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Biomedical subjects

S L Shore

Publications and source records attributed to S L Shore.

At least 37 records · Page 2Linked to original sources

Human polymorphonuclear leucocytes as mediators of antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.

Human polymorphonuclear leucocytes (PML) were able to mediate antibody-dependent cellular cytotoxicity (ADCC) against target cells acutely infected with type 1 Herpes simplex virus. The reaction mediated by PML occurred more slowly and required higher concentrations of immune serum than that mediated by human mononuclear cells (MC). At the same ratio of effector cells to target cells, PML-mediated ADCC was less than MC-mediated ADCC. The observed relationship between the number of effector cells added, and the number of target cells lysed, showed that cytolysis mediated by both PML and MC was consistent with 'one hit' probability predictions. This suggested that target cell death resulted from an interaction with a single effector cell. The calculated frequency of effector cells in PML preparation was similar to that in MC, approximately 3-5%. Preliminary examination of the nature of the effector cells suggested that they did not comprise a morphologically distinct subclass of PML. These experiments demonstrate a possible new role for PML in host defence against viral infections.

Antibodies, Viral↗

The mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity to virus-infected target cells. II. Identification as a K cell.

Studies were carried out to determine whether the mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity (ADCC) to herpes simplex virus (HSV)-infected target cells has surface Fc receptors which participate in the reaction. The F (ab')2 fragment of human IgG antibody was inactive both in ADCC and in complement-mediated cytolysis, but retained the capacity to neutralize infectious virus, to agglutinate erythrocytes coated with viral antigens, and to bind to the surface of virus-infected cells. Treatment of sensitized virus-infected target cells with staphylococcus protein A, which has affinity for the Fc epitope of IgG, strongly reduced their susceptibility to lysis by ADCC in a dose-dependent relationship. These findings indicate that the Fc portion of IgG antibody to the virus is necessary for cytotoxicity. Treatment of blood mononuclear cells with either heat-aggregated gamma-globulin or HSV immune complexes inhibited effector cell activity. The presence of "third party" cellular immune complexes also strongly inhibited ADCC. Adsorption of mononuclear cells to plastic surfaces coated with soluble third party immune complexes resulted in a significant reduction in effector cell activity. These findings demonstrate that the ADCC effector cell possesses surface Fc receptors which are utilized in the ADCC reaction. The presence of Fc receptors on the surface of the effector cell indicates that it is a K cell rather than a null cell.

Antibodies, Viral↗

Antibody-dependent cell-mediated cytotoxicity to target cells infected with type 1 and type 2 herpes simplex virus.

The phenomenon of antibody-dependent cell-mediated cytoxicity (ADCC) has been extended to include target cells acutely infected with herpes simplex type 1 virus (HSV-1) or herpes simplex type 2 virus (HSV-2) in an in vitro system that employs immune human serum and human blood mononuclear cells. The cytotoxic reaction was detectable after 1 hr of incubation and was complete between 4 and 8 hr. The amount of ADCC noted was directly proportional to the logarithm(10) of the effector: target cell ratio (E:T), and ADCC was noted at E:T as low as 1:1. The mononuclear effector cell was present in the blood of both HSV immune and non-immune individuals. The immune serum factor was demonstrated to be an antibody with specificity for HSV membrane antigen(s) and was reactive with target cells infected with either of the two HSV types. The antibody rendered the mononuclear cell cytotoxic by sensitization of the target cell rather than by direct attachment to or "arming" of the mononuclear cell. The physiochemical properties of the antibody as well as its presence in cord blood demonstrated that it is an immunoglobulin on the IgG class.

Absorption↗

Analysis of mononuclear cell surfaces with fluoresceinated staphylococcal protein A complexed with IgG antibody of heat-aggregated gamma-globulin.

Fluorescein-conjugated staphylococcal protein A (SPA) was complexed with either: 1) heat-aggregated IgG, 2) B cell specific antibody, or 3) T cell specific antibody and then used for an immunofluorescent analysis of mononuclear cell surfaces. Cellular Fc receptors failed to recognize the Fc region of aggregated IgG that had been blocked by SPA. Moreover, fluoresceinated SPA that had been complexed either with anti-Fab (B-cell specific) or T cell-specific antisera prevented the nonspecific binding of these reagents to the IgG-Fc receptors on mononuclear cells, thereby permitting the latter to be properly identified as B or T lymphocytes. In addition, when unconjugated SPA was added to presensitized target cells in a test for antibody-dependent cell-mediated cytotoxicity, cytolysis was abrogated.

Animals↗

Immunology of herpes simplex virus infection: relevance to herpes simplex virus vaccines and cervical cancer.

The immunology of herpes simplex infections has been reviewed, particularly in relation to potential herpes simplex virus (HSV) vaccines, and to the association between HSV and cervical cancer. Relevant data from humans, experimental animals, and in vitro systems implicate both specific immune mechanisms and nonspecific factors in the course of HSV infections. There appear to be complex interactions between the various populations of mononuclear cells, marcrophages, and lymphokines or other humoral factors. It is not yet possible, however, to pinpoint the crucial factors determining the different manifestations of the viral infection (primary infection, endogenous recurrence, or exogenous reinfection) in the various human hosts, although genetic factors may be important. While numerous animal models of HSV infection are available for the evaluation of HSV vaccines, models of HSV-induced cervical cancer require further exploration.

Age Factors↗

Stimulation of human lymphocytes by Herpes simplex virus antigens.

Lymphocytes from individuals with laboratory evidence of prior infection with herpes simplex virus (HSV) type 1 or type 2 demonstrated transformation (av antigens. Higher stimulation indexes were obtained when lymphocytes were incubated with the homologous as compared with the heterologous antigen. Higher mean lymphocyte stimulation indexes were also demonstrated in seropositive as compared with seronegative individuals. Lymphocytes from children with HSV-1 stomatitis usually became responsive to HSV-1 antigen within 2 to 6 weeks after the onset of illness. Lymphocytes from infants with neonatal HSV-2 infection were stimulated by HSV-2 antigen.

Antibodies, Viral↗

Immunity to influenza in ferrets. V. Immunization with inactivated virus in adjuvant 65.

Ferrets infected with influenza virus A2/Hong Kong/3/68 responded with a febrile reaction; the temperature was elevated by 1.0 degrees C. or greater to a level of 40 degrees C. or more. In addition, relatively high titres of virus were recovered from nasal washings taken 3 days after virus infection, serum antibody was produced, increased nasal protein was detected and nasal washings contained both HI and neutralizing antibody. Of four ferrets immunized with 400 CCA units of inactivated influenza virus A2/Aichi/2/68 in saline, only one produced detectable serum HI antibody, and none produced detectable nasal antibody. These ferrets were subsequently found to be susceptible to intranasal infection with influenza virus A2/Hong Kong/3/68. Thus, the temperature response, the titre of virus recovered from nasal washings and the serum HI antibody response found after virus infection was similar to that found after infection of non-immunized ferrets. However, the increase in protein concentration and the titre of HI and neutralizing antibody found in nasal washings after virus infection was detectably less than that found after virus infection of non-immunized ferrets.Four ferrets were immunized with 400 CCA units of inactivated A2/Aichi/2/68 virus in adjuvant 65, and these ferrets produced relatively high titres of serum HI antibody but no detectable nasal antibody. After subsequent virus infection with influenza virus A2/Hong Kong/3/68, these ferrets showed a modified temperature response, reduced titres of virus in nasal washings compared to that found in nasal washings from non-immunized ferrets, no increase in nasal protein and no detectable nasal HI antibody. Thus, immunization with inactivated virus in adjuvant 65 resulted in a significant modification of the response of ferrets to challenge virus; however, the immunity was not complete, and appreciably less than that found after infection with live homologous virus.

Adjuvants, Immunologic↗