TMAO, 4-EPS, SCFAs, bile acids and AHR ligands.
Describe mucosal defense
Anatomical: Epithelial barriers and peristalsis
Chemical: Enzymes and acidic pH
Immunological: MALT (mucosal-associated lymphoid tissue) and GALT (gut-associated lymphoid tissue)
Epithelial barrier: Mucus layer (goblet cell), epithelial monolayer (tight junctions), Paneth cells (small intestine)
Where are Paneth cells found and what is their role?
Bases of crypts of Lieberkühn.
Secrete antimicrobial peptides (defensins) & lysozyme.
Where is MALT found?
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.
What is GALT responsible for?
Responsible for both adaptive & innate immune responses. Consists of B & T lymphocytes, macrophages, APC (dendritic cells), and specific epithelial & intra-epithelial lymphocytes.
What are organised and non-organised GALT?
Non-organised
Intra-epithelial lymphocytes - Make up 1/5th of intestinal epithelium, e.g. T-cells, NK cells
Lamina propria lymphocytes
Organised Peyer’s patches (small intestine) Caecal patches (large intestine) Isolated lymphoid follicles Mesenteric lymph nodes (encapsulated)
Where are Peyer’s patches found?
Found in submucosa small intestine – mainly distal ileum. Aggregatedlymphoid follicles covered with follicle associated epithelium (FAE). FAE has no goblet cells, no secretory IgA, no microvilli.
What are Peyer’s patches?
Organised collection of naïve T cells & B-cells. Development requires exposure to bacterial microbiota. Antigen uptake via M (microfold) cells within FAE. M cells expressIgA receptors, facilitating transfer of IgA-bacteria complexinto the Peyer’s patches.
Describe B cell adaptive response
Mature naïve B-cells express IgM in Peyer’s Patches. On antigen presentation class switches to IgA. T-cells & epithelial cells influence B cell maturation via cytokine production. B cells further mature to become IgA secreting plasma cells. Populate lamina propria.
What is the mechanism of cholera infection?
Cholera -acute bacterial disease caused by Vibrio cholerae serogroups O1 & O139. Bacteria reaches small intestine, contactswith epithelium & releasescholera enterotoxin.
How does cholera transmission work?
Transmitted through faecal-oral route. Spreads via contaminated water & food.
Main symptoms: Severe dehydration & watery diarrhoea
Other symptoms: Vomiting, nausea & abdominal pain.
Describe diagnosis and treatment of cholera
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.
What is the vaccination for cholera?
Vaccine: Dukoral, oral, inactivated.
Globally 1.3 - 4 million cases, avg. 95,000 deaths/year
What are other causes of infectious diarrhoea?
Viral
Rotavirus (children)
Norovirus
Bacterial Campylobacter jejuni Escherichia coli Salmonella Shigella Clostridium difficile
Protozoal parasitic
Giardia lamblia
Entamoeba histolytica
Describe rotaviruses and epidemiology
RNA virus, replicates in enterocytes. 5 types A – E, type A most common in human infections.
Most common cause of diarrhoea in infants & young children worldwide.
What is treatment for rotaviruses?
Oral rehydration therapy
Still causes ~ 200,000 deaths/year.
Before vaccine, most individuals had an infection by age 5, repeated infections develop immunity.
What is the vaccination programme against rotaviruses?
Live attenuated oral vaccine (Rotarix) against type A introduced in UK July 2013.
Describe norovirus, its transmission route and symptoms
RNA virus, Incubation period 24-48 hours.
Transmission: Faecal-oral transmission. Individuals may shed infectious virus for up to 2 weeks. Outbreaks often occur in closed communities
Symptoms: Acute gastroenteritis, recovery 1 – 3 days
What is the treatment, diagnosis and epidemiology of norovirus
Treatment: Not usually required
Diagnosis: Sample PCR
Epidemiology: Estimated 685 million cases per year.
What are most common species of campylobacter and how is it transmitted?
Campylobacter jejuni, Campylobacter coli. Transmitted by undercooked meat (especially poultry), untreated water & unpasteurised milk. Low infective dose, a few bacteria (<500) can cause illness.
Describe treatment and epidemiology of campylobacter
Treatment: Not usually needed. Azithromycin (macrolide) is standard antibiotic. Resistance to fluoroquinolones is problematic.
Epidemiology: Estimated 280,000 cases per year in UK, 65,000 confirmed. Commonest cause of food poisoning in the UK.
What are the 6 pathotypes of E.Coli?
- Enterotoxigenic E. coli (ETEC) - Cholera like toxin, watery diarrhoea
- Enteroinvasive E. coli (EIEC) - Shigella like illness, bloody diarrhea
- 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
- Enteropathogenic E. coli (EPEC)
- Enteroaggregative E. coli (EAEC)
- Diffusely adherent E. coli (DAEC)
How is clostridium difficile managed?
Isolate patient (very contagious)
Stop current antibiotics
Metronidazole, Vancomycin
Recurrence rate 15-35% after initial infection, increasingly difficult to treat.
Faecal Microbiota Transplantation (FMT) – 98% cure rate
