AS Lecture 13 - Infection and Immunology of the Gut

Question 1

What is the GIT immunology status?

Answer 1

Massive antigen load - resident microbiota, dietary antigens, exposure to pathogens State of restrained activation

Question 2

What does immune homeostasis require?

Answer 2

Presence of bacterial microbiota

Question 3

What are the 4 major phyla in the gut microbiota?

Answer 3

Bacteriodetes, Firmicutes, actinobacteria, proteobacteria

Question 4

What are the abnormalities present in ‘germ-free’ animals - with no gut microbiota?

Answer 4

Immune function (oral tolerance) Metabolic function (altered enzymes) Physiological function (altered motility) Trophic function (altered cell turnover)

Question 5

What are 4 infections of the GIT?

Answer 5

Oral candidiasis Helicobacter pylori Infective diarrhoea (bacterial, viral, amoebic) Clostridium difficile

Question 6

What is oral canidiasis?

Answer 6

Yeast/fungal infection by Candida albicans Carried in 50% of individuals - asymptomatically usually

Question 7

What patients are affected by oral candidiasis?

Answer 7

Immunocompromised patients

Question 8

How is oral candidiasis treated?

Answer 8

With oral anti-fungals or IV antifungals is immunocompromised

Question 9

What is helicobacter pylori?

Answer 9

GNB, microaerophilic rod

Question 10

What are the symptoms of H. pylori?

Answer 10

Gastritis/ gastric or duodenal ulcers/ gastric carcinoma BUT 80% infected individuals are asymptomatic

Question 11

How is H. pylori investigated and treated?

Answer 11

Investigated: Blood Ab, stool Ag, urea breath test, biopsy ureases test Treatment: 1 week eradication therapy with proton pump inhibitor and clarithromycin/amoxicillum

Question 12

What are the main causes of traveller’s diarrhoea?

Answer 12

Escherichia coli (E coli) Shigella Salmonella Cholera Rotavirus Norovirus Giardia

Question 13

What are the symptoms and transmission of Norovirus?

Answer 13

Acute gastroenteritis for less than 3 days with incubation of 24-48hrs Faeco-oral transmission Infectious for up to 2 weeks

Question 14

What are the 4 strains of E. coli and what do they cause?

Answer 14

Enterotoxigenic - cholera-like toxin causing watery diarrhoea Enterhaemorrhagic - verotoxin/shigatoxin causing haemolytic uraemic syndrome Enteropathogenic - occurs in nurseries Enteroinvasive - shigella-like illness, bloody diarrhoea, megacolon

Question 15

How does C. difficile colonise the colon?

Answer 15

Question 16

What disease does C. difficile cause?

Answer 16

Pseudomembranous colitis (AB-associated colitis) A and B toxin

Question 17

How is a C. difficile infection treated?

Answer 17

Isolate, stop current antibiotics and treat with metronidazole and vancomycin Then undergo faecal microbiota transplation

Question 18

What is the success of faecal transplantation in C. difficile?

Answer 18

Cure rate of 98% - stool resembles donor stool in 2 weeks

Question 19

How does the gut’s mucosal layer provide defense?

Answer 19

Physical barrier - epithelial and peristalsis, chemical (enzymes and pH) Commensal bacteria Immunological after invasion - MALT/GALT

Question 20

How does the epithelial layer act as a barrier?

Answer 20

Mucus layer (goblet cells) Epithelial monolayer (tight junctions, antimicrobial peptides and transports IgA) Paneth cells (bases of crypts and have defensins and lysozymes)

Question 21

Where are MALT most present?

Answer 21

In the oral cavity - the palatine tonsil, lingual tonsils and pharyngeal tonsil

Question 22

What is GALT and what are the 2 types?

Answer 22

Gut-associated lymphoid tissue - not organised OR organised

Question 23

What are some not organised GALT?

Answer 23

Intra-epithelial lymphocytes and lamina propria lymphocytes

Question 24

What are some organised GALT?

Answer 24

Cryptopatches, peyer’s patches, isolated lymphoid follicles, mesenteric lymph nodes

Question 25

What does GALT do?

Answer 25

Generates lymphoid cells and antibodies -\> IgA (secretory and interstitial), IgG, IgM and cell mediated immunity

Question 26

What are peyer's patches and where are they located?

Answer 26

Small intestine - mainly distal ileum (similar elsewhere in GIT) Covered by follicle associated epithelium (no goblet cells, secretory IgA, lack microvilli and infiltrated by T/B cells, macrophages and dendritic cells) Organised collection of naive T and B cells

Question 27

How do peyer's patches develop?

Answer 27

Requires exposure to bacterial microbiota

Question 28

What is the structure of Peyer's patches? FITB

Answer 28

Question 29

What is the function of peyer's patches?

Answer 29

Antigen sampling by M cells Transport to APC in subepithelial dome, where DC's take up Ag and process it They then present to naive B/T cells in Peyer's patch or transport to lymph nodes - results in development on gut homing markers They then transfer to mesenteric lymph node to proliferate

Question 30

What is the B-cell adaptive response?

Answer 30

Naive B cells expressing IgM in peyer's patches, which upon presentation switch to IgA, under influence from T cells and epithelium Then further maturation to become IgA secreting plasma cells, populating lamina propria

Question 31

What are intraepithelial lymphocytes?

Answer 31

Make up 1/5th of intestinal epithelium Made from: conventional T cells (lamina propria) - migrated from other tissue; unconventional T cells (innate) - resident, express unusual combinations of CD4/8 gamma/delta TCR Other innate immune cells - resident NK cells

Question 32

How is the T cell adaptive response activated and what does it lead to?

Answer 32

3 signals: presentation of Ag within MHC, co-stimulatory signals on DC and secretion of cytokines by DC Leads to: cell mediated immunity, normal gut response, inflammatory disease, tolerance

Question 33

What are the different types of T cells that can be formed from different IL stimulations?

Answer 33

Question 34

What is gut homing?

Answer 34

Lymphocytes proliferate in MLN and enter lymphatics to thoracic duct where they enter circulation, selectively home to sites similar to initial priming - Ag presentation in GALT favours gut homing characteristics (intergrins/chemokine receptors) Integrins act as a postcode marker so that the lymphocytes know to return to that site

Question 35

Why does the gut have a dual immunological role?

Answer 35

Immunoreactivity to pathogens BUT tolerance to food Ag and commensal bacteria

Question 36

What is immune tolerance?

Answer 36

Suppression of immune responses towards Ag via deletion of responding lymphocyte, anergy or TReg cells

Question 37

What may loss of tolerance underlie?

Answer 37

Inflammatory bowel disease Coeliac disease Food allergy

Question 38

What are some common food allegies?

Answer 38

Nuts Hen egg white Cows milk Wheat Sesame seeds Soya Shell fish

Question 39

What causes inflammatory bowel disease?

Answer 39

Genetic background, immune system and/or environmental factor With some factors like: smoking (sometimes the removal can cause bloody diarrhoea), stress, diet and vitamin D affecting

Question 40

What alleviates or worsens Crohn's disease?

Answer 40

Faecal stream diversion alleviates but reanastomosis triggers recurrence Infusion of luminal contents into excluded normal bowel reduces inflammation

Question 41

Which gut flora are associated with certain symptoms of crohn's disease?

Answer 41

Fusobacteriaceae - biomarker, progression of colorectal cancer Pastueurellacaea, Veillonellaceae, pathogenic E coli - linked with ulcer formation

Question 42

What does microaerophilic mean?

Answer 42

Needs a little bit of oxygen to survive

Question 43

How do dendritic cells sample the gut bacteria?

Answer 43

They stick their dendrites into epithelial barrier, so they can sample the lumen on the other side. It then takes the antigens to the MNL

Question 44

What is coeliac disease?

Answer 44

40-50% and most patients can be asymptomatic and others have bloating/abdominal pain, dermatitis

Question 45

How does coeliac disease present histologically?

Answer 45

Villus atrophy and many infiltration of intraepithelial lymphocytes