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Biomedical subjects

T C Merigan

Publications and source records attributed to T C Merigan.

At least 307 records · Page 17Linked to original sources

'Non-specific' mediators in host defense against respiratory viruses: assay methods and results.

Understandably, there is interest in further defining the nature of 'non-specific' defenses. This, in fact, would clarify the specific nature of their appearance and action, as well as their role in host defense. Therefore, 'non-specific' defenses in my discussion will be taken to mean non-immune defenses in virus infections. Tissue or respiratory tract organ cultures are convenient means of studying host defenses in the absence of immune responses. Factors to be controlled in making observations with such systems will be discussed which help 'in vitro' results to parallel 'in vivo' findings. 'In vitro' and 'in vivo' methods and results probing importance of mucous barrier, ciliary activity, temperature and pH will be reviewed. Critical points in separating cellular and humoral immune functions from non-specific mediators will also be touched on. This distinction is complicated by the fact that both limbs of immunity work in close concert with macrophages, PMN's complement and other inflammatory responses. Interferon and macrophage mobilization are examples of 'non-specific' responses which have more recently become complicated by their recognition as part of the effector limb of the cell-mediated immune responses. Finally, methods will also be presented for distinguishing human interferon of the immune-specific variety associated with cell-mediated immunity from that produced by viral infection of non-immune cells.

Antigens, Viral↗

Mechanism of the suppressive effect of interferon on antibody synthesis in vivo.

Mouse interferon preparations significantly suppress the in vivo antibody response to sheep red blood cells (SRBC), a thymus-dependent antigen, and to Salmonella typhimurium lipopolysaccharide (LPS), a thymus-independent antigen. It is also possible to effect the late responses of antigen sensitive "memory" cells observed during secondary immunization by administration of interferon prior to primary immunization. The immunosuppressive activity of interferon was time- and dose-dependent. Maximum suppression was produced when animals were given 1.5 times 10-5 units of interferon between 4 and 48 hr before antigenic stimulation. These findings suggested that interferon affects some early event(s) in the process of antibody synthesis which might be related to the general inhibitory effect of interferon on rapidly dividing cells and viral m-RNA translation. In addition, the use of nonadherent spleen cell cultures from interferon-treated mice, immunized in vitro with a thymus-independent antigen, indicated that in this situation the inhibitory effect of interferon was due to an action on B lymphocytes. A variety of soluble "suppressive" factors are secreted by T cells as a consequence of activation by mitogens or specific antigens in vitro. Since T cells are recognized as one of the sources of interferon, it is suggested that interferon should be investigated as a suppressor T cell-produced lymphokine which can regulate B cell expression.

Animals↗

Characteristics of immune interferon produced by human lymphocyte cultures compared to other human interferons.

A factor with antiviral activity has been produced in vitro by combined macrophage-lymphocyte cultures from patients with recent herpes labialis in response to HSV antigen stimulation. It has been designated "immune interferon" and characterized in comparison to several other human interferons. It was shown to be relatively unstable at pH 2 and at 56 degrees C. Rabbit anti-human leukocyte interferon serum was shown to be less active against immune interferon than against diploid cell interferon or against vesicle fluid interferon. The possibility of immune interferon being a totally different anti-viral protein or a protein with certain shared antigen determinants or structures with classical viral interferon is discussed. A simplified method for the assay of anti-interferon sera with microtiter plates is also described.

Antigens, Viral↗

Immune specific production of interferon by human T cells in combined macrophage-lymphocyte cultures in response to Herpes simplex antigen.

Human peripheral blood lymphocytes, highly enriched for T cells, were obtained by passing gravity-sedimented leukocytes through nylon wool columns. The eluted cells were cultured with autologous macrophages and the mixture was studied for its capacity to produce interferon in vitro in response to stimulation with herpes simplex virus antigen. The interferon produced by the combined macrophage-lymphocyte cultures was shown to depend upon the presence of T cells; elimination of these cells by treatment with an anti-T cell serum plus complement greatly diminished the amount of interferon produced. The memory for the immune-specific release of interferon also appeared to be carried by the T lymphocytes rather than the glass-adherent macrophages. Furthermore, the results suggest that under our conditions of culture immune-specific interferon originates from T cells.

Animals↗

Replication or inactivation of different viruses by human lymphocyte preparations.

Cultures of phytohemagglutinin-stimulated, unstimulated, and frozen and thawed mononuclear (as controls) cells from normal human donors were infected with different viruses. A variable pattern of virus infectivity was noted, and influenza and Coxsackie virus were rapidly inactivated even by stimulated lymphocytes. Direct inactivation by lymphocytes may be one form of host defense in infection by some viruses.

Adenoviridae↗