Innate Lymphoid Cells Flashcards
NK Cell Review
What cytokine NK cells produce?
Which germiline receptors NK cells use?
- 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
Cell Types Blur Adapative vs. Innate
ILC and unconventional provide a critical role early in life, and early in infection
Unconventional T-Cells
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)
Unconventional T-Cells
Unconventional T-Cells exit the thymus fully functional without prior stimulus
They typically make helper cytokines. But, may have some cytotoxic capability and granules
Unconventional T-Cells
- 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.
Unconventional T-Cells
(NKT, MAIT, and gamma-delta T-Cell)
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
Mucosal-Assocaited Invariant T-Cell
(MAIT)
- 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
Natural Killer T (NKT) Cellls
CD-1 restricted T-cells
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.
Gamma-Delta T cells
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.
Gamma-Delta T cells
CD8 - CD4 - CD8doublealpha
(Part 1)
Non-functional T-Cells
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
CD8 - CD4 - CD8doublealpha
(Part 2)
- 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
Intra Epithelial Lymphocytes
(IEL)
Unconventional T-Cells
Review Reference Slide
Unconventional T-cells moslty make helper cytokines, but can be cytotoxic
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?
NKT
Gamma-Delta T-cells are some others that these subsets.
TAP is needed to load peptide to MHC-I in the ER.
What T-cell responses should be TAP-dependent and TAP-dependent?
- TAP-dependent -> NKT cells
- TAP-independent -> MAIT cells
Innate Lymphoid Cells
Cell Types Blur Adapative vs. Innate
Let’s take a T-helper cell and make it innate
Innate Lymphoid Cells
Programming
- Pathogen and/or tissue resident patterns
- Signal
- Polarization-specific STAT
- Lineage determining TF
- Effector cytokine
Differentation depends on:
Innate Lymphoid Cells
Type 3 ILC
Type 3 ILC induce barrier healing and defense
Maintain “immunologic tone” of tissues barrier reinforcement ILC3s participate in containment of commensals
Innate Lymphoid Cells
Type 3 ILC
Type 3 ILC require AHR to make IL-22
Innate Lymphoid Cells
ILC2
To what signals ILC2 respond?
ILC2 respond to neuronal and adipose signales
There are a vast repertoire of receptors for neuropeptides
Innate Lymphoid Cells
ILC1
How do ILC1 acts?
ILC1 acts as tissue protectors
What cytokine ILC1 produce?
What roles does ILC have over mice?
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.
Development
Representation on how NFIL3, ID2, and PLZF commit to ILC
Representation of how ID2&PLZF blocks NK cell in mice
What is consider as an specialized ILC?
- 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
ILC convert during inflammation
Learning Check
What is the cell type that is cover?
Diagram of severe, chronic itch observed in atopic dermatitis (AD) patients
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
Learned table
Review Table
