Chronic Exercise and Immunity
James M. Rippe in Lifestyle Medicine, 2019
Natural killer cells are cytotoxic lymphocytes and a major constituent of the innate immune system. They protect against certain tumors and virally infected cells by releasing granules containing proteases and porins that induce apoptosis in the target cell. Yan et al. reported that the proportion of NK cells (CD16+CD56+) in isolated peripheral blood mononuclear cells was higher in older subjects who exercised regularly than those who did not,26 but the NK activity against K562 target cells was not different between these subject groups. Further, there were no differences in either NK cell number or activity between exercisers and non-exercisers in the young and middle-aged groups. In another study, there were no differences in the expression of NKG2D or NKG2A receptors, but young athletes had a greater NK cell activation and degranulation in response to cells from the K562 and .221 cell lines, though not .221-AEH, when compared with young non-athletes.27
Adaptive Tumor Suppression
John Melford in Pocket Guide to Cancer, 2017
Although they both kill cells infected with viruses, there is an important distinction between the capabilities of natural killer cells of the innate immune system and cytotoxic T-cells of the adaptive immune system. Both can kill cells displaying antigens attached to MHC Class I proteins on their outer membrane, but natural killer cells also kill cells with suppressed levels of MHC Class I proteins. Thus, natural killer cells are primed to eliminate cells that cytotoxic T-cells miss, because they do not display antigens, while cytotoxic T-cells kill cells that natural killer cells may miss because they (natural killer cells) only recognize a limited range of signature pathogen antigens. The arming of natural killer cells of the innate immune system, with a limited number of receptors coded for by genes, means they are less likely to be of significance in eliminating incipient cancer cells than cytotoxic T-cells, which are primed with wide array of protein antibodies. There are billions of different cytotoxic T-cells, each with its own unique antibody receptor. This receptor enables the adaptive immune system to attack virtually any cell displaying molecules that are not self, including incipient tumor cells.
Vaginal Immunology
William J. Ledger, Steven S. Witkin in Vulvovaginal Infections, 2017
Natural killer cells recognize and destroy cells that are infected with microbial pathogens. This activity is not learned and is not microorganism specific, and so these cells are a component of the innate immune defense system. The natural killer cells are inhibited from reacting with uninfected healthy cells by the expression of specific receptors, called killer cell immunoglobulin-like receptors (KIR), on their surface. The recognition of MHC class I molecules on healthy cells by KIR prevents natural killer cell–mediated cell lysis. Infection, however, results in a marked downregulation of MHC class I cell surface expression, and under these altered conditions, natural killer cell binding is no longer blocked and lysis occurs. Cytokines such as interferon gamma that are capable of activating the acquired immune system are also released from activated natural killer cells.
Recalcitrant Herpes Zoster Ophthalmicus in a Patient Discovered to Have Underlying Functional Natural Killer Cell Deficiency
Published in Ocular Immunology and Inflammation, 2022
Brent J. Deibert, Kurtis C. Johnson, Luke W. Desilet, Andrew C. Rorie
Natural killer cells are a vital part of the innate immune response. These cells are especially important in the body’s protection from viral infections. Varicella zoster virus (VZV) is essentially ubiquitous in the aging population. In those who experienced a childhood infection with VZV, known as chicken pox, the virus typically reactivates as the immune system wanes with age and is unable to keep the dormant virus contained. The re-activation of this virus causes the disease shingles, which presents as painful, dermatomal, vesicular lesion. This disease can affect almost every part of the body and is especially problematic when the eye is affected. In cases of immunodeficiency the course of the disease can be altered regarding age of onset or re-occurrence of the disease. Despite appropriate response from the adaptive immune system, deficiencies in cells of the innate response that preform viral surveillance can have a large impact on the disease course that would normally be self-limited.
Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved and future perspectives
Published in Expert Review of Hematology, 2018
Vania Lo Presti, Stefan Nierkens, Jaap Jan Boelens, Niek P. van Til
Another clinical approach of interest has been to obtain tumor-reactive T cells through in vitro generation of T cells, but this method has long been very inefficient. Culturing CB hematopoietic precursors on OP9 stromal cells that expresses Notch human ligand Delta-like1 showed that functional T cells with controlled antigen specificity in an HLA-restricted manner could be obtained after transduction with a TCR-specific retroviral vector [44]. In another similar study, these cells also acquired additional natural killer cell-like killing of tumor cell lines. Furthermore, the in vitro propagation of retroviral TCR transduced CD34+ CB-derived T cells also displayed little endogenous TCR expression with the tumor-reactive TCR highly expressed on the surface [45]. More recent reports show that human CB T cells could also be efficiently generated from HSPCs specific for CMV or Influenza-A virus epitopes without direct stromal co-culture or retroviral TCR transduction [46], which was also a tool to generate tumor-specific T cells against the antigen dopachrome tautomerase (hTRP-2) [47]. Using gammaretroviral vectors to introduce CAR or TCRs in CB CD34+ progenitor cells, van Caeneghem et al. [48], demonstrated that endogenous TCR expression was eliminated in most of the CD34 progenitor-derived T cells, which could make this an excellent method to generate universal T cell products. Since CB HSPCs are highly amenable to lentiviral transduction [49], this may increase overall production of gene-modified tumor-specific T cells generated by this method.
Synergistic induction of interferon-γ by interleukin-2, interleukin-12 and poly(I:C) in a human natural killer cell line
Published in Immunological Medicine, 2018
Hiroko Majima-Horiuchi, Shihoko Komine-Aizawa, Miki Karasaki-Suzuki, Yasuyuki Izumi, Shin Aizawa, Satoshi Hayakawa
Natural killer cells are an important part of the innate immune system to kill tumors and virally infected cells without MHC restriction or previous antigen exposure [18]. NK cells also produce cytokines that contribute to early host defense responses against pathogens [19]. Mucosal NK cells, including uterine NK (uNK) cells, frequently contact pathogens and virus-infected cells. We have recently reported that IL-2 is important for lipopolysaccharide-induced IFN-γ production by human decidual mononuclear cells [20]. However, because of the difficulty of maintaining freshly prepared decidual NK cells, a detailed analysis has not been possible. Thus, we employed the large granular human NK cell line KHYG-1 in this study as a model for mucosal NK cells. The KHYG-1 cell line was established from a patient with NK cell leukemia [13], and it has been employed as a human NK cell model in multiple studies [21–25].