Immune system NK cells

NK cells are important constituents of the primary natural immune system. NK cell function is modulated by the surface expression of MHC molecules. Unlike T cells, NK cells form a first line of defense and kill target cells without prior sensitization. In addition, stimulatory and inhibitory receptors signal and control NK cell function. Therefore, it is plausible that herpesviruses also address this aspect of natural immunity. The status of this emerging field of research is presented in two reviews. An even more recent addition to the field is the recognition of the importance of chemokines, cytokines and their receptors. As expected from a virus which has co-speciated with the host, herpesviruses use this information and divert it to their advantage. For a virus it makes no difference whether the cell itself responds to virus infection, e.g. by apoptosis or any other type of internal cellular antiviral regulation, or whether the reaction is systemic and involves several specialized cells. It is therefore not surprising that viruses have also found principles to avoid induced cell death. 

The basis for the effector function by antigen-specific lymphocytes - especially antibody-secreting B cells, Td cells, and Tc cells - and the participation of other cellular components of the immune system in acquired immunity - including NK cells, macrophages, and neutrophils - have already been emphasized in other sections of this volume. It has also been emphasized that Th cells play an important effector role in acquired immunity as regulators in the growth and differentiation of B cells and Tc cells. In this regard, it is important to note that both populations of T cells whose participation in an acquired immune response is mediated by the secretion of lymph-okines, that is, Th and Tq cells, are characterized by the expression of CD4. 

Camaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A (1999) Cutting edge Cross-talk between cells of the innate immune system NKT cells rapidly activate NK cells. J Immunol 163 4647 650... 

The role of NFAT in the immune system is not restricted to T cells. NFAT proteins are also expressed in other cells of the immune system, such as B cells, NK cells, and mast cells, where they have been shown to regulate the expression of cytokines, cell surface receptors, and immunoglobulins [4, 5]. 

The theoretical complications posed by random chromosomal integration became a medical reality in 2002, when two children who had received retroviral-based gene therapy 2 years previously developed a leukaemic-like condition. The initial clinical trial aimed to treat X-linked severe combined immunodeficiency (SCID-X1), a hereditary disorder in which T-lymphocytes and NK cells in particular do not develop, due to a mutation in the gene coding for the yc cytokine receptor subunit. The clinical consequence is near abolition of a functional immune system. 

The receptor for RANKL is RANK, also known as ODAR (Anderson et al. 1997 Hsu et al. 1999). RANK is expressed in osteoclast precursors, mature osteoclasts, condrocytes, fibroblasts, and immune system cells (Anderson et al. 1997 Hsu et al. 1999). The binding of RANKL with RANK on preosteoclasts initiates the OCS and the activation of osteoclasts (Anderson et al. 1997 Hsu et al. 1999 Nakagawa et al. 1998). RANK-deficient mice display a phenotype characterized by osteopetrosis and several defects in the immune system similar to that observed in RANKL-deficient mice (Dougall et al. 1999). Consistent with this hypothesis, RANK-deficient mice are resistant to bone resorption induced by TNF-a, IL-l/J, or vitamin D3 (Li et al. 2000). In agreement with this, mice deficient in molecules implied in the transduction pathway from RANK like TRAF-6 or NF-/c Bl/NK-/c B2 also show an osteopetrotic phenotype,... 

In contrast to adaptive immune function, fewer studies have examined effects of TCDD on the innate immune system. Furthermore, of the limited data available, much of it is inconsistent. For example, natural killer (NK) cell activity has been reported to be unaffected,80,93 diminished,94 and increased95 following exposure to TCDD. Although a thorough assessment of AhR expression in all innate cell lineages has not been conducted, neutrophils and macrophages express the AhR,8,96 and neutrophils are affected... 

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