gut immunology

Question 1

what does it mean that the gut is in a state of restrained activatiom?

Answer 1

dual immunological role between tolerance and active immune response

Question 2

what are the major phyla of gut bacteria?

Answer 2

bacteriodetes
firmicutes
actinobacteria
proteobacteria

Question 3

host factors influencing bacterial cell numbers

Answer 3

nutrients (bacterial growth)

digestive factors, peristalsis, defecation (elimination of bacteria)

Question 4

where is gut bacteria most prevalent and why?

Answer 4

colon

no digestive factors so numbers highest here, increases along tract

Question 5

what is dysbiosis?

Answer 5

microbial imbalance (pathobionts and symbionts)

Question 6

causes of dysbiosis?

Answer 6

infection and inflammation
diet
xenobiotics
hygiene
genetics

Question 7

types of anatomical mucosal defences in GI tract

Answer 7

Epithelial barrier

Peristalsis

Question 8

factors produced by pathobionts contributing to disease development

Answer 8

TMAO
4-EPS
SCFAs
AHR ligands

Question 9

what is the bacterial factor TMAO indicated in?

Answer 9

increased cholesterol deposition so athersclerosis

Question 10

what are the chemical mucosal defences against pathogens in GI tract

Answer 10

Enzymes

Acidic pH

Question 11

how do commensal bacteria form a mucosal defence?

Answer 11

occupy an ecological niche

act as second line to anatomical/chemical defences

Question 12

what are the immunological mucosal defences of GI tract?

Answer 12

MALT (Mucosa Associated Lymphoid Tissue)

GALT (Gut Associated Lymphoid Tissue)

Question 13

how does the epithelial barrier protect against infection?

Answer 13

mucus layer produced by goblet cells
tight junctions between epithelium
paneth cells (small intestine)

Question 14

what is the role of paneth cells and their location?

Answer 14

small intestine, bases of crypts of Lieberkuhn

secrete antimicrobial peptides and lysozyme

Question 15

what are MALTs?

Answer 15

mucosa associated lymphoid tissue esp in oral cavity

Question 16

structure and location of MALTs?

Answer 16

below epithelium as a mass of lymphoid follicles
surrounded by high endothelial venules allowing easy passage of lymphocytes
oral cavity; linguinal tonsils, palatine tonsils, adenoid tonsils

Question 17

what are GALTs?

Answer 17

gut associated lymphoid tissue
responsible for GI tract adaptive and innate response - B&T cells, macrophages, DCs, specific epithelial and intra-epithelial lymphocytes

Question 18

what are organised GALTs?

Answer 18

peyers patches - distal ileum
caecal patches- large intestine
isolated lymphoid follicles
mesenteric lymph nodes

Question 19

location of peyers patches?

Answer 19

distal ileum

Question 20

what are non-organised GALTs?

Answer 20

intraepithelial lymphocytes

lamina propria lymphocytes

Question 21

what are the nonorganised GALTs of small intestine?

Answer 21

intraepithelial lymphocytes - antimicrobial peptides
goblet cells
paneth cells
lamina propria

Question 22

what are the non organised GALTs of large intestine?

Answer 22

goblet cells
intraepithelial lymphocytes

no paneth cells like small i

Question 23

describe structure of peyers patches

Answer 23

aggregated lymphoid follicles underneath FAE (follicle associated epithelium) and M cells
sub epithelial dome of dendritic cells
B cells in follicle
naive t cells surround B cells

Question 24

what are M cells in peyers patches?

Answer 24

microfold cells
antigen uptake through them via IgA receptors
allow IgA-bacteria complexes to enter peyers patches

Question 25

what are follicle associated epithelial cells?

Answer 25

cells overlying peyers patches | have no microvilli, goblet cells or IgA

Question 26

how can antigen sampling occur in the GI tract

Answer 26

via M cells | OR independent of M cells by transepithelial dendritic cells

Question 27

how do transepithelial dendritic cells sample antigens?

Answer 27

can open tight junction proteins and send dendrites to lumen of gut directly samples the bacteria and can transfer to mesenteric lymph nodes

Question 28

describe the B cell adaptive response in the gut/GALT

Answer 28

mature (but naive) B cells express IgM on antigen presentation, class switch to IgA T cells and epithelial cells produce cytokines to influence maturation B cells then mature to be IgA producing plasma cells plasma cells then migrate and populate lamina propria

Question 29

how does secretory IgA help immunological defence of gut

Answer 29

sIgA binds to luminal antigen, prevents adhesion and consequent invasion

Question 30

how can circulating lymphocyte reenter intestinal GALTs?

Answer 30

process of lymphocyte homing

Question 31

where do GALT lymphocytes travel after activation?

Answer 31

mesenteric lymph nodes to enter thoracic duct, enter broad circulation from there return to lamina propria (via lymphocyte homing) or move to peripheral lymph tissue

Question 32

what is peripheral lymph tissue?

Answer 32

skin tonsils BALTs - bronchus associated lymphoid tissue

Question 33

what is the process of lymphocyte homing?

Answer 33

lymphocytes in HEVs MAdCAM-1 on HEVs binds to lymphocyte 𝝰4β7 Integrin lymphocytes roll until tethered by MAdCAM-1 for activation and rolling arrest move through walls to lamina propria

Question 34

why is there rapid turnover of enterocytes?

Answer 34

first line of defence - may be directly affected by toxic substances in diet therefore any agents affecting cell function die off and effect is diminished therefore any lesions will be short lived and not have long lasting effects

Question 35

what bacteria is cholera caused by incl serotype

Answer 35

vibrio cholerae O1 and O139

Question 36

MOA of cholera infection

Answer 36

Bacteria reaches small intestine → contact with epithelium & releases cholera enterotoxin enterotoxin internalised via retrograde endocytosis causes activation of adenylate cyclase to increase cAMP causes active secretion of salt and fluid (via CFTR) leads to watery diarrhoea via osmosis

Question 37

transmission of cholera

Answer 37

faecal oral route - contaminated food and water

Question 38

symptoms of cholera

Answer 38

severe dehydration and watery diarrhoea vomiting nausea abdo pain

Question 39

how to diagnose cholera

Answer 39

bacterial culture of stool sample | rapid dipstick also available

Question 40

what protections are there against cholera

Answer 40

vaccine - oral inactivated (Dukoral)

Question 41

what viruses cause gastroenteritis

Answer 41

rotavirus in children | noravirus

Question 42

rotavirus treatment (gastroenteritis)

Answer 42

oral rehydration therapy

Question 43

what are rotaviruses

Answer 43

RNA viruses replicate in enterocytes subtypes A-E live attenuated vaccine against type A (most common)

Question 44

what are noroviruses

Answer 44

RNA viruses faecal oral transmission usually outbreak in closed communities (cruises) cause acute gastroenteritis symptoms - recovery 1-3 days

Question 45

what is the treatment for norovirus gastroenteritis

Answer 45

none required

Question 46

what is campylobacter gastroenteritis

Answer 46

commonest UK cause of food poisoning low dose required for illness treatment typically not required

Question 47

which pathogens causing gastroenteritis typically require no treatment?

Answer 47

campylobacter norovirus some e coli

Question 48

clostridium difficle gastroenteritis facts

Answer 48

often due to long term antibiotics very contagious - isolate patient start metronidazole/vancomycin

Question 49

treatments for clostridium difficile

Answer 49

metronidazole or vancomycin stop current antibiotics can give faecal microbiota transplantation

Question 50

pathotypes of e coli causing diarrhoea

Answer 50

``` enterotoxigenic enterohaemorrhagic enteroinvasive enteropathogenic enteroaggregative diffusely adherent ```

Question 51

transmission of campylobacter

Answer 51

undercooked meat esp poultry untreated water unpasteurised milk