Article

PREVENTION OF CELL-TO-CELL SPREAD OF HERPES SIMPLEX VIRUS BY LEUKOCYTES

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Abstract

Antibody to herpes simplex virus (HSV) plus complement destroyed HSV-infected cells but did not stop the spread of the infection. Studies on the relationship between the time of appearance of viral antigens on the cell surface, immunological destruction of the cells by antiviral antibody and complement, and transfer of the virus to adjacent cells showed that the virus spread from infected to uninfected cells before the infected cells were susceptible to immunological destruction. Incubation of infected monolayers with leukocytes, however, stopped the spread of the virus by nonspecifically damaging both infected and uninfected cells and by presumably breaking intercellular bridges. When leukocytes were removed from infected monolayers, viral plaques developed. If, however, antiviral antibody and complement were added to monolayers before the leukocytes were removed, the development of plaques was prevented. These findings suggest that both antibody and leukocytes are needed to cure HSV infections.

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... The explanation could be the fact that in this way the cells are able to maintain ion levels more effectively, granting some protection against the virus infection [64]. Moreover, spread of the HHV-1 virus within the human body occurs by travelling from cell to cell via the tight cell junctions [78], and therefore, the virus is not exposed to the hostile extracellular environment. This fact contributes to the decreasing inhibitory effect of the metal ions. ...
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The epidemiology of infectious diseases is concerned with the circumstances under which both infection and disease occur in a population and the factors that influence their frequency, spread, and distribution. This concept distinguishes between infection and disease because the factors that govern their occurrence may be different and because infection without disease is common with many viruses. Infection indicates the multiplication of an agent within the host and is determined largely by factors that govern exposure to the agent and by the susceptibility of the host. Disease represents the host response to infection when it is severe enough to evoke a recognizable pattern of clinical symptoms. The factors that influence the occurrence and severity of this reponse vary with the particular viruses involved and their portal of entry, but the most important determinants for many common infections lie within the host itself. Of these, the age at the time of infection, genetic background, and immune status of the host are the most crucial.
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There is little doubt that immunologic processes play an important role in the pathogenesis of multiple sclerosis (MS). Here we shall review certain aspects of cell-mediated immunity (CMI) in MS, as it may be reflected in various in vitro assays.
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Two major types of immune response have been described in man. One type is mediated by thymus-derived (T) lymphocytes and is characterized by cellular interactions. The other type is produced by the activities of immunoglobulins secreted by bone marrow (B) lymphocytes when these have differentiated to become plasma cells. Since T-cell immunity requires cellular functions for both development and expression, this type of response has been termed cell-mediated immunity. In contrast, B-cell-associated immune response depends on immunoglobulins carried in the serum and has been called humoral immunity. T-cell immune functions include those effective in host defense against spread of certain infectious agents, contact sensitivity, allograft rejection, and graft-vs.-host disease. B-cell-associated immune responses provide protection against encapsulated bacteria and many viruses, participate in formation of immune complexes, are essential for antibody-mediated cytotoxicity, and affect many aspects of immune reactions through the production of specific antibodies. The ontogeny and development of T and B lymphocytes are described elsewhere. Humoral immunity and the specificity of immunoglobulin production by differentiated B cells are discussed in Chapter 3. In this chapter some characteristic features of cell-mediated immunity will be presented.
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Herpes simplex viruses (HSV) belong to a family of over 70 viruses—Herpesviridae— which have the following main characteristics: They consist of a core surrounded successively by an icosadeltahedral capsid, a globular tegument, and an envelope derived primarily from the nuclear membrane. There are two distinct serotypes of herpes simplex viruses (HSV-1 and HSV-2) which can be differentiated by serological, biological, and biochemical means and which share about half their base sequences [151].
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Herpes simplex viruses (HSV) are among the most common infectious agents of man. There are at least two distinct serotypes (HSV-1 and HSV-2), which have different modes of transmission. HSV- 1 is transmitted chiefly via a nongenital route, whereas HSV-2 is most often transmitted venereally or from a mother’s genital infection to the newborn. The mode of spread of each of the two virus types is reflected by its relative prevalence at different ages and by its pattern of clinical distribution within the host. Thus HSV-1 infections occur most frequently during childhood and usually affect body sites above the waist. HSV-2 infections, on the other hand, occur most often during adolescence and young adulthood and involve body sites below the waist, primarily the genitals. Most infections in newborns are also caused by HSV-2.
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It is suggested that Fc receptors which appear on the surface of cells infected by herpes-simplex virus confer a biological advantage on the virus--perhaps by binding immunoglobulin molecules or antigen-antibody complexes on the cell surface, thus blocking viral antigenic sites, or by consuming antibody directed at surface viral antigen or by modifying replication of the virus.
Chapter
Humans are blessed with at least five herpesviruses, i.e., herpes simplex 1 (human herpesvirus 1, HSV-1), herpes simplex 2 (human herpesvirus 2, HSV-2), herpes zoster virus (human herpesvirus 3, HZV), Epstein-Barr virus (human herpesvirus 4, EBV), cytomegalovirus (human herpesvirus 5, CMV). In recent years three of these viruses, EBV, HSV-1, HSV-2, have become prominently associated with human cancer. The purpose of this chapter is to describe briefly the biology of these three herpesviruses in human cells and tissues. The chapter is organized into four sections dealing respectively with the virion and its components, the replication of herpesviruses in permissive cells, the infection of restrictive and nonpermissive cells, with the acute diseases, latency, neoplastic diseases associated with these herpesviruses.
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This introductory chapter is an attempt to combine our knowledge of the general features of viral replication studied at the molecular level (usually in cell culture) with some information on the course and outcome of infection (insofar as it can be studied) in the whole animal. A comprehensive review of molecular virologic studies would be so diverse that it would be beyond the scope of this chapter and would probably be superfluous for the majority of readers. However, some remarks on the underlying principles of the immune response to viral infection and on viral pathogenesis seem to be appropriate, along with some specific comments on integration of viral DNA into cell genomes and on defective interfering particles. Paradoxically, the host’s immune response to virus infection can play several roles: it can provide both short- and long-term assistance in combating the infection, but also may be at least partially responsible for development of disease symptoms.
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Summary Pretreatment of mice with cyclophosphamide (CY) increases susceptibility of adult mice to herpes simplex type I (HSV-I) infection. In searching for a CY sensitive mechanism, our attention has been focused on natural killer (NK) cells. Activity of these cells was increased in spleens of adult mice after inoculation with HSV-I and depressed after CY administration. The timing of recovery of NK cell activity after the administration of CY, was consistent with a role for these cells in collaboration with immune T lymphocytes when transferred to pre-treated, virus infected animals. It is postulated that sensitized T lymphocytes reacting with virus antigens release products that activate macrophages which in turn produce interferon. Interferon increases NK cell activity and NK cells inhibit viral replication. A correlation between resistance to HSV-I infection and NK cell activity of CBA or C57BL/10 mice was found. It is suggested that NK cells play a role in defence, not only against tumour cells, but also against a wide range of infective agents.
Article
Complement components 1,2,3,4 and total complement hemolytical activity CH50 were studied in 39 patients with serve recurrent genital herpes simplex. The results show statistically significant and selective diminution of C4 (P>0.001) The other components were normal. C4 has a specific action against herpesvirus by itself or associated to some other elements over C4 failure, local or systemic disturbances alter the homeostasis of specific and nonspecific immune system, provking a disbalance host-virus which would explain the recurrence.
SYNOPSISA large part of clinical paediatrics deals with infectious disease, inflammatory conditions, allergy, auto-immune disease and cancer. The immune system plays a critical role in these diseases and in addition presents a perplexing number of conditions arising from defects in the immune system itself. This review seeks to highlight immune mechanisms in selected diseases of children and to explore the clinical value of these mechanisms in terms of diagnostic or therapeutic application. Some of the principles and mechanisms involved in immune defence have been previously considered (Jose, 1973).
Article
Infection with the human immunodeficiency virus type 1 (HIV-1) can cause a dementing illness. Astrocytes, the most numerous cells within the central nervous system, can be infected with HIV-1. These cells are infected by predominantly lymphotropic strains of HIV-1. The mode of infection does not involve CD4 or galactocerebroside C and is, most likely, due to a unique binding-site protein located on the surface of astrocytes. The virus produces low levels of infection. Astrocytic function is significantly altered by viral proteins and nonviral products released by other infected cells. Future therapeutic developments for treating HIV-1 infection will need to take into account the unique mechanisms of interaction of HIV-1 with astrocytes. This review discusses astrocyte involvement in the pathogenesis of the HIV-1 cognitive motor complex.
Article
Intravenous inoculation of BCG was found to be both prophylactic and therapeutic in BALB/c mice against challenge with amastigotes of Leishmania donovani. Spleens and livers of mice inoculated with BCG maintained total parasite burdens at significantly lower levels when compared to controls. BCG administered intravenously 14 days prior to and on the same day of protozoan challenge was more protective than vaccine given 30 and 14 days prior to challenge. A level of 10(7) viable units of BCG provided more protection against challenge with parasites than did 10(6) viable units. BCG given the same route as the challenge dose of amastigotes provided more protection than if administered via some other route. BCG given to mice with an already established infection was shown to significantly reduce their parasite burdens.
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Within hours after infection of cells with herpes simplex, vaccinia, influenza, or Newcastle disease virus, new antigens appeared on the surface of infected cells. The interaction of specific antiviral antibody and complement with these antigens resulted in cell destruction, which was quantitated by the release of (51)Cr. A number of factors can influence the degree of cell destruction, including the density of viral antigens on the surface of infected cells, the nature of the antiviral antibody, and the presence of anti-immunoglobulins. The immunological destruction of virus-infected cells may on the one hand serve as a defense mechanism against certain viral infections, while on the other hand it may contribute to the pathology of the host.
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Human blood lymphocytes stimulated with nonviral antigens in vitro produce an antiviral substance with the biological and biochemical characteristics of interferon. The induced response was specific for cells obtained from immune donors. Cells from nonimmune donors did not produce interferon on exposure to these substances. The quantity of interferon produced by antigen stimulation was related to concentration of antigen over a relatively narrow range; with higher concentrations induction was decreased. Interferon production was maximum during days 4 to 7 in culture. In contrast, phytohemagglutinin-induced interferon was primarily produced during the first 4 days in culture.
Article
Recent studies, primarily with mouse, rat, and chicken cells, have provided evidence to support the concept that vertebrates contain the genetic information for producing a type-C RNA tumor virus in an unexpressed form in their somatic cells as well as in their germ cells. This information, which our associates and we postulated has been part of the genetic makeup of vertebrates since early in evolution, can persist for hundreds of generations in cell culture without overt production of virus. It is proposed that the endogenous virogenes (the genes for the production of type-C viruses) and the oncogenes (that portion of the virogene responsible for transforming a normal cell into a tumor cell) are maintained in an unexpressed form by repressors in normal cells. Various agents, including radiation, chemical carcinogens, and, perhaps, exogenously added viruses, may transform cells by “switching on” the endogenous oncogenic information. Some other implications of the viral oncogene theory are presented.
Article
We reported previously that HEp-2 cells infected with herpes simplex virus (HSV) for 2 hours fail to produce plaques (i.e., they are “killed”) following exposure to rabbit anti-uninfected cell serum (A-UCS) and complement (C′). We have extended these studies and have found that new antigens appear on the surface of cells infected in vitro with this virus for 24 hours or longer.Cells infected for 2 hours or for 24 hours and sensitized with A-UCS were killed on incubation with C′. A-UCS lost its activity following absorption with uninfected cells. Cells infected for 2 or 24 hours were killed on incubation with C′ and rabbit anti-infected cell serum (A-ICS). However, A-ICS absorbed with uninfected cells killed 24-hour, but not 2-hour, infected cells. Therefore, A-ICS contained a new lytic antibody lacking in A-UCS.In other experiments, attempts were made to determine the source of the new antigen. A-ICS absorbed with uninfected cells and then passed through a CaHPO4·2H2O column charged with virus showed diminished ability to neutralize virus and to kill with C′, 2-hour or 22-hour infected cells. However, the purity of virus placed on the column was uncertain. The new antigen could thus be a subunit of the virus contained or bound by the cell membrane or it could be a new or altered component of the uninfected cell.
Article
A suspension of L cells (target cells), a permanent line of C3H-derived fibroblasts, was obtained by treating confluent monolayers with 0.25% trypsin for 15 min. The action of trypsin was stopped by addition of 3 ml.
Article
The 7 S and 19 S rabbit antibodies to herpes simplex virus (HSV) from early and late (hyperimmune) sera differed in their ability to sensitize virus for subsequent neutralization by either complement (C′) or anti-γ-globulin (GAR). The early 7 S and 19 S antibodies showed low to negligible neutralizing activity in the absence of C′ or GAR. When C′ was added, however, both of these antibodies showed enhanced neutralizing activity. The early 7 S but not the early 19 S antibody was also capable of sensitizing virus for subsequent neutralization by GAR. The late 19 S antibody could neutralize virus in the absence of C′ or GAR, but its activity was enhanced in the presence of C′ or GAR. The late 7 S antibody showed high neutralizing activity in the absence of C′ or GAR. In the presence of C′, the neutralization rate constants (K) but not the neutralization titers of the late 7 S antibody were enhanced. In contrast, the neutralization titers of the late 7 S antibody were enhanced approximately threefold with GAR. The neutralizing activity of the early and late 19 S antibodies with C′ or GAR was sensitive to inactivation by 2-ME. Similarly, the neutralizing activity with C′ of the early 7 S antibody and the enhanced rate of neutralization with C′ of the late 7 S antibody were sensitive to inactivation by 2-ME. In contrast, 2-ME did not reduce the neutralization titers of the early and late 7 S antibodies in the presence of GAR.
Article
Experiments in vitro have demonstrated that splenocytes from mice immunized 4 to 5 days previously with mumps virus destroy and/or inhibit the growth of epithelial cells persistently carrying a non-cytocidal mumps virus infection. Because this cytotoxic reaction is immunologically specific and appears to be induced by contact between immune leukocytes and virus antigen associated with target cell plasma membranes, it can be evaluated as a manifestation of the efferent arc of a homograft response to viral infection, and is therefore considered to be a component of cellular immunity.
Article
Peritoneal macrophages transferred from adult CBA mice protected suckling syngeneic mice from intraperitoneal infection with herpes simplex virus. Macrophages from adult mice stimulated with proteose-peptone solution were more effective in providing protection than were unstimulated macrophages. The enhanced resistance provided by stimulated macrophages was associated with more efficient phagocytosis and intracellular destruction of virus, and with greater production of interferon. In contrast to the effects of stimulation on the adult mouse, the suckling mouse did not respond to proteose-peptone inoculation with the production of a population of macrophages that ingested more virus, produced more interferon, or more effectively destroyed virus.
Article
Weanling mice were treated with relatively specific suppressants of macrophages or lymphocytes and infected intraperitoneally with herpes simplex virus. Ingestion of silica particles or anti-macrophage serum impaired macrophage function and allowed virus to spread to the liver parenchyma with resulting hepatitis and early death. Anti-lymphocytic serum allowed the development of persistent viremia with subsequent spread of virus into the brain and development of fatal meningitis and encephalitis. These results are discussed in relation to the role of macrophage-dependent and lymphocyte-dependent reactions in protection of the host against parenteral virus infections.
Article
Mice were protected from infection with Semliki Forest virus and encephalomyocarditis virus by the transfer of peritoneal macrophages that were stimulated to produce interferon in vitro by exposure to a nonreplicating virus. This method of therapy was also utilized in animals infected with encephalomy-ocarditis virus after onset of clinical signs. Of these animals 40 percent recovered, but only 9 percent of the control group recovered.
Article
Macrophages restrict herpes simplex virus replication and can prevent the development of herpetic disease in mice. In an attempt to define the nature of this restriction, an analysis of virus-specified macromolecular syntheses in infected macrophages was undertaken. The significant results were the following: All cells were killed, but the infection was considered to be abortive since the level of infectious virus in macrophage cultures dropped steadily to a level beyond detection by 25 hr after infection. This restriction appeared to be specific for macrophages; the virus replicated efficiently in other mouse cells. DNA with a density characteristic for herpes simplex virus DNA was extracted from infected cultures, and the proportion of macrophages synthesizing DNA increased from less than 1% to greater than 50% by 6 hr after infection. Studies employing polyacrylamide gel electrophoresis indicated that the major viral-specific proteins were induced in macrophage cultures. In addition, all cells showing cytopathic changes characteristic of herpes virus infection also contained viral antigens which could be detected by fluorescent antibody techniques and, by 15 hr after infection, most contained nascent capsids lacking central dense cores. It is suggested that an error in DNA metabolism may be the primary cause of restriction.
Article
Histological and immunofluorescence techniques showed that mononuclear cells invaded virus-infected foci in the livers of passively immunized mice within 10 hr of the receipt of immune spleen cells or hyperimmune serum; by 24 hr, marked destruction of virus antigens had occurred in these lesions. Immune cell transfer promoted denser packing of mononuclear cells in the foci and more efficient destruction of infectious material than immune serum. Similar liver lesions developed by the 6th day after sublethal, primary, subcutaneous infection in normal mice. In contrast, in mice with GVHR which were immunosuppressed but possessed hyperactive macrophages and unimpaired splenic interferon response, mononuclear cells did not invade liver lesions and the animals died. These results, together with data reported previously, indicated that mononuclear cell invasion of infected liver foci, triggered by CMI, was of key importance in recovery from primary mousepox. The roles of specifically sensitized lymphocytes and macrophages within lesions were not directly evaluated, but indirect evidence suggested that lymphocytes could cause no more than a halt in virus multiplication, and that macrophages were required for the inactivation of preformed virions. Possible augmentation of the efficiency of macrophages by locally-produced lymphocyte interferon, neutralizing antibody, or stimulation of their phagocytic and intracellular digestive capacity cannot be excluded.
Article
The microepidemic in primary human amnion cells infected with herpes simplex virus was studied by tritiated thymidine (Tdr3H) autoradiography, time-lapse cinematography, and fluorescent antibody techniques. The plaque is formed by retraction of the cell sheet and the sequence of infection is preserved in rings of cells around the plaque. The progress of the plaque may be followed in irradiated cultures in which essentially all of the DNA synthesis is virus induced. The cell-to-cell transmission as opposed to the cell generation time was 8-10 hr as determined by three different techniques. The presence of labeled DNA and specific HSV protein in the intercellular bridges indicates the means by which the virus spreads in a culture.
Article
Splenic lymphocytes from rabbits immunized with herpes simplex virus (HSV) were incubated in vitro with ultraviolet light-inactivated HSV, and the degree of lymphocyte transformation was determined by measurement of the incorporation of [(3)H]thymidine into acid-insoluble material. Lymphocytes from immunized rabbits were stimulated as much as 30-fold, whereas lymphocytes from control rabbits were unaffected. Lymphocyte sensitization occurred within 3 days after immunization; sensitized lymphocytes could still be detected 120 days after immunization. The antigenicity of the ultraviolet light-inactivated crude virus pool was found to reside primarily in the virion. Infectious virus, in comparison with inactivated virus, produced less lymphocyte stimulation. Studies on the interaction of the humoral and cellular immune responses showed that incubation of anti-HSV antibody with HSV antigens did not reduce the capacity of the viral antigens to stimulate sensitized lymphocytes. Other experiments revealed that lymphocytes from both the spleen and peripheral blood of animals immunized with vaccinia virus could be stimulated by vaccinia, but not by HSV. Conversely, lymphocytes from animals immunized with HSV could not be stimulated by vaccinia. The transformation of sensitized lymphocytes by viral antigens appears to be a simple, highly specific, and quantitative in vitro technique for the study of the cellular immune response to viral infections.
Article
The specific binding of iodine-125-labeled antibody to viral antigens can be used to detect newly synthesized viral antigens and determine the time of appearance of these antigens on the surface of infected cells. Incubation of infected cells with unlabeled antibody to viral antigens specifically blocks the attachment of labeled antibody, and by this inhibition technique the titer of unlabeled antibody to viral antigens can be calculated. The attachment of the labeled antibody to virus-infected cells offers an objective and sensitive method of detecting viral antigens and measuring antibody to virus.
Article
Primary rabbit-kidney cells labelled with 51Cr were infected with herpes simplex virus (HSV). When newly synthesized viral antigens appeared on the surface of the cells, the monolayers were incubated with antibody to HSV and complement. One hour later, cellfree supernatants were assayed for chemotactic activity for polymorphonuclear and mononuclear leukocytes. Injury to the primary rabbitkidney cells was evaluated by measurement of the release of 51Cr. From five to 10 times more chemotactic activity and 10 times more 51Cr were present in supernatants from infected cells that had been exposed to antibody to HSV and complement than in the supernatants from controls. Moreover, it was shown that the interaction of antiviral antibody and complement with viral antigens absorbed to the surface of cells (before penetration) also resulted in the generation of chemotactic activity but did not cause injury to the cell. The data support the hypothesis that activation of the complement system is responsible, at least in part, for the inflammatory response observed in certain viral infections.
Article
Publisher Summary This chapter discusses the cytotoxic effects of lymphoid cells in vitro . The chapter discusses the complex problem of different types of cytotoxic effects of lymphoid cells. These outstanding workers in the field have managed to present a cohesive picture of the various effects on the target cells. The role of “nonspecific” factors is particularly well clarified. The interrelationships among contact lysis, release of pharmacologically active substances, and the terminal components of the complement system are given in the chapter for special consideration. In an in vitro model, it is shown that lymphoid cells from sensitized donors destroy tissue culture cells carrying the antigen to which the cell donor is sensitized. This type of cytolytic reactions is encountered in a great variety of immune situations, comprising all those mentioned in the chapter. The cell that initiates in vitro cytotoxic reaction is assumed to be the sensitized lymphocyte, equipped with its own recognition sites for antigen on the cells that are destroyed. Although this may be true in many situations, it now seems clear that “normal” lymphoid cells can become cytotoxic to other cells by a variety of pathways. The study of the various pathways by which lymphoid cells can become cytotoxic has been helpful for the understanding of effector role of these cells in cell-destructive reactions in general.
Article
The cell-mediated and antibody responses to Herpesvirus hominis type 1 were investigated in patients with primary and recurrent herpetic infections. Stimulation of lymphocyte transformation with the virus and the complement fixing antibody titre did not differ significantly between patients and controls. However, macrophage migration inhibition and lymphocyte cytotoxicity were impaired in patients. The defects were specific to H. hominis, as Candida oblicans, which was used as an unrelated antigen, failed to show a similar abnormality. These results and preliminary sequential studies suggest that the susceptibility to recurrent herpesvirus infection may be due to an impaired production of macrophage migration inhibition factor and lymphocyte cytotoxicity in the presence of intact lymphocyte sensitization and antibody formation.
Article
THE increase in anti-microbial activity of macrophages which occurs in animals that have been infected with living microorganisms is frequently non-specific1. In contrast, the anti-tumour activity of macrophages from immunized animals has been demonstrated in vitro to be immunologically specific2,3. The experiments to be described may throw light on this paradox. They show that the killing of tumour cells by macrophages is made up of an immunologically specific interaction which is followed by a non-specific lethal reaction. A similar pattern has been described for the bactericidal action of immune macrophages3. We have described three ways of obtaining immunologically specific macrophages cytotoxic to tumour cells3,5. These are (1) from the peritoneal cavity of suitably immunized mice (see later); (2) ``arming'' in vitro by contact of non-immune macrophages with spleen cells from hyperimmunized mice, and (3) ``arming'' in vitro by exposure of non-immune macrophages to the cell-free supernatant obtained when spleen cells from immunized mice are cultured with the specific antigen. All such macrophages, on coming into contact with specific antigens, undergo a transformation (referred to as ``activation'') which renders them capable of killing. The actual destruction of the target cell following direct contact with the ``activated'' macrophages is non-specific. Moreover, this non-specific killing may also be demonstrated by macrophages ``armed'' against tubercle bacilli (BCG) which are ``activated'' after exposure to the solubilized protein derivative from tubercli bacilli, PPD, and are able to kill tumour cells. In the original experiments3,5 in which target lymphoma cells were added to ``armed'' macrophages the immunologically specific stage and the non-specific stage of the cytotoxic reactions were not separated and occurred sequentially (Fig. 1).
Article
A modification of the macrophage migration inhibition test using infected monolayers as a source of antigen was applied to the in vitro study of cellular immunity to fibroma virus infection. The capacity of infected monolayers or infected cell homogenates to inhibit migration of peritoneal exudate cells from fibroma virus-infected rabbits paralleled the onset of a cutaneous delayed hypersensitivity response and resistance to re-infection in the intact animal. Studies using antigens prepared at different intervals after infection of cells with the virus suggest that the test is measuring specific antigen(s) associated with the cell surface and probably not a component of the intact infectious virion. Immune serum did not prevent the antigen from inhibiting migration of sensitized cells, but instead enhanced the inhibition. The data obtained demonstrate that the macrophage migration test has practical application in the study of cell-mediated immunity to animal virus infections.
Article
When spleen or lymph node cells from mice infected with or immunized against lymphocytic choriomeningitis virus are incubated with living or killed virus in vitro, a cell-free cytotoxic factor (CT) is made. Production of CT appears immunologically specific in that it is formed only when LCM immune lymphoid cells are incubated with LCM virus and not with either mumps or lactic dehydrogenase virus or human immunoglobulin G (HuIgG). Once released, the biological activity of the CT is nonspecific as it injures both viral infected and noninfected target cells. The time required for elaboration and action of CT, as well as its effect on both infected and noninfected cells, suggests that the cellular injury it causes may perhaps be different from the immunologically specific, direct in vitro injury caused by immune lymphoid cells.
Article
Specific adherence of immune macrophages to monolayers of target cells is a passive phenomenon which represents only the first step in the mutually destructive interaction of immune macrophages and target cells. A specific hemagglutinin, responsible for specific adherence, was eluted from well-washed immune macrophages by heat treatment. The nature of the events in the interaction subsequent to adherence are unknown, but apparently demand the biosynthetic activities of the immune macrophage.
Article
1. Investigation of the role of leukocytes in vaccinia virus infection is reported in an in vitro model, in the absence of an immune response. 2. Mouse leukocytes were shown to be capable of inhibiting the progression of vaccinia virus infection in primary mouse embryo fibroblast cultures. The degree of protection varied from slowing of spread of infection to complete control of the infection with eventual elimination of detectable virus and recovery of the culture. 3. Interferon production by leukocytes is thought to be an important factor in the observed protective effect.
Article
The micro-epidemiology of poliomyelitis and of herpes-B in tissue culture, the mechanisms by which the viruses pass from one cell to another, have been studied. Poliomyelitis virus is not capable of spreading to new cells at an appreciable rate after immune serum has been added to the system. B virus is disseminated most rapidly by passage directly from infected to neighboring cells and thus forms plaques even when bathed in a fluid medium. After a latent period of 16 to 20 hours virus also passes through the culture medium to cause infection some distance from the original host cells. The addition of immune serum blocks the second method of dispersion, but not the first, and infection proceeds in the presence of antibody by means of steadily expanding foci. The results of these studies are taken as evidence that poliomyelitis virus chiefly passes through a free extracellular phase before infecting new cells, while B virus may make use of an alternative route in which it is not exposed to the action of immune serum. Even when no immune serum is present, this second route is the one by which most dissemination of B virus occurs.
Interaction between antigenically different ceils
  • C Lundstedt
Lundstedt, C. 1969. Interaction between antigenically different ceils. Acta Pathol. Microbiol. Scand. 75:139.
Leukocytes and interferon in the host response to viral infections . I. Mouse leukocytes and leukocyte-produced interferon in vaccinia virus infection in vitro
  • L A Glasgow
Glasgow, L. A. 1965. Leukocytes and interferon in the host response to viral infections. I. Mouse leukocytes and leukocyte-produced interferon in vaccinia virus infection in vitro. J. Exp. Med. 19.1:1001.
Comparison of antiviral action of interferon, interferon inducers, and IDU against herpes simplex and other viruses
  • N Schachter
  • M A Galin
  • M Weissenbacher
  • S Baron
  • A Billiau
Schachter, N., M. A. Galin, M. Weissenbacher, S. Baron, and A. Billiau. 1970. Comparison of antiviral action of interferon, interferon inducers, and IDU against herpes simplex and other viruses. Ann. Ophthalmol. 2:975.