Jack F. Woodruff

THE EFFECT OF VIRAL INFECTIONS ON THE FUNCTION OF THE IMMUNE SYSTEM

Publisher Summary This chapter discusses the effect of viral infections on the function of the immune system. Immunologic dysfunction induced by virus must reflect changes in the physiologic and immunologic function of T (thymus-dependent) lymphocytes, B (thymus-independent) lymphocytes, or macrophages, as it is the interaction between these cells and their products that generates immunity. It is known that macrophages play a role in processing of antigen and in its presentation to lymphocytes. B cells stimulated by antigen differentiate into antibody-secreting cells. T cells act directly in cellular immune reactions and also exert a helper effect on antibody production even though they do not themselves become plasma cells. Virus replication could lead to stimulation of suppressor cells that might inhibit responsiveness of T and B lymphocytes that are not themselves directly affected by the infection.

Virus-induced alterations of lymphoid tissues: I. Modification of the recirculating pool of small lymphocytes by Newcastle disease virus

Abstract Intravenous inoculation of Newcastle disease virus (NDV) altered the character of the recirculating pool of small lymphocytes. In mice severe lymphocytopenia and depletion of small lymphocytes from the deep cortex of lymph nodes and from the periarteriolar lymphoid sheaths of the spleen were found 24 hr after virus challenge. By 72 hr the concentration of blood lymphocytes was normal and the areas in the lymph nodes and spleens which were depleted at the earlier interval showed an increased concentration of lymphocytes. In virus-treated rats it was also shown that depletion and repopulation of blood with lymphocytes were paralleled by similar changes in the output of small lymphocytes from the thoracic duct. Thus, a marked deficit of small lymphocytes in the thoracic duct lymph was observed when rats were cannulated at the time of virus challenge; the output of small lymphocytes in the lymph was normal when rats when cannulated 72 hr after virus inoculation. Evidence was obtained that the ability of NDV to modify the recirculating lymphocyte population was independent of its capacity for complete viral replication and independent of functioning adrenal gland tissue. Possible mechanisms that may account for these abrupt and marked shifts in the concentration of recirculating lymphocytes in the blood, lymph, and lymphoid tissues are discussed.

Virus-induced alterations of lymphoid tissues: IV. The effect of Newcastle disease virus on the fate of transfused thoracic duct lymphocytes

Abstract 51 Cr-labeled thoracic duct lymphocytes were briefly incubated at 4 °C with Newcastle disease virus (NDV) and then infused into syngeneic rats. Virus diverted the homing of many donor cells from lymph nodes and spleen to the liver. Evidence was obtained suggesting that some NDV-treated lymphocytes initially trapped in the liver subsequently migrated into the lymph nodes. The results imply that NDV transiently interrupts the normal route of lymphocyte migration. Alterations in lymphocyte distribution were mediated by attachment of virus to the cell surface and were the same as those induced by incubating lymphocytes with V. cholera neuraminidase before infusion. It appears that reactions involving 2–3′ and/or2–8′ linked sialyl residues on the surface of recirculating lymphocytes can markedly affect their distribution in the body.

Virus-induced alterations of lymphoid tissues: II. Lymphocyte receptors for Newcastle disease virus

Abstract Newcastle disease virus (NDV) agglutinates rat, mouse and human lymphocytes. Viral agglutination of rat thoracic duct lymphocytes was specifically inhibited by N-acetylneuraminic acid implying that the receptors terminate in sialic acid. While the attachment of virus to lymphocytes was rapid the reaction was unstable and NDV was shown to elute at 37 °C. Evidence was obtained that the eluting virus cleaved sialic acid from the surface of lymphocytes and concomitantly destroyed this lymphocyte receptor.

Virus-induced alterations of lymphoid tissues: III. Fate of radiolabeled thoracic duct lymphocytes in rats inoculated with Newcastle disease virus

Abstract The influence of Newcastle disease virus (NDV) challenge on the distribution of injected thoracic duct lymphocytes was investigated. NDV was was inoculated into rats immediately after transfer of 51 Cr-labeled lymphocytes. Significantly less radioactivity was recovered in lymph nodes of virus-treated animals within 24 hr of cell transfer. By 48 hr, however, lymph nodes of virus-treated recipients contained normal concentrations of radioactivity. It is suggested that the virus transiently impairs the homing of donor lymphocytes into lymph nodes. These results support the proposition that NDV challenge reduces the size of the circulating T-lymphocyte pool by interfering with the normal pattern of lymphocyte migration. Evidence was obtained which indicated that NDV-induced lymphocytopenia was not mediated by abnormalities of the endothelial cells lining the postcapillary venules in the lymph node cortex.

Interferon production in neonatally thymectomized mice.

Summary No significant difference in serum interferon titers could be demonstrated in neonatally thymectomized and litter mate control mice inoculated with NDV intravenously. Although the blood lymphocyte counts of the thymectomized mice were not consistently depressed, there was other evidence that the lymphoid tissue of these animals was markedly altered.

Influenza A virus interaction with murine lymphocytes: III. Recirculating rat T and B cells differ on the basis of receptors for Cam (H1N1) virus☆

Abstract The presence of receptors for influenza A viruses on rat lymphocytes was determined by autoradiography using radioiodinated Cam (H1N1) and Japan 305 (H2N2) strains. With Cam influenza only 20 to 30% of TDL from normal donors bound the virus, whereas nearly all the cells had binding sites for Japan influenza. However 125 I-Cam readily attached to B-TDL (cells obtained from adult thymectomized, lethally irradiated, and bone-marrow-reconstituted rats) and under optimal conditions 75 to 90% of these lymphocytes became labeled. The incidence of labeled B-TDL was reduced 90% by pretreatment of 125 I-Cam with fetuin or pretreatment of cells with unlabeled Cam virus. Fractionation of TDL from normal rats via the nylon wool column technique revealed that the incidence of Cam binding lymphocytes increased from 12% in the nonadherent population (7% Ig + ) to 72% in the adherent fraction (86% Ig + ). Thus among recirculating lymphocytes B cells, but not the vast majority of T cells, had receptors for this agent. It was also found that Cam influenza attached to approximately 70% of spleen and bone marrow mononuclear cells, 39–47% thymocytes and 14–21% lymph node lymphocytes. The results demonstrate the existence of heterogeneity among lymphocytes with respect to their capacity to interact with influenza A subtypes and indicate that subpopulations of lymphocytes can be differentiated on the basis of receptors for Cam influenza virus.