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Cellular and Molecular Immunology > Innate Lymphoid Cells > Flashcards

Innate Lymphoid Cells Flashcards

1
Q

NK Cell Review
What cytokine NK cells produce?
Which germiline receptors NK cells use?

A
  • NK cells fill a critical gap between non-lymphocyte innate and lymphocyte-mediated adaptive immunity
  • NK cells produce robust IFN-gamma to activate immunity and directly kill cells.
  • NK cells use germiline receptors like NKG2D
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2
Q

Cell Types Blur Adapative vs. Innate

A
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3
Q

ILC and unconventional provide a critical role early in life, and early in infection

A
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4
Q

Unconventional T-Cells

A

Includes: NKT, MAIT, gamma/delta T cells, CD8 double alpha
Develop via V(D)J and Rag
However, cells do not react with classical peptide-loaded MHC
Use conserved TCR segments to react with nonclassical MHC or other receptors
Often express NK cell receptors (e.g. NKG2D, CD94, KIRs)

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5
Q

Unconventional T-Cells

A

Unconventional T-Cells exit the thymus fully functional without prior stimulus
They typically make helper cytokines. But, may have some cytotoxic capability and granules

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6
Q

Unconventional T-Cells

A
  • Unconventional T-Cells depend upon conserved T-Cell receptor segments.
  • In conventional alpha-beta T-Cells, V(D)J recombination can choose between an unrestricted repertoirse of segments.
  • Valpha14 has identical sequence across multiple strains of mouse thymus.
  • Thus, unlike most other TCR segements, Valpha14 is conserved.
  • Further 2-4% of thymocytes are Valpha14+. which is 1000x more than exprected by chance.
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7
Q

Unconventional T-Cells
(NKT, MAIT, and gamma-delta T-Cell)

A

Recognize nonclassical MHC, which are distinct than the polymorphic MHC recognized by classical T-Cells.
MR1 presents vitamins B derivates, which is recognized by Balpha19 on MAIT cells,
CD1 presents lipids, which is recognized by Valpha14 (m) on NKT-cells
NK cell receptors are non-classical MHC

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8
Q

Mucosal-Assocaited Invariant T-Cell
(MAIT)

A
  • Up to 10% of human blood T-Cells
  • Thymus development with strict TCR
  • Human: Valpha7.2 and Valpha33
  • Mouse: Valpha19, Jalpha33 paired with Vbeta2 or Vbeta13
  • Sense microbial riboflavin metabolims captured by extracellular environment and displayed on MR1
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9
Q

Natural Killer T (NKT) Cellls

CD-1 restricted T-cells

A

Two groups:
* Type 1 NKT have restricted Valpha24-Jalpha18 (h) or Valpha14 (m) receptor for CD1.
* Type 2 NKT bind CD1 but have a diverse repertoire

NKT recognize microbial glycolipids, phospholipids, lipopeptide antigens.

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10
Q

Gamma-Delta T cells

A

Arise from double negative (DN) thymocytes that recombine TCRg+TCRd.
Express combinations of TCR Vgamma and Vdelta, with varying specificity.
Highly abundant in skin and barrier tissues and intra epithelial sites
Recognize:
* Phosphoantigens
* Others

Polarization is dependent upon Vgamma and Vdelta combination rearranges in the thymus.

Example: Vgamma9Vdelta2+ Tcells recognize BTN2A1 that is stabilized by phosphopeptides. In response, they make IFN-gamma.

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11
Q

Gamma-Delta T cells

A
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12
Q

CD8 - CD4 - CD8doublealpha
(Part 1)

Non-functional T-Cells

A

Reminder:
* CD8alpha binds MHC-I
* CD8a/b is complete co-receptor for signaling

CD4-CD8-CD8doublealpha arise from double negative precursors and migrate to mucosa epithelia.
Oligoclonal, but TGF-Beta induces CD8doublealpha, which downregulates TCR.
Express:
* NKG2D (recognize stress)
* TRAIL

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13
Q

CD8 - CD4 - CD8doublealpha
(Part 2)

A
  • Positioned at barrier sites (skin, instestine, lung, etc.)
  • Dominate intra epithelial lymphocytes (IEL)
  • Most abundant in proximal small intestine, where 1 for every 10 epithelial cell.
  • Embedded and migrate within and between epithelial cells.
  • Able to migrate to sites of infection, cell stress, DNA damage (i.e. NKG2D ligands), rapidly supporting immunity
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14
Q

Intra Epithelial Lymphocytes
(IEL)

A
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15
Q

Unconventional T-Cells
Review Reference Slide

A

Unconventional T-cells moslty make helper cytokines, but can be cytotoxic

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16
Q

B2M is needed for MHC-I stabilization, which includes non-classical MHC-I such as MR1, CD1, HFE (iron homeostasis), and ZAG (fatty acid homeostasis).

Which unconventional T-Cell subset requires B2M on the target recognition?

A

NKT

Gamma-Delta T-cells are some others that these subsets.

17
Q

TAP is needed to load peptide to MHC-I in the ER.
What T-cell responses should be TAP-dependent and TAP-dependent?

A
  • TAP-dependent -> NKT cells
  • TAP-independent -> MAIT cells
18
Q

Innate Lymphoid Cells
Cell Types Blur Adapative vs. Innate

A

Let’s take a T-helper cell and make it innate

19
Q

Innate Lymphoid Cells
Programming

A
  1. Pathogen and/or tissue resident patterns
  2. Signal
  3. Polarization-specific STAT
  4. Lineage determining TF
  5. Effector cytokine

Differentation depends on:

20
Q

Innate Lymphoid Cells
Type 3 ILC

A

Type 3 ILC induce barrier healing and defense
Maintain “immunologic tone” of tissues barrier reinforcement ILC3s participate in containment of commensals

21
Q

Innate Lymphoid Cells
Type 3 ILC

A

Type 3 ILC require AHR to make IL-22

22
Q

Innate Lymphoid Cells
ILC2

A
23
Q

To what signals ILC2 respond?

A

ILC2 respond to neuronal and adipose signales

There are a vast repertoire of receptors for neuropeptides

24
Q

Innate Lymphoid Cells
ILC1

How do ILC1 acts?

A

ILC1 acts as tissue protectors

25
Q

What cytokine ILC1 produce?
What roles does ILC have over mice?

A

ILC1 cytokine (IFN-gamma) largely protects against mycobacterial disease.
The roles of ILC in mouse are numerous - Cancer protection, T.Gondii, C difficile, etc.

Despite the numerous roles for IFN-gamma in mouse, humans deficient for IL-12 and IFN-gamma signaling have a phenotype restricted to Mycobacteria susceptibility.

26
Q

Development
Representation on how NFIL3, ID2, and PLZF commit to ILC

A
27
Q

Representation of how ID2&PLZF blocks NK cell in mice

A
28
Q

What is consider as an specialized ILC?

A
  • Lymphoid Tissue inducer (LTi) is considered as an specialized ILC
  • It develop in fetal liver independent of other ILC
  • Constitutively express cytokines before microbiota
  • Migrate and induce secondary lymphoid tissues
29
Q

ILC convert during inflammation

A
30
Q

Learning Check

What is the cell type that is cover?

Diagram of severe, chronic itch observed in atopic dermatitis (AD) patients

A

IL-72
The star covers a cell type that is require for the itching feeling, sits next to the nueron and mkaes abundant IL-5 and IL-13 in response to IL-33

31
Q

Learned table

Review Table

A

Cellular and Molecular Immunology (20 decks)

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