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BRS 1b > Immunology of the Gut > Flashcards

Immunology of the Gut Flashcards

1
Q

What is the definition of gut microbiota?

A

The gut microbiome is a community of commensal organisms that are found within the gastrointestinal tract.

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2
Q

What are the four major phyla of commensal bacteria?

A
  1. Bacteroidetes
  2. Firmicutes
  3. Actinobacteria
  4. Proteobacteria
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3
Q

Which region of the GI tract has the greatest bacterial content?

A

Colon - due to the absence of digestive host factors (pancreatic enzymes, bile acids and acid)

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4
Q

Why is there restricted bacterial load in the stomach?

A

Due to acidic pH (1-4)

Pepsin - digestive enzymes

Gastric lipase

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5
Q

Which digestive factor is produced by the liver, reducing the bacterial load in the duodenum?

A

Bile acids

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6
Q

What is dysbiosis?

A

Dysbiosis refers to a reduction in microbial diversity, especially in the incumbent commensal organisms that colonise the gastrointestinal tract, and a rise in pathobionts – there is an imbalance in the immunological equilibrium.

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7
Q

What is a pathobiont?

A

• Pathobionts are symbiotic bacteria that have become pathogenic under specific conditions.

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8
Q

What is a symbiont?

A

• A symbiont is an organism that interacts with the host such that there is a mutual benefit.

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9
Q

What are the main causes of dysbiosis?

A 
Infection or inflammation 
Diet
Xenobiotics
Hygiene
Genetics
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10
Q

What is the bacterial metabolite, TMAO?

A

• TMAO (Trimethylamine N-oxide) – Alters cholesterol metabolism in the intestine – there is an increased deposition of cholesterol within the artery walls, potentiating the development of atherosclerosis.

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11
Q

Which junctions hold the epithelial monolayer together?

A

Tight junctions- minimising the available space to which toxins can pass through

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12
Q

Which cells secrete mucin, forming a protective mucous layer, in the gut?

A

Goblet cells

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13
Q

What function is performed by goblet cells in the gut, in terms of immunology?

A

• Mucosal goblet cells secrete mucin forming a protective mucous layer that promotes immunological clearance to limit inflammation and infection.

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14
Q

What happens to the distribution of goblet cells within the small intestine?

A

progressively increase

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15
Q

Which part of the small bowel has the greatest proportion of goblet cells?

A

Ileum

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16
Q

Where do Paneth cells reside?

A

• Paneth cells reside within the base of the crypts of Lieberkühn and secrete antimicrobial peptides (defensins) and lysozyme.

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17
Q

What function is performed by Paneth cells?

A

Secrete anti-microbrial peptides (defensins) and lysozyme.

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18
Q

What effect do defensins have?

A

Defensins increase membrane permeability.

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19
Q

What is MALT?

A

Mucosa Associated Lymphoid Tissue (MALT)

Found within the submucosa below the epithelium, as a lymphoid mass that contains lymphoid follicles.

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20
Q

Which types of venules surround lymphoid follicles?

A

HEV - post capillary venules- allowing for the easy passage of lymphocyte migration into the tissue

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21
Q

What are pharyngeal tonsils?

A

• Pharyngeal tonsils refer to a collection of lymphoid tissue within the mucosa of the roof to the nasopharynx (referred to adenoids when enlarged)  Forms Waldeyer ring.

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22
Q

Which zones are located within MALT?

A

Distinct B and T-cell zones

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23
Q

Which lymphoid structures are the first line of defence for pathogens entering the nasopharynx or oropharynx?

A

Pharyngeal tonsils (palatine and lingual)

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24
Q

What are secondary lymphoid organs?

A

Secondary lymphoid organs are sites at which lymphocytes interact with antigen-presenting cells (dendritic cells) bearing antigens from peripheral tissues and differentiating into effector and memory cells that eliminate antigen.

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25
Q

Which lymphoid structures are classified as GALT?

A

Peyer’s patches

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26
Q

Where are Peyer’s patches predominantly found?

A

Within the small bowel

27
Q

Which immune cells are associated with Peyer’s patches?

A

B and T lymphocytes, macrophages, dendritic cells and intra-epithelial lymphocytes

28
Q

What are intra-epithelial lymphocytes?

A

NK cells analogues

29
Q

What happens in germinal centres within Peyer’s patches?

A

B-cells undergo mutation and selection - generating high affinity antibodies by somatic hypermutation and class-switch recombination

30
Q

Which immune cell forms 20% of the intestinal epithelium?

A

Intra-epithelial lymphocytes

31
Q

Which organised GALT centres are found in the small intestine?

A

Peyer’s patches

32
Q

Which organised GALT centres are found within the large intestine?

A

Caecal patches

33
Q

What are the two main differences, immunologically between the small and large intestine?

A

Absence of villi, and paneth cells within the large bowel in comparison to the small bowel.

There is a greater distribution of IEL and goblet cells in the large bowel.

34
Q

Which epithelial cells are associated with Peyer’s patches?

A

Follicle associated epithelium (FAE)

35
Q

What is essential for the development of functional Peyer’s patches?

A

• Development requires exposure to bacterial microbiota (50 in last trimester foetus, 250 by teens).

36
Q

how do B-cells undergo antibody affinity maturation in Peyer’s patches?

A

Exposed to antigens presented by dendritic cells to generate IgA gut-specific secreting plasma cells

37
Q

Which type of gut-specific secreting plasmas cells are produced by Peyer’s patches?

A

IgA

38
Q

How are antigens taken up into Peyer’s patches?

A

M (micro-fold) cells within FAE, which express IgA receptors

39
Q

Which type of receptor is expressed by M-cells?

A

IgA

40
Q

What function is performed by M-cells?

A

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

41
Q

What are FAE?

A

Specialised epithelial cells surrounding Peyer’s patches – absent of goblet cells, no secretory IgA or microvilli.

42
Q

What class switch occurs upon the interaction between antigen-presenting cells and B cells?

A

IgM to IgA

43
Q

What type of IgA is secreted from plasma cells?

A

Dimeric IgA which binds to poly-Ig receptors on the basal surface on epithelial cells and are internalised and proceeded within the cells before being secreted as secretory IgA

44
Q

How do dendritic cells gain access to the gastrointestinal lumen?

A

Interfere with tight junction proteins in order to gain access to the lumen, dendrites interact with antigens - transported to the mesenteric lymph node to activate B and T cell lymphocytes

45
Q

How are activated lymphocytes transported into mesenteric lymph nodes?

A

Mucosal addressin cell adhesion molecule 1 (MAdCAM1) is tissue specific and is presented by endothelial cells within the high endothelial venule.
• MAdCAM1 interacts with 𝝰4β7 integrins expressed by lymphocytes.
• Adhesion to the endothelium elicits transmigration into the lamina propria.

46
Q

Which tissue-specific molecule supports lymphocyte homing?

A

MAdCAM1

47
Q

How do cholera enterotoxins cause toxicity?

A

Binds to GM-1 receptors that irreversibly stimulates the intracellular enzyme adenylate cyclase, potentiating the action at which ADP decomposes into cAMP- an intracellular molecule

  • Increased chloride secretion and inhibition of sodium chloride resorption increases intestinal lumen solute concentrations – promotes release of water into the lumen (movement of water along a water potential gradient).
  • Serogroups O1 & O139
  • Enterotoxins are released when the bacteria reach contact with the epithelium.
48
Q

How is cholera transmitted?

A

• Transmitted through faecal-oral route – and spreads via contaminated water & food.

49
Q

What are the symptoms of cholera?

A
  • Severe watery diarrhoea
  • Vomiting
  • Nausea
  • Abdominal pain
50
Q

How is a cholera diagnosis made?

A

Bacterial culture from stool sample, grown on selective agar – rapid dipstick tests are also available, although a stool sample is first line.

51
Q

What is the main treatment for cholera?

A

Oral rehydration solution for diarrhoea associated symptoms

52
Q

What type of virus is rotavirus?

A

RNA viruses that lyrically replicates within enterocytes existing as 5 serotypes (A-E), with type A rotavirus being most prevalent in human infections.

53
Q

How many serotypes are there for rotavirus?

A

5 serotypes (A-E)

54
Q

Which serotype of rotavirus is most prevalent?

A

Type A rotavirus

55
Q

What is the treatment for rotavirus?

A

Oral rehydration therapy

56
Q

What type of vaccine is administered as prophylaxis for rotavirus?

A

• Live attenuated oral vaccine (Rotarix) against type A introduced in July 2013 – saw a significant reduction in cases within the UK.

57
Q

What type of virus is norovirus?

A

An RNA virus with an incubation of 24-48 hours.

58
Q

What is the transmission of norovirus?

A
  • Faecal-oral transmission
  • Individuals may shed infectious virus for up to 2 weeks
  • Outbreaks are common within closed communities.
59
Q

What are the symptoms of norovirus?

A

Acute gastroenteritis – recovery 1-3 days.

60
Q

how is a diagnosis made for norovirus?

A

Sample PCR

61
Q

How is campylobacter transmitted?

A
  • Undercooked meat (especially poultry), untreated water & unpasteurised milk
  • Low infective dose, a few bacteria (<500) can cause illness.
62
Q

Which standard antibiotic is administered to patients with a campylobacter infection?

A

Azithromycine (Marcolide)

63
Q

What is the number of pathotypes that exist for e.coli?

A

6

64
Q

What is the risk of E.coli 0157?

A

Haemolytic uraemic syndrome

BRS 1b (62 decks)

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