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Immunology Of The Gut Flashcards

1
Q

Give 3 examples of antigens that the GI tract is exposed to

A

Resident bacteria
Dietary antigens
Exposure to pathogens

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2
Q

What is required for immune homeostasis and the development of a healthy immune system?

A

Presence of bacterial microbiota

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3
Q

Define the term ‘Microbiota’

A

Mixture/blend of microorganisms that makes up a community within an anatomical niche

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4
Q

Define the term ‘Microbiome’

A

Collective genomes of all of the microbiota, so in all of the different anatomical niches

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5
Q

Why is the GI Tract immune system in a state of ‘restrained activation’?

A

It balances tolerance of food antigens and commensal bacteria vs immunoreactivity against pathogens

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6
Q

What are gnotobiotic mice?

A

These are mice which have been colonized to be germ-free
They are used in experiments, e.g. to compare development of the immune system between germ-free and conventionally housed mice

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7
Q

What are the 4 major phyla of bacteria seen in the gut?

A

Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria

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8
Q

What functions of the gut microbiota make it useful for us humans?

A
  • Provide essential nutrients which we can’t make ourselves
  • Digest otherwise indigestible compounds
  • Defense against colonization by opportunistic pathogens
  • Contribute towards intestinal architecture
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9
Q

Describe how the environment provided by the host can lead to the stimulation or inhibition of the gut microbiota

A
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10
Q

In general, explain why bacterial content varies as you pass down the GI tract

A

Chemical digestive factors produced by the host impact viability of the bacteria to survive in different parts of the GI tract
Bacterial content increases as you pass down the GI tract - factors produced are less hostile to bacterial growth (or no DF produced - colon)

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11
Q

List the chemical digestive factors produced by the stomach, liver, pancreas, small intestine and colon respectively

A
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12
Q

What is Dysbiosis?

A

Altered microbiota composition

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13
Q

Define the term ‘Symbiont’

A

Lives with a host but no benefit/harm to either

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14
Q

Define the term ‘Commensals

A

Microorganisms that benefit from association with the host (nutrients) but don’t affect the host

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15
Q

Define the term ‘ Pathobiont’

A

Initially acts like a symbiont (doesn’t naturally produce an immune response) but under certain environmental conditions can produce dysregulated inflammation/disease

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16
Q

Describe the proportion of symbionts, commensals and pathobionts during a state of immunological equilibrium and immunological dysregulation

A
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17
Q

Give 5 factors that can either contribute to the maintenance of healthy microbiota or towards dysbiosis

A

1) Infection or inflammation
2) Diet
3) Xenobiotics
4) Hygiene
5) Genetics

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18
Q

Give 5 examples of metabolites and toxins which bacteria produce that can cause damage to body systems

A

TMAO
4-EPS
SCFAs (short-chain fatty acids)
Bile acids
AHR Ligands

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19
Q

What dysfunction can TMAO cause in the body?

A

TMAO = Trimethylamine N-oxide

Can cause atherosclerosis due to increased cholesterol deposition

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20
Q

What has 4-EPS been associated with?

A

4-EPS = 4-Ethylphenylsulfate

Increased levels are associated with autism

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21
Q

What are decreased numbers of SCFAs associated with?

A

SCFAs = Short-chain fatty acids

Decreased numbers of SCFAs are associated with Inflammatory bowel disease

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22
Q

What are increased numbers of SCFAs associated with?

A

Neuropsychiatric disorders such as stress

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23
Q

What are AHR ligands associated with?

A

AHR = Aryl hydrocarbon receptor

Increased AHR ligands are associated with MS, Rheumatoid arthritis and asthma

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24
Q

What three different groups make up the mucosal defense of the body?

A

Physical barriers
Commensal bacteria (occupy an ecological niche)
Immunological barriers

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25
Give an overview of the 2 types of physical barrier the body has towards microbes
Anatomical: - Epithelial barrier - Peristalsis Chemical: - Enzymes - Acidic pH
26
What are two important layers of the epithelial barrier?
Mucus Layer - produced by goblet cells Epithelial monolayer - with tight junctions in the middle
27
Where are Paneth cells found and what is their role?
Found in the bases of crypts of Lieberkühn in the small intestine Secrete antimicrobial peptides (defensins) and lysozyme
28
What are the 2 immunological defense mechanisms following invasion
MALT (Mucosa associated lymphoid tissue) GALT (Gut associated lymphoid tissue)
29
Where is MALT tissue particularly rich?
MALT is particularly rich within the oral cavity (the three tonsils - palatine, lingual and adenoid/pharyngeal) It is found in the submucosa below the epithelium as a lymphoid mass containing lymphoid follicles
30
How does the structure of MALT tissue assist its function?
Follicles are surrounded by HEV (high-endothelial venules) postcapillary venules, allowing easy passage of lymphocytes to the tonsils where they can defend against pathogens
31
What is GALT tissue responsible for?
Responsible for both adaptive and innate immune response
32
What does GALT consist of?
Consists of B and T Lymphocytes, macrophages, APC (dendritic cells) and specific epithelial and intra-epithelial lymphocytes
33
Give 2 examples of non-organized GALT tissue
Intra-epithelial lymphocytes - Make up 1/5th of intestinal epithelium, eg. T-cells, NK cells ( most common) Lamina propria lymphocytes
34
Give 4 examples of organized GALT tissue
Peyer’s patches (small intestine) Caecal patches (large intestine) Isolated lymphoid follicles Mesenteric lymph nodes (encapsulated)
35
Describe how the architecture of the bowel changes as you move through the gut?
Lymphocytes/ immune cells decrease Goblet cells/mucus-producing cells increase
36
What are Peyer’s patches?
Aggregated lymphoid follicles covered with follicle associated epithelium ( FAE) —> Found in submucosa of small intestine eg. mainly distal ileum Act as 'immune sensors'
37
What is special about FAE?
No goblet cells, no secretory IgA, lack microvilli Therefore no barrier to pathogens
38
Describe the growth of the Peyer’s patches from fetus to teenage years
Peyer’s patches contain an organized collection of naïve T cells and B cells Development requires previous exposure to bacterial microbiota Grows over time - 50 in last trimester as a foetus, 250 by teens
39
How do M cells carry out their function?
Antigen uptake occurs via these M (microfold cells) within FAE M cells express IgA receptors, facilitating transfer of IgA-bacteria complexes into the Peyer’s patches
40
Describe the role trans-epithelial dendritic cells play in the immunological response
Dendritic cells can get through tight junction proteins and send dendrites from the outside into the lumen of the intestinal tract where they directly sample bacteria They can then bring the bacteria back and transport them into mesenteric lymph nodes
41
Describe the B cell adaptive response
Pathogen uptake via M cell —> Excreted into pocket found on the inner surface of the enterocyte containing APCs —> APCs engulf pathogen and display on their surface using MHC II —> DCs migrate to Peyers patches (and some to mesenteric lymph nodes where they activate more lymphocytes) —>Mature naive B-cells express IgM in these Peyers patches but on antigen presentation switches to IgA -> B cells further mature to become IgA secreting plasma cells -> migrate to/populate lamina propria - T-cells and epithelial cells influence B cell maturation via cytokine production -
42
Describe the formation of secretory IgA within the lumen
Enzymatic cleavage within epithelial cells converts dimeric IgA into secretory IgA which is then released into the lumen
43
What is the function of sIgA?
Secretory IgA binds to luminal antigen, thereby preventing its adhesion and consequent invasion Up to 90% of gut B -cells secrete IgA
44
Describe lymphocyte homing and circulation
NB : BALT = bronchus associated lymphoid tissue
45
Describe alpha4beta7/ MADCAM-1 adhesion
Allows movement of lymphocytes from circulation back to lamina propria Lymphocyte expresses alpha4beta7 integrin High endothelial venule expresses MADCAM-1 Chemotactic stimulation of lymphocytes leads to rolling, then activation, then arrest and internalization into the lamina propria from blood
46
Why do enterocytes and goblet cells of the small bowel have such a short life-span (36 hours)?
- Enterocytes are first line of defense against GI pathogens & may be directly affected by toxic substances in diet. - Effects of agents which interfere with cell function, metabolic rate etc will be diminished. - Any lesions will be short-lived
47
What are 2 protozoal parasitic causes of infectious diarrhoea - Gastroenteritis?
Giardia lamblia - contaminated food or water, can also affect cats and dogs Entamoeba histolytica- tropical areas
48
What is Cholera and what agents is it caused by?
Cholera is an acute bacterial disease caused by vibrio cholerae serogroups O1 and O139
49
Describe the mechanism of Cholera infection
Bacteria reaches small intestine —> makes contact with epithelium and releases cholera enterotoxin It is internalised by retrograde endocytosis Increases adenylate cyclase activity -> increased cAMP production Activates CFTCR causing active secretion of Na+, Cl-, HCO3-, K+ and subsequently water (causing diarrhoea and dehydration)
50
How is cholera transmitted?
Faecal-oral route Spreads via contaminated water and food
51
What are the main symptoms of cholera?
Main: Severe dehydration and watery diarrhoea Other: Vomiting, nausea and abdominal pain
52
What investigations do you need to do to reach a diagnosis of cholera?
Bacterial culture from stool sample on selective agar is the gold standard Rapid dipstick is also available
53
What is the treatment of cholera?
Oral rehydration therapy is the main management; up to 80% of cases can be treated successfully
54
Is there a vaccine for cholera?
Yes, Dukoral (oral, inactivated)
55
Name two types of virus associated with infectious diarrhoea?
Rotavirus (children) Norovirus
56
Name five other bacteria associated with infectious diarrhoea?
Campylobacter jejuni Escherichia coli Salmonella Shigella Clostridium difficile
57
What class of viruses are the most common cause of diarrhoea in infants and young children worldwide?
Rotaviruses
58
Describe rotaviruses and which one is the most common in humans?
RNA Virus, replicates in enterocytes 5 types A-E, type A most common in human infections
59
What is the treatment for a rotavirus infection?
Oral Rehydration Therapy Before vaccine, most individuals had an infection by age 5, repeated infections develop immunity
60
Is there a vaccine for this virus?
Live attenuated oral vaccine (Rotarix) against type A introduced in UK July 2013
61
What type of virus is Norovirus?
It is an RNA virus with an incubation period (time between exposure and when symptoms apparent) of 24-48 hours
62
What is method of transmission for Norovirus?
Faecal-oral transmission. Individuals may shed infectious virus for up to 2 weeks Outbreaks often occur within closed communities ( eg. Cruise ships)
63
What are some symptoms of norovirus and what treatment is usually offered to patients?
Acute gastroenteritis, diarrhoea, recovery occurs within 1-3 days Tx is not usually required.
64
How would you diagnose a norovirus infection?
Sample PCR
65
What is the method of transmission for Campylobacter and is a high infective dose required to cause illness?
Undercooked meat (especially poultry), untreated water and unpasteurized milk Low infective dose, a few bacteria <500 can cause illness
66
What is the treatment for Campylobacter?
Not usually required Again, oral rehydration therapy Azithromycin (macrolide) is standard antibiotic Resistance to Fluoroquinolones is problematic
66
What is the treatment for Campylobacter?
Not usually required Again, oral rehydration therapy Azithromycin (macrolide) is standard antibiotic Resistance to Fluoroquinolones is problematic
67
What are the 6 pathotypes of E.coli that are associated with diarrhoea?
1) Enterotoxigenic E.Coli ( ETEC) - Cholera like toxin - Watery diarrhoea 2) Enterohaemorrhagic or shiga-toxin producing E.Coli ( EHEC/STEC) - E.Coli 0157 serogroup, Shigatoxin/verotoxin - 5-10% get haemolytic uraemic syndrome : loss of kidney function. Therefore, this is the most worrying one. 3) Enteroinvasive E.Coli ( EIEC) - Shigella like illness - BLOODY diarrhea 4) Enteropathogenic E.Coli (EPEC) 5) Enteroaggregative E.Coli ( EAEC) 6) Diffusely adherent E.Coli (DAEC)
68
Do E.Coli species usually cause problems?
Most are harmless Usually there but don't cause problems
69
Is E.Coli gram positive or negative?
Gram-negative intestinal bacteria
70
How would you manage a patient who has a C.Diff. infection?
- Isolate patient (very contagious) - Stop current antibiotics - Give them Metronidazole and Vancomycin (but be cautious, as these can pre-dispose the pt to further C.Diff infections as well!) - Fecal Microbiota Transplantation (FMT) – 98% cure rate Recurrence rate 15-35% after initial infection, increasingly difficult to treat NB : Paradoxically Metronidazole can give you C.diff as well!

BRS Flashcards (Y2) (79 decks)

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