Gábor Ringwald

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

SummaryWe 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.

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.

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

Summary. 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.

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.

The Role of Antibody Density in the Immune Lysis of Sensitised Erythrocytes: A Mathematical Appreciation

Abstract. The influence of sensitizing antibody density on target cell selection by effector monocytes was examined by modifying the sensitization of red cells either by dilution of the antiserum, variation of the number of erythrocytes or both in a cold target competition assay of antibody‐dependent cellular cytotoxicity (ADCC). Human A1 and B erythrocyte target and competitor cells were employed in the presence of hyperimmune anti‐A and anti‐B sera at concentrations above that necessary for saturation of red cells with respect to lytic susceptibility. When the number of red cells was kept constant and the dilution of antisera was varied a linear relationship between the competitive capacity of erythrocytes and the concentration of sensitizing antiserum was observed. When the number of target (competitor) cells and the concentration of antisera were varied simultaneously it was apparent that the competitive capacity was dependent upon the relative densities of the sensitizing antibodies. When competition was tested in the presence of suboptimal concentrations of complement, rather than effector cells it was observed that, in common with ADCC, the effectiveness of cold competition was dependent upon the concentration of sensitizing antibody.

NK AND K CELL ACTIVITY IN MAMMARY AND CERVIX CARCINOMA PATIENTS IN RELATION TO RADIATION THERAPY AND THE COURSE OF DISEASE

Publisher Summary This chapter reviews natural killer (NK)- and K-cell activity in mammary and cervix carcinoma patients in relation to radiation therapy and the course of disease. In a study described in the chapter, 79 patients with mammary tumors and 40 cervical cancer patients were tested before and after surgical and X-ray therapy. The patients were categorized in stage I–IV according to the definition of UICC and FIGO. The patients were not given antitumor therapy before the surgical intervention. The control group consisted of 70 healthy women. Two methods were used for examining cytotoxicity with the lymphocytes separated from the peripheral blood. One of them was the conventional cytitoxic assay and the other method was the cytotoxic capacity test. The data obtained show a general decrease of the NK- and K-cell activity of mammary carcinoma patients and a decrease of the NK-cell activity of cervix carcinoma patients, in comparison with the healthy controls. Irradiation did not influence the NK- and K-cell function in comparison to the values obtained before radiotherapy. NK activity is increased by average of 72.6% by the serum of mammary tumor patients and 41.6% by the serum of cervix carcinoma patients.

Inhibition of the anti-D antibody-dependent cellular cytotoxicity against O,Rh-positive (R1R2) erythrocytes by O,Rh-negative (rr) competitor cells

Anti-D antibody-dependent lymphocyte-mediated lysis of O,Rh-positive (R1R2) erythrocytes was inhibited by O,Rh-negative (rr) erythrocytes in cold target competition experiments. The degree of inhibitory effects was different with the different antisera used for sensitization. Under the same conditions the inhibition varied between 23 and 79%. The difference did not relate to the titres of the sera.

The Role of Antibody Density in the Immune Lysis of Sensitised Erythrocytes

The influence of sensitizing antibody density on target cell selection by effector monocytes was examined by modifying the sensitization of red cells either by dilution of the antiserum, variation of the number of erythrocytes or both in a cold target competition assay of antibody-dependent cellular cytotoxicity (ADCC). Human A1 and B erythrocyte target and competitor cells were employed in the presence of hyperimmune anti-A and anti-B sera at concentrations above that necessary for saturation of red cells with respect to lytic susceptibility. When the number of red cells was kept constant and the dilution of antisera was varied a linear relationship between the competitive capacity of erythrocytes and the concentration of sensitizing antiserum was observed. When the number of target (competitor) cells and the concentration of antisera were varied simultaneously it was apparent that the competitive capacity was dependent upon the relative densities of the sensitizing antibodies. When competition was tested in the presence of suboptimal concentrations of complement, rather than effector cells it was observed that, in common with ADCC, the effectiveness of cold competition was dependent upon the concentration of sensitizing antibody.