Title:
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Experimental studies of the pathogenesis of the viruses of vaccinia and louping-ill, with particualr reference to the mechanism of antiviral immunity
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In the past much attention has been devoted to the properties of antiviral sera but only recently has an attempt been made to determine precisely how they act. In 1928, Andrewes performed experiments with the vaccinie virus, and ceme to the conclusion that there was no union of antigen and antibody in neutral mixtures in vitro, but in a later communication (1930) he reported that firm antigen -antibody union took piece though extremely slowly. As no attempt has been made to repeat and develop his work, the experiments recorded in this thesis were undertaken to throw some further light on the problem. The discovery of Alston and Gibson (1931) in this laboratory that Louping-ill is transmissible to small inexpensive animals, viz. mice, has greatly facilitated work on the pathogenesis and immunity reactions -of e neurotropic virus. Moreover it has been possible to compare the mechanism of antiviral immunity to this virus with that to the vaccinia virus and thus to obtain additional data towards the solution of the question at issue. This experimental study of the mechanism of antiviral immunity revealed the following data and conclusions; (1) When vaccinia virus was mixed with appropriate amount of antiserum-end immediately injected into rabbits, inactivation of the virus to e. greater or less degree was demonstrable. (2) The virus could be recovered from neutral serum -virus mixtures, which were more or less balanced. (3) Those neutral serum -virus mixtures which contained an excess of immune serum or minimal concentrations of the virus could not he dissociated. (4) Partial antibody absorption was clearly shown, when en excess of virus was in prolonged contact with minimal mounts of antibody. (5) Firm antigen- antibody union could not be demonstrated after intracerebrel injection of neutral serum -virus mixtures. This was considered to he due to lack of excess of immune serum in such mixtures. (6) In the case of another neurotropic virus, viz. that of louping-ill, it was found that firm antigen-antibody union could he demonstrated in mixtures containing either an excess of immune serum or low concentrations of the virus. (7) Neutral serua-virus mixtures could be subdivided into (a) balanced, and (b) overneutralised. Balanced mixtures were reactivable, while definite inactivation of the virus occurred in overneutralised mixtures. (8) No major differences have been elicited between the mechanism of anti-viral and anti-bacterial immunity. (9) Attempts to produce manifestations of encephalitis after administration of vaccinia virus by routes other than intracerebral failed, but administration of the Virus by the intravenous route along with cerebral trauma precipitated the characteristic disease. An analogous phenomenon was elicited with a louping-ill virus of low virulence.
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