Mechanisms of viral immunopathology.
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Animals↗
Biomedical subjects
B T Rouse
Publications and source records attributed to B T Rouse.
Immune control of herpesvirus latency.
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Animals↗
Characterization of bovine leukocytes involved in antibody-dependent cell cytotoxicity.
By the use of cell surface markers combined with physical separation techniques, bovine mononuclear leukocytes active as K cells in antibody-dependent cell cytotoxicity were characterized. The most active cells were glass wool adherent and were presumed to be macrophages. In the glass wool nonadherent population, heterogeneity was detected with respect to the complement (C) receptor but all cells expressed the Fc receptor. The C receptor-positive population adhered to nylon wool but was not a B cell and was assumed to be monocyte. The C receptor-negative population, the true lymphoid K cell, was nonadherent to nylon and was suggested to be an Fc receptor-positive null lymphocyte. The results were compared to those obtained with other species.
Animals↗
Neutrophils are mediators of antiviral immunity.
The paper presents evidence that polymorphonuclear neutrophils upon stimulation with herpesvirus-induced antigens release a material inhibitory to virus infection. The material does not appear to be identical to type I or II interferon.
Animals↗
Listeriosis in an Arabian foal with combined immunodeficiency.
A 1-month-old Arabian foal with signs of central nervous system disease was found to have combined (B- and T-lymphocyte) immunodeficiency. The foal died in spite of intensive antibiotic therapy. At necropsy, generalized lymphoid hypoplasia and acute necrotizing and granulomatous inflammation of the brain, heart, and adrenal glands were found. In addition, there were spinal meningitis and focal hepatic necrosis. Listeria monocytogenes was isolated on primary culture from the brain.
Animals↗
Immune effector cell activity in canines: failure to demonstrate genetic restriction in direct antiviral cytotoxicity.
Experiments were undertaken to establish whether the cytotoxic activity of canine immune effector cells against viral antigens was affected by the genotype of the target cell (genetic restriction). Puppies from three different breeds were infected with vaccinia virus, and the peripheral blood leukocytes were collected at various times for measurement of their cytotoxicity against autologous and heterologous vaccinia virus-infected and uninfected skin fibroblasts. In all cases cytotoxicity only occurred against virus-infected targets, and there was no consistent evidence of preferential killing of autologous targets. Several indirect approaches were used to demonstrate that direct, presumably T cell, cytotoxicity was being measured rather than antibody-dependent cell cytotoxicity. On the basis of the evidence from cross mixed-lymphocyte assays and cell-mediated lympholysis assays, the dogs were shown not be be identical with respect to their histocompatibility antigens. The significance of our findings to the phenomenon of genetic restriction as observed for mouse-derived immune effector cells is briefly discussed.
Animals↗
Human neutrophil--mediated destruction of antibody sensitized herpes simplex virus type I infected cells.
Human peripheral blood polymorphonuclear neutrophils (PMN) were tested for their ability to act as effector cells in antibody-dependent cell cytotoxicity (ADCC) against Herpes simplex virus (HSV) infected target cells sensitized with anti-HSV serum. The PMN from all 29 individuals tested could mediate ADCC in the presence of a standard human anit-HSV serum. Since PMN are prominent cells early in herpes lesions, it was hypothesized that because ADCC could represent an in vitro model for antiviral recovery, perhaps the efficacy of PMN at mediating ADCC might be impaired in those subjects to frequent recrudescent herpes. However, evidence for the hypothesis was not obtained since the PMN from individuals with frequent, infrequent, or unrecorded herpes labialis all showed approximately the same activity at mediating ADCC. Alternative ways in which PMN could be involved in antiviral recovery were discussed.
Adult↗
Direct lymphocytotoxicity against herpes simplex virus infected cells.
This study was undertaken to determine if direct cytotoxicity (DC) against herpes simplex virus infected cells, perhaps mediated by T cells, could be demonstrated in individuals subject to recurrent herpes labialis. The mononuclear cells from 7 out of 17 individuals with recurrent herpes expressed DC whereas no DC was ever exhibited by 7 individuals without a previous history of herpes infections. Several approaches were used to show that the cytotoxicity being detected was predominately of the direct type rather than antibody-dependent cell cytotoxicity (ADCC). Since the effector cells of the DC were sensitive to trypsin treatment and behaved as do natural killer (NK) cells upon cell fractionation, the results were taken to imply that the DC was attributable to a NK-effector cell type rather than a classical T lymphocyte.
Antibody-Dependent Cell Cytotoxicity↗
Characterization of surface receptors on bovine leukocytes.
Three bovine leukocyte populations--peripheral blood lymphocytes (PBL), mammary gland polymorphonuclear neutrophils (PMN) and macrophages (Mo)--were characterized with respect to five surface markers: surface immunoglobulin (SIg), sheep erythrocyte receptor, complement (C) receptor and Fc receptors for both IgG and IgM. The majority of PMN and Mo possessed C and Fc receptors for IgG, but lacked SIg and the erythrocyte receptor. The PMN, but not Mo, also expressed a Fc receptor for IgM. The PBL were heterogeneous with respect to their surface characteristics and evidence was presented for the following subtypes: (a) cells with the E receptor alone; (b) cells with E receptor plus the Fc(IgG) receptor; (c) cells with SIg plus the C receptor but minus the Fc(IgG) receptor; (d) lymphocytes with SIg plus the C receptor and the Fc(IgG) receptor, and (e) cells lacking E receptors and SIg but bearing Fc(IgG). It was assumed, but not proven, that some of these latter cells must also bear the C receptor. The significance of the various cell types in antiviral defense is briefly discussed.
Animals↗
Interactions between effector cell activity and lymphokines: implications for recovery from herpesvirus infections.
The destruction of herpesvirus-infected target cells by antibody-dependent and direct cell cytotoxicity was enhanced by the presence of bovine lymphokine-containing preparations. To relate these effects to possible in vivo mechanisms of recovery, several in vitro approaches were used to measure the effects of lymphokine-containing preparations on controlling viral spread. In the first approach it was shown that in the presence of lymphokines, virus-infected cells could be killed earlier in the replication cycle by the mechanism of antibody-dependent cell cytotoxicity, thus possibly limiting spread of virus. That this was indeed the case was demonstrated by a decrease in the area of viral-induced cytopathology as well as in the total number of infected cells present. Secondly, the amount of infectious virus released was also markedly reduced in cultures incubated with lymphokines and immune peripheral blood lymphocytes as compared to cultures treated with either component alone. Finally, lymphokines caused the activation of macrophages. These results are discussed in terms of how various immune parameters may interact in a positive way so as to aid in the recovery from virus infection.
Antibody-Dependent Cell Cytotoxicity↗
Mechanisms of recovery from Herpesvirus infections -a review.
A variety of specific immunological mechanisms have been shown to be effective at neutralizing herpesviruses or destroying herpesvirus infected cells. These include both humoral and cell mediated immune responses or combinations thereof. Thus, it is genarlly accepted that humoral immunity is probably responsible for preventing reinfection whereas cellular immunity, mediated by T lymphocytes or by the interaction of antibody and Fc receptor bearing cells, is more important in recovery from infections. In addition to these specific responses to herpesvirus infection, a number of nonspecific cellular and humoral components have been shown to inhibit the progression of virus replication and therefore, have been implicated in assisting the host in the recovery process. The various interactions and counteractions between the various nonspecific and specific components of the immune response are discussed with respect to their role in recovery from both primary and recurrent disease as well as how they may eventually be manipulated so as to control herpesvirus recrudescent disease.
Animals↗
Complement enhances antiviral antibody-dependent cell cytotoxicity.
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Animals↗
Mechanisms of resistant of herpesviruses: comparison of the effectiveness of different cell types in mediating antibody-dependent cell-mediated cytotoxicity.
Enriched populations of polymorphonuclear leukocytes (PMN) and macrophages obtained from the mammary gland and of granulocytes (PBG) and lymphocytes (PBL) prepared from peripheral blood of the same animal were compared for their ability to mediate antibody-dependent cell cytotoxocity against antibody-sensitized infectious bovine rhinotracheitis virus-infected target cells (IBR-GBK) and antibody-sensitized chicken erythrocyte targest (CRBC). The order of effectiveness was PMN leads to macrophages leads to PBG leads to PBL. The reason why PBG (86% PMN) were less than 50% as active as mammary PMN (99% PMN) was explored and discussed. The findings that PMN were more effective on a cell-to-cell basis, required less antiserum to sensitize for cytotoxicity, and destroyed IBR-GBK cells faster and more completely than other cell types could mean that PMN may be the cell type most importnat in causing early recovery from herpesvirus infections.
Animals↗
Enhancement of antibody-dependent cell-mediated cytotoxicity of herpesvirus-infected cells by complement.
An investigation was made of the effects of complement on the levels of antibody-dependence cytotoxicity (ADCC) mediated by bovine leukocytes against herpesvirus-infected target cells. Neutrophil-mediated ADCC was considerably enhanced upon the addition of low levels of complement that alone failed to induce lysis of antibody-sensitized target cells. This enhancement was most apparent under suboptimum conditions such as at low effector-to-target cell ratios, low levels of sensitizing antiserum, and short-duration assays. Furthermore, cells and classes of immunoglobulin unable to induce ADCC could do so in the presence of complement. The action of complement is considered in terms of a more tenacious bond formed between effector and target cells. The implications of the results are discussed in terms of the part that complement might play in enhancing antiviral recovery processes.
Antibodies↗
Solid-phase radioimmunoassay for detecting bovine (neonatal calf diarrhea) rotavirus antibody.
An indirect solid-phase microradioimmunoassay is described for detecting antibodies against rotaviruses. The test involved ethanol fixation of microcultures of bovine rotavirus-infected BSC-1 cells and reacetion with bovine antirotavirus serum, followed by 125I-labeled rabbit anti-bovine immunoglobulin G. The technique was shown to be virus specific and highly sensitive. The fixed microcultures could be stored at 4 degrees C for at least 2 months without affecting the sensitivity of the test. The application of this system for the detection of rotavirus antibodies in humans is briefly discussed.
Animals↗
The effect of the antiherpesvirus drug 5-methoxymethyl-2'-deoxyuridine on the humoral immune response in vivo.
5-Methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity in vitro against Herpes simplex virus, was investigated for its immunosuppressive effects. Doses as high as 2000mg/kg given daily for 9 days were not immunosupporessive as judged by the fact that treated animals produced normal immune responses to sheep erythrocytes, Brucella bacteria, and Herpes simplex virus.
Animals↗
Bovine type II interferon: activity in heterologous cells.
The antiviral and cell growth inhibition spectra of bovine and human interferons are described. The antiviral activity of type II interferon in heterologous cells far exceeded that of the corresponding type I interferon. Antiviral activity of bovine type II interferon parallels cell growth inhibition activity both in thermal inactivation kinetics as well as in the rate of synthesis. Furthermore, the spectrum of antiviral activity against heterologous cells was the same as that seen for cell growth inhibition suggesting that one molecule may mediate both effects. The therapeutic implications of type II interferon prepared in animals for use in human medicine are discussed briefly.
Animals↗
The direct antiviral cytotoxicity by bovine lymphocytes is not restricted by genetic incompatibility of lymphocytes and target cells.
Experiments were designed to determine if in the ox a requirement for genetic compatibility between antiviral cytotoxic cells and target cells was needed for cytotoxicity to occur. Unrelated bovine animals were immunized with vaccinia or IBR virus (a herpesvirus), and PBL were collected at various times for measurement of their cytotoxicity against autologous or heterologous uninfected or virus-infected fibroblasts. In all instances, cytotoxicity was expressed against heterologous as well as autologous targets and in most cases there was no evidence of enhanced killing of autologous cells. The cytotoxicity was shown to be direct, presumably T cell mediated, and was not attributable to ADCC. The likelihood of the animals under investigation sharing histocompatibility antigens was considered extremely remote but was not formally excluded.
Animals↗