Current Topics In Microbiology And Immunology Ergebnisse Der Mikrobiologie Und Immunitatsforschung

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 doubleƯ 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 herpesƯ 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.

Phenomena as diverse as tuberculin sensitivity, delayed sensitivity to soluble proteins other than tuberculin, contact allergy, homograft rejection, experimental autoallergies, and the response to many microorganisms, have been classified as members of the class of immune reactions known as delayed or cellular hypersensitivity. Similarities in time course, histology, and absence of detectable circulating immunoglobulins characterize these cell-mediated immune reactions in vivo. The state of delayed or cellular hypersensitivity can be transferred from one animal to another by means of sensitized living lymphoid cells (CHASE, 1945; LANDSTEINER and CHASE, 1942; MITCHISON, 1954). The responsible cell has been described by GOWANS (1965) as a small lymphocyte. Passive transfer has also been achieved in the human with extracts of sensitized cells (LAWRENCE, 1959). The in vivo characteristic of delayed hypersensitivity from which the class derives its name is the delayed skin reaction. When an antigen is injected intradermally into a previously immunized animal, the typical delayed reaction begins to appear after 4 hours, reaches a peak at 24 hours, and fades after 48 hours. It is grossly characterized by induration, erythyma, and occasionally necrosis. The histology of the delayed reaction has been studied by numerous investigators (COHEN et al., 1967; GELL and HINDE, 1951; KOSUNEN, 1966; KOSUNEN et al., 1963; MCCLUSKEY et al., 1963; WAKSMAN, 1960; WAKSMAN, 1962). Initially dilatation of the capillaries with exudation of fluid and cells occurs.

Expression of an immune response is the net result of complex synergisƯ 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 resƯ 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 immunoƯ 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, proƯ 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.

"When we give a definition it is for the purpose of using it". HENRI POINCARE in Science and Method A. Objectives The first version of this paper was written to introduce new students and fellows of my laboratory to the mysteries of herpesviruses. Consonant with this design sections dealing with well documented data were trimmed to the bone whereas many obscure phenomena, controversial data and seemingly trivial observations were discussed generously and at length. There is some doubt as to whether it was meant to be published, but it was not a review. The objective of reviews is frequently to bring order. But alas, even the most fluent summation of credible data frequently makes dull reading and too much plausible order, like very little entropy in chemical reactions, is not the most suitable environment on which to nurture the urge to discover. This version is more charitable but not less inbalanced. The bibliography reflects the intent of the paper and was updated last in December of 1968. It should be obvious without saying that no single account such as this can do justice or injustice, as the case may be, to the several hundred papers published on herpesviruses each year or to the many thousand papers published on herpesviruses since the first of the members of the family was experimentally transmitted to a heterologous host more than half a century ago (GRUTER, 1924). B. Definition 1.

Phenomena as diverse as tuberculin sensitivity, delayed sensitivity to soluble proteins other than tuberculin, contact allergy, homograft rejection, experimental autoallergies, and the response to many microorganisms, have been classified as members of the class of immune reactions known as delayed or cellular hypersensitivity. Similarities in time course, histology, and absence of detectable circulating immunoglobulins characterize these cell-mediated immune reactions in vivo. The state of delayed or cellular hypersensitivity can be transferred from one animal to another by means of sensitized living lymphoid cells (CHASE, 1945; LANDSTEINER and CHASE, 1942; MITCHISON, 1954). The responsible cell has been described by GOWANS (1965) as a small lymphocyte. Passive transfer has also been achieved in the human with extracts of sensitized cells (LAWRENCE, 1959). The in vivo characteristic of delayed hypersensitivity from which the class derives its name is the delayed skin reaction. When an antigen is injected intradermally into a previously immunized animal, the typical delayed reaction begins to appear after 4 hours, reaches a peak at 24 hours, and fades after 48 hours. It is grossly characterized by induration, erythyma, and occasionally necrosis. The histology of the delayed reaction has been studied by numerous investigators (COHEN et al. , 1967; GELL and HINDE, 1951; KOSUNEN, 1966; KOSUNEN et al. , 1963; MCCLUSKEY et al. , 1963; WAKSMAN, 1960; WAKSMAN, 1962). Initially dilatation of the capillaries with exudation of fluid and cells occurs.

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.