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Aktivierung des Komplementsystems — Ein Monopol des Immunkomplexes?

Activation of complement—an exclusive domaine of immune complexes?

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Summary

The classical tool for complement research is the sensitized erythrocyte. The position of this complement activating system in modern complement research is evaluated. Since a considerable number of complement reactions independent of the hemolytic antibodies have been described, the definition of the antigen-antibody complex as being the single possibility to activate complement should be abandoned. The alternate pathways that also lead to the activation of the C-system are presented and compared between themselves. Their common point of attack is the component C3. This component is activated by a number of proteases, by some polysaccharides such as dextran, and Zymosan, by cobra toxin, by endotoxin and also by antibodies which were not able to fix C1—for instance theγ1 antibody of guinca pig. A cofactor system independent from C is essential for the effect of these substances.

The C3 activation by cobra toxin is the first of the by-pass activation systems which can be characterized in terms of protein chemistry. Its effect on C3 shows the characteristic kinetics of an enzymatic process. Based on these data, the fact can be well understood that animals with hereditary defects in the complement system are well able to survive. In these cases a circumscript gap in the classical reaction chain of the C-system can be compensated by the by-pass mechanism of C3 activation. This means that complement plays not only a role in the classical immune reactions but also in various fields of general defense.

Zusammenfassung

Das Komplementsystem wird herkömmlicherweise als ein Reaktionspartner des AgAk-Komplexes beschrieben. In jüngster Zeit hat sich aber herausgestellt, daß seine Aktivierung kein Monopol des Immunkomplexes bzw. des Antikörpers ist. An geeigneten Einzelfaktoren ansetzend kann man die Reaktionskette des Komplements auch unabhängig vom Antikörper auslösen. Es werden diejenigen Reaktionen beschrieben, welche, unabhängig vom Antikörper, von C1, C4 und C2 die dritte Komplementkomponente aktivieren und die Reaktionskette des restlichen Komplementsystems bis zum Terminalschritt in Gang setzen. Zu solchen Aktivatorsubstanzen gehören Proteasen, hochmolekulare Polysaccharide (Dextran, Zymosan), Cobratoxin, Endotoxine der Enterobakterien und schließlich Immunaggregate nicht-komplementbindender Antikörper. Die Wirkung dieser Stoffe ist von einem nicht zum Komplementsystem gehörigen Cofaktorensystem abhängig.

Die durch Cobratoxin induzierte „Bypass“-Aktivierung der Reaktionskette C3, C5, C6, C7, C8, C9 ist das erste immunchemisch charakterisierte und enzymkinetisch gründlich untersuchte Modell einer solchen Bypass-Aktivierung von C3. Die Tatsache, daß Tiere mit umschriebenen, erblichen Komponenten-Defekten in ihrem Komplementsystem ein normales Immunverhalten zeigen können, spricht dafür, daß die Rolle von Bypass-Mechanismen der C3-Aktivierung in vivo sehr gewichtig ist: Offenbar existiert neben dem spezialisierten Apparat der Komplement-Aktivierung durch Antikörper ein zweiter funktionell leistungsfähiger Apparat, der entsprechende Ausfälle im ersten System befriedigend kompensieren kann. — Durch den Nachweis des Bypass rückt das Komplementsystem aus einer funktionellen Unterordnung im Hinblick auf den AgAk-Komplex in den Rang eines höherwertigen und selbständigen Systems; seinc Bedeutung für die Auslösung von Entzündungsreaktionen vervielfacht sich hierdurch.

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Bitter-Suermann, D. Aktivierung des Komplementsystems — Ein Monopol des Immunkomplexes?. Klin Wochenschr 50, 277–286 (1972). https://doi.org/10.1007/BF01485175

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