Lymphocyte-activated killer activity

Ah = Antibody IL = interleukin TNF =tumornecrosis factor INF = interferon LAK =lymphocyte-activated killer CSF =colony stimulating factors and FGF = fibroblast growth factor. 

LAD Leucocyte adhesion deficiency LAK Lymphocyte-activated killer (cell) LAM, LAM-1 Leucocyte adhesion molecule, -1... 

Kay, N., Allen, J., Morley, J.E., Endorphins stimulate normal human peripheral blood lymphocyte natural killer activity, Life Sci., 35, 53, 1984. 

To date, cellular and gene therapy products submitted to FDA have included clinical studies indicated for bone marrow marking, cancer, cystic fibrosis, AIDS, and inborn errors of metabolism and infectious diseases. Of the current active INDs approximately 78% have been sponsored by individual investigators or academic institutions and 22% have also been industry sponsored. In addition to the variety of clinical indications the cell types have also been varied. Examples include tumor infiltrating lymphocytes (TIL) and lymphocyte activated killer (LAK) cells, selected cells from bone marrow and peripheral blood lymphocytes, for example, stem cells, myoblasts, tumor cells and encapsulated cells (e.g., islet cells and adrenal chromaffin cells). 

IL-2 (Proleukin) is a cytokine that promotes the proliferation, differentiation, and recruitment of T and B lymphocytes, natural killer cells, and thymocytes. Human recombinant IL-2 is designated as rIL-2. rIL-2 binds to IL-2 receptors on responsive cells and induces proliferation and differentiation of T helper cells and T cytotoxic cells. It also can induce B-lymphocyte proliferation, activate macrophage activity, and augment the cytotoxicity of natural killer cells. 

Lipoxins have diverse effects on leukocytes, including activation of monocytes and macrophages and inhibition of neutrophil, eosinophil, and lymphocyte activation. Both lipoxin A and lipoxin inhibit natural killer cell cytotoxicity. 

In rat liver, 1,2-dimethylhydrazine had no consistent effect on the relative focal volume of y-glutamyltranspeptidase-positive preneoplastic foci (Denda et al., 1988). Locniskar et al. (1985) treated Brown-Norway and Fischer rats with 150 mg/kg bw 1,2-dimethylhydrazine by gavage five times over a three-week period. Five months after the final treatment, isolated splenic, colonic intraperithelial lymphocytes and lamina propria lymphocytes from the Brown-Norway strain exhibited low natural killer cell activity and reduced splenic T-lymphocyte proliferation in response to autologous non-T lymphocytes. Furthermore, colonic lamina propria lymphocyte proliferation was low, and Brown-Norway rats had a low incidence of 1,2-dimethylhydrazine-induced colonic neoplasms (7%) in comparison with Fischer rats, which had more effective splenic and colonic intraperithelial lymphocyte natural killer cell activity, enhanced splenic autologous mixed lymphocyte response, enhanced colonic lamina propria lymphocyte proliferation and a higher incidence of colon tumours (20%). 

Li, Q., Nagahara, N., Takahashi, H., Takeda, K., Okumura, K. (2002). Organophosphorus pesticides markedly inhihit the activities of natural killer, cytotoxic T lymphocyte and lymphocyte-activated killer a proposed inhihiting mechanism via granzyme inhibition. Toxicology 172 181-90. 

Li, Q., Hirata, Y., Piao, S., Minami, M. (2000). The byproducts generated during sarin-synthesis in the Tokyo sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity. Toxicology 146 209-20. 

Exercise poses a stress on the immune system however, moderate chronic exercise may enhance positive immune functions. Severe or intense long-term exercise may compromise the immune system by suppressing concentrations of lymphocytes, natural-killer cell activity, lymphocyte proliferation, and secretory IgA. During the period of immune impairment ( open window"), microbial agents may invade the host and cause infections. The changes in immune functions, lower exercise capacity, and nutritional factors in the elderly may lead to a greater and longer open window period, increased risk of infections which may contribute to morbidity and mortality. 

Smdies in the 1970s showed that cyclosporin inhibits humoral immunoreactions, and that it had a selective effect on T-cell dependent immunoreactions and that its effect was reversible. Cyclosporin is considered to interfere with the process for primary T-cell activation. In this way the formation of T-effector cells, cytotoxic T-lymphocytes or killer lymphocytes, which have the dominant function in cell mediated immune reactions like rejecting an allograft in transplantation surgery and delayed hypersensitivity reaction, is prevented. 

The immune system does mount a vigorous response in these early days. Macrophages ingest the viral particles and degrade them, and then display small portions of the virus (small peptides called epitopes) on their surface, and this attracts the attentions of helper T-cells, which in turn activate killer T-cells and B-lymphocytes. The killer T-cells attack cells displaying the viral epitopes, and the B-cells produce dedicated antibodies that also seek out and destroy such cells. Not surprisingly, in the early days after infection, around 30% of patients exhibit typical symptoms of their immune response to viral... 

Natural killer (NK) cells and cytotoxic T lymphocytes (CTL) are the primary line of defense against viruses and other intracellular pathogens in the immune system. The cytotoxic lymphocytes recognize infected host cells and kill them with the help of the pore-forming protein perforin and by proteolytic events carried out by members of the granzyme family of serine proteases. Although an essential component of immunity under normal conditions, aberrant cytotoxic lymphocyte activity has been associated with autoimmune disorders such as rheumatoid arthritis, diabetes, or allograft rejection [65],... 

Azathioprine, 6-(l-methyl-4-nitro-imidazole-5-yl)-thiopurine (see Figure 1), is an immunosuppressive agent [1,2], which is widely used in clinical treatment of autoimmune disorders as weU as in prevention of graft rejection or graft-versus-host disease in organ and tissue transplantation [3-10], Azathioprine acts on several activities in cellular immunity processes. It inhibits lymphocyte activation [11], lymphocyte differentiation [12], in-vitro lymphocyte stimulation [13,14], in-vitro mixed lymphocyte reaction [15] and it reduces the activity of natural killer lymphocytes [16,17],... 

In mice with immune suppression induced by cyclophosphamide, intraperitoneal administration of 2.5, 25, or 250 mg/kg of reishi polysaccharides daily for 7 days enhanced the function of immunological effector cells. The 2.5 mg/kg dose accelerated recovery of bone marrow cells, red blood cells, white blood cells, splenic natural killer cells, and natural killer T cells, and enhanced T and B cell proliferation responses, cytotoxic T lymphocyte activity, and NK cell and lymphokine activated killer cell activity (Zhu etal. 2007). 

In rat lymphoid cells exposed to concentrations of ochratoxin A of 0, 0.5, 2 or 20 pmol/l (equivalent to 0, 0.2,0.8 or 8 mg/l), the cytotoxic activity of natural killer cells was dose-dependently decreased, reaching statistical significance at the highest dose. The cytotoxic T lymphocyte activity was significantly decreased at the lowest concentration only. The bacteriolytic activity of macrophages varied only slightly, and the proliferative response of lymphocytes to concanavalin A and lipopolysaccharide was not affected (Alvarez-Erviti et al., 2005). 

---