Dr. A. Horuzsko
Mechanisms of Disease, Lecture 9
February 7th, 2006
- Natural Killer and Natural Killer T Cells
- Classification of T Cells
- Biology of Human NK Cells
- Biology of Human NKT Cells
- NKT Cell-Mediated Tumor Rejection
- Conventional T cells express utilize the T-cell-receptor/MHC pathway.
- Unconventional T cells are the NK T cells.
- NK cells are CD56+ and CD3-.
- Produce cytokines and chemokines, including IFN-γ (gamma), TNF-α (alpha), IL-10, and GM-CSF.
- Support adaptive immune responses through antibody-dependent cellular cytotoxicity through FCγRII (CD16).
- Demonstrate spontaneous cytotoxic activity against virus-infected, leukemic, and other tumor cells.
- Two subtypes of NK cells, CD56bright and Cd56dim, exist:
- NKT cells are both CD56+ and CD3+.
- Their T-cell receptor (TCR) contains Vα24Jα18 and Vβ11 chains in humans and Vα14Jα18 and Vβ8 chains in mice; and recognizes α-galactosylceramide (α-gal-cer).
- NKT cells are present in most tissues where T cells are found, such as liver, bone marrow, spleen, and thymus, but are difficult to differentiate, since they express an activation or memory cell phonotype of CD44, CD69, and Cd122.
- Secrete TH!1and T!H2 cytokines, express perforin and Fas ligand.
- Activated NKTcells kill specifically by TCR ligand recognition, differentiating them from NK cells.
- The NK complex is a set of genes (on human chromosome 9 and mouse chromosome 6) encoding for the activation and inhibitory NK receptors.
- The ITIM motif on the intracellular domain is a marker for the inhibitory NK receptor.
- IL-12 is a powerful signal inducing tumor rejection.
- IL-12 acts in low doses on NKT cells (specific response) and in high doses on NK cells (non-specific response).
- IL-12 mediates signal transduction between antigen-presenting cells (APCs) and NK and NKT cells.
- NKT cell activation involves a three-step sequence of events.
- NKT cell must recognize the APC through binding CD1d by TCR.
- The NKT cell upregulates CD40L which signals the APC by CD40 binding of CD40L, which then begins to produce IL-12.
- Upon reception of IL-12, NKT and NK cells activate and begin producing IFN-γ (interferon gamma).
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