Natural killer cells are a recently discovered subpopulation of lymphoid cells that are present in most normal individuals of a range of mammalian and avian species. Natural killer cells have spontaneous cytolytic activity against a variety of tumor cells and some normal cells, and their reactivity can be rapidly augmented by interferon. They have characteristics distinct from other types of lymphoid cells and are closely associated with large granular lymphocytes, which comprise about 5 percent of blood or splenic leukocytes. There is increasing evidence that natural killer cells, with the ability to mediate natural resistance against tumors in vivo, certain virus and other microbial diseases, and bone marrow transplants, may play an important role in immune surveillance.

https://science.sciencemag.org/content/sci/214/4516/24.full.pdf

Natural killer cells: their roles in defenses against disease

Invasive aspergillosis is a severe pneumonia that is usually fatal despite currently available therapy. The disease disproportionately afflicts immunocompromised patients, indicating the critical importance of the immune status of the host in this infection, but the defense mechanisms against this pathogen remain incompletely understood. In the current study, we hypothesized that the chemokine ligand monocyte chemotactic protein-1, also designated CC chemokine ligand-2 (MCP-1/CCL2) is necessary for effective host defense against invasive aspergillosis in immunocompromised hosts. We found a rapid and marked induction of MCP-1/CCL2 in the lungs of neutropenic mice with invasive aspergillosis. Neutralizing MCP-1/CCL2 resulted in twofold greater mortality and greater than threefold increase in pathogen burden in the lungs. Neutralization of MCP-1/CCL2 also resulted in reduced recruitment of NK cells to the lungs at early time points, but did not affect the number of other leukocyte effector cells in the lungs. Ab-mediated depletion of NK cells similarly resulted in impaired defenses against the infection, resulting in a greater than twofold increase in mortality and impaired clearance of the pathogen from the lungs. These data establish MCP-1/CCL2–mediated recruitment of NK cells to the lungs as a critical early host defense mechanism in invasive aspergillosis and demonstrate NK cells to be an important and previously unrecognized effector cell in this infection.

/pdf/chemokine-mediated-recruitment-of-nk-cells-is-a-critical-t3pqai6it5.pdf

Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis

Melatonin, a neurohormone produced mainly by the pineal gland, is a modulator of haemopoiesis and of immune cell production and function, both in vivo and in vitro. Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines, and its administration favours Th1 priming. In both normal and leukaemic mice, melatonin administration results in quantitative and functional enhancement of natural killer (NK) cells, whose role is to mediate defenses against virus-infected and cancer cells. Melatonin appears to regulate cell dynamics, including the proliferative and maturational stages of virtually all haemopoietic and immune cells lineages involved in host defense - not only NK cells but also T and B lymphocytes, granulocytes and monocytes - in both bone marrow and tissues. In particular, melatonin is a powerful antiapoptotic signal promoting the survival of normal granulocytes and B lymphocytes. In mice bearing mid-stage leukaemia, daily administration of melatonin results in a survival index of 30-40% vs. 0% in untreated mice. Thus, melatonin seems to have a fundamental role as a system regulator in haemopoiesis and immuno-enhancement, appears to be closely involved in several fundamental aspects of host defense and has the potential to be useful as an adjuvant tumour immunotherapeutic agent.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.0959-9673.2006.00474.x

The role of melatonin in immuno-enhancement: potential application in cancer.

The role of natural killer cells in the control of tumor growth and metastasis.

The immune system is increasingly found to be involved in the development of several chronic illnesses, for which allopathic medicine has provided limited tools for treatment and especially prevention. In that context, it appears worthwhile to target the immune system in order to modulate the risk of certain chronic illnesses. Meanwhile, natural health products (NHPs) are generating renewed interest, particularly in the prevention and treatment of several chronic diseases. Over 20 scientists from fields related to immune function and NHPs were thus convened to establish the state of knowledge on these subjects and to explore future research directions. This review summarizes the result of discussions held during the symposium. It thus seeks to be thought provoking rather than to comprehensively cover such broad areas of research. Notably, a brief overview of the immune system is presented, including potentially useful targets and strategies to keep it in an equilibrated state, in order to prevent certain disorders. The pertinence and limitations of targeting the immune system to prevent chronic diseases is also discussed. The paper then discusses the usefulness and limitations of current experimental tools available to study the immune modulating effects of NHPs. Finally, a concise review of some of the most studied NHPs showing promising immunomodulatory activity is given, and avenues for future research are described.

/pdf/natural-health-products-modulation-of-immune-function-and-10ox0mftkb.pdf

Natural Health Products, Modulation of Immune Function and Prevention of Chronic Diseases

Transfer to cyclophosphamide-treated mice of natural killer (NK) cells and in vivo natural reactivity against tumors.

Publisher Summary This chapter focuses on regulation of in vivo reactivity of natural killer (NK) cells. The results with normal bone marrow cells are consistent with previous indications that NK cells mediate in vivo natural resistance against bone marrow transplants but differ in that some reactivity has been found against syngeneic cells and the stronger reactivity of allogeneic or parental cells, suggesting an autoreactive nature of NK cells. In view of the accumulating evidence for a possible in vivo role of NK cells in defenses against tumor cells, virus infections, and in homeostatic regulation of normal nonneoplastic tissues, it is particularly important to develop procedures to more definitively document their in vivo importance and to determine how to manipulate the levels of in vivo natural reactivity. The suppressor cells present in the spleen of normal SJL/J mice could account for the lower reconstitution of such mice and for the low NK activity of this strain. The data support the in vivo relevance of in vitro defined suppressor cells for NK activity.

C. Cesarini

Papers

Transfer to cyclophosphamide-treated mice of natural killer (NK) cells and in vivo natural reactivity against tumors.

Regulation of in vivo reactivity of natural killer (nk) cells