Stages Of Natural Killer Cell Activation

Changes in the microscopic appearance of an NK cell can be used to mark different stages of activation. These changes in the spatial relationships of the cellular components result from intracellular signals that in turn result from signals from the NK cell receptors. During the stages of activation, changes in appearance and function are used to determine whether inhibition, overexpression, or knockout of a molecule is playing a role in NK cell processes.

The first step toward NK cell cytotoxicity is the physical association of the NK cell and its target. During conjugate formation, the NK cell attaches to ligands on the target via a variety of receptors and integrins. Determining if the number of NK:target cell conjugates is affected by a given molecule provides a way to determine if the molecule is involved in controlling the association of the two cells.

Shortly after the association of the NK cell and its target an immunological synapse is formed

[77]. This assembly indicates a reorganization of the bound receptors into specific regions within the membranes between the target and the effector cell. Intracellular signaling is both a cause and an effect of this synapse formation; signaling is necessary for the membrane reorganization and is propagated by the synapse formation [78,79],

As part of this synapse formation and the resulting NK cell activation, microdomains enriched in sphingolipids and cholesterol, called lipid rafts, polarize to the site of NK:target cell contact

[78], The lipid rafts contain a different subset of proteins than the rest of the plasma membrane, and the composition of proteins in the lipid raft changes with lymphocyte activation. Thus, lipid rafts recruited as a result of signaling may then enhance signaling by aggregating activating receptors and other signaling and adapter molecules. Once aggregated, lipid rafts may also serve as a possible down-regulator of future signaling by recruiting phosphatases [80],

As proteins move into and out of the lipid rafts, other proteins must move about the NK cell to support its function. The cytoskeleton of the NK cell reorganizes as part of activation. This reorganization of the backbone of the cell facilitates the movement of other proteins about the cell, including proteins packaged in granules. After cytoskeleton reorganization, granules polarize to the site of target cell contact and are then exocytosed into the space between the NK cell and target cell. Both the microtubule organizing centre and the actin cytoskeleton participate in this reorganization. The dramatic changes in cell polarity that result from these cytoskeletal changes indicate the activation of the NK cell.

Natural Treatments For Psoriasis

Natural Treatments For Psoriasis

Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.

Get My Free Ebook

Post a comment