innate lymphoid cells 1

Question 1

3 Features of innate cells

Answer 1

Not specific, can respond quickly, larer number of cells which have same responders at same time.

Question 2

In RAG deficinet mice (no T/B cells) there was still Th2 and Th17 cytokines found. What does this suggest?

Answer 2

That another population of innate cells that lacks the TCR produce these cytokines. e.g. ILCs.

Question 3

What makes ILCs more innate like than unconventional T cells?

Answer 3

They have no TCRs, or few PRRs. They respond to infection independently of antigens.
They are tissue resident, found at many mucosal surfaces.
Act early in immune responses.
I

Question 4

What do ILCs respond to? And how do they respond?

Answer 4

Respond to cytokines e.g. from innate cells and respond with cytokines to influence APCs and Teffectors.

Question 5

Do ILCs express innate and T/B cell makers?

Answer 5

No they don’t express these markers.

Question 6

What role do ILC 3s play in development?

Answer 6

LTis are particularly important in lymph node organogenesis.

Question 7

What molecule is particularly important in LN organogensis and is secreted by LTis?

Answer 7

lymphotoxin (an alpha beta heterdimer) that binds to LTB receptor on stromal organiser cells.
Induces them to produce chemikones and adhesion molecules.
More and more cells are attracted and stick, which are then replaced by T and B cells

Question 8

What groups of ILCs are there?

Answer 8

ILC1s (like Th1), ILC2s (like Th2) and ILC3s ( like Th17 and Th22) and includes LTis.
Also regulatory like ILCs not sure how similar to Tregs they are.

Question 9

What is defining functional feature of NK cells not present in ILCs?
what adaptive counterpart are NK cells?

Answer 9

NK cells are cytotoxic, highly express granzyme B and perfoirn and are granular. ILCs are not.

NK cells are like the CD8+ innate counterpart.

Question 10

Do ILCs express KIRs and NK receptors?

Answer 10

Yes, but not CD94 (NKG2A1).

Question 11

What TF are NK cells dependent on vs ILCs? and When are ILCs and NK cells first present?

Where are ILC1s and NK cells found?

Answer 11

NK cells dependent on EOMes (and less extent T-bet). ILC 1s are not dependent on Eomes.
ILCs present before birth, whereas NK cells only present after birth.
ILCs found in tissue mucosal barriers, NK cells recirucalte.

Question 12

Do NK cells express IL-7R like ILCs?

Answer 12

Only ILCs and not NK cells express IL-7R. NK cells dependent on IL-15.

Question 13

What cytokines can induce ILC1s and NK cells and what cytokines do they both secrete?

Answer 13

Both induced by IL-12 and Il-18, and both secrete INF-y and TNF.

Question 14

what TF for ILC2s?

Answer 14

GATA3

Question 15

Do ILC2s respond to epithelial alarmins? What are examples?

Answer 15

Yes , epitheilial alarmins can include IL-25 and IL33, and TSLP.

Question 16

what cytokines do ILC2s express, and what other molecule important for tissue repair?

Answer 16

Type 2 cytokins, and also amphiregulin for tissue repair.

Question 17

What cytokines do ILC3s secrete and what tow populations can you separate them into?

Answer 17

IL-17, Il-22 and GM-CSF. NCR+ and NCR-.

Question 18

When do Peyer’s patches, crypto patches and tertiary lymphoid tissue develop? Do they require Lti?

Answer 18

Peye’s patches before birth, crypto patches after birth (with microbiome?) can developed into lymphoid follicles high in B cells.
Both above thought to involve LTis.
tertiary lympoid tissue forms in response to inflammation.

Question 19

What TFs do controversial ILCreg population express and what is their development like?

Answer 19

Express ID3 and Sox2. Derived from the common innate lymphoid progenitor which expresses ID2.

Question 20

What other cells derived from CILP which expresses ID2?

Answer 20

Nk cells, as well as ILCregs and LTis.

Question 21

What two regulatory cytokines are found in ILC regs? Do other ILCs produce IL-10?

Answer 21

TGFB and IL-10.

Yes ILC2s found to develop into IL 10+ ILC2s.

Question 22

Are ILCs plastic? What natural plasticity is seen like in Th cells?

Answer 22

yes plastic, and ILCs can differentite into others with cytokine and cell combination.
Naturally, ILC3s become more ILC 1 like as they mature (like Th17 becoming more Th1 like).

Question 23

How can you image only ILCs in microscopy? Markers for DCs?

Answer 23

e.g. In RAG KO mice (no T/B cells) so stain for markers like RORyt (or IL-23 receptor)
Or you can stain for CD3, ILCs are CD3 negative cells.
DC markers MHC II and CD11c.

Question 24

What do you see that is significant about ILCs localisation in crypto patches during activation?

Answer 24

They cluster- to increase cytokine concentrations to effective levels from a small cell population.

-they closely associate with T cells. There is cross talk between them.

Question 25

What FSC and SSC do lymphocytes have?

Answer 25

lymphocytes have low FSC and SSC.

Question 26

What THree populatinos likely to be iwhtin lymphocyte pouplation?

Answer 26

CD8/ CD4 and B cells.

Question 27

What panel used to identify ILCs in FACs?

Answer 27

CD3-, CD19/CD21/Cd79 negative, CD94/ NKG2A negative, linage negative and IL-7R positive. Shows a small population.

Question 28

Which population of ILCs thought to be most ancient?

Answer 28

ILC2s because of GATA3 seen in jawless vertrabates.

Question 29

What protective responses may ILC1s (and ex- ILC3s) be invoved in?

Answer 29

immunosurveillance and intracellular pathogens (type 1 responses), e.g.g C. difficile and salmonella.

Question 30

Do ILC1s directly respond to anitgens during infection?

Answer 30

No, may be activated by DCs expressing IL-12 to produce IFNy and TNFa, which may stimulate macrophage/ neutrophil mediated killing.

Question 31

Difference between NK and iLC response to pathogens?

Answer 31

NK cells would be mostly activated by IL-15 in the LN, ILC1s activated by IL-12 in tissues. ILCs rapidly activated in tissue to furtheractivate immune response.

Question 32

3 ILC2 protective roles?

Answer 32

response to intestinal parastie infecitons, tissue repair and lipid metabolism

Question 33

How can ILC2 cytokines improve response against pathogens?

Answer 33

IL-5 recruits eosinophils. IL-13 activates goblet cells to produce mucus and intiates smooth muscle contraction. May support Th2 resposes by interacting with them via MHC II.

Question 34

How can ILC2s be involved in tissue repair in influena infection?

Answer 34

In repsonse to epithelial alarmins (e.g. IL-33) ILC3 produce of amphiregulin can be important in tissue repair.

Question 35

How are ILC2s involved in metabolism of obese people where ILC2s are found in lower numbers in white adipose tissue.

Answer 35

In repsonse to epithelial alarmins (e.g. IL-33 they secrete enkephalin peptides within white adipose tissue, which promotes bigning (adpipose cells that expend more energy.

Question 36

ILC3 response is against extracellula bacteria and fungi, e.g. C difficle and candida albicans. How can IL-22 help?

Answer 36

ILC3 IL-22 secretion acts on panneth cells to increase production of AMPs like RegIIIy(and also stimulates mucus production). IL-17 increases proliferation. ILC3s also express MHCII and may interact with Th17.