Immunology Of The Gut Flashcards

1
Q

GI tract

A
  • surface area of 200m squared
  • Massive antigen load
  • 10^14 resident bacteria in the microbiota
  • State of restrained activation
    Dual immunological role - tolerance vs active immune response (tolerance would be food antigens and commensal bacteria) (immune reactivity would be pathogens)
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2
Q

What did germ free mice show

A

maldevelopment of small intestine
- fewer Peyer’s patches
- angiogenin 4 expressed less

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3
Q

4 Major phyla of bacteria

A

Bacteroidetes, firmicutes, actinobacteria, proteobacteria
Provide traits we have not had to evolve individually
Genes in gut flora 100 times our own genome

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4
Q

Dysbiosis

A

Symbionts regulate
Pathobionts cause inflammation
Commensals do not effect the equilibrium

Xenobiotics - small chemical compounds that enter unnaturally - drugs, pollutants

Dysbiosis is related to a multitude of disorders, including autism (4-EPS), cancers (short chain fatty acids), pancreatic diseases (bile acids)

Cancer development may also include overgrowth of certain biota - so cancer patients may be given probiotics

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5
Q

Mucosal defenses physical barrier

A
  • Epithelial barrier
    1. Mucus layer - goblet cells
    2. Epithelial monolayer - tight junctions
    3. Paneth cells (in small intestine)
      - At the base of the crypts of Lieberkuhn
      - Secrete antimicrobial peptides (defensins) & lysozyme
  • Peristalsis
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6
Q

Chemical mucosal defense

A

Enzymes
Ph

Commensal bacteria occupy an ecological niche

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7
Q

Immunological barriers

A

MALT (Mucosa Associated Lymphoid Tissue)

GALT (Gut Associated Lymphoid Tissue)

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8
Q

MALT (Mucosa Associated Lymphoid Tissue)

A
  • Found in submucosa below the epithelium, as lymphoid mass containing lymphoid follicles
  • Follicles are surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes
  • Oral cavity rich in this tissue
    HEVs are found in lymph nodes and other secondary lymphoid organs but not in the spleen
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9
Q

GALT (Gut Associated Lymphoid Tissue)

A
  • Responsible for both adaptive and innate immune responses through generations of lymphoid cells and Abs
    1. Non organised
  • Intra-epithelial lymphocytes - make up 20% of intestinal epithelium, such as T cells and NK cells
  • Lamina propria lymphocytes
  • Less surface area in large intestine so more Ig-A secretion
    2. Organised
  • Peyer’s patches (small intestine)
  • Caecal patches (large intestine)
  • Isolated lymphoid follicles
  • Mesenteric lymph nodes (encapsulated)
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10
Q

Peyer’s patches:

A

Act as immune sensors
Mainly found in the distal ileum

Aggregated lymphoid follicles covered with follicle associated epithelium (FAE)

FAE - no goblet cells. no secretory IgA, lack microvilli

Organised collection of naive T and B cells
Development requires exposure to bacterial microbiota
- 50 in last trimester of pregnancy, 250 by teens

Antigen uptake via M (microfold) cells within the FAE
- M cells express IgA receptors, and facilitate transfer of IgA bacteria complex into the Peyer’s patches

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11
Q

Antigen sampling

A

Trans-epithelial dendritic cells capture an antigen from beyond the epithelial barrier, and then relocate to the mesenteric lymph nodes

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12
Q

B cell Adaptive Response

A
  • Mature naive B cells express IgM
  • This switches to IgA on antigen presentation
  • T-cells and epithelial cells secrete cytokines which influence B cell maturation
  • B cells further mature and become IgA secreting plasma cells
  • These populate the lamina propria

Formation of Secretory IgA (sIgA)

  • Up to 90% of gut B cells secrete IgA
  • sIgA binds the luminal antigen to prevent adhesion and therefore invasion
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13
Q

Lymphocyte homing and circulation

A

Peyer’s patches - antigen presented and activated

Travels to mesenteric lymph node (lymphocyte proliferation)

This goes to the thoracic duct, into circulation

It can then go back to lamina propria, or skin, tonsils, or BALT

Tight junctions formed of a4b7 integrins where T cells bind causing cytokine release and MAdCAM-1s which causes cell adhesion . Directs circulating T cells to peyers patch to mount response

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14
Q

What is the life span of enterocytes and goblet cells of the small bowel?

A

36 hours

  • Enterocytes are the first line of defence against GI pathogens, may be directly affected by toxins
  • This means diminishing the effects of agents which interfere with cell function
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15
Q

Cholera

A

Caused by Vibrio cholerae serogroups O1 and O139
Releases cholera enterotoxin on contact with small intestine epithelium which causes increased adnelytate cyclase activity this increased water pump activity
Transmitter via faecal oral route, contaminated food and water
Main symptoms - diarrhoea, dehydration, vomiting, abdominal pain

Diagnosis: Bacterial culture taken from faecal sample on selective agar, or dipstick test may be performed

Treatment: Oral rehydration

Dukoral - oral, inactivated vaccine against the pathogen - useful where there is a lack of clean water

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16
Q

Gastroenteritis

A
  • ViralRotavirus (children)Norovirus (Winter vomiting bug)
  • Protozoal parasiticGiardia lambliaEntamoeba histolytica
  • BacterialCampylobacter jejuniEscherichia coliSalmonellaShigellaClostridium difficile
17
Q

Rotaviruses

A

RNA virus, replicating in enterocytes

Types A-E, with A causing most human infections

Most common cause of diarrhoea in infants and young children

Still causes around 200,000 deaths per year

Treated with oral rehydration therapy

Rotarix - attenuated oral vaccine against type A, intoduced in UK in July 2013

18
Q

Norovirus

A

RNA virus

Incubation period of 24 to 48 hours

Faecal-oral transmission

Individuals may shed infectious virus for up to 2 weeks

Diagnose via sample pcr

Outbreaks often occur in closed communities - especially cruise ships

Symptoms - Acute gastroenteritis, recovery in 1-3 days

685 million cases per year, 200,000 deaths

19
Q

Campylobacter

A
  • Campylocbacter jejuni / coli most common
  • Transmitted via undercooked meat, untreated water & unpasteurised milk
  • Low infective dose, less than 500 can cause illness
  • Treatment usually isn’t necessary, azithromycin may be used as a standard antibiotic resistance to fluoroquinolones problematic
  • Estimated 280,000 causes per year in UK
  • Commonest cause of food poisoning in UK
20
Q

Escherichia coli

A
  • Mostly harmless
  • 6 “pathotypes” associated with diarrhoea
    -Enterotoxigenic E coli - causes watery diarrhoea
    -Enterohaemorrhagic or Shiga toxin-producing E. Coli (EHEC/STEC) - 5-10% get haemolytic
  • uraemic syndrome, loss of kidney function
    -Enteroinvasive E. coli (EIEC) - causes bloody diarrhoea
    -Enteropathogenic E. coli (EPEC)
    -Enteroaggregative E. coli (EAEC)
    -Diffusely adherent E. coli (DAEC)
21
Q

Clostridium difficile

A

Management:

  • Isolate patient
  • Stop current Abs
  • Metronidazole, vancomycin
  • Recurrence rate of 15-35% after initial infection, gets increasingly difficult to treat
  • Faecal Microbiota Transplantation (FMT) - 98% cure rate

Toxin by-products (inflammatory metabolites) may be used to help determine C dif

22
Q

Clinical assessment

A
  • When did it start?
    -may suggest contaminated food (S. aureus, Salmonella, E. coli, Bacillus cereus toxin, norovirus)
  • What does it look like?
    -Amount, consistency, frequency
    -Blood, mucus, pus suggests severe inflammatory or infectious cause
    -Mucus and pus indicate a chronic inflammatory cause
  • How do you feel?
    -Pain, bloating, nausea, vomiting, fever, tenesmus
    -Thirsty, no appetite
  • Where have you been recently?
    -Recent travel or consumption of food (meat, eggs, dairy, seafood) indicates infection
    -Exposure to pets or cattle indicates infection
    -Working in day care centres, hospitals or care homes indicates infection
    -Social history, including sexual practice, alcohol or drug use
    -IBD, coeliac, IBS
23
Q

What does ingested nutrients,secreted nutrients, chemical digestive factors and peristalsis/contraction cause

A

Ingested and secreted nutrients contribute to bacterial growth causing an increase in cell numbers

Chemical digestive factors and peristalsis contractions/defecation eliminate bacteria thus decreasing cell numbers Chemical

24
Q

Symbionts

A

Organism that loves with a history without benefit or harm to either

25
Q

Commensalism

A

A microorganism that benefits from association but has no known effects on host

26
Q

Pathobiont

A

Symbiont that doesn’t normally elicit an inflammatory response but under particular conditions (usually environmental) has potential to cause dysrefllated inflammation and disease

27
Q

Gnotobiology

A

Selective colonization of germ free animals

28
Q

Importance of HEV

A

Immune surveillance allowing to identify foreign invaders such as neoantigens in cancer
Lymphocyte recirculation so supports high levels of lymphocyte extravasation from the blood
And helps initiate and maintain immune response in lymph nodes