ABSTRACT
Natural killer cells are an essential component of the immune system, but also an integral part of the anti-cancer T cell immune response. Humans who have a genetic defi ciency in NK cells almost always suffer from fatal infections during childhood. The NK cell is a very different type of immune cell. It is thought that a cytotoxic effector cell, which would be a part of the primordial “innate” immune system, would be similar to an NK cell. This would have occurred prior to the development of T and B cells of today’s “adaptive” immune system that has existed for 500 million years. Even though it has been proven that the NK cell of today developed after the existence of T and B cells, it still exhibits primordial functions. Initially it was thought that NK cells were cytotoxic only to cells that lacked selfMHC class I proteins. This was called the “missing self” theory of NK cell function. However, as knowledge grew about how NK cells recognized their targets, it was clear that they have many receptors that recognize MHC class I and MHC class I-like proteins, as well as proteins not related to MHC class I, which is why they have the ability to attack MHC class I negative targets. Because NK cells and T cells kill their targets by a similar mechanism (perforin), it is thought that these two cells developed from a common ancestor. Despite this similarity to T cells, NK cells express totally different cell surface proteins. For instance, they do not express the CD3 protein (Caligiuri 2008). As outlined in Chapter 9, this is an essential protein expressed by T cells because it is intimately associated with the assembly and function of the T cell receptor (TCR).
