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T Bakács

Publications and source records attributed to T Bakács.

At least 37 records · Page 2Linked to original sources

K cell activity is low in newborn infants.

K cell activity of 18 mature, healthy newborns was measured against O,Rh(D)-positive erythrocytes, sensitized by anti-D antibodies, in cord and venous blood (later obtained 3-4 days after delivery). 53 healthy women served as controls. Activity was determined as a function of target cell number in the enzyme-like kinetic model of cytotoxicity. It was low in cord blood, increased in venous blood by days 3-4 but it did not reach the level of adults. While cytotoxic activity of male infants increased significantly from birth to the 3rd-4th day of life, it did not change in female infants. No correlation was found between the weight and K cell activity of newborns.

Birth Weight↗

The influence of antibody sensitization on target cell selection in monocyte-mediated antibody-dependent cellular cytotoxicity.

The role of sensitizing antibody in monocyte-mediated antibody-dependent cellular cytotoxicity (ADCC) has been investigated using human erythrocyte target cells and hyperimmune anti-A and anti-B antisera. The influence of sensitizing antibody concentration on target cell selection by effector monocytes was measured using a cold target competition assay. It was observed that even when red cells were saturated with sensitizing antibody with respect to lytic susceptibility further increases in the density of membrane bound IgG continued to influence their capacity to inhibit lysis in cold target competition assays. It is suggested that although a critical level of sensitization is required for the initiation of lysis, the avidity of interaction between monocyte and target erythrocytes is significantly influenced by further increases in the availability of target-bound antibody.

ABO Blood-Group System↗

Comparison of monocyte and complement mediated haemolysis of human A1 erythrocytes: the relationship between antibody, target and effector concentrations in the induction of lysis.

Haemolysis of sensitized A1 erythrocytes by blood monocytes or complement was measured under conditions where antibody, complement, target and effector concentrations varied relatively to each other. When sensitization was limiting, cell-mediated lysis remained constant with increasing red cell number. When antibody was in excess and complement was limiting, complement-mediated lysis remained constant with increasing red cell number. These effects could be explained if a non-homogeneous expression of A1 antigens on individual erythrocytes is assumed. Considering that the capacity of antibody to bind to the antigen is random and uniform, at high dilution of antibody only those erythrocytes with sufficiently high antigen density will be appropriately sensitized for cell-mediated lysis. At antibody excess binding sites are saturated, and therefore the number and distribution of cell bound antibodies reflect the number and distribution of antigens. The fact that under such conditions increasing target concentrations did not reduce lysis induced by a suboptimal complement concentration also argues for an uneven antigen distribution among erythrocytes.

ABO Blood-Group System↗

Quantitative comparison of direct and cold-target competition assay in monocyte- and complement-mediated lysis of sensitized erythrocytes.

Differences in the number of the antigenic determinants of A1 and B erythrocytes were exploited to study the influence of the sensitization on antibody-dependent monocyte- and complement-mediated cytotoxicity. Lysis was compared in direct and cold target competition assays. The findings were: (1) Monocyte mediated lysis of both targets was similar; A1 erythrocytes, however, showed stronger competitive inhibition than B cells; (2) the competitive inhibition was influenced by the antiserum concentration in a range where the direct lysis was not; (3) in the presence of optimal concentrations of hyperimmune antisera and complement, A1 erythrocytes were lysed, while B erythrocytes were not; and (4) A1 cells exposed to suboptimal concentrations of complement consumed complement, while B cells did not. It was concluded that the cold target competition assay is more sensitive than the direct cytotoxicity test to detect differences in the sensitization of erythrocytes.

Antibodies↗

Quantitative determination of anti-A-dependent cytotoxicity of human peripheral blood monocytes.

A simple test is suggested for the quantitative measurement of the cytotoxic activity of human peripheral monocytes. Adherent cells are separated from non-adherent cells in the wells of the microtiter plates, thus tedious resuspension of effector cells can be omitted. Effector cell number is accurately determined by isotope labelling. Maximum of cytotoxic activity is measured in the enzyme-like kinetic model of cytotoxicity as a function of target cell number. It was found that 34.2-51.2% of unseparated peripheral blood mononuclear cells (PBMC) were adherent. More than 80% of these were shown to be monocytes by monoclonal antibodies and alpha-naphthyl acetate esterase (ANAE) staining. Depletion of SRBC rosette forming cells prior to adherence (PBMC, E-) resulted in enrichment of adherent cells (61.3-82.8%), which were exclusively monocytes. Cytotoxic activity of both adherent populations (PBMC and PBMC, E-) for human red blood cells sensitized with anti-A was determined experimentally and also extrapolated by using the Michaelis-Menten equation. It was estimated that one monocyte was able to lyse more than 4 erythrocytes.

ABO Blood-Group System↗

Monocyte-mediated haemolysis: influence of antibody concentration on the inhibition of antibody-dependent lysis of human A1B erythrocytes by large numbers of unsensitized erythrocytes.

Antibody-dependent monocyte-mediated haemolysis of human group A1B erythrocytes was inhibited by O, Rh/D/-ve unsensitized erythrocytes. Effector cells were sterically isolated to prevent binding, recognition, and subsequent lysis of target cells. Reduction of cytotoxicity was strongest when only B, intermediate when only A1 antigens were saturated, whereas haemolysis could not be significantly inhibited by 200-fold excess of inhibitor cells if both A1 and B antigens were simultaneously saturated. Dilution of anti-A,B serum of between 1:32-1:512 did not reduce cytotoxicity in the absence of inhibitor cells, while inhibition of cytotoxicity grew proportionally stronger by every dilution step in the presence of inhibitor cells. If effector cells were immobilized by adherence, inhibition was strong and could not be influenced by the sensitizing antibody concentration. It was concluded that motility of monocytes was influenced by the number of sensitized antibody binding sites.

ABO Blood-Group System↗

Enhanced K-cell activity in the peripheral blood of patients with malignant disease.

We have analysed the influence of human malignant, inflammatory and infectious disease on the capacity of peripheral lymphocytes to mediate antibody-dependent haemolysis. The application of an enzyme-like kinetic model for measurement of maximal cytotoxic function has permitted reproducible and sensitive determinations of the K-cell function. The results show that malignant disease is associated with enhancement of ADCC capacity.

Antibody-Dependent Cell Cytotoxicity↗

K cell mediated haemolysis: influence of large numbers of unsensitized cells on the antibody-dependent lysis of anti-D-sensitized erythrocytes by human lymphocytes.

The inhibition of K cell mediated haemolysis of anti-D-sensitized human red blood cells by unsensitized erythrocytes has been demonstrated. Inhibition of lysis was non-competitive in nature and influenced by the size and number of unsensitized cells. However, even in the presence of high inhibitor: target cell ratios (50:1) haemolysis, although reduced, was still effected suggesting that K cells are highly motile and capable of recognizing and destroying minority populations of antibody-sensitized erythrocytes. These data are compatible with a role for cytotoxic lymphocytes in the intravascular lysis of autoantibody or alloantibody-sensitized red cells.

Antibody-Dependent Cell Cytotoxicity↗

Influence of chemotherapy on the phagocytic activity of mononuclear cells in patients with Hodgkin's disease.

The phagocytic activity of mononuclear cells (MNC) was measured in 18 healthy blood donors and 16 patients with Hodgkin's disease (HD) before and after a new chemotherapeutic cycle (Cyclophosphamide - Vincristine - Prednisone - Procarbazine, CVPP; Adriamycin - Bleomycin - Vinblastine - Decarbazine, ABVD) using radiolabeled, opsonized yeast cells. The phagocytic activity of the MNC of HD patients was found to be significantly higher than that of the healthy controls. In patients in whom chemotherapy induced remission or partial remission, phagocytic activity of MNC was also reduced significantly, while phagocytic activity was increased in two patients, whose clinical course was not influenced by therapy.

Adolescent↗

Increased number of phagocytic cells among the peripheral blood lymphocytes of mammary tumor patients.

Blood lymphocytes of 15 malignant mammary tumor patients and 16 healthy blood donors were tested for latex particle phagocytosis. The mononuclear cell fraction of breast cancer patients has been shown to contain significantly higher number of phagocytic cells (39.13 +/- 13.93%) compared to the values of healthy controls (20.34 +/- 6.96%) (p less than 0.01). It was demonstrated that the majority of phagocytic cells adhered to the glass of the hemocytometer, thus they could be distinguished morphologically from the non-adherent, non-phagocytic cells. The number of ingested latex particles per phagocytic cell was also higher in patients. This result shows that the activity of phagocytic cells was also increased in mammary tumor patients compared to controls.

Breast Neoplasms↗

Influence of lectin-free interleukin-2 on natural and antibody-dependent cellular cytotoxicity.

Supernatants derived from MLA-144, a gibbon T cell line that constitutively releases interleukin-2 (IL-2) and which lack detectable interferon (IFN) had the capacity to enhance the natural killer (NK) cells function of human peripheral blood lymphocytes. Percoll fractionation revealed that like IFN-inducible cytotoxic cells lymphocytes responding to MLA-144 supernatants cofractionate with native NK cells. Exposure to MLA-144 conditioned medium also potentiated the cytotoxic capacity of extravascular effector cells which are either unresponsive or weakly responsive to interferon-alpha (IFN-alpha). Moreover lymphocyte (K cell)-mediated antibody-dependent cellular cytotoxicity (ADCC) which is unresponsive to IFN-alpha was in most cases subject to a modest potentiation following treatment with MLA-144 supernatants. These data confirm previous reports that IL-2 can regulate peripheral blood NK cell function and also demonstrate that this lymphokine can also influence those natural cytotoxic mechanisms which are unresponsive to IFN-alpha.

Animals↗

Human K cell-mediated haemolysis: determination of the cytotoxic capacity and antibody sensitization requirements of T lymphocyte enriched and depleted populations.

We have examined the cytotoxic activity of unfractionated peripheral blood lymphocytes (PBL) and T cell-enriched and depleted populations for human red blood cells (HRBC) sensitized with anti-D. Although K cell function was frequently enriched in non-sheep red blood cell (SRBC) rosetting (E-) fractions in some cases cytotoxic activity was equivalent in SRBC rosetting (E+) and non-rosetting cells or greater in E+ populations. The distribution of antibody induced haemolytic activity was similar, but not identical, to that of natural killer (NK) cell-mediated lysis. The sensitization requirements of E- and E+ populations measured as the concentration of anti-D capable of inducing 50% of maximum lysis (Ab50) were similar or identical. In addition it was apparent that the differences in cytolytic potential of E- and E+ are quantitative rather than qualitative since E+ cells exhibited lytic profiles equivalent to E- populations following increase of the effector cell concentration. Despite the similar antibody requirements of E- and E+ effectors these populations exhibited markedly different sensitivity to inhibition of haemolysis by heat-aggregated gammaglobulin (HAG). We conclude that functional K cells are variably distributed between E- and E+ populations and that differences in cytotoxic activity are a reflection of the relative number of effector cells in each fraction. The differences in the sensitivity of E- and E+ K cells to HAG do not influence the apparently identical sensitization requirements of the 2 populations, possibly because receptors for aggregated IgG are independent of those involved in the induction of ADCC.

Antibody-Dependent Cell Cytotoxicity↗

The relationship between antibody concentration and target cell number in the induction of K cell-mediated haemolysis: evidence for asymmetry among reactants.

The cytotoxic capacity of peripheral blood mononuclear cells for anti-D sensitized human O Rh(D) + ve (R1R2) erythrocytes was measured under conditions where antibody concentrations and target cell number were varied with respect to each other. It was observed that where sensitization was limiting, due either to target cell excess or increased antibody dilution, the relationship between lysis and antibody concentration was non-linear, and that the end-point dilution of anti-D at which measurable cytotoxicity occurred was dependent upon the source or concentration of effector cells. The asymmetrical relationship between cytotoxic activity and the degree of sensitization suggests that, in this system at least, there is extensive heterogeneity either among target erythrocytes in terms of their degree of sensitization and consequent susceptibility to lysis, and/or among effector cells in terms of their sensitization requirements for induction of cytotoxicity.

Antibody-Dependent Cell Cytotoxicity↗

Regulation of natural and antibody-dependent cellular cytotoxicity by staphylococcal enterotoxin A.

The capacity of staphylococcal enterotoxin A (SEA), a potent T cell mitogen and inducer of interferon-gamma (IFN-gamma), to modulate human lymphocyte cytotoxic function has been examined and compared with the influence of purified and/or gene cloned IFN-alpha. While the natural killer (NK) cell function of peripheral blood lymphocytes is significantly augmented after exposure to IFN-alpha, levels of cytotoxicity were even greater following pre-treatment with optimal concentrations (0 X 1 microgram/ml) of SEA. Moreover lymphocyte (K cell)-mediated antibody-dependent cellular cytotoxicity (ADCC), which is uninfluenced by exposure to IFN-alpha, was, in most instances, potentiated by SEA. However the efficacy with which SEA augmented natural cytotoxic function was most apparent from experiments utilizing extravascular lymphoid effectors in which basal NK activity is weak and the response to IFN-alpha variable (in the case of lymph node cells) or undetectable (in the case of tonsillar lymphocytes). Co-fractionation on Percoll gradients of lymphocytes responding to SEA with native NK cells suggested that SEA affects NK cells or their non-cytolytic precursors possibly by elaboration of soluble mediators rather than by the induction of a ligand binding mechanism analogous to lectin-dependent cytotoxicity. This system could have important implications for the regulation of NK cell function by lymphocyte stimulatory factors, particularly in lymphoid tissues where indigenous NK activity is low and relatively unaffected by IFN-alpha.

Antibody-Dependent Cell Cytotoxicity↗

The phagocytosis capacity assay: a new radiometric phagocytosis test for clinical use.

A radiometric technique is described for measuring phagocytosis which does not require separation of extra- and intracellular microorganisms. Following phagocytosis of optimally opsonized yeast cells (Saccharomyces cerevisiae) by mononuclear cells (MNC) or granulocytes, yeast cells remaining extracellular are labeled with [75Se]L-selenomethionine. To measure the phagocytic capacity of the cell population investigated, 1-4 x 10(6) leukocytes are incubated with 5, 10, 20, 30 and 40 x 10(6) yeast cells/ml for testing. Depending on the actual number of phagocytes in the cell populations investigated, different optimal yeast cell concentrations may be determined. Provided measurements are carried out at these optima even moderate effects of therapy can be detected. In a preliminary study of 22 patients with Hodgkin's disease it was shown, that the phagocytic activity of the MNC fraction was higher, but the activity of granulocytes lower, than that of the healthy controls. After combined chemotherapy the above mentioned values returned to normal. This simple, exact method is recommended for clinical use.

Granulocytes↗

Direct ADCC lysis of O,Rh-positive (R1R2) erythrocytes by lymphocytes of individuals sensitized against antigen D.

Non-T-cells from individuals sensitized against antigen D were found to lyze O,Rh-positive erythrocytes. The lytic effect was abolished by incubation of the effector cells at 37 degrees C for 30 min, and was reconstituted by addition of anti-D antibodies. These results suggested that sensitized donors have lymphocytes armed with specific antibodies in vivo.

ABO Blood-Group System↗