Increased (2'-5')-oligo-A synthetase activity in patients with prolonged illness associated with serological evidence of persistent Epstein-Barr virus infection.
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Biomedical subjects
Publications and source records attributed to A Morag.
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Seven patients with prolonged atypical illness were followed up for more than a year. Sera taken during that period showed significantly increased titres of IgM antibodies against the viral capsid antigen (VCA) of Epstein-Barr virus (EBV). In four of the patients antibodies to the R component of the early antigen (EA) complex of EBV were clearly detectable. Only one of these seven patients had presented with symptoms of classic infectious mononucleosis. Serological and clinical observations in these patients suggest that the prolonged atypical illness was probably the result of persistent EBV infection.
Cellular response of peripheral blood lymphocytes to influenza antigens was measured in a group of young nurse-student volunteers (17-24 years old), following vaccination with a formol-inactivated trivalent influenza vaccine (Gripax). Cord blood lymphocytes (controls) did not react with any of the antigens. This excluded the possibility of any nonspecific mitogenicity of viral antigens. Viability of the cells was indicated by their responsiveness to phytohemagglutinin (PHA). Prior to immunization antigenic recognition to circulating strains (A/England (H3N2) and B/Hong Kong) was found in about 44% of the vaccinees; recognition of the recent strain A/USSR (H1N1) was found in only 10.5%. Following vaccination, approximately 80% of the subjects exhibited cellular response to all three vaccine strains. This includes the negative subjects, who showed an approximate 70% rate of conversion. There was no correlation between the antibody state and cellular response prior to and following vaccination as gathered from matched data of each participant.
Indirect immunoperoxidase method was used to evaluate retrospectively a case of cytomegalovirus (CMV) mononucleosis. Specific rabbit antiserum against CMV was used as primary reagent in routinely prepared paraffin sections of lymph node and in fixed slide preparations of the bone marrow aspirate. Staining specific for CMV antigen was observed in the lymphoid cells of the lymph node in the predominantly T-cell area and in the large lymphoid cells of the bone marrow. Bone marrow lymphoid cells with morphologic characteristics similar to those of the cells positive for CMV antigen showed positive immunoperoxidase reaction with specific rabbit antihuman T-cell serum. The data strongly indicate that CMV antigen was localized predominantly in the cells of lymphoid origin during the acute stage of the CMV mononucleosis; some data also suggest that infected lymphoid cells may be of T-cell origin. An immunoperoxidase technique is advantageous in both diagnosing and evaluating CMV mononucleosis.
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An analysis of the etiology of acute viral hepatitis in 172 hospitalized patients showed that 70.9% suffered from hepatitis A (HA), 12.2% from hepatitis B (HB), 1.7% from infectious mononucleosis and 15.1% (26 cases) from non-A, non-B hepatitis. Patients who had received blood transfusions during the 6 mo preceding the onset of the disease were not included in the present survey. The male:female ratio in the patients with non-A, non-B hepatitis was 1:88; 73% were Ashkenazic and 27% non-Ashkenazic Jews. The ethnic distribution of patients with non-A, non-B hepatitis was similar to that of patients with HA but differed from that of HB patients (only 41% Ashkenazic). Thirty-eight percent of the non-A, non-B group had had contact with jaundiced patients during the 6 mo preceding the onset of the disease, and 46% were students or soldiers. The clinical course of the disease was, on the whole, milder than that of HB and similar to that of HA. Since many cases of non-A, non-B hepatitis are anicteric, it is concluded that the disease is a significant problem in Israel.
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Employing the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation assay, the antibody and cell-mediated immunity to cytomegalovirus (CMV) were studied in the serum, peripheral blood lymphocytes, tonsillar lymphocytes, and cord blood lymphocytes. The study population consisted of 32 children undergoing tonsillectomy and adenoidectomy. In the lymphocyte transformation assay, three strains of CMV (AD-169, ADH-1-41, and Davis), herpes simplex type 1, and phytohemagglutinin were employed as antigens. Sixty-five percent of the subjects were found to have CMV-specific antibody activity. The lymphocyte transformation response to phytohemagglutinin was similar in all subjects. No CMV-specific lymphocyte transformation activity was detected in cultures of cord blood lymphocytes. Significant cell-mediated immunity was observed in the tonsillar lymphocytes of 30% (3/10) of the seronegative individuals and in the peripheral blood lymphocytes obtained from one such subject. Over 75% (16/21) of the seropositive subjects demonstrated cell-mediated immunity against one or more strains of CMV in the peripheral blood lymphocytes and tonsillar lymphocytes. In the lymphocyte transformation assay, no cross-reactivity was apparent between CMV and herpes simplex type 1. These studies demonstrate the presence of strain-specific systemic and mucosal cell-mediated immune response to CMV in humans. The frequency and distribution of lymphocyte transformation responses to the three CMV strains suggest antigenic heterogeneity of CMV.
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The antibody and cell-mediated immune response to mumps virus infection was studied in groups of subjects after natrually acquired mumps virus infection, after parenteral immunization with live attenuated mumps vaccine, and in a population of mumps seronegative subjects. The technique of neutralization of tissue culture infectivity was utilized to study mumps specific antibody. The cell-mediated immunity (CMI) was detected by specific immune release (SIR) of radioactivity by purified lymphocytes after they were reacted with radioactive chromium (51Cr) labeled human conjunctival cell cultures chronically infected with mumps virus. No SIR activity was observed in lymphocytes obtained from cord blood and young individuals seronegative for antibody to mumps virus. Detectable SIR activity was observed in a few older seronegative subjects; however, immunization with mumps vaccine in such antibody negative subjects failed to result in the development of any antibody response in the serum. High SIR activity was observed in the lymphocytes of naturally infected and vaccinated subjects. Although all naturally infected or immunized subjects had varying levels of mumps specific antibody activity in the serum, no correlation existed between the levels of antibody and SIR activity. These observations suggest the development of mumps specific in vitro correlates of CMI after naturally acquired or vaccine-induced mumps virus infection.
Antibody and cell-mediated immune response in systemic and external mucosal sites was studied after natural or vaccine induced infections with rubella and mumps viruses. Natural rubella infection or immunization with RA27/3 rubella vaccine by intranasal and frequently by the subcutaneous route resulted in regular appearance of antibody response in the serum and respiratory tract and cellular immunity in circulating lymphocytes and tonsillar lymphoid tissue. Subcutaneous immunization with HPV-77 and Cendehill rubella vaccine resulted in antibody response in the serum with little or no response in the respiratory tract. A minimal cell-mediated immune response in systemic or respiratory lymphoid tissue was observed after such immunization. Intranasal immunization with HPV-77 frequently elicited a transient antibody and cell-mediated activity in the respiratory tract with no response in the serum and peripheral lymphocytes. Studies carried out with natural mumps infection or subcutaneous immunization with live attenuated mumps vaccine suggested that either route of infection may result in the development of antibody and cell-mediated immune responses in systemic sites as well as in the respiratory tract. These observations suggest that the immunologic outcome of immunization by non-parenteral route may be determined by the types of viral antigen employed, the nature of locally available immuno-competent tissue, the ability of mucosal site to capture an antigen or accept replication of live virus vaccines, and the degree of prior sensitization with the same antigen.
Tonsillar lymphocytes from children immunized against rubella were cultured with various mitogens, including phytohemagglutinin and rubella virus. Sheep red cells were subsequently added to detect rosette-forming T-lymphocytes, and the suspension tested by autoradiography to identify transformed cells. With PHA, 60--80% of the cells were transformed, of which 37% were rosette-forming T-cells. With rubella antigen only 31% of lymphocytes were transformed, but almost all of these formed rosettes. It is concluded that PHA stimulates B- as well as T-cells alone; such stimulation may therefore be a more reliable test of T-cell function and of cell-mediated immunity.
The techniques of hemagglutination inhibition and in vitro lymphocyte transformation and the assay of migration inhibitory factor were used for study of the development of rubella antibody activity in serum and tonsillar tissue washings and of the appearance of rubella-specific, cell-mediated immunity in circulating and tonsillar lymphocytes in groups of children who underwent tonsillectomy at various intervals after natural rubella infection, subcutaneous immunization with HPV-77 DE/5 vaccine, or intranasal inoculation with RA27/3 live, attenuated rubella virus vaccine. Antibody response in serum and tonsillar tissue washings was detected regularly after natural infection or immunization. Development of specific cell-mediated immunity in circulating lymphocytes was regularly observed after natural infection and frequently after immunization. Natural infection or intranasal immunization with rubella vaccine resulted in the appearance of cell-mediated immunity in the tonsillar lymphoid tissue, and the response was detectable up to several years after natural infection in several cases. It is significant, however, that the level of cell-mediated immunity in tonsils was conspicuously low after subcutaneous immunization. These data suggest the induction of local cell-mediated immunity in tonsillar lymphoid tissue after local mucosal application of rubella virus.