Gut as an Immune Organ

Question 1

within the GI:
where are the CD4 T cells usually found?
where are the CD8 T cells usually found?

what do each do there?

Answer 1

CD4 T cells usually found: cells sit in the lamina propria to produce lots of cytokines (primarily Th1 cells)

the CD8 T cells usually found: epithelium, kill virally infected cells​

Question 2

which cells do HIV kill?

what does this mean occurs in the gut?

Answer 2

HIV: kills CD4 T cells

= when kills T cells in the gut, patients get gut and lung infections from low grade pathogens. -> e.g. get wasting disease from chronic diarrhoea

Question 3

why is the gut vulnerable to infections? (2)

Answer 3

gut is vulnerable:

• bc has only a single layer of epithelium (not much of distance between BV and lumen: blood in stools)
• lumen = essentially outside the tissues

Question 4

fyi: organisms which cause infections of the gut or which enter body thru ut

Answer 4

Question 5

what are peyers patches?
where usually found?
function?
how are they different to lymph nodes?

what are M cells? where found?

Answer 5

peyers patches:

• groupings of lymphoid follicles in the mucus membrane that lines your small intestine
• very similar to lymph nodes in structure, except they **aren’t surrounded by a connective tissue capsule.
• function:** analyse and respond to pathogenic microbes in the ileum
• location: usually the ileum

m cells;
* - function: sample everything that goes into gut and transport gut antigens across the epithelium into the body *
-location: in peyers patch

Question 6

what is gut associated lymphoid tissue?

Answer 6

gut associated lymphoid tissue:

Gut-associated lymphoid tissues (GALT) are the key antigen sampling and adaptive immune inductive sites within the intestinal wall. Human GALT includes the multi-follicular Peyer’s patches of the ileum, the vermiform appendix, and the numerous isolated lymphoid follicles (ILF) which are distributed along the length of the intestine

Question 7

Answer 7

Question 8

which cells aggregate in this image of payers patch @ 1 & 2?

what is the tissue outlined in pink?

Answer 8

1 = B cell response
2 = T cell response

pink: submucosal tissue

Question 9

after antigen from pathogen stimulate T&B cells, how do they get to mucosal layer where there might be a pathogen?

where do they go?

Answer 9

gut specific honing:

• antigens from pathogen stimulate T & B cells = clonal expansion.
• leave peyers patch via the afferent lymph -> mesenteric lymph node -> blood stream -> lamina propria

- retinoic acid ( formed from vitamin A) is a signalling molecule: acts on niave T cells to make gut homing effector T cell

• a4B7 (found on surface of T cell), recognises an adhesion molecule: MadCAM, only found in enodthelial cells in gut

Question 10

which arethe main antibodies that protects you in the gut? which one is more?

Answer 10

• *IgA** - 80% of the antibodies in the gut are IgA
• *IgM - 13%**

(in lymphoid organs, like lymph nodes / bone marrow - IgG is the majority)

Question 11

describe the structure of IgA and IgM - how many binding sites do they have?

what do they both contain?

Answer 11

IgA: dimer !! (know this) - can form 4 binding sites

IgM: pentamer - can form 10 bindings sites

= form multimers

• both have J chain: (The joining (J) chain is a small polypeptide, expressed by mucosal and glandular plasma cells)

Question 12

how does IgA get into where its needed?

Answer 12

• polymeric Ig receptor is made by the epithelial cells of the gut
• IgA & IgM J chains bind to polymeric Ig receptor, and IgA & IgM is actively transported across epithelium.
• IgA & IgM transcyosied (moved by cytosis) in to gut lumen

Question 13

which antibody is commonly (1/200) deficient?
why is this very often not recognised?

Answer 13

IgA deficiency is quite common, yet no one knows they have it.

This is because IgM has a J chain so IgM undergoes a compensatory response and does the same job IgA would

Question 14

what is IgA (and IgM) good (1) why? / (bad (3)) at?
what is their function???

Answer 14

IgA antibodies

• (bad at: complement activation, neutrophil chemotaxis, phagocytosis)
• good at: agglunation: the IgA in the mucus and agglutinates pathogens to keep them away from the epithelial, and therefore it keeps them in a hostile environment and they will be washed away, prevented from binding and entering gut cells. They are usually swept away by peristalsis

Question 15

why is breast feeding important immunologically?

Answer 15

• Newborn babies have no IgA, which is why it’s a really good idea to be breast-feed as you are getting passive immunity

Question 16

how does passive transfer of gastrointestinal pathogen immunisation to the baby from the mother occur?

Answer 16

passive transfer of gastrointestinal pathogen immunisation to the baby from the mother

• During lactation, B cells leave the peyer’s patch and move to the breast via the thoracic duct
• breast blood vessels cells express MADCAN
• epithelial cells express secretory component

Question 17

What drives the extensive immune system we have in the gut?

Answer 17

- peyers patches immune activation depends on the flora

• In the absence of microbes, we have no immune system. Mucosal lymphocytes are dependent on bacterial flora. Without this, there is no drive for the gut immune system.

Question 19

* know this * (from mess)

draw basic structure of IgA, IgM, IgG, IgD, IgE

Answer 19

IgA = dimer ! = 4 binding sites

IgM = pentamer = 10 binding sites

IgG, IgD, IgE = monomers = 2 binding sites

Question 20

(in the whole body): rank antibodies in their order

Answer 20

IgG most common 75% of Ig are IgG

IgM 3rd most common but 1st to be made

IgA 2nd most common

IgD very low

IgE least common in serum as binds tightly to basophils and mast cells even before interacting with antigen

Question 21

explain the WHOLE mechanism of gut homing -> up to IgA interacting with bacteria and viruses

Answer 21

Gut specific homing:

- activated B and T cells leave Peyer’s patches and move to lamina propria. They are targeted to different regions of the gut to provide effective immune response.

• Gut dendritic cells produce retinoic acid (vitamin A) which induce gut homing T cells to express α4β7 and CCR9.
• Epithelial cells lining gut home T cells by expression of CCL25 (ligand for CCR9) while endothelial cells express MadCAM (ligand for α4β7).

. After binding, activated immune cells produce IgA (secretory antibody).

• IgA is actively transported across epithelium by polymeric Ig receptor
• Epithelial cells express secretory component on its surface-
• .IgA/IgM binds to secretory component via J-chain and enters the cell via endocytosis at basal membrane

.IgA is secreted into lumen via exocytosis at apical membrane

In the lumen IgA agglutinates viruses and bacteria