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At the end of the last century and the beginning of this century, the prob­ lems of immunity in lower vertebrates and the influence of environmental temperature attracted attention for the first time (ERNST, 1890; WIDAL and SICARD, 1897; METCHNIKOFF, 1901). However, relatively little work has been done on this subject until recently. The early investigators were chiefly in­ terested in the immuno-pathological problems. They immunized various species of lower vertebrates essentially with bacterial vaccines; agglutinating, neutralizing and protective antibodies were detected in their blood. The in­ fluence of environmental temperature on the immune response was investigated, since this subject represented great economical and theoretical importance. Epizootic diseases were observed to occur in relation to the cold season of the year, when the decrease or spontaneous increase of water temperature occurred (SCHAPERCLAUS, 1965; BESSE et al., 1965; KLONTZ et al., 1965 WOOD,1966). The immunological deficiency of fish, caused by their natural or experimental stay in cold water, is now evident for both humoral and cellular immunity. In this review we will focus on two points: We shall attempt (1) to explain the mechanism by which the environmental temperature influences the immune resistance of fish to pathogens, (2) to determine the chronological location of this temperature-sensitive stage in the process of antibody formation, and to make some approaches to the general antibody formation mechanism.

Influenza continues to be one of the major epidemic diseases of man and is, in fact, his only remaining pandemic disease (BEVERIDGE, 1969). This is largely because influenza virus undergoes extreme antigenic variation, the mechanism of which is still poorly understood. Two kinds of antigenic variation occur in influenza viruses, antigenic drift and major antigenic shifts; both involve chan­ ges in the hemagglutinin and neuraminidase antigens on the surface of the virus. Antigenic drift, which involves gradual changes in the surface antigens of influenza virus, is thought to result from the selection by an immune popula­ tion of mutant virus particles with altered antigenic determinants. These mutants therefore possess a growth advantage in the presence of antibody (FRAN­ CIS and MAASSAB, 1965; ARCHETTI and HORSFALL, 1950; HAMRE et aI., 1958). It has been shown that antigenic mutants isolated in vitro by selection with antibody have changes in amino acid sequence in the polypeptides of the hem­ agglutinin subunits (LAVER and WEBSTER, 1968) and it is likely that antigenic drift in the neuraminidase occurs by the same mechanism.

The study of the genetic regulation of immune response to natural multidetermi­ nant immunogens was undertaken by the method of bidirectional selective breed­ ing of High or Low antibody responder lines of mice. Five Selections are described: Selection I, carried out for agglutinin responsiveness to sheep erythrocytes and pigeon erythrocytes alternated in each generation. Selection II, carried out for agglutinin responsiveness to sheep erythrocytes repeated in each generation. Selection III and Selection IV performed respectively for agglutinin response to flagellar or somatic antigens of Salmonella typhimurium and Salmonella oranienburg alternated in each generation. Selection V, performed for passive agglutinin response to bovine serum albumin and rabbit gamma globulin alternated in each generation. In each Selection the character investigated is polygenic. High and Low responder lines diverge progressively during the selective breeding. The maximal interline separation (selection limit) is reached in the 7th-16th generations. High and Low responder lines at selection limit are considered homozygous for the character submitted to se~ection. Their variance is therefore only due to environ­ mental effects. The difference in agglutinin titre between High and Low lines is 220-fold in Selection I, 103-fold in Selection II, 90-fold in Selection III, 85-fold in Selection IV and 275-fold in Selection V. The partition of genetic and environmental variances in the foundation popu­ lations of the five Selections is established. The proportion of genetic variance is 60% in Selection I; 49% in Selection II; 51% in Selection III; 47% in Selection IV and 76% in Selection V.

Expression of an immune response is the net result of complex synergis­ tic and antagonistic activities performed by a variety of cell types. It includes macrophages, T and B populations which may interact in performance of a response, and suppressor cells interfering with it. Accordingly, a lack of res­ ponse may not necessarily indicate absence of immunocompetent cells, but rather nonexpression of competence. Thus, one should consider two possible situations, which are by no means mutually exclusive, to account for immuno­ logic unresponsiveness: (a) one or more of the cell populations composing the synergistic unit is absent or immature, and (b) an antagonistic unit which interferes with the response is dominating. In view of this, an approach to development of immune reactivity necessitates parallel surveys of development of cells with the potential to perform, as well as of cells which can suppress the response. Classification of the various cell types has been based so far on their phenotypic properties (e. g., membrane antigen markers, cell receptors, pro­ duction and secretion of immunoglobulins, etc.). Genotypically, T and B cells may represent either separate, independent cell lines, or different stages of development within the same cell lineage.

The processes involved in herpesvirus replication, latency, and oncogenic transformation, have, in general, been rather poorly defined. A primary reason for this is the size and complexity of the herpesvirus genome. Undoubtedly, a better understanding of the functions of the viral genome in infected and transformed cells will be achieved through studies with temperature-sensitive (ts) mutants of herpesviruses since, theoretically, any essential gene function can be affected by mutants of this type. A. The Herpesviruses A consideration of the genetic analysis of members of the herpesvirus group necessitates a description, albeit brief, of the properties of the group and, most importantly, of their genetic material. The herpesviruses comprise a group of relatively large (100-150 nm), enveloped viruses. The envelope surrounds an icosahedral capsid enclosing a core which contains double­ stranded DNA (ROIZMAN, 1969). The group is thus defined on the basis of a common virion morphology. In addition to a common structure, members of the group share a number of biological properties such as a similar replicative cycle, the ability to cause latent and chronic infections, and the ability to induce antigenic modifications of infected cell membranes. Several herpes­ viruses have been associated recently with malignancies in man and animals (KLEIN, 1972). Herpesviruses are ubiquitous and have been described in over 30 different species (HUNT and MELENDEZ, 1969; WILDY, 1971; FARLEY et aI., 1972; KAZAMA and SCHORNSTEIN, 1972; NAHMIAS et aI., 1972; ROlZMAN et aI., 1973). Their widespread occurrence in nature suggests a common ancestor.