L12 - Mucosal immunology 2 COPY

Question 1

SUMMARY PART I

i) what site plays a major role as an induction site in the gut apart from peyers patches? where is this site found? name one other role it plays
ii) name the two broad groups of intraepithelial lymphocytes? what makes these cells so important?
iii) what are the two subtypes of IEL CD8 cells?
iv) what are the two main types of IEL CD4 T cell? what is the role of each and what do they each secrete?
v) what are Tregs important for? why does this matter?

Answer 1

i) mesenteric LNs - found at the base of the mesentery
- major role in inducing tolerance to foods

ii) two main groups of IEL
- resident memory T cells
- innate like/innate cells

iii) CD8 T cells = convential CD8 cells (alpha and beta)
unconventional CD8 (2x alpha)

iv) two main types of CD4 T cell are
- non toxic Th17 - produce IL-17 and IL-22 - stabilise intestinal barrier by TJs and mucus secretion
- toxic Th17 - produce IFNy - tissue damage

v) Tregs are important for tolerance to food antigens
- important as abs of nutrients and inflammation are incompatible

Question 2

SUMMARY PART II

i) where are mucosal B cells located? what do they do here?
ii) what is the main Ig secreted in mucus? what structure does it have?
iii) what mechanism is this Ig secreted by? what additional transport molecule does this require? what receptor does this molecule originate from?
iv) how strongly does this Ig activate complement? what are its main roles (2)
v) what does commensal gut flora induce? what does this aim to do?

Answer 2

i) mucosal B cells located in the lamina propria
- secrete Ig

ii) main Ig secreted is IgA
- dimeric IgA joined by a J chain

iii) IgA is secreted by transcellular transport and requires the secretory component of the poly Ig receptor
- poly Ig receptor expressed on basal surface of gut ep cells

iv) IgA weakly activates complement
- can neutralise toxins and prevent microbial invasion

v) commensal gut flora induces low affinity IgA response aimed at immune exclusion

Question 3

SUMMARY PART III

i) which cells do antigen primed B and T cells originate from? where is their recirculation pattern restricted to? (2)
ii) how do naiive B and T cells reach peyers patches and MLNs?
iii) which two events happen to naiive cells before they travel back to the blood stream? how do they get to the blood?
iv) where do they ultimately return to?
v) how do they leave the blood stream? what mediates this? where do they go?

Answer 3

i) antigen primed B and T cells orig from naiive b and t cells
- recirc restricted to blood and lymph nodes

ii) naiive b and t cell > PP and MLNs via high endothelial venules

iii) naiive cells have antigen contact (induction) and tissue specific imprinting > then back to blood
- get to blood via lymphatic system and thoracic duct

iv) ultumately return to the gut via the blood

v) leave the blood by adhesion to the endothelium small venules (NOT HEVs) expressing ligands for CCR9 and a4b7
- then transmigration to the lamina prop and intraep sites

Question 4

SUMMARY PART IV

i) what process leads to the upregulation of adhesion molecules on the surface of antigen primed B and T cells? what does this serve as?
ii) what can be upegulated on venular endothelial cell surfaces in the gut? which situation may these be upregulated in? what does this allow in relaion to T and B cells?
iii) which vitamin in the gut plays a role in tissue imprinting and homing in naive B and T cells? what can deficiency in this vitamin cause?

Answer 4

i) imprinting leads to upregulation of tissie adhesion molecules on the surface of primed T and B cells > serves as key to lock
ii) venular endothelial cells can upregulate receptors for ligands during inflammation - can grant access to cells expressing the right ligands eg primed T and B cells > migration

iii) vitamin A plays an importany role in imprinting and homing
- Vit A deficiency > decreases gut immunity probably due to decreased homing