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Biomedical subjects

F R Seiler

Publications and source records attributed to F R Seiler.

At least 91 records · Page 5Linked to original sources
PubMed1984

The influence of classical pathway components during alternative pathway--modulated immune complex aggregation: the role of C1 INH.

Alternative pathway (AP)-triggered reactions as well as classical pathway (CP)-mediated ones, were investigated turbidimetrically and/or immune electrophoretically, either in the presence or in the absence of in situ-generated immune complexes (ICs; tetanus toxoid/human anti-tetanus toxoid-IgG; ICs of equivalence) during the early stages of reaction. Monospecific Fab'- or Fab-fragments (rabbit) were used to block the complement function in normal human serum (NHS). C1q, functionally available following the addition of ethylene-glycol-bis-(beta-aminoethyl ether), N,N'-tetraacetic acid to NHS (EGTA-NHS), was found to increase the IC aggregation, thereby producing a biological surface upon which AP-dependent proteins were deposited. The functional inhibition of C1INH caused a C1s-mediated C3 conversion irrespective of the fact whether C1s was incorporated within macromolecular C1 (NHS) or dissociated from it (EGTA-NHS), thus, in the latter case inhibiting the AP-dependent portion of turbidity. It seemed probable that C3 conversion was effected by a fluid-phase CP C3 convertase. This process, normally counteracted by C1INH, worked more efficiently in EGTA-NHS than in NHS, indicating that the C1s-mediated reactions, initiated by presently unknown mechanisms, were less extensively regulated outside of the Ca2+-dependent C1 complex. The study demonstrates that in EGTA-NHS, too, where AP-triggered reactions have usually been investigated, sections of CP activation may play an important role, especially in situations where the function of C1INH is restricted.

Antigen-Antibody Complex↗
PubMed1984

Immunotoxins--theoretical and practical aspects.

The clinical application of immunotoxins is still hampered by a number of unsolved problems. These include difficulties associated with each of the components of the conjugates, i.e., antibody, coupling agent, and cytotoxic drug. Additional problems are caused by the conjugate formation itself. Major obstacles are the lack of data relating to the pharmacokinetics of immunotoxins and their fate after binding to the target cells. This article reviews these problems and indicates possible solutions, including two suggestions for model immunotoxins.

Antibodies, Monoclonal↗
PubMed1984

Specificity of murine monoclonal antibodies induced by a choriocarcinoma cell-line (BEWO).

The specificity of two murine monoclonal antibodies (BW 252/104, IgG3 and BW 241/10, IgM) which recognize two different antigens is described. BW 252/104 recognizes an epitope detectable on all human cell lines and most of the human tissues tested. On account of this reactivity this antibody could be said to possess a "pan human" specificity. BW 241/10 is mainly reactive with human granulocytes but shows some binding to certain solid tissues (breast, stomach). Because of its lack of reactivity to human lymphocytes and monocytes this antibody could be of interest in the detection of human granulocytes.

Animals↗
PubMed1984

Basic relationships in precipitating antigen-antibody systems: a comparison of a simple theory with experiment.

Theoretical predictions from a simple theory for a homogeneous system with respect to some fundamental functional relations between amount of precipitate or extent of turbidity, initial antigen (Ag) respectively antibody (Ab) concentration, and solubility of immune complexes (ICs) are discussed in comparison with experimental results in a heterogeneous system. Experiments were performed with the aim to render possible and intuitive picture of the relationships considering different aspects. It was found that the theory derived from the equilibrium state of the reaction is also able to describe the non-equilibrium state in a qualitatively correct manner. The influence of Ab affinity on precipitation is discussed. Moreover, it is shown that the theory developed by Pauling et al. in the 1940's although too simple in several details, does, however, consider the most important basic principles of more extensive theories developed by other authors. Precisely because of its simplicity, this model may be a useful help in the discussion of precipitate formation on a molecular level.

Antigen-Antibody Complex↗
PubMed1983

The biological properties of immunoglobulin G and its split products [F(ab')2 and Fab].

Antibodies of the IgG class possess antibacterial, antiviral and toxin neutralizing properties and for this reason are administered prophylactically and therapeutically. In the case of the immunoglobulin preparations commercially available for i.v. application a basic distinction must be made between unsplit immunoglobulins and those antibody preparations obtained by enzymatic digestion, such as F(ab')2 or Fab antibodies. This survey deals with the largely experimental evidence describing the biological properties of these preparations. Administration of antibodies in the presence of the corresponding antigens leads to the formation of immune complexes in the organism. These immune complexes can activate, either directly or indirectly, the cellular and humoral systems which are involved in phagocytosis and the elimination of antigens, in the regulation of the body's own antibody production and in inflammatory reactions. As a result of their inability to interact with Fc receptors, immune complexes with F(ab')2 or F(ab) antibodies appear to be less active in the release of inflammation mediators from leucocytes and thrombocytes than immune complexes with unsplit immunoglobulins. These, on the other hand, can antigen-specifically and non-antigen-specifically suppress the immune system which is not the case for immune complexes with F(ab')2 or Fab antibodies. There are indications that these split products also occur in vivo due to the action of tissue and leucocyte proteases. Unlike Fab preparations, F(ab')2 antibodies have antibacterial and antiviral potencies similar to unsplit immunoglobulins, which is probably due to the ability of F(ab')2 molecules to activate complement, not by the classical but by the alternative pathway. Like Fab preparations, F(ab')2 molecules appear to be superior to unsplit IgG in the elimination of haptens. On account of the relatively long period of time unsplit immunoglobulins remain in the blood, they are well suited for prophylactic treatment and substitution over longer periods. The extent to which indications, obtained predominantly from experimental studies, of a reduced release of inflammation mediators, a lack of immune suppression and a lack of augmentation of IgG catabolism would advocate the use of F(ab')2 split products, especially for therapeutic purposes, can only be ascertained after prospective and comparative studies have been carried out.

Antigen-Antibody Complex↗
PubMed1983

S-sulfonation: a reversible chemical modification of human immunoglobulins permitting intravenous application. I. Physicochemical and binding properties of S-sulfonated and reconstituted IgG.

S-sulfonation represents a reversible chemical modification of disulfide bonds by which under the special conditions chosen only about 2.2 cystine units per IgG molecule are cleaved. Physicochemical and functional evidence for reconstitution is presented. Molecules reconstituted in vitro or in vivo regain, within a few hours, a reactivity (antigen binding, immunoprecipitation, Clq-mediated cross-linking of immune complexes) comparable to equimolar control preparations.

Animals↗
PubMed1983

S-sulfonation: a reversible chemical modification of human immunoglobulins permitting intravenous application. II. Effect on Fc-mediated effector functions.

The generation and release of mediators of inflammation and anaphylaxis via activation of complement or of Fc receptor-bearing cells is held responsible for adverse reactions observed upon intravenous administration of standard immunoglobulins. They are caused by immunoglobulin G (IgG) effector functions predominantly located in the Fc region of the molecule and 'activated' by aggregate formation. Their functional activity depends on the correct conformation of the C gamma 2 domains of Fc and are therefore impaired or even abrogated by S-sulfonation of the hinge disulfide bonds, as demonstrated in this communication: S-sulfonated IgG (S-IgG) has no anticomplementary activity and does not interact with Fc-receptors anymore. After antigen binding, i.e. immune complex (IC) formation, sulfonated IgG is about half as potent as standard IgG in complement activation or phagocyte stimulation (human monocytes and granulocytes). The two activities synergize, however, so that in the presence of complement S-IgG IC are as effective phagocyte activators as standard IC. Moreover, S-sulfonation being the only chemical modification of immunoglobulins that is reversible, it can be demonstrated that all IgG effector functions important for antigen removal are regained by reconstitution of the disulfide bonds.

Antigen-Antibody Complex↗