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Immuno 12/14/12 NK Cells and Innate Immunity
HDPP final at UMMSM
28
Immunology
Graduate
12/14/2012

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Term
What are general characteristics of gamma-delta T-cells?
Definition
There is no memory as they are not MHC-restricted. They are found in mucosal epithelium, rarely in blood
Term
What do gamma-9-delta-2 T-cells recognize?
Definition
Phosphorylated metabolism intermediates and M. tuberculosis
Term
What are gamma-delta-1-T-cells?
Definition
Intra-epithelial lypmhocytes that recognize MICA and MICB. These receptors are upregulated by infected cells, turning them into APCs
Term
What do NKT cells recognized?
Definition
They have ab TCRs but instead of recognizing antigens on MHC they recognize lipids on CD1D
Term
What do NK cells respond to?
Definition
They don't have TCRs or CD3; they are an early response to intracellular infections, responding to MICA/B
Term
How do NK cells arise?
Definition
They come from common lymphoid progenitor (CLP) cells in the bone marrow
Term
What are the physical characteristics of NK cells?
Definition
Larger than T-cells with more granules. Armed for immediated release of cytolytic granules. No memory. Not sensitive to antigens. Highly expressed CD56 in tissues.
Term
What effect do infected cells have on NK cells?
Definition
They produce IFN-a and IFN-b, which induce further NK activation and proliferation
Term
What do effector NK cells do?
Definition
They produce IFN-y, which inhibits viral replication, and TNF-a, inducing macrophages to release IL-12 (activates NK cells) and IL-15 (necessary for survival)
Term
What is release by effector NK cells?
Definition
Cytotoxic perforin, granzymes, and FasL, like CTL-cells
Term
What links the adaptive and innate immune systems?
Definition
Macrophages and dendritic cells
Term
Why can the innate immune system not adapt?
Definition
There is no V(D)J recombination or Rag genes
Term
What are the receptors on NK cells?
Definition
Two functional groups: activating and inhibiting
Term
What are ITIMs?
Definition
They are found on inhibitory receptors and have phosphatase activity and cease signaling
Term
What provides activating signals?
Definition
Immunoreceptor tyrosine-based activating motifs
Term
What are the forms the receptors can take?
Definition
Immunoglobulin-like proteins or lectin-like carbohydrates
Term
What is NKG2D?
Definition
An activating lectin-like receptor for MIC ligands found on every NK-cell
Term
What are MIC ligands similar to?
Definition
They are structurally similar to HLA class I, but do not involve B2-ug
Term
What mediates NK cell activation?
Definition
The summation of activating and inhibitory signals mediates activation similar to neurons
Term
What are common inhibitory signals?
Definition
Usually binding to HLA class I. HLA-E acts as a ligand and presents elader sequences from HLA-A, B, and C from healthy cells to the CD94:NKG2A receptor. HLA class I binding to Killer-cell Ig-like receptors (KIRs).
Term
What happens to cells without HLA class I?
Definition
Some pathogens can down-regulate HLA class-I. CTL cells can't respond but NK cells can.
Term
Does a lack of inhibition stimulate NK cells?
Definition
No, they must be activated too
Term
How do NK cells signal antibody-dependent cell-mediated cytotoxicity?
Definition
They can bind to Fc regions on IgG1 and IgG3 causing receptor-cross-linking
Term
What are the Fc regions on IgG1 and IgG3?
Definition
FcyRIII and CD16
Term
What is the closest NK cells can get to memory?
Definition
FcyRIII receptors are complexed to ITAMs. The ADCC (antibody-dependent cell-mediated cytotoxicity) signal results in apoptosis of the target cell as a secondary immune response.
Term
What require important responses by NK cells?
Definition
Viruses, intracellular bacteria, tumor cells, and rejection of transplanted allogeneic hematopoietic grafts
Term
What is the "missing-self" hypothesis?
Definition
NK cells do not attack healthy autologous cells because NK cells express inhibitory receptors (ITIM) which recognize "self" MHC (HLA) class I molecules
Term
What is Antibody-dependent cell-mediated cytotoxicity (ADCC)?
Definition
Antibody binds antigens on surface of target cell. Fc receptors on NK cell recognize bound Ab. Cross-linking of Fc receptors signals the NK cell to kill the target cell, which dies by apoptosis
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