A tribute to the first four Presidents of the Hungarian Society for Microbiology.
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History, 20th Century↗
Biomedical subjects
I Béládi
Publications and source records attributed to I Béládi.
Study on the glycoprotein nature of chicken IFNs by chemical cleavage and inhibition of glycosylation.
The considerable molecular heterogeneity of chicken IFNs suggested the possible glycoprotein nature of these IFNs. The carbohydrate-specific oxidation and cleavage by neuraminidase indicated that fibroblast IFN may contain sugar moieties. Among the antimetabolites preventing glycosylation, monensin diminished IFN production. However, since it had the same effect on unglycosylated human leukocyte IFN, the drug very probably blocks intracellular transport. It rather proved that chicken IFNs are also secretory proteins. Tunicamycin diminished the formation of leukocyte IFN, but the decrease in titre of this IFN is due to the inhibition of protein synthesis. It is suggested that chicken fibroblast IFN is a glycoprotein, while leukocyte IFN lacks a sugar moiety. The IFN produced on induction with mitogen is closely related to leukocyte IFN, and therefore it seems that the chicken IFN system does not involve the conventional gamma type.
Animals↗
Inhibition of cytotoxicity of chicken granulocytes by serotonin and ketanserin.
Serotonin (5-HT) has been observed to impair the cytotoxicity of human natural killer (NK) cells. A study has now been made of the effect of 5-HT on the cytotoxic activity of chicken granulocytes. 5-HT at concentrations of 10(-3) to 10(-6) M inhibited the cytotoxicity of chicken granulocytes when added at the onset of the short-term cytotoxicity assay. Ketanserin, a 5-HT2 receptor antagonist, did not reverse the inhibitory effect of 5-HT on chicken granulocyte cytotoxicity. Moreover, ketanserin at concentrations of 5 x 10(-4) to 5 x 10(-7) M inhibited the cytotoxicity mediated by chicken granulocytes. Pretreatment of the effector cells for 2 h with chick fibroblast interferon reduced the inhibition of chicken NK cytotoxicity induced by 5-HT and by ketanserin. These data indicate that, in birds, the neurotransmitter 5-HT serves as a link between the central nervous system and the immune system, and that interferon can modulate the inhibitory effect of 5-HT on the function of cytotoxic granulocytes.
Animals↗
The inhibitory effect of interferon-alpha on the serotonin-induced impairment of human NK cell activity in whole blood.
Serotonin (5-HT) at a concentration of 10(-4) to 10(-10) M impaired the cytotoxicity of human natural killer cells in whole blood. 5-HT added at the onset of the short-term cytotoxic assay had a pronounced inhibitory effect. It is very likely that the 5-HT2 receptor is involved in the inhibition of cytotoxicity because ketanserin, an inhibitor of the 5-HT2 receptor, partially prevented the effect of 5-HT. Treatment with 10(2)-10(4) IU/ml of interferon-alpha before or after the application of 5-HT decreased its inhibitory effect on the cytotoxicity. Radioligand binding studies revealed that the antagonistic effect of interferon was not due to the competition for the 5-HT2 receptors. Cycloheximide, an inhibitor of protein synthesis, did not block the suppression of natural killer activity by 5-HT, but it exerted a blocking effect on the acquisition of resistance to 5-HT induced by interferon.
Cells, Cultured↗
[Tumor necrosis factor production in septic conditions following pancreatitis (preliminary report)].
Detectable TNF levels in sera 33% of patients with sepsis following pancreatitis have been found. No correlation was observed between serum TNF concentration and the severity of illness. However, monocytes and granulocytes of septic patients exerted higher TNF-mediated cytotoxicity than leukocytes of normal blood donors. The in vitro TNF-producing capacity was also higher in the patients in the study group, and it decreased only before fatal outcoming of sepsis. Our results suggest that determination of the TNF-producing capacity of leukocytes might be more informative than measurement of the serum TNF level in the evaluation of the severity or prognosis of sepsis.
Cytotoxicity, Immunologic↗
[Activity of natural killer cells and granulocytes in peripheral blood and separated cells].
The natural killing of K 562 cells by whole blood from normal subjects was comparable with that shown by separated mononuclear cells. In order to establish the conditions for a reliable natural killer assay by using very small numbers of effector cells in whole blood, the isotope uptake of target cells was increased by a modified labelling method, which permitted the use of fewer target cells in the assay. The natural cytotoxicity of whole blood was augmented by interferon to the same extent as observed with separated mononuclear cells. The chemiluminescence of granulocytes in whole blood comparable with that of separated granulocytes. Taken together, these methods are considerably less tedious than the conventional methods, technique is also economical, and the results may reflect in vivo cytolytic processes much better.
Cytotoxicity, Immunologic↗
Combined effects of flavonoids and acyclovir against herpesviruses in cell cultures.
The combined antiviral effects of some flavonoid compounds and acycloguanosine (acyclovir, Zovirax) were studied on the multiplication of herpes simplex virus types 1 and 2 in HEp-2 cells and on pseudorabies (Aujeszky) virus in chick embryo fibroblast cells by the yield reduction method. The flavonoids quercetin, quercitrin (quercetin-3-L-rhamnoside) and apigenin exhibit antiviral activity against these herpesviruses, and acyclovir is currently one of the most effective antiherpetic agents. In these studies, the simultaneous application of flavonoids with acyclovir resulted in an enhanced antiviral activity. A mathematical formula was used to interpret the drug interaction, resulting in FIC (fractional inhibitory concentration) indices. Meaning a synergic interaction, all combinations exhibited synergy, FIC values of 0.6-0.8 being commonly observed.
Acyclovir↗
Immunoenhancement and suppression induced by adenovirus in chicken.
Chickens injected intravenously (i.v.) with human adenovirus type 6 (Ad6) reveal a 2-17-fold increase in the number of plaque-forming cells producing antibody (Ab) against sheep red blood cells (SRBC) 2-6 days after virus infection. Further, polyclonal B-cell activation has been demonstrated by the quantitation of immunoglobulin-producing cells (IgPC) and cells producing immunoglobulin (Ig) of IgM isotype (IgPC mu) in the spleen of chicken inoculated with Ad6. Ad6 infection in chicken results in immunosuppression against SRBC when this unrelated antigen is given after virus infection. It seems that coincidence occurs between the B-cell mitogenic activation and the immunosuppression caused by Ad6, as the most pronounced change in both activities appears on the fourth day following virus infection. These findings suggest that the B-cell mitogenicity of the virus contributes to the impairment of the humoral immune response to SRBC.
Adenoviridae Infections↗
Tumor necrosis factor production by human granulocytes.
Human polymorphonuclear leukocytes kill WEHI 164 cells in an 18-hour 51Cr release assay. Antibody to human tumor necrosis factor (TNF) blocks the lysis of targets mediated by human granulocytes. Resting granulocytes produce an undetectable amount of TNF, if any. Granulocytes stimulated with Staphylococcus aureus release 250-500 U/ml TNF alpha. The specificity of the released TNF in the WEHI 164 cytotoxicity assay was confirmed by using neutralizing anti-TNF alpha monoclonal antibodies. The thymidine uptake of endothelial cells was inhibited by granulocyte-derived TNF. The identity of TNF alpha was further confirmed by molecular weight determination, by gel filtration on Sephacryl S-200, with a result of approximately 44,000. Besides their antimicrobial capacity, therefore, granulocytes may contribute to tumor rejection, inflammation and septic infections by releasing TNF.
Animals↗
Impaired interleukin 2 production by spleen cells from mice infected with human adenovirus.
Spleen cells from mice infected with human adenovirus type 6 (Ad6) showed defective interleukin 2 (IL2) production 3-5 days after the infection. The response of spleen cells to exogenous IL 2 was also deficient. The impaired capacity of concanavalin A--(Con A)-activated spleen cells from Ad6--infected mice to utilize IL 2 seemed to be related to the depressed capacity of the infected splenocytes to express IL 2 receptors. The immunologic dysfunction following infection with Ad6 may be a consequence of deficiencies in both the elaboration of and response to IL 2.
Adenoviruses, Human↗
Interactions between human and porcine interferons.
To investigate the possible interactions between human and porcine interferons (IFNs) in vitro, human transformed (FL) and nontransformed (HEF) cells were treated with either HuIFN alpha and/or gamma and porcine alpha and/or gamma. In both cases the antiproliferative activity was measured to determine the effects of different combinations between human and porcine IFNs on cell proliferation. Combinations of human and porcine IFNs acted mostly antagonistically with exception of IFN combination Hu-alpha/Po-gamma which showed a synergic cooperativity in therms of antiproliferative activity on human transformed cells.
Amniotic Fluid↗
Comparison of roles of serine esterase in chicken and human natural cytotoxicity.
The requirements for serine esterase activity in the spontaneous cell-mediated cytotoxicity of human lymphocytes and chicken granulocytes have been compared. The lysis of K-562 target cells and of LSCC-H32 chicken target cells was prevented by the serine esterase inhibitor TPCK. ATEE, the substrate of chymotrypsin, impaired both cytotoxic reactions, but to a lesser degree the cytotoxicity of chicken granulocytes. TPCK inhibited the "trigger" mechanism in an early calcium-dependent step and later calcium-independent events in both systems. However, calcium-independent lysis was depressed by serine esterase inhibitor only in the avian cytotoxicity. These findings suggest that avian target cell cytolysis consists of similar sequential phases to those already demonstrated in the human NK cell reaction, and serine esterase is required during several stages of cytotoxicity in the avian system.
Animals↗
Involvement of tumor necrosis factor in human granulocyte-mediated killing of WEHI 164 cells.
Human polymorphonuclear leukocytes (PMNLs) kill WEHI 164 clone 13 cells in an 18-hour 51Cr release assay. Antibody to human tumor necrosis factor (TNF) blocks the lysis of targets mediated by human granulocytes. PMNLs triggered by sensitive targets not only displayed cytotoxic activity, but also released a soluble factor capable of selectively lysing WEHI 164 cells. The killing of these cells by supernatants of triggered granulocytes was totally inhibited by anti-TNF antibody. These experiments suggest that the killing of WEHI 164 sarcoma cells by human PMNLs involves TNF or TNF-like molecules.
Antigen-Antibody Reactions↗
Effects of phorbol myristate acetate on interleukin-2 and accompanying interferon production of human leukocytes induced by heat-inactivated Staphylococcus aureus.
Interleukin-2 (IL-2) production induced by heat--inactivated Staphylococcus aureus (SAU) was enhanced by simultaneous addition of phorbol myristate acetate (PMA). The effect was optimal at a concentration of 10 ng/ml SAU; in the presence of 10 ng/ml PMA, the amount of SAU required for maximal IL-2 production was lower. The kinetics of SAU and of SAU plus PMA-induced IL-2 production were similar. Stimulated mononuclear cells produced interferon (IFN) in addition to IL-2. The titre of accompanying IFN was decreased in cultures stimulated with the SAU plus PMA combination. Plastic nonadherent sheep erythrocyte-positive cells were the most active in the SAU-induced IL-2 production. In contrast, the bulk of the IFN activity was produced by the nonadherent E rosette-nonforming cells. Neutralization of IFN with specific antibodies and pH 2 treatment indicated that SAU-induced IFN consisted mainly of alpha-IFN.
Hot Temperature↗
The multi-factorial pathogenesis of autoimmune disease.
Development of organ-specific autoimmune diseases depends on both an abnormal immune regulation and a genetically determined primary susceptibility of the target organ to the autoimmune attack. In addition to the essential genetically determined prerequisites there are also facultative, modulating factors that influence the outcome of an autoimmune disease. This concept is exemplified in the Obese strain (OS) chicken model which develops a spontaneous autoimmune thyroiditis closely resembling human Hashimoto disease. Three modulating factors are specifically addressed, viz. (a) the lower threshold of OS thyroid epithelial cells for the gamma-interferon-induced MHC class II antigen expression as compared to normal controls, (b) the decreased glucocorticoid tonus of the OS and (c) the presence of a new endogenous virus (ev 22) locus in the OS that has so far not been found in any normal strain and which seems to influence the glucocorticoid-mediated immunoregulatory process.
Animals↗
Synergistic action of quercetin and murine alpha/beta interferon in the treatment of Mengo virus infection in mice.
ABD2F1 mice were infected intraperitoneally (i.p.) or intranasally (i.n.) with Mengo or Sindbis virus and treated with either crude murine alpha/beta interferon (MuIFN-alpha/beta) or quercetin, or both. MuIFN-alpha/beta given i.p. or intramuscularly (i.m.) 1-3 h before the infection had a dose-dependent protective effect regardless of the route of administration. When given after the infection, IFN did not show any effect. Oral quercetin, capable of protecting cardio, i.e. Mengo virus-infected mice, failed to show antiviral efficacy in Sindbis virus-infected animals. Of various combinations of quercetin and MuIFN-alpha/beta, a certain well defined regimen resulted in a significant enhancement of protection in Mengo, but not Sindbis, virus-infected mice. A marginally effective treatment regimen of quercetin (20 mg/kg, given 12 h before Mengo virus infection, and 10 mg/kg given both 1 h before and 12 h after infection) potentiated the activity of a single dose of MuIFN-alpha/beta (5000 IU 3 h prior to infection), giving 85-100% survivors compared to 50% for MuIFN-alpha/beta when applied alone (p less than 0.001).
Animals↗
Granulocyte-specific monoclonal antibody inhibiting cytotoxicity reactions in the chicken.
Monoclonal antibody (MAb) 1C3, specific for chicken granulocytes, is described for the first time. Treatment of peripheral blood leukocytes with this MAb markedly decreased natural cytotoxicity reaction against the target cell line. The antibody-dependent cellular cytotoxicity (ADCC) activity of purified granulocytes was also severely affected by treatment with MAb 1C3. These results suggest that 1C3 detects a functional surface antigen on chicken granulocytes and support the hypothesis that granulocytes are the main effector cells in natural cytotoxicity in the chicken.
Animals↗
The role of interferon in the adenovirus-induced augmentation of granulocyte-mediated cytotoxicity in chicken.
The effects of human adenoviruses on the granulocyte-mediated natural cytotoxicity of chicken leukocytes were investigated. A significant, but transient augmentation of granulocyte cytotoxicity was observed 24 h after virus injection, followed by a relatively long period of its suppression. A good correlation was found between the augmented cytotoxicity and interferon induction. The interferon-inducing capacity of adenovirus type 6 and type 12 in vitro similarly ran parallel with their ability to stimulate granulocyte-mediated cytotoxicity. An adenovirus-induced elevation of cytotoxicity was not observed when IFN production was inhibited by pretreatment of the leukocytes with monoclonal antibody specific for bursal cells and monocytes. In addition, anti-IFN antibody abrogated the stimulation of cytotoxicity as well. During the in vitro experiments in which granulocyte-specific monoclonal antibody was applied, evidence was found that the effector cell activity is associated with the granulocytes. These results suggest that both the in vitro and the in vivo adenovirus-induced augmentation of granulocyte-mediated cytotoxicity is due to the IFN-inducing capacity of the virus. In chickens, the rapid augmentation of the granulocyte cytotoxicity may be important in the acute stage of infection, increasing the resistance to the virus in question and also to bacterial infections.
Adenoviridae Infections↗