Infection and immunology of Gut

Question 1

What are the four main mechanisms for protection from infection?

Answer 1

Physical Barriers
Chemical Barriers
Bacteria protection
Immunological protection

Question 2

What are the physical barriers for mucosal defense?

Answer 2

Tight epithelial wall
Glycocalyx
Mucous and unstirred layer
Peristalsis to keep things moving along the GI tract

Question 3

What are chemical barriers for mucosal defense?

Answer 3

Bacteriacidal enzymes from paneth cells and acid from stomach

Question 4

What are bacteria protection for mucosal defense?

Answer 4

Commensal bacteria maintain immune system priming and may attack foreign species

Question 5

What are immunological forms of mucosal defense?

Answer 5

Mucosa associated lymphoid tissue (MALT) rich in T cells and B cells whose components can be further categorized into G (Gut) ALT, B (bronchus) ALT etc

Question 6

What are the two categories of GALT

Answer 6

Organised sites of lymphoid tissue such as Peyer’s patches in the small intestine and lymphocytes in mesenteria lymph nodules (where lymph from villi drain)
Disorganised sites inc lymphocytes in the lamina propria (mainly IgA) and lymphocytes in the interstitial space below the basolateral membrane of the epithelium (intra-epithelial cells)

Question 7

What are Peyers patches?

Answer 7

Aggregated lymphoid follicles covered in follicle associated epithelium FAE

Question 8

Where are Peyers patches found?

Answer 8

In small intestine with highest conc in distal ileum

Question 9

What do Peyer’s patches do?

Answer 9

Function as immune sensors since they are capable of monitoring local bacteria and provide protection against pathogenic bacteria

Question 10

What do Peyer’s patches contain

Answer 10

B cells
T cells
macrophages
dendritic cells

Question 11

What are M cells?

Answer 11

Specialised enterocytes in follicle associated epithelium

Question 12

What do M cells do?

Answer 12

Perform transcytosis of luminal bacteria, antigens and proteins.

Question 13

What do M cells express?

Answer 13

IgA receptors that facilitate the transfer of IgA bacteria complex into peyer’s patches

Question 14

What happens to antigens taken up by M cells?

Answer 14

Presented to lymphocytes for assessment and potential immunological response. Activated cells develop gut homing markers and migrate to mesenteric lymph nodes for proliferation

Question 15

Why is IgA the most abundant antibody in the body even tho IgG is the most abundant circulating immunoglobulin?

Answer 15

IgA highly prevalent in mucosal secretions bc MALT associated with IgA plasma cells (B cell secreting a single antibody). The no. of activated plasma cells reflect the bacterial load and up to 90% gut B cells secrete IgA

Question 16

What is SIgA

Answer 16

Secretatory IgA is a dimeric form of IgA

Question 17

Where is SIgA produced?

Answer 17

In B cells in lamina propria.`

Question 18

How is SIgA formed?

Answer 18

In plasma cell, two IgA bound together by J chain. Dimer binds to special receptor on external basolateral surface of enterocytes (pIgR). Receptor = secretatory component and binds to length of IgA dimer becoming SIgA

Question 19

What does the secretory component of SIgA do?

Answer 19

Help IgA move through the enterocyte

Protects the antibody dimer from enzymatic and acidic degeneration

Question 20

What does SIgA do?

Answer 20

Binds to pathogens, preventing adherence to mucosal wall.

Question 21

How is antigen specific SIgA production stimulated?

Answer 21

Actions of M cells and dendritic cells in Peyer’s patches

Question 22

What happens to mucosal lymphocytes once stimulated by an antigen?

Answer 22

Migrate into local mesenteric lymph nodes and drain into lymphatic sstem

Question 23

What is lymphocyte homing

Answer 23

Transmigration of lymphocytes into gut mucosa stimulated by tissue specific endothelial adhesion molecules at the site of inflammation

Question 24

What does lymphocyte homing require? - what special type of cells?

Answer 24

Specialised post capillary microvascular endothelial cells such as high endothelial venules of lymphoid tissue

Question 25

What is L selectin? - where is it expressed

Answer 25

A carbohydrate binding lectin that is constitutively expressed on the surface of lymphocytes

Question 26

What does L selectin do?

Answer 26

Mediates the low adhesive interactions that enable leukocytes to roll in post capillary venules and HEVs

Question 27

What happens in HEVs?

Answer 27

L selectin mediates lymphocyte rolling by it's binding to mucosal addressin cell adhesion molecule MAdCAM-1

Question 28

Where is MAdCAM-1 expressed?

Answer 28

HEVs of peyer's patches and mesenteric lymph nodes | Flattened endothelial cells localised in lamina propria of small and large intestines

Question 29

What else does MAdCAM-1 do?

Answer 29

Enable lymphocyte recruitment in chronic gut inflammation

Question 30

What are treatment options for irritable bowl syndrome?

Answer 30

``` Diet modification Treatment of constipation Treatment of spasms Management of stress, anxiety, depression Most of these target the symptoms^ ```

Question 31

Explain the role of dietary management to treat irritable bowel syndrome

Answer 31

Short chain carbohydrates cause symptoms, act as solutes that draw water from GI wall into lumen, causing visceral hypersensitivity (pain) and smooth muscles to spasm and cause diarrhea if water not reabsorbed properly. These carbs are metabolised by bacterial flora that produce gas that causes even more bloating, spasm or pain

Question 32

Recall the mechanism of coeliac disease

Answer 32

Gliadin is not broken down in the stomach, so reaches small intestine and binds to secretory IgA in the mucosal membrane. Gliadin secretory IgA complex binds to transferrin receptor and are transferred to the lamina propria Enzyme tissue transglutaminase cuts off amide group from protein Deamidated gliadin phagocytosed by macrophages and presented by MHC II molecules leading to activation of immune system - destruction of epithelial cels

Question 33

What is gliadin?

Answer 33

33aa peptide component of gluten

Question 34

What is the dietary management of coeliac disease?

Answer 34

Gluten free diet (wheat, barley, rye exclusion) and medication. Can also get gluten free foods on prescription. Factors that affect compliance are lifestyle, eatin out, cross contamination at home and holidays

Question 35

What is Crohn's disease

Answer 35

Causes inflammation anywhere along GI tract - inflammatory bowl disease Immune related disorder

Question 36

What is an immune related disorder?

Answer 36

Immune system triggered by foreign pathogen in GI tract eg mycobacterium paratuberculosis, pseudomonas, and listeria Inflam response large and uncontrolled and leads to distruction of cells in GI tract

Question 37

Explain the dietary management and nutritional significance of Chron's disease

Answer 37

liquid diet, low fibre/low residue, food reintroduction Managing strictures: decrease obstruction, pain and gas production. Need to change diet so that food can get through the stricture; fibre can block the intestines. Avoid fibrous parts of fruit and vegetables (skins, seeds, woody stalks), whole- grains, nuts, seeds, gristle and skin from meat and fish, bones etc. May require different consistency e.g. liquidising

Question 38

Explain the dietary management and nutritional significance of Ulcerative colitis

Answer 38

Dietary manipulation to minimise exacerbation of diarrhoea. Diarrhoea: drink fluid, nutritious drinks, replace salt. Eating soluble fibre helps the gut absorb more water from stool. Avoid gas producing foods, high fibre or whole- grain cereals, alcohol (worsens dehydration), caffeine and personal triggers

Question 39

What is ulcerative colitis?

Answer 39

An autoimmune disorder where T cells destroy the cells lining the walls of the large intestine