Mucousal immunity II

Question 1

What polarity is important in inetestinal epithelial cells? And what molecules are polarised?

Answer 1

Apical basal polarity important. Polarity of TLRs is thought to be important.

Question 2

What TLRs are expressed basolaterally in IECs?

Answer 2

TLR3,4 and 5 are expressed basolaterally on IECs.

Question 3

What TLRs are expressed on follicular associated epithelial cells overlaying peyers patches? ANd what is their expression pattern?

Answer 3

TLR2 and TLR9. Expressed apically and basally.

Question 4

Why might polarisation of TLRs be important?

Answer 4

Because TLR induciton of NF-KB contrasts depedning on polarity of TLR9.

Question 5

what other cell apart form IECs and follicular IECs expresses TLRs?

Answer 5

enteroednocrine cells.

Question 6

Apart from gut homeostasis, what is TLR4 important for?

Answer 6

TLR4 can also be important for foetal development of the gut- highly expressed during gestation.

Question 7

Expressino of TLR4 inhibits the developent of what cells from epithelial stem cells?

Answer 7

inhibits goblet cell differentiation.

Question 8

What disease associated with over activation of TLR4? Often in premature babies.

Answer 8

necrotising enterocolitis.

Question 9

3 Risk factors of necrotising enterocolitis?

Answer 9

formula feed, excessive antibiotics, episodes of hypoxia.

Question 10

what factors of breast milk may be protective?

Answer 10

IgA, probiotics and EGF (which has been shown to inhit TLR4)

Question 11

What are three different populations of CD103+ DCs?

Answer 11

CD103+ CD11b+, CD103+ CD11b+ CX3CR1, CD103+ CD11b-.

Question 12

What induces CD103+ expression in these DCs and what effects does RA have?

Answer 12

RA can induce CD103+ expression, and these cells express RA.
ALong with TGF-B, RA production by these cells is important for tolerance in gut by promoting Treg and inhibiting Th17 responses.

Question 13

What is special about CD103+ DCs regarding TGF-B?

Answer 13

They express an integrin, aVb8 whihc activates latent TGF-B.

Question 14

Are CD103+ DCs migratory?

Answer 14

Thought to be migratory and presnet antigen in the mesenteric lymph nodes.

Question 15

Do CX3R1+ macrophages also sample? What addtional marker distinguishes them from DCs?

Answer 15

Yes they also appear to sample, and may also do transendocytosis. CD11c can separate them

Question 16

What other funcitons might CX3CR1 macrphages play?

Answer 16

engulfment of apoptotic cells, Il-10 production, may help control the translocation of bacteria to the lymph nodes. Absenece makes mice mores suscuspetible to DSS induced colitis.

Question 17

What two groupd of T cells atgut surface?

Answer 17

Intraepithelial cells and lamina propria lymphocytes.

Question 18

Features of intraepithelial T lymphocytes?

Answer 18

Mainly CD8+ yD T cells, which recognise antigens independently of MHC (so innate like).

Question 19

Functions of intraepithelial T lymphocytes?

Answer 19

may have cytotoxic and immunoregulatory roles.

Question 20

What can lamina propria lymphocytes be?

Answer 20

Whole repertoire of T cell subsets, mostly CD4+ under the epithelium.

Question 21

What does the GALT look like?

Answer 21

Peyer’s patch, hase a T cell zone and B cell follicle that forms GCs. M cells above will translocate antigens from across lumen.

Question 22

How can immune cells enter and leave peyers patches?

Answer 22

Enter via blood capillaries and once activated can leave via efferent lymphatics to reneter blood at thoracic duct (via messenteric LN).

Question 23

What have different species of microflora been shown to influence (in lymphocytes)?

Answer 23

Differen species can influence lyphocyte repoertoire by activating Tregs or Th17.

Question 24

what are the main producers of Il-22 in intestine?

Answer 24

Th17 and Th22, as well as ILCs, NK cells, neutrophils fibroblast etc.

Question 25

What effect does IL-22 have on the panneth cells?

Answer 25

Can induce panneth cell production of RegIIIy AMP- help maintain barrier integrity.

Question 26

What two subuinits make up the IL-22 heterodimeric receptor?

Answer 26

IL22R and IL-10R.

Question 27

What evidence in disease is there that IL-22 is protective?

Answer 27

In HIV progresino to AIDs, there is depletion of IL22 and IL-22 producing cells (e.g. CD4+ and ILCs IL-22+).

Progression of HIV/AIDs leads to deterioration of thee gut epithelium.

Question 28

In vitro evidence IL-22 is protective?

Answer 28

Il-22 in vitro could protect HIV infeced epithelial cells.

Question 29

Evidence that T regulatory cells are important in gut homeostasis?

Answer 29

trnasfer of Tregs can inhibit colitis that is caused by autoreactive T cells by interacting with autoreactive T cells and DCs.

Question 30

How can ILC2s support Th2 responses?

Answer 30

By binding to Th2 via MHC antigen presentation and producing IL-13 to support Th2 response and expulsion of parasites.

Question 31

What happened when ILC 3s were depleted?

Answer 31

Increased immune responses against commensal bactria.

Question 32

What mechanisms might ILC3s regulate responses against commensal bacteria?

Answer 32

By presenting MHCII to T cells (independent of type 3 cytokines to limit responses.

Or macrophages release IL-1B which induces ILC3 produciotn of csf2, that upregulates IL-10 and RA expression of DCs and macrophages.
this may indirectly expand Tregs.