innate lymphoid cells 1 Flashcards

1
Q

3 Features of innate cells

A

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

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2
Q

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

A

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

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3
Q

What makes ILCs more innate like than unconventional T cells?

A

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.
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4
Q

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

A

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

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5
Q

Do ILCs express innate and T/B cell makers?

A

No they don’t express these markers.

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6
Q

What role do ILC 3s play in development?

A

LTis are particularly important in lymph node organogenesis.

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7
Q

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

A

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

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8
Q

What groups of ILCs are there?

A

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.

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9
Q

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

A

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

NK cells are like the CD8+ innate counterpart.

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10
Q

Do ILCs express KIRs and NK receptors?

A

Yes, but not CD94 (NKG2A1).

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11
Q

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?

A

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.

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12
Q

Do NK cells express IL-7R like ILCs?

A

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

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13
Q

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

A

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

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14
Q

what TF for ILC2s?

A

GATA3

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15
Q

Do ILC2s respond to epithelial alarmins? What are examples?

A

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

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16
Q

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

A

Type 2 cytokins, and also amphiregulin for tissue repair.

17
Q

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

A

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

18
Q

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

A

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.

19
Q

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

A

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

20
Q

What other cells derived from CILP which expresses ID2?

A

Nk cells, as well as ILCregs and LTis.

21
Q

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

A

TGFB and IL-10.

Yes ILC2s found to develop into IL 10+ ILC2s.

22
Q

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

A

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).

23
Q

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

A

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.

24
Q

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

A

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.

25
Q

What FSC and SSC do lymphocytes have?

A

lymphocytes have low FSC and SSC.

26
Q

What THree populatinos likely to be iwhtin lymphocyte pouplation?

A

CD8/ CD4 and B cells.

27
Q

What panel used to identify ILCs in FACs?

A

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

Shows a small population.

28
Q

Which population of ILCs thought to be most ancient?

A

ILC2s because of GATA3 seen in jawless vertrabates.

29
Q

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

A

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

30
Q

Do ILC1s directly respond to anitgens during infection?

A

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

31
Q

Difference between NK and iLC response to pathogens?

A

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.

32
Q

3 ILC2 protective roles?

A

response to intestinal parastie infecitons, tissue repair and lipid metabolism

33
Q

How can ILC2 cytokines improve response against pathogens?

A

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.

34
Q

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

A

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

35
Q

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

A

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.

36
Q

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

A

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.