Immunity to influenza

Immunity to influenza virus may be considered from the standpoints of viral and hostfactors. Amonst viral factors the phenomena of antigenic 'shift' and 'drift' of the surface antigens. Hemagglutinin HA and neuraminidase NA, are of utmost importance in enabling the virus to combat host immunity and to produce recurrent pandemics and epidemics of disease. 'Shift' involves major changes in the antigenic character of the HA and NA antigens, and serological studies reveal little or no crossreactions between antigens of different subtypes. However, immunological 'memory' may exist between the surface antigens of viruses of different subtypes, for example between the hemagglutinins of Asian (H2) and Hong Kong (H3) subtypes. Antigenic 'drift' occurs more frequently than 'shift' and involves subtle changes in the antigenic configuration of HA and NA within a subtype. It is clear that the hemagglutinin antigen contains a multiplicity of antigenic determinants, one or more of which remain stable (CR determinants) whilst others (strain-specific determinants) change completely during antigenic 'drift'. Amongst host factors humoral antibody to HA and NA appears to be a reasonable index of natural or vaccine induced immunity to infection. As far as the specificity of such antibodies is concerned, it is likely that future studies will place considerable emphasis on the distinction between antibody for the stable (CR) antigenic determinants and antibody to strain-specific determinants. It seems likely that antibody to strain-specific determinants is of more relevance to immunity than CR antibody. The studies of Virelizier et al. described elsewhere in this Symposium employing single-radial-diffusion tests give hope of simple methods for the investigation of such antibody specificity. There is no evidence that antibody to the internal, antigenically stable ribonucleoprotein is related to immunitywhilst the role of the other internal antigen, the membrane protein, in immunity is at present unknown. Numerous studies have been carried out to establish the importance of secretory antibody in the respiratory tract. Although secretory IgA specific for the influenza virus has been clearly demonstrated in the respiratory tract, the levels are low and its significance is not yet established. Whilst the role of cellular aspects of immunity to influenza in man remains to be established there is no doubt from the recent studies of Tyrrell and his colleagues that delayed hypersensitivity to influenza antigens can be demonstrated. In considering the host aspects of immunity it is important to attempt to distinguish factors which are merely an index of past exposure and those which are involved with the actual mechanism of immunity. It is likely that animal experimental models, in particular with inbred mice, will provide an important contribution in this field of investigation.