Natural killer (NK) cells are populations of lymphocytes that can be activated to mediate significant levels of cytotoxic activity and produce high levels of certain cytokines and chemokines. NK cells respond to and are important in defense against a number of different infectious agents. The first indications for this function came from the observations that virus-induced interferons alpha/beta (IFN-alpha and -beta) are potent inducers of NK cell-mediated cytotoxicity, and that NK cells are important contributors to innate defense against viral infections. In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production. Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms. However, high levels of IFN-alpha/beta appear to be unique and/or uniquely dominant in the context of viral infections and act to regulate other innate responses, including induction of NK cell proliferation in vivo and overall negative regulation of IL-12 production. A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.

NATURAL KILLER CELLS IN ANTIVIRAL DEFENSE: Function and Regulation by Innate Cytokines

Publisher Summary This chapter focuses on the important discovery that virus-specific cytotoxic T cells are dually specific for virus and for a self cell surface antigen encoded by the major histocompatibility complex (MHC). The initial work was carried out on the lymphocytic choriomeningitis virus system but it soon became evident that the same phenomenon applied to many other viruses. In addition, the same principle has been found to hold for other antigenic systems, such as trinitrophenyl coupled to cells, minor histocompatibility antigens, and the H-Y model. Graft rejection and the need for genetically homogeneous inbred mouse strains for cancer research led to the development of transplantation immunology and immunogenetics. The result is that the gene complex coding for major transplantation antigens is one of the better understood mammalian genetic regions. Cytotoxic T-cell specificity is comparable to serological specificity. Because quantification of specificity or cross-reactivity is difficult, and because of the technical limitations of these cytotoxic T-cell assays, results are interpreted with great reservation. MHC restriction reflects the fact that the effector function of T cells is determined by the kind of Self-H recognized together with the foreign antigen on cell surfaces: K and D are receptors for lytic signals, I determinants are receptors for cell differentiation signals that are delivered antigen-specifically by T cells.

MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness.

Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice.

Publisher Summary The term “cell-mediated cytotoxicity” applies to lytic reactions that require the participation of lymphoid or non-lymphoid cells but not of added complement. It has been clearly established that several pathways, including different cell types, are involved in cytotoxic reactions in vitro. With membrane-associated antigens, such as transplantation, and tumor-associated antigens, the cytotoxic effect of effector cells on adequate target cells is most often highly specific and requires intimate contact rather than release of diffusible toxic factors. Specific cell-mediated cytotoxicity in vitro can be divided into three categories according to the nature of the effector cells.

Cell-Mediated Cytotoxicity, Allograft Rejection, and Tumor Immunity

From the combination of knowledge and actions, someone can improve their skill and ability. It will lead them to live and work much better. This is why, the students, workers, or even employers should have reading habit for books. Any book will give certain knowledge to take all benefits. This is what this the interferon system tells you. It will add more knowledge of you to life and work better. Try it and prove it.

The Interferon System

Mouse interferon preparations enhanced the specific cytotoxicity of sensitized lymphocytes for allogeneic target tumor cells. The factor responsible for the enhancement of cytotoxicity could not be dissociated from the antiviral activity of interferon by standard physicochemical means. Thus, in addition to its well-known antiviral activity, and its effect on cell division, interferon also appears to enhance a specialized cellular function. It is suggested that a common mechanism of action underlies these seemingly different biologic phenomena, and that interferon may play a role in the regulation of fundamental cellular processes.

https://www.pnas.org/content/pnas/69/3/721.full.pdf

Enhancement by Interferon of the Specific Cytotoxicity of Sensitized Lymphocytes

Preparations of mouse interferon enhanced the expression of surface antigens of murine leukemia L 1210 cells, as determined by their alloantibody-absorbing capacity. The factor responsible for the enhancement of surface antigen expression could not be dissociated from the antiviral activity of interferon by standard physicochemical means. Likewise, interferon did not increase the antibody-absorbing capacity of an interferon-resistant subline of L 1210 cells. We conclude that interferon treatment of L 1210 cells is accompanied by modifications of the cell surface.

Enhancement by Interferon of the Expression of Surface Antigens on Murine Leukemia L 1210 Cells

Mouse interferon preparations inhibited the antibody response to sheep erythrocytes (SRBC) in spleen cell cultures. The effect was seen when the cultures were pretreated with interferon for 6 hr, or when interferon was added up to 40 hr after addition of SRBC. The factor responsible for this inhibition could not be dissociated from the antiviral activity of interferon by standard physicochemical means. The application of a mosaic cell culture system suggested that the inhibitory effect of interferon was due to an action on B cells. Interferon treatment of T cells and macrophages did not affect their normal function as helper cells in this system. To our knowledge, these findings constitute the first example of an effect of interferon on B lymphocytes. In addition, it was found that in “low-responder” composite cultures, pretreatment of the B cell population with low amounts of interferon led to a considerable enhancement of the antibody response, whereas higher concentrations of interferon gave a similar degree of inhibition as that found for “high-responder” cultures. Late addition of mouse interferon preparations to SRBC-stimulated spleen-cell cultures augmented the number of plaque-forming cells (PFC). This effect was most pronounced when interferon was added only 4 hr before the plaques were counted on day 4. This increase was followed on day 5 by a decrease in the number of PFC compared with that of control cultures.

Effects of Interferon on Antibody Synthesis in Vitro

Treatment of young and mature mice with potent mouse interferon preparations results in a marked enhancement of the expression of histocompatibility antigens on the surface of thymocytes and splenic lymphocytes as measured by an enhanced absorption of alloantiserum. We postulate that such modifications of the cell surface may reflect an effect of interferon on lymphocyte maturation and may be relevant to the effect of interferon on lymphocyte function.

Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells.

The expression of surface antigens of thymocytes and splenic lymphocytes was determined by quantitative absorption of alloantibodies. Mouse interferon preparations enhanced the expression of histocompatibility antigens of thymocytes from mice of different ages, but of splenic lymphocytes only from young mice. Interferon did not affect the expression of the theta antigen of thymocytes or splenic lymphocytes.

Pernilla Lindahl

Papers

Enhancement by Interferon of the Specific Cytotoxicity of Sensitized Lymphocytes

Enhancement by Interferon of the Expression of Surface Antigens on Murine Leukemia L 1210 Cells

Effects of Interferon on Antibody Synthesis in Vitro

Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells.

Enhancement of the expression of histocompatibility antigens of mouse lymphoid cells by interferon in vitro.