NK-cells are defined as large granular lymphocytes that do not express T-cell antigen receptors (TCR) or Pan T marker CD3 or surface immunoglobulins (Ig) B cell receptor but that usually express the surface markers CD16 (FcγRIII) and CD56 in humans, and NK1.1/NK1.2 in certain strains of mice. Up to 80% of NK cells also express CD8.
They were named "natural killers" because of the initial notion that they do not require activation in order to kill cells that are missing "self" markers of major histocompatibility complex (MHC) class I.
NK cells are activated in response to interferons or macrophage-derived cytokines. They serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection. Patients deficient in NK cells prove to be highly susceptible to early phases of herpes virus infection.
In order for NK cells to defend the body against viruses and other pathogens, they require mechanisms that enable the determination of whether a cell is infected or not. The exact mechanisms remain the subject of current investigation, but recognition of an "altered self" state is thought to be involved. To control their cytotoxic activity, NK cells possess two types of surface receptors: activating receptors and inhibitory receptors. Most of these receptors are not unique to NK cells and can be present in other T cell subsets as well.
These inhibitory receptors recognize MHC class I alleles, which could explain why NK cells kill cells possessing low levels of MHC class I molecules. This inhibition is crucial to the role played by NK cells. MHC class I molecules consist of the main mechanism by which cells display viral or tumor antigens to cytotoxic T-cells. A common evolutionary adaption to this seen in both intracellular microbes and tumours is a chronic down-regulation of these MHC I molecules, rendering the cell impervious to T-cell mediated immunity. It is believed that NK cells, in turn, evolved as an evolutionary response to this adaption, as the loss of the MHC would deprive these cells of the inhibitory effect of MHC and render these cells vulnerable to NK-cell mediated lysis.
NK cell receptors can also be differentiated based on function. Natural cytotoxicity receptors directly induce apoptosis after binding to ligands that directly indicate infection of a cell. The MHC dependent receptors (described above) use an alternate pathway to induce apoptosis in infected cells.
However, by 1973, 'natural killing' activity was established across a wide variety of species, and the existence of a separate lineage of cells possessing this ability was postulated. Through the use of monoclonal antibodies, natural killing ability was mapped to the subset of large, granular lymphocytes known today as NK-cells.
The cells were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self" recognition ("missing-self" recognition is a term used to describe cells with low levels of MHC class I cell surface marker molecules — a situation that could arise due to viral infection, or in tumors under strong selection pressure of killer T cells).
With the discovery of activating receptors almost two decades after the discovery of the inhibitory receptors these cells continue to be called by the same name, though “natural” no longer means the same thing. The term “natural killer” continues to be justified by:
NK-cells are defined as large granular lymphocytes that do not express T-cell antigen receptors (TCR) or Pan T marker CD3 or surface immunoglobulins (Ig) B cell receptor but that usually express the surface markers CD16 (FcγRIII) and CD56 in humans, and NK1.1/NK1.2 in certain strains of mice. Up to 80% of NK cells also express CD8.
They were named "natural killers" because of the initial notion that they do not require activation in order to kill cells that are missing "self" markers of major histocompatibility complex (MHC) class I.
NK cells are activated in response to interferons or macrophage-derived cytokines. They serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection. Patients deficient in NK cells prove to be highly susceptible to early phases of herpes virus infection.
In order for NK cells to defend the body against viruses and other pathogens, they require mechanisms that enable the determination of whether a cell is infected or not. The exact mechanisms remain the subject of current investigation, but recognition of an "altered self" state is thought to be involved. To control their cytotoxic activity, NK cells possess two types of surface receptors: activating receptors and inhibitory receptors. Most of these receptors are not unique to NK cells and can be present in other T cell subsets as well.
These inhibitory receptors recognize MHC class I alleles, which could explain why NK cells kill cells possessing low levels of MHC class I molecules. This inhibition is crucial to the role played by NK cells. MHC class I molecules consist of the main mechanism by which cells display viral or tumor antigens to cytotoxic T-cells. A common evolutionary adaption to this seen in both intracellular microbes and tumours is a chronic down-regulation of these MHC I molecules, rendering the cell impervious to T-cell mediated immunity. It is believed that NK cells, in turn, evolved as an evolutionary response to this adaption, as the loss of the MHC would deprive these cells of the inhibitory effect of MHC and render these cells vulnerable to NK-cell mediated lysis.
NK cell receptors can also be differentiated based on function. Natural cytotoxicity receptors directly induce apoptosis after binding to ligands that directly indicate infection of a cell. The MHC dependent receptors (described above) use an alternate pathway to induce apoptosis in infected cells.
However, by 1973, 'natural killing' activity was established across a wide variety of species, and the existence of a separate lineage of cells possessing this ability was postulated. Through the use of monoclonal antibodies, natural killing ability was mapped to the subset of large, granular lymphocytes known today as NK-cells.
The cells were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self" recognition ("missing-self" recognition is a term used to describe cells with low levels of MHC class I cell surface marker molecules — a situation that could arise due to viral infection, or in tumors under strong selection pressure of killer T cells).
With the discovery of activating receptors almost two decades after the discovery of the inhibitory receptors these cells continue to be called by the same name, though “natural” no longer means the same thing. The term “natural killer” continues to be justified by:
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