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H Panitch

Publications and source records attributed to H Panitch.

5 recordsLinked to original sources
PubMed1977

The ultrastructure of early visna lesions.

The ultrastructure of visna, a slowly progressive menigo-encephalomyelitis of sheep, was studied in animals sacrificed one month after intracerebral inoculation of visna virus. The major pathological changes, representative of those seen during the first year after infection, consist of inflammation and minor focal destructive lesions of grey and white matter. The inflammatory infiltrates, both subependymal and perivascular as well as of the choroid plexus, were composed mainly of lymphocytes and macrophages with varying numbers of plasma cells. The demyelination seen was of the secondary or Wallerian type. There was no evidence of primary demyelination. Visna virions were not seen in any of the CNS material studied. The ultrastructural findings are compatible with the view that lesions in visna may be induced by a cell-mediated immune response. However, changes characteristic of an autoimmune reaction to myelin antigens were not observed.

Animals↗
PubMed1976

Pathogenesis of visna. I. Sequential virologic, serologic, and pathologic studies.

A total of 56 Icelandic sheep were infected with visna virus by intracerebral injection of strain 1514 and the course of infection was followed for 12 months. Virus was isolated from more than 90 per cent of the animals, primarily from central nervous system and lymphoid tissues. However, titers of free infectious virus were minimal and virus isolation often required the use of tissue explants. All sheep raised serum-neutralizing and complement-fixing antibodies beginning 1 to 3 months after infection. Differences in neutralization titers against the infecting strain (1514) and a reference strain (796) suggested that antigenic drift might occur during prolonged infection. High cerebrospinal fluid neutralization titers in the spinal fluid indicated local antibody production in the central nervous system. Although the incidence of clinical disease during the 1st year of infection was less that 10 per cent, approximately 80 per cent of the sheep examined had central nervous system histologic lesions of variable severity, which were marked 1 month after infection with little progression during the subsequent year. There was a striking correlation between the severity of central nervous system lesions and the frequency of virus isolations from all tissues. These observations provide detailed base line data on visna infection, suggest some of the mechanisms responsible for the persistence of infection and for the slowness and irregularity of disease occurrence, and form the basis for further experiments on the role of immunologic mechanisms in the pathogenesis of this slow infection.

Animals↗
PubMed1976

Pathogenesis of visna. II. Effect of immunosuppression upon early central nervous system lesions.

It was hypothesized that the lesions of visna might represent an immunopathologic process. To test this hypothesis, a 1-month schedule of immunosuppressive treatment was devised, using horse anti-sheep thymocyte serum. In Hampshire sheep, this regime was shown to protect against experimental allergic encephalomyelitis, to inhibit development of tuberculin hypersensitivity, to retard rejection of skin homografts by 3 weeks, and to markedly reduce the number and mitogenic responsiveness of peripheral blood lymphocytes. Two groups of Icelandic sheep received intracerebral inoculations of visna virus, and one group was treated with horse antisheep thymocyte serum supplemented by a short terminal course of cyclophosphamide. Central nervous system lesions were seen in only one of eight suppressed animals at sacrifice 25 days after infection, whereas definite lesions were present in eight of eight infected control animals. The frequency of central nervous system virus isolation was similar in the two groups, indicating that treatment suppressed the cellular proliferative response without preventing the central nervous system phase of infection. Sheep receiving horse antisheep thymocyte serum had a reduced number of virus isolations from peripheral lymphoid tissue, presumably reflecting the lympholytic effect of treatment. These observations are consistent with the immunopathologic hypothesis and suggest several different ways in which suppression could modify the immune response to visna virus.

Animals↗
PubMed1976

Pathogenesis of visna. III. Immune responses to central nervous system antigens in experimental allergic encephalomyelitis and visna.

Experimental allergic encephalomyelitis (EAE) was induced in sheep in pursuit of the hypothesis that an immune response against central nervous system antigens might play a role in the pathogenesis of visna. Nine to 12 days after sensitization with whole sheep brain and complete Freund's adjuvant, approximately 50% of sheep developed a fulminating lethal form of EAE. Following a second sensitization, another 20% of animals developed EAE whereas a residual 30% failed to develop any signs or histologic evidence of disease. A histologic comparison of EAE and visna indicated considerable similarity in the nature of the pathologic process. However, the distribution of lesions was quite different, suggesting cellular responses to two different antigens, Cell-mediated immunity to myelin basic protein, as measured by lymphocyte blast transformation, was minimally elevated in sheep sensitized with whole brain suspension in complete Freund's adjuvant, whereas no response could be detected in visna-infected sheep. Complement-fixing antibody titers to basic protein and to a lipid antigen of brain, probably galactocerebroside, rose briskly after sensitization. In visna-infected sheep, on the other hand, there was no increase in either antibody. A large proportion of both Hampshire and Icelandic sheep had low levels of complement-fixing antibody to central nervous system antigens prior to induction of EAE or infection with visna virus. The origin of this antibody is undetermined, but it appeared to have no effect on the course of either disease. Immunosuppression of sheep with antilymphoid serum prevented induction of EAE. Acute EAE was, thus, successfully induced in sheep and used as a model to measure immune responses to central nervous system antigens and as an index of immunosuppression. However, these comparative studies did not provide any evidence for the role of an autoimmune response, to the two central nervous system antigens tested, in the pathogenesis of visna.

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