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Gastroenterology > Gut Immunology > Flashcards

Gut Immunology Flashcards

1
Q

GI tract balance

A

State of ‘restrained activation’

  • tolerance vs active immune response
  • dual immunological role
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2
Q

‘Virtual’ organ

A

Microbiota

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3
Q

Factors that stimulate bacterial growth

A

Ingested nutrients

Secreted nutrients

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4
Q

Factors that stimulate bacterial lysis or elimination

A

Chemical digestive factors

Peristalsis, contractions, defecation

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5
Q

Chemical digestive factors in stomach

A

HCl
Pepsin
Gastric lipase

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6
Q

Chemical digestive factors in liver

A

Bile acid

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7
Q

Chemical digestive factors in pancreas

A

Trypsin
Amylase
Carboxypeptidase

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8
Q

Chemical digestive factors in small intestine

A

Brush border enzymes

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9
Q

Chemical digestive factors in colon

A

None

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10
Q

Bacterial content in stomach

A

10^1

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11
Q

Bacterial content in duodenum

A

10^3

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12
Q

Bacterial content in jejunum

A

10^4

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13
Q

Bacterial content in ileum

A

10^7

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14
Q

Bacterial content in colon

A

10^12

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15
Q

Immunological equilibrium

A

Symbionts, commensals, pathobionts

Balance tips to inflammation when pathogens are involved with pathobionts - dysbiosis

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16
Q

Factors that may cause dysbiosis

A 
Infection or inflammation
Diet
Xenobiotics 
Hygiene
Genetics
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17
Q

Mucosal defense - physical barrier

A

Anatomical - epithelial barrier and peristalsis

Chemical - enzymes and acidic pH

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18
Q

Epithelial barrier

A

Mucus layer made by goblet cells

Epithelial monolayer by tight junctions

Paneth cells

  • bases of crypts of Lieberkühn
  • secrete antimicrobial peptides (defensins) and lysozyme
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19
Q

Mucosal defense - other barrier

A

Commensal bacteria - occupy ‘ecological niche’

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20
Q

Mucosal defense - immunological

A

Following invasion

MALT - mucosa associated lymphoid tissue
GALT - gut associated lymphoid tissue

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21
Q

MALT

A

Found in submucosa below epithelium. Exist as lymphoid mass containing lymphoid follicles.
Follicles are surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes

Oral cavity is rich in immunological tissue

  • palatine tonsil
  • lingual tonsil
  • pharyngeal tonsils (adenoids)
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22
Q

GALT

A

Responsible for both adaptive and innate immune responses
Consist of B and T lymphocytes, macrophages, APC (dendritic cells), and specific epithelial and intra-epithelial lymphocytes

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23
Q

Non organised GALT

A

Intra-epithelial lymphocytes
-make up 1/5 of intestinal epithelium - T-cells, NK cells etc.
Lamina propria lymphocytes

24
Q

Organised GALT

A

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

25
Stem cell of intestine location
In crypts
26
Commonest cells of intestine
Enterocytes (intestinal epithelial cells) | Migrate towards tip of villi
27
Goblet cells
Mucus secreting | Cell of intestine
28
Paneth cells
Migrate to bottom of crypt | Characterised by presence of dense granules and antimicrobial peptides
29
Lamina propria lymphocytes
Central part of villus | T cell, macrophages, dendritic cells, IgA B cells
30
Intraepithelial lymphocytes
Dotted between enterocytes
31
Peyer’s patches
Found in submucosa small intestine - mainly distal ileum Aggregated lymph’s follicles covered with follicle associated epithelium (FAE - no goblet cells, no secretory IgA, lack microvilli) Organised collection of naive T cells and B cells, and subepithelial dome of dendritic cells Development requires exposure to bacterial microbiota - 50 in last trimester fetus, 250 by teens Antigen uptake via M (microfold) cells within FAE M cells express IgA receptors, facilitating transfer of IgA bacteria complex into Peyer’s patches
32
Antigen sampling
M cells Dendritic cells - open up tight junctions to send dendrites into lumen to sample bacteria and bring back to transport to mesenteric lymph nodes
33
B cell adaptive response
Pathogen taken up by M cells Excreted into pocket formed in inner surface of enterocytes which contains antigen presenting cells such as dendritic cells Antigen engulfed and presented to MHC II molecules on surface Dendritic cells then migrate to Peyer’s patch DC, T and B cells all aggregate in patch and form an organised lymphoid follicle Other antigen loaded dendritic cells escape and migrate through lymphatic system where they activate B cells, T cells, other plasma cells in mesenteric lymph nodes Some activated cells then return to GALT tissue effector sites and produce antibodies secreted from intestinal lumen
34
B cell maturation
``` Mature naive B cells express IgM in Peyer’s patches On antigen presentation class switched to IgA ``` T cells and epithelial cells influence B cell maturation via cytokine production B cells further mature to become IgA secreting plasma cells Populate lamina propria
35
Secretory IgA
Up to 90% of gut B cells secrete IgA | sIgA binds luminal antigen - preventing adhesion and consequent invasion
36
Lymphocyte homing and circulation
Lymphocytes travel to mesenteric lymph nodes - lymphocyte proliferation - return to circulation via thoracic duct Either enter peripheral immune system (skin, tonsils, bronchus associated lymphoid tissue) or exit peripheral immune system and return to intestinal mucosa via vessels in lamina propria
37
Cholera mechanism
Acute bacterial disease caused by vibrio cholerae serogroupd O1 and O139 Bacteria reaches small intestine - contact with epithelium and releases cholera enterotoxin via retrograde endocytosis Once inside it increases adenylate cyclase activity - increased cAMP - active secretion of salt, potassium, chloride, bicarbonate - water follows
38
Cholera transmission
Faecal oral - spreads via contaminated water and food
39
Cholera symptoms
Severe dehydration and watery diarrhoea | Vomiting, nausea, and abdominal pain
40
Cholera diagnosis
Bacterial culture from stool sample, selective agar is standard, rapid dipstick also available
41
Cholera treatment
Oral rehydration is main management Up to 80% get better by itself Vaccine
42
Other causes of infectious diarrhoea (gastroenteritis)
Viral - Rotavirus (children) - norovirus Bacterial - salmonella - shigella - c.diff
43
Rotavirus
RNA virus, replicates in enterocytes | Five types A-E, A most common in Human infections
44
Rotavirus treatment
Oral rehydration therapy | Vaccine - live attenuated oral vaccine (Rotarix) against type A
45
Norovirus Norwalk virus
RNA virus | Incubation 24-48 hours
46
Norovirus Norwalk transmission
Faecal oral May shed infectious virus for up to 2 weeks Outbreaks often in closed communities
47
Norovirus Norwalk symptoms
Acute gastroenteritis, recovery 1-3 dats
48
Norovirus Norwalk treatment
Not required
49
Norovirus Norwalk diagnosis
Sample PCR
50
Campylobacter
Curved bacteria | Jejuni or coli
51
Campylobacter transmission
Undercooked meat, untreated water and unpasteurised milk | Low ineffective dose, a few bacteria can cause illness
52
Campylobacter treatment
Not required | Azithromycin standard antibiotic
53
E. Coli
``` Diverse group of gram negative intestinal bacteria Most harmless 6 pathotypes associated with diarrhoea EHEC/STEC most problematic ETEC EIEC EPEC EAEC DAEC ```
54
C. Diff
More C. Diff than normal leads gut from health stable state to intermediate dysbiotic state Could either go back to recovery or diseased state where pathogen induced disturbance (toxin production) create supportive environment
55
C. Diff management
Isolate patient - very contagious Stop current antibiotic - caused by antibiotics Metronidazole or vancomycin Recurrence rate 15-35% after initial infection, increasingly difficult to treat Faecal microbiota transplantation (FMT) 98% cure rate

Gastroenterology (11 decks)

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