Gut Immunology Flashcards by Meley Gdey

surface area of the GI tract

200m^2

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antigen load of the GI tract

massive antigen load
resident microbiota
dietary antigens
exposure to pathogens

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GI state ‘restrained activation’

tolerance vs active immune response

dual immunological role

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GI has tolerance for?

food antigens

commensal bacteria

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GI has immunoreactivity to?

pathogens

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is the presence of the bacterial microbiota required?

yes

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what makes up the gut microbiota?

4 major phyla of bacteria: bacteroidetes, firmicutes, actinobacteria, proteobacteria
viruses
fungi

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what is dysbiosis?

altered microbiota composition

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causes of dysbiosis

infection and inflammation
diet
xenobiotics
hygiene
genetics

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disease development of dysbiosis - brain

stress
autism
MS

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disease development of dysbiosis - lung

asthma

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disease development of dysbiosis - liver

NAFLD

NASH

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disease development of dysbiosis - adipose tissue

obesity

metabolic disease

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disease development of dysbiosis - intestine

IBD

coeliac disease

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disease development of dysbiosis - systemic

T1DM
atherosclerosis
rheumatoid arthritis

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anatomical physical barriers to pathogens in GI tract

epithelial barrier

peristalsis

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chemical physical barriers to pathogens in GI tract

enzymes

acidic pH

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immunological barriers to pathogens in GI tract

following invasion
MALT
GALT

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epithelial barrier is made up of?

mucus layer - goblet cells
epithelial monolayer - tight junctions
Paneth cells - bases of crypts, secrete antimicrobial peptides (defensins) and lysozymes

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how do commensal bacteria act as mucosal defense?

occupy ecological niche

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where is MALT found?

Found in the submucosa below the epithelium, as lymphoid mass containing lymphoid follicles

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follicles in MALT are surrounded by?

HEV postcapillary venules, allowing easy passage of lymphocytes

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what cavity is rich in immunological tissue?

oral

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GALT consists of what?

Consists of B & T lymphocytes, macrophages, APC (dendritic cells), and specific epithelial & intra-epithelial lymphocytes

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GALT - non-organised

intraepithelial lymphocytes e.g. T cells, NK cells | lamina propria lymphocytes

GALT - organised

Peyer's patches (small intestine) Caecal patches (large intestine) Isolated lymphoid follicles Mesenteric lymph nodes (encapsulated)

where are Peyer's patches found?

submucosa small intestine mainly distal ileum

peyer's patches consist of?

Aggregated lymphoid follicles covered with follicle associated epithelium (FAE)

what is not included in FAE (follicle associated epithelium)?

goblet cells secretory IgA microvilli

peyer's patches have an organised collection of what cells?

naive T cells | B cells

development of the Peyer's patches requires what?

exposure to bacterial microbiota

how does antigen uptake occur in peyer's patches?

via M (microfold) cells within FAE

M cells express what receptors?

IgA receptors

expression of IgA receptors on cells facilitates what?

uptake of IgA-bacteria complex in the Peyer's patches

mature naive B cells express which immunoglobulin on its surface in Peyer's patches?

IgM

when does the immunoglobulin on the surface of mature naive B cells switch class? to what?

on antigen presentation | IgA

what cells influence B cell maturation and via what?

T cells and epithelial cells | via cytokines

B cells can further mature into?

IgA secreting plasma cells

what cells secrete IgA?

90% of gut B cells

what does secretory IgA do?

binds luminal antigen > prevents adhesion and consequent invasion

formation of secretory IgA

plasma cell in submucosa secretes dimeric IgA > binds to polyIg receptor > enters cell in vesicle w/ receptor > enzymatic cleavage > secretory IgA

lymphocyte homing and circulation

Peyer's patch (antigen presentation and activation) > mesenteric lymph node (lymphocyte proliferation) > thoracic duct > circulation > lamina propria/skin, tonsils, BALT

𝝰4β7 Integrin/MAdCAM-1 Adhesion is a crucial pathway for?

B cell migration

why is the turnover of enterocytes so rapid?

lesions are short lived, effects of agents that interfere w/ cell fx, metabolic rate is diminished, enterocytes maybe directly affected by toxic substances in diet

what is cholera?

acute bacterial disease caused by Vibrio cholerae serogroups O1 & O139

mechanism of cholera

Bacteria reaches small intestine > contact with epithelium & releases cholera enterotoxin

transmission of cholera

faecal oral route | spreads via contaminated water and food

main symptoms of cholera

``` severe dehydration watery diarrhoea vomiting nausea abdominal pain ```

diagnosis of cholera

bacterial culture from stool sample on selective agar is the gold standard, rapid dipstick tests also available

treatment of cholera

oral-rehydration is the main management | vaccine (Dukoral, oral, inactivated)

viral causes of infectious diarrhoea

rotavirus (children) | norovirus (winter vomiting virus)

protozoal/parasitic causes of infectious diarrhoea

Giardia lamblia | Entamoaeba histolytica

bacterial causes of infectious diarrhoea

``` Campylobacter jejuni E.coli Salmonella Shigella Clostridium difficile ```

description of rotaviruses

RNA virus, replicates in enterocytes. | 5 types A – E, type A most common in human infections

epidemiology of rotavirus

Most common cause of diarrhoea in infants & young children worldwide

treatment of rotavirus

Oral rehydration therapy

vaccine against rotavirus

Live attenuated oral vaccine (Rotarix) against type A

description of norovirus

RNA virus | Incubation period 24-48 hours

transmission of norovirus

Faecal-oral transmission. Individuals may shed infectious virus for up to 2 weeks Outbreaks often occur in closed communities

symptoms of norovirus

Acute gastroenteritis, recovery 1 – 3 days

treatment of norovirus

not usually required

diagnosis of norovirus

sample PCR

most common species of campylobacter

campylobacter jejuni | campylobacter coli

transmission of campylobacter

``` Undercooked meat (especially poultry), untreated water & unpasteurised milk Low infective dose, a few bacteria (<500) can cause illness ```

treatment of campylobacter

Not usually required | Azithromycin (macrolide) is standard antibiotic

what is problematic in the treatment of campylobacter infections?

resistance to fluoroquinolones

campylobacter infection is the commonest cause of what illness in the UK?

food poisoning

description of E.coli

Diverse group of Gram-negative intestinal bacteria

how many pathotypes of E.coli are associated with diarrhoea?

list pathotypes of E.coli are associated with diarrhoea

``` Enterotoxigenic E. coli (ETEC) Enterohaemorrhagic or Shiga toxin-producing E. coli (EHEC/STEC) Enteroinvasive E. coli (EIEC) Enteropathogenic E. coli (EPEC) Enteroaggregative E. coli (EAEC) Diffusely adherent E. coli (DAEC) ```

Enterotoxigenic E. coli (ETEC) causes what? has what type of toxin?

Cholera like toxin | Watery diarrhoea

Enteroinvasive E. coli (EIEC) causes what?

Shigella like illness | Bloody diarrhea

5-10% of people with Enterohaemorrhagic or Shiga toxin-producing E. coli (EHEC/STEC) have what negative consequence?

haemolytic uraemic syndrome > loss of kidney function

management of clostridium difficile

isolation, stop current antibiotics, Metronidazole, Vancomycin, faecal microbiota transplantation

recurrence rate of clostridium difficile after initial infection

15-35%