Immunology

Question 1

Define MALT

Answer 1

Mucosa-associated lymphoid tissue

Contains M-cells

Question 2

Define GALT

Answer 2

Gut-associated lymphoid tissue

Question 3

Describe the structure of Peyer’s Patches

Answer 3

M cells in follicle-associated epithelium overlie subendothelial dome
SED - contains DCs, CD4+/CD8+ T cells and lymphoid follicles of naive B cells (germinal centres)
Connected to efferent lymph vessel to mesenteric lymph node

Question 4

What are the functions of Peyer’s Patches?

Answer 4

Aggregated lymphoid tissue (GALT) capable of sampling local gut contents
Assess whether immunological response required

Question 5

Describe the distribution of Peyer’s Patches

Answer 5

Mostly in distal ileum

Question 6

How is follicle-associated epithelium specialised?

Answer 6

No goblet cells
No secretory IgA
No microvilli (microfolds instead)

Question 7

How are M-cells specialised for their function?

Answer 7

Invaginated BLM forms “pockets” that harbour infiltrating lymphocytes, decrease intracellular distance antigens must travel from apical to BLM

Reduced glycocalyx - no membrane hydrolytic enzymes

Fewer lysosomes - allows M-cells to transport MOs w/o altering antigenic properties

Produce IL-1

Question 8

What happens after antigen uptake by an M-cells or DC?

Answer 8

Antigen presented to lymphocytes for assessment and potential immune response
Activated cells develop gut homing markers and migrate to mesenteric lymph nodes for proliferation

Question 9

What is the role of IgA in the GIT?

Answer 9

SIgA binds to pathogens

Prevents adherence to gut wall

Question 10

Which cells stimulate antigen-specific IgA production?

Answer 10

M-cells and DCs in Peyer’s Patches, then lymphocytes

Question 11

What is secretory IgA?

Answer 11

Dimeric form of IgA made by B cells in lamina propria, transported across enterocyte

Question 12

Explain the synthesis of SIgA

Answer 12

1. 2 IgA molecules bound together by J chain
2. Secreted into IS
3. Dimer binds to pIgR on enterocyte BLM
4. pIgR becomes secretory component by binding to length of IgA dimer = SIgA
5. SIgA endocytosed into enterocyte and actively transported in vesicle to apical membrane
6. Exocytosed into gut lumen

Question 13

How are lymphocytes circulated in the alimentary system?

Answer 13

1. Mucosal lymphocytes in PPs stimulated by antigen and migrate to local mesenteric LN, drain into lymphatics
2. Enter systemic circulation via thoracic duct and spread thr/o body in blood
3. Lymphocytes remain in blood until activated by tissue-specific endothelial adhesion molecules at inflamm site
4. Activation allows transmigration of lymphocytes into gut mucosa (lymphocyte homing)

Question 14

How does lymphocyte homing occur?

Answer 14

L-selectin on lymphocytes mediates rolling by binding to MAdCAM-1 on HEVs of PPs and mesenteric LNs

MAdCAM-1 on flattened endothelial cells in lamina propria of S/LI enables lymphocyte recruitment in chronic gut inflammation

Question 15

How is dietary management involved in treating IBS?

Answer 15

AVOID:

FODMAPS - fermentable/oligo/di/monosaccharides and polyols in fruit and veg

Apples, beans, cauliflower with short chain carbs - act as solutes, draw water into SI -> diarrhoea

Wheat, rye, onion, garlic, sweeteners, dairy

Find out problem food to safely avoid
Not cure, but improves symptoms

Question 16

How is dietary management involved in treating Coeliac Disease?

Answer 16

Gluten-free diet

No wheat or grains (barley and rye)

Question 17

What is the pathophysiological mechanism behind Coeliac Disease?

Answer 17

1. Wheats and grains contain gluten, gluten broken down into gliadin in stomach, gliadin resists enzymatic degradation
2. Gliadin binds to SIgA in mucosal membrane of SI, complex resists destruction, binds to transferrin R on enterocyte (over-expressed in CD)
3. Complex transcytosed to BLM into lamina propria
4. Tissue transglutaminase (tTg) cuts off amide group, deamidated gliadin phagocytosed by MPs and presented on MHC II
5. CD4+ T cells activated - release inflamm cytokines IFN-y, TNF - damage/destroy enterocytes
6. CD4+ T cells stimulate B cells to pump out IgA against gliadin, tTg and anti-endomyial/anti-tTg ABs
7. CD4+ T cells recruit CD8+ T cells - destroy enterocytes
8. Enterocyte destruction allows more gliadin across epithelium

Question 18

Explain the dietary management involved in treating Crohn’s (IBD)

Answer 18

Crohn’s -
Liquid diet - nutritionally complete
Low fibre/low residue
Avoid fibrous parts of fruit and veg, wholegrains, nuts, seeds, gristle, skin from meat and fish, bones

Question 19

Explain the dietary management involved in treating Ulcerative Colitis (IBD)

Answer 19

Ulcerative colitis -
Minimise exacerbation of diarrhoea
Drink fluid, nutritious drinks, replace salt
Soluble fibre - helps gut absorb more water
Avoid gas-producing foods, high fibre/wholegrain cereals, alcohol, caffeine, personal triggers

Question 20

Describe the distribution of MALT

Answer 20

Oral cavity rich, specifically tonsils (palatine, lingual, adenoid)

Question 21

What are the two types of GALT?

Answer 21

Organised sites - Peyer’s Patches

Disorganised sites - lymphocytes in lamina propria or interstitium below epithelial BLM