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Alimentary system > 8. Infection & immunology of the gut > Flashcards

8. Infection & immunology of the gut Flashcards

1
Q

Why does the GI tract always needs to be in a state of “restrained activation”?

A

Needs to display tolerance to dietary antigens and resident microbiota
At the same time it needs to have an active response against pathogenic bacteria

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2
Q

Why is gut microbiota essential?

A

It plays a key role in development of immune system

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3
Q

What determines distribution of microbiota through the gut?

A

Combination of factors:
Increased: ingested nutrients, secreted nutrients
Decreased: chemical digestive factors, peristalsis contractions, defecation

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4
Q

Where is the majority of gut microbiota?

A

Colon

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5
Q

What are the 3 categories of organisms in microbiota?

A

Symbionts: Takes some nutrients but also provide some nutrients and helps regulate/ immune system
Commensals: Occupy space in gut, prevent adhesion and invasion of pathogens
Pathobionts: capable of causing inflammation

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6
Q

What happens when the balance of the 3 types of microbiota is altered?

A

Dysequilibrium: Leads to inflammation

Harmful bacteria produce metabolites and toxins which are associated with various diseases

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7
Q

List 5 causes of dysbiosis

A 
Infection/ Inflammation
Diet
Xenobiotics
Poor hygiene 
Genetics
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8
Q

What are the physical barriers of defence in the gut?

A

Anatomical (epithelial barrier, peristalsis)

Chemical (Enzymes, acidic pH)

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9
Q

Describe the epithelial barrier in the gut

A 
Epithelial monolayer of gut has TJ's preventing entry
Mucous secreted by goblet cells traps pathogens
Paneth cells (small intestine) secrete antimicrobial peptides (defensives) and lysozyme
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10
Q

What is the 2nd line of defence in the gut?

A

Commensal bacteria

Occupy space in gut, preventing pathogenic bacteria adhering to epithelial lining

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11
Q

What are the “immunological” defences in the gut?

A

MALT (mucosa associated lymphoid tissue)

GALT (gut associated lymphoid tissue)

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12
Q

Where and how is MALT found?

A

Submucosa below epithelium
As lymphoid mass containing lymphoid follicles
Follicles surrounded by HEV post capillary venules, allowing easy passage of lymphocytes

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13
Q

What are lymphoid follicles?

A

Collections of lymphocytes

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14
Q

Name 2 places in the oral cavity with organised lymphoid follicles

A

Lingual tonsils

Pharyngeal tonsils

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15
Q

What type of response does GALT provide?

A

Innate and adaptive immune responses

Through generation of lymphoid cells and antibodies

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16
Q

In what forms are GALT in the gut found?

A

Not organised

Organised

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17
Q

Describe the not organised GALT

A

Intra-epithelial lymphocytes: Make up 1/5 of intestinal epithelium, e.g. T cells, NK cells
Lamina propria lymphocytes

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18
Q

Describe the organised GALT

A

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

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19
Q

Where are peyers patches mainly found?

A

Lamina Propria of Distal ileum

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20
Q

What are peyers patches?

A

“Immune sensors”
Aggregated lymphoid follicles covered with follicle associated epithelium (FAE)
Organised collection of naive T and B cells

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21
Q

Describe Follicle associated epithelium (FAE)

A

No goblet cells
No secretory IgA
Lack microvilli

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22
Q

What does development of Peyer’s patches require?

A

Exposure to bacterial microbiota

23
Q

What occurs in follicle associated epithelium?

A

Antigen uptake via M (microfold) cells

M cells express IgA receptors, facilitating transfer of IgA bacteria complex into the peyers patches

24
Q

What can mesenteric lymph nodes do?

A

Antigen sampling as they are transepithelial dendritic cells

Form such TJ with epithelial cell that no pathogens can enter at TJ

25
Q

Where do activated T and B cells go to proliferate?

A

Superior Mesenteric Lymph Nodes

26
Q

Upon antigen presentation, B cells in peyers patches undergo what change?

A

Upon class switch
T cells and epithelial cells influence B cell maturation via cytokine production
B cells become IgA secreting plasma cells

27
Q

What form of IgA do plasma cells produce IgA?

A

Dimeric (secretion)

28
Q

How does IgA prevent invasion by a pathogen?

A

Dimeric IgA binds to Poly-Ig receptor on endothelial cells and is endocytosed
Enzymatic cleavage allows formation of secretory IgA that’s protected against digestive enzymes
sIgA binds to luminal antigen, prevents adhesion to epithelial lining, thus preventing invasion

29
Q

How does the wall of the large intestine differ to that of the small intestine with regard to immune features?

A

SI: Has mucous, panted cells, lamina propria rich with lymphocytes
LI: Has shallower crypts, inner and outer mucosal layer, lamina propria rich with lymphocytes

30
Q

Where do activated B and T cells go after the superior mesenteric lymph nodes?

A

Can travel back to lamina propria or go to other lymphoid organs
Majority return to gut lumen: as met antigen there (has a tendency to return as more likely to be more of the same there)

31
Q

What facilitates lymphocyte gut homing?

A

Rolling of lymphocytes is mediated by weak selection binding
MAdCAM-1 presented on epithelial cells and Alpha-4-Beta-7 Integrin on the lymphocytes
Strong binding between these 2 molecules leads to activation and arrest

32
Q

Describe the transmission and symptoms of cholera

A

T: Faecal-oral route, contaminated water and food.
S: Severe dehydration and watery diarrhoea, (+vomiting, nausea, abdominal pain)

33
Q

Describe the MOA causing cholera

A

Vibrio cholerae serogroups O1 and O139 (cholera toxin).
Reaches small intestine where on making contactwith the epithelium releasescholera toxin.
Cholera toxin enters epithelial cell, starts a series of biochemical reactions resulting in exit of ions (Na+, K+, Cl-) and water from the epithelial cell.

34
Q

Describe diagnosis and treatment of cholera

A

D: bacterial culture from stool sample on selective agar or rapid dipstick tests
T: oral-rehydration
Vaccine: Dukoral, oral, inactivated

35
Q

List an example of a bacterial, viral and protozoic parasite that cause gastroenteritis

A

B: E. coli
V: Norovirus
P: Giardia lamblia

36
Q

E Coli as a cause of diarrhoea

A

Gram negative
6 pathotypes cause diarrhoea
Can cause bloody diarrhoea e.g. EHEC, EIEC

37
Q

Rotavirus as a cause of diarrhoea

A

RNA virus
Most common cause of diarrhoea in kids
Treatment: Oral rehydration
Vaccination: Rotarix

38
Q

Norovirus as a cause of diarrhoea

A

RNA virus
Diagnosed with sample PCR
Causes acute gastroenteritis
Faecal-oral transmission

39
Q

Campylobacter as a cause of diarrhoea

A

Transmitted in undercooked meat

Treatment not usually required

40
Q

When does Clostridium difficile become pathogenic?

A

When there is dysbiosis in the body
Pathogenic toxins destroy epithelial lining, allow leakage of neutrophils
Cause diarrhoea (possibly bloody)

41
Q

What is the mechanism causing coeliac disease?

A

Gliadin is not broken down in the stomach, reaches small intestine, binds to sIgA and is transferred to the lamina propria
presented to T cells by APCs, causes activation and co-stimulation of B cells (produce Antibodies)
Leads to intestinal inflammation

42
Q

Symptoms of coeliac disease

A 
Abdominal distension (bloating)
Diarrhoea
43
Q

Diagnosis and treatment for coeliac disease

A

D: Antibody (anti-gliadin) in blood test, biopsy test of duodenum
T: gluten free diet

44
Q

What is the mechanism associated with causing irritable bowel syndrome?

A

Visceral hypersensitivity

Triggered by diet/ stress

45
Q

Symptoms of IBS

A

Recurrent abdominal pain
Abnormal bowel motility
Constipation and/ or diarrhoea

46
Q

Treatment of IBS

A

Diet modification e.g. avoiding beans
Treatment of constipation e.g. osmotic laxatives
Treatment of spasms/ pain e.g. antidiarrheals
Management of stress/ anxiety

47
Q

Which form of inflammatory bowel disease is more common in the UK?

A

Ulcerative colitis

48
Q

What area of the bowel is effected in Crohns disease and ulcerative colitis?

A

CD: Distal ileum and colon
UC: Colon only

49
Q

What is the pathology in Crohns disease and ulcerative colitis?

A

CD: Patches of inflammatory damage and healthy tissue, cobblestone appearance
UC: Continuous inflammation

50
Q

What are the symptoms of crohns disease?

A 
Diarrhoea
Abdominal cramping
Fever
Anaemia
Weight loss
Fatigue
51
Q

What are the symptoms of ulcerative colitis?

A 
Bloody diarrhoea
Abdominal cramping
Anaemia
Weight loss
Fatigue
52
Q

How are inflammatory bowel diseases diagnosed?

A

Antibody blood tests
Endoscopy
Barium X-ray

53
Q

What are the treatment options for Crohn’s disease?

A

Anti-inflammatory drugs
Immunosuppressants
Surgery (not curative)

54
Q

What are the treatment options for Ulcerative colitis?

A

Anti-inflammatory drugs
Immunosuppressants
Surgery (Curative)

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