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Biomedical subjects

S J Lucas

Publications and source records attributed to S J Lucas.

6 recordsLinked to original sources

Antibody production and protection against influenza virus in immunodeficient mice.

The roles of T and B cells in the immune response to influenza virus were studied by using mice deficient in either T cells (athymic nude) or immunoglobulin production (CBA/N). The serological responses of these mice to either whole or disrupted A/Aichi/2/68 influenza virus vaccines were examined, and the protective effect of these inoculations was tested by challenge infection with mouse-adapted A/Aichi/2/68 influenza virus. In contrast to normal mice, neither strain of immunodeficient mouse produced detectable serum antibody after inoculation with either type of vaccine. CBA/N mice immunized with intact virus vaccine were protected, however, against subsequent lethal challenge. CBA/N mice inoculated with disrupted virus vaccine and nude mice inoculated with either disrupted or whole virus vaccine were not protected against viral challenge. Evidence of immunological memory was observed in CBA/N and nude mice that had survived live virus challenge after immunization with inactivated vaccine.

Animals

Acute and chronic infection of human lymphoblastoid cell lines with measles virus.

Several human continuous lymphoblastoid cell lines (LCL) having T or B characteristics were infected with low and high passage strains of measles virus. All of the cell lines were susceptible to one or the other or to both strains of measles virus with the production of typical syncytial giant cells and released cell-free infectious virus into the supernatant medium. There was no consistent pattern of susceptibility of LCL with either T or B characteristics to infection by measles virus. Viral induced cytolysis of the lymphoblastoid cells in many of the lines was marked, but in the LCL that could be maintained over longer periods of time, a state of chronic, less cytolytic and persistent infection could be established. The infection was characterized by the production of moderate amounts of cell-free infectious virus for up to 4 1/2 months after initial infection with little change in the number of viable cells in culture. Long-term low multiplicity of infection (MOI) experiments demonstrated that the cell-free infectious virus was being produced only by a small number of cells, but the majority of cells in culture contained measles antigen that was in a cell-restricted, noninfectious, or defective form. Electron microscopic examination of the chronically infected cells demonstrated that many of them contained aggregates of hollow tubular intranuclear nucleocapsids whose "stripped" appearance was in marked contrast to the larger granular intracytoplasmic nucleocapsids found during earlier stages of infection. It is theorized that the persistent infection of LCL may serve as a model in understanding the immune mechanisms which permit latent and chronic measles infection in man.

Acute Disease

Measles infection of human mononuclear cells. I. Acute infection of peripheral blood lymphocytes and monocytes.

A study of the susceptibility of human peripheral blood mononuclear cells to measles virus infection and replication is reported. Resting lymphocytes obtained from adults showed very low levels of infection and virus replication while lymphocytes activated by plant mitogens or allogenic lymphocytes supported mononuclear cells obtained from the umbilical cord of healthy neonates were more susceptible to measles virus infection than those of adults; however, activated cord lymphocytes supported viral replication in the range observed with adult activated lymphocytes. Monocytes obtained from adults were relatively resistant to measles virus infection and replication while neonatal cord blood monocytes supported viral replication to the degree observed with activated lymphocytes. It is hypothesized that infection of acitivated lymphocytes may explain the depression of cell-mediated immunity seen during acute measles virus infection. The significance of the finding that neonatal monocytes are more susceptible to viral infection and replication than adult monocytes is discussed.

Adult

Inhibition of lymphocyte stimulation by measles virus.

The effect of measles virus on phytohemagglutinin-(PHA) induced stimulation of human peripheral blood mononuclear cells was investigated to delineate possible mechanisms for viral suppression of cell-mediated immunity (CMI). it was noted that medium which had several days contact with uninfected monolayers as well as unpurified measles virus preparations produced significant inhibition of 3H-thymidine incorporation by PHA-stimulated lymphocytes. When partially purified measles virus preparations were used, however, marked inhibition was observed and the inhibitory effect of cell-derived factors could be separated easily from the virus-induced inhibition. Experiments to determine the mechanisms of this virus-induced inhibition of 3H-thymidine incorporation showed the following: 1) live measles virus and not UV-irradiated or heat-inactivated virus produced inhibition; 2) the inhibitory effect observed was not the result of a viral-induced inhibitor being released from measles-infected lymphocytes; and 3) monocyte depletion had no effect on the ability of measles virus to inhibit 3H-thymide incorporation by PHA-stimulated lymphocytes. Since it was found that measles virus-infected lymphocytes display an impaired response to in vitro PHA stimulation, perhaps this dysfunction may be extended to mediator release and other functions associated with delayed cutaneous hypersensitivity (DCH) in vivo.

Animals