Natural Killer (NK) Cells

and NKT cells

• host cells that have become infected with virus;
• host cells that have become cancerous.

Features of NK Cells

• The specificity of the receptors with which NK cells recognize potential targets are NOT diversified like the
  • αβ and γδ receptors (TCRs) of T cells and the
  • antigen receptors (BCRs) of B cells.

    Link to discussion of how a diverse repertoire of TCRs and BCRs is generated.

• However, we do inherit multiple genes for NK receptors and these are polymorphic so that the repertoire of NK receptors differs from person to person.
• NK cells have
  • activating receptors, that activate the NK cell when it binds to a target cell, and
  • Killer Inhibitory Receptors (KIRs) that transmit an inhibitory signal if they encounter class I MHC molecules on a cell surface. (This is in sharp contrast to T cells that can only recognize antigens when presented within a MHC molecule. [Discussion])
• Because viruses often suppress class I MHC expression in cells they infect, the virus-infected cell becomes susceptible to killing by NK cells.
• Because cancer cells have reduced or no class I MHC expression, they, too, become susceptible to killing by NK cells.
• The killing is done by the exocytosis of granules containing perforin and granzymes.
• Because NK cells are
  • preprogrammed to recognize their targets and
  • have no need to develop into a clone of identical cells (as T cells and B cells do),
• they are able to respond rapidly, thus providing another arm of innate immunity.
• In addition to killing target cells, NK cells secrete cytokines such as the
  • anti-viral cytokine IFN-γ and the
  • inflammatory cytokine TNF-α

NKT Cells

NKT cells are NOT the same as NK cells.

NKT cells are T cells with an αβ TCR. However, they also express some of the cell-surface molecules of NK cells — hence their name.

They differ from most T cells

• in the sharply limited diversity of their αβ TCRs [Discussion];
• and these respond to glycolipid antigens presented by a cell-surface molecule designated CD1d (rather than to peptide antigens presented by MHC molecules [Discussion]).

• IFN-γ, a major cytokine of Th1 immune responses or
• IL-4, the major cytokine of Th2 responses.

Perhaps the function of NKT cells is to provide quicker help for a cell-mediated immune response (IFN-γ) or antibody-mediated response (IL-4) than the several days needed by conventional T-helper cells. If so, NKT cells would represent a link between innate and adaptive immunity.

• autoimmune diseases
• graft rejection
• tumors