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B Heyman

Publications and source records attributed to B Heyman.

70 records · Page 4Linked to original sources

IgM-mediated enhancement of in vivo anti-sheep erythrocyte antibody responses: isotype analysis of the enhanced responses.

The direct splenic anti-sheep erythrocyte (anti-SRBC) responses as well as the serum IgG1, IgG2a, IgG2b, and IgG3 anti-SRBC responses of CBA/CaJ mice were monitored 4-35 days after immunization with: (1) a suboptimal dose of SRBC, (2) a suboptimal dose of SRBC plus monoclonal IgM anti-SRBC, or (3) a high dose of SRBC. The direct plaque-forming cell (PFC) responses of mice in treatment group 2 were significantly higher than those in group 1 but similar to the responses in group 3. The serum anti-SRBC antibody responses of all IgG subclasses were significantly enhanced by IgM anti-SRBC and were generally even higher than the responses obtained with high doses of SRBC. The relative proportions of each serum IgG subclass were similar in all three groups. These data suggest that the enhancement of suboptimal anti-SRBC antibody responses by IgM anti-SRBC extends through IgM and all of the IgG subclasses and, further, that the isotype profile in antibody-enhanced responses is similar to that obtained with high doses of SRBC.

Animals↗

Specific IgM enhances and IgG inhibits the induction of immunological memory in mice.

The effect of priming mice with IgM anti-SRBC (sheep erythrocytes) together with SRBC or IgG anti-SRBC together with SRBC on the development and expression of memory cells was studied. Mice primed with specific IgM and SRBC showed a much more efficient secondary plaque-forming cell and serum antibody response after challenge with SRBC in an adoptive transfer system than did controls primed with SRBC only. The expression of this enhanced memory of IgM-primed spleen cells was counteracted by the high levels of internal IgG anti-SRBC (also the result of priming with IgM) when the mice, instead of being tested in adoptive transfers, were challenged directly. The antigen-specific feedback suppression of the primary antibody response by specific IgG antibodies was also seen to inhibit partially the development of memory cells. The suppressive effect on priming could be demonstrated both in adoptive transfer systems and after direct boost of the same mice that received the primary immunization. Both the IgM enhancement and the IgG suppression of memory cell development were antigen-specific, since no effect on the antibody response to a non-cross-reacting antigen, horse erythrocytes, was seen. The effect of these up- or down-regulations of immunological memory could be demonstrated after secondary injections as long as 90-280 days after priming.

Animals↗

Carbohydrate chains on IgG2b: a requirement for efficient feedback immunosuppression.

The in vitro immunosuppressive ability of a monoclonal IgG2b-anti-trinitrophenyl antibody lacking carbohydrate chains (GORK-Tm) has been compared with the immunosuppressive ability of the intact antibody (GORK). The carbohydrate depletion of GORK-Tm was achieved by culturing the GORK hybridoma cells in media containing tunicamycin, an inhibitor of glycosylation. Both antibodies have been shown to have the same antigen and protein A-binding capacity, although GORK-Tm is deficient in complement fixation, antibody-dependent cellular cytotoxicity, binding to Fc receptors on macrophages, and rapid elimination of antigen-antibody complexes from the circulation. It is shown in these studies that although GORK antibodies are efficient immunosuppressors, suppressing up to 95% of the plaque-forming cell response, GORK-Tm antibody preparations with identical hemagglutinating and antigen-binding capacity are highly deficient in suppressing the immune response. These findings are of interest in two ways. First, it shows that the carbohydrate chains are of great importance for the immunosuppressive effects of IgG. Secondly, it also shows that the isotype IgG2b, in addition to all other murine isotypes, can efficiently suppress the humoral immune response.

Animals↗

An enzyme-linked immunosorbent assay for measuring anti-sheep erythrocyte antibodies.

A simple ELISA assay for detecting murine anti-SRBC antibodies of IgG class was developed and the variation of the results according to different experimental conditions was investigated. Erythrocytes were left to settle in flexible plastic microtiter plates, after which they were fixed with glutaraldehyde and the remaining binding sites in the plates saturated with ovalbumin. Serum or monoclonal IgG antibodies were then allowed to react with the erythrocytes. Protein A coupled to alkaline phosphatase caused a color change in the subsequently added enzyme substrate. The results proved to be of good reproducibility, specificity and sensitivity. The assay can be used for measuring IgG concentration, estimating antibody avidity and number of antigenic determinants on the SRBC, as well as screening IgG anti-SRBC hybridomas. The precision of concentration estimates was very good when standard curves were used.

Animals↗

Immunoregulation by monoclonal sheep erythrocyte-specific IgG antibodies: suppression is correlated to level of antigen binding and not to isotype.

Six different monoclonal IgG antibodies with specificities for sheep erythrocytes (SRBC) were tested for immunosuppressive ability. Four of them, one IgG3, two IgG2a, and one IgG1, could yield suppression of more than 90% of the anti-SRBC response. The remaining two antibodies, which were both IgG2a, were found to have no significant effect. The degree of suppression correlated well with the amount of antibodies used that could bind to SRBC, as measured by an ELISA assay. High avidity for SRBC was also a factor making the monoclonal antibody more efficient as an immunosuppressor. The response against antigenic determinants on the SRBC other than those for which the monoclonals were specific, was suppressed to an equal degree. This was established by immunizing mice with SRBC using monoclonal anti-SRBC antibodies that did or did not bind to goat RBC (GRBC). The PFC responses against both SRBC and GRBC were then measured. The anti-SRBC and GRBC responses were suppressed in parallel regardless of whether or not the monoclonal reacted with GRBC. None of the tested antibodies displayed any significant ability to enhance the anti-SRBC response. Thus, IgG1 is not the only murine isotype that can efficiently suppress the immune response against SRBC, but IgG2a and IgG3 can also exert this capacity. The mechanism of IgG-mediated suppression is not one of merely blocking single epitopes but involves the immunogenicity of the entire SRBC.

Animals↗

Characterization of effector cells mediating IgG and IgM antibody-dependent cellular cytotoxicity.

Spleen effector cells for IgG- and IgM-induced antibody-dependent cellular cytotoxicity (ADCC) were characterized with respect to density and cell surface markers by using sheep erythrocytes (SRBC) coated with hybridoma-derived monoclonal anti-SRBC IgG or anti-SRBC IgM antibodies as targets. While basically the same effector cells are cytolytic for IgG and IgM antibody-coated SRBC, they differ with respect to their relative killing capacity for IgG- versus IgM-coated target cells. On the basis of physical and biochemical properties three populations with cytolytic capacity could be separated: (I) A light fraction of large cells had high cytolytic potential for both IgG- and IgM-coated SRBC. The cells were negative for the Fc receptor for IgG (Fc gamma-R-) and the C3-receptor (C3-R-), they carried the receptor for Helix pomatia A agglutinin (HP-A+), and reactivity was strongly reduced after treatment with anti-Thy-1 and complement (C). (II) High activity was also observed with a medium-dense fraction, preferably lysing IgG antibody-coated cells. The cells were Fc gamma-R+, partly C3-R+, mostly HP-A-, and only a minor portion of the cells were Thy-1+. (III) A dense fraction, displaying on a per cell basis low cytolytic potential, was more active in IgM than IgG ADCC. The cells were Fc gamma-R+, HP-A+ and Thy-1+. All three effector cell populations were non-adherent, non-phagocytic, and surface immunoglobulin-negative (s-Ig-).

Animals↗

Antigen-dependent IgM-mediated enhancement of the sheep erythrocyte response in mice. Evidence for induction of B cells with specificities other than that of the injected antibodies.

Monoclonal or polyclonal IgM-anti-SRBC antibodies were used to enhance the anti-SRBC PFC response in mice. For potentiation to occur, the IgM antibodies must always be presented with the antigen for which they have specificity. No enhancement of anti-SRBC response above control levels was noted with either antibodies alone or with antibodies used together with non-cross-reacting antigens. The degree of enhancement was independent of whether only one or several different monoclonal IgM antibodies were used. Likewise, the fine specificity variation among the antibody clones failed to influence the anti- SRBC potentiation, which was shown to vary only with the amount of IgM bound to SRBC measured by hemolytic titers. The response against epitopes on the SRBC other than those the IgM recognized was also enhanced. This was determined by injecting SRBC and a monoclonal anti-SRBC IgM that did not crossreact with GRBC into mice, and measuring the response against both antigens. Normally SRBC and GRBC cross- react at the B cell level to approximately 30 percent, and in this experiment they did so both in the control group and in the IgM group. Using antigens that only cross-react significantly at the T cell level (SRBC and HRBC), IgM-antibodies would only enhance the anti-HRBC response if SRBC and HRBC were inoculated together. No anti-HRBC potentiation was noted when antibodies were injected alone or together with either SRBC or HRBC. The data indicate that the constant part of the IgM molecule is of major importance in determining its enhancing properties in acute IgM-mediated potentiation of the immune responses. No evidence was obtained for a decisive role of variable regions. Furthermore, no general B cell activating properties of either mono- or polyclonal IgM-anti-SRBC antibodies could be demonstrated.

Animals↗

Natural and antibody-dependent killer cells in the thymus.

Thymocytes contain a small population of light (o = 1.067), large cells with high cytolytic potential against natural killer target as well as against IgG- or IgM-coated erythrocytes and nucleated cells, thus displaying natural killer and antibody-dependent cellular cytotoxicity functions, but not exhibiting T killer cell capacity. As far as characterized, the cells show T cell characteristics: they are nonadherent, nonphagocytic, surface immunoglobulin-negative, C3 receptor-negative, partly Fc gamma receptor-positive, carry the receptor for Helix pomatia A agglutinin, and are, at least partly, cortisone-resistant and Thy-1-positive. The implications of this finding with respect to the lineage of natural killer and killer cells and their interdependence will be discussed briefly.

Animals↗

Changes in patterns of care of the mentally handicapped: implications for nurses' perceptions of their roles and hospital decision making processes.

This paper reports on the findings of a longitudinal study of a mental subnormality hospital in the North of England. The focus is upon how nurses have experienced a major change in care and treatment of residents from 1978 to 1980. We explore, through the eyes of nurses, the change in their role from a predominantly nurturing/custodial one to a mainly educational/community orientated role. The research findings demonstrate that this change has increased nurses' self-esteem and their satisfaction with important areas of their work. There is some evidence also that nurses/resident relationships have improved in spite of reservations felt about new forms of treatment and community care. We suggest that such reservations may be linked to critical views expressed by nurses, particularly sisters and charge nurses, that decisions were taken about residents by other more senior personnel who had little contact with residents. One important conclusion of this study is that the traditional processes of decision making in the hospital appears to impede the full implementation of a major change which requires nurses to be involved in a potentially threatening process of altering their perceptions of themselves and residents.

Attitude of Health Personnel↗

Constructs of relationships and issues of authority in nursing.

The research on which this paper is based was designed to investigate nurses' perceptions of relationships in their work. The most important issue to emerge from their descriptions of relationships was that of the nature of authority. From their own accounts; examples of which are included in this paper; it can be seen that views of authority in the hospital setting are both complex and varied. We have identified four different types of authority as seen by nurses: parental, reciprocal, political and arbitrary. Our research suggests that any analysis of authority relationships based purely on structural arrangements would be too simplistic. One possible implication of the findings we present might be that more explicit discussion of the nature of authority in nursing relationships should be encouraged both in training and subsequently.

Authoritarianism↗

Nurses' perceptions of the British hospital nursing officer.

A major objective of the Report of the committee on senior nursing staff structure (Salmon Report) was to clarify the role of middle-management nurses. This paper analyses the views of 170 nurses in two general, one psychiatric, and one mental subnormality hospital, about nursing officers. A nursing officer was mentioned as the person with most say or influence over them by more nurses of all grades in the two non-general than in the two general hospitals, a difference explained in terms of the greater role of the medical model, and hence the sister consultant relationship in the latter. There were, however, also marked differences between the responses received from staff in the two general and between the two non-general hospitals in the perceived influence of the nursing officer which could not be explained in this way. Analysis of repertory grids suggested more problems in relations with senior nurses overall in the general hospitals. Nurses' descriptions of relationships with superiors suggested that nursing officer superiors were seen more as 'socio-emotional' whilst sisters and charge nurses were seen as 'instrumental' leaders. Asked to choose a person who had annoyed them at work, nurses chose a nursing officer more frequently than other grades of nurse, particularly in the non-general hospitals. Reasons for annoyance with a nursing officer included unwarranted interference, destructive criticism, and lack of specialized knowledge.

Administrative Personnel↗