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Immunologische Toleranz

Immunological tolerance

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Summary

Immunological tolerance denominates a specific unresponsiveness of the lymphoid system on a cellular level. The phenomenon is preceded by specific recognition of the tolerogen. — Induction of tolerance is possible in the immunologically incompetent as well as the competent organism. — The achievement of immunological tolerance depends on the complexity of the antigen used. In the case of biological antigens increasing the genetic disparity between donor and recipient always increases the antigen complexity. In adults, the induction of immunological tolerance toward cells of another subject is possible only when both of them are highly compatible. In immunological immature subjects the number of potential tolerogens is larger. It can be assumed therefore that immunological tolerance develops under quantitatively and/or qualitatively different conditions in immature individuals. — The persistence of tolerance seems to be dependent on the continuous presence of the tolerogen. — The various known hypotheses of the development of immunological tolerance are discussed and a new one is presented. This theory is based on the following premises: (a) The phagocytic function of macrophages is a necessary step for the evocation of the immunological response. After phagocytosis and processing, the antigenicity of the antigen is increased. (b) Antigens of small or missing adjuvanticity can react directly with lymphocytes to block their immune response. Such antigens are not or to a lesser extent taken up by macrophages. (c) Blocked lymphocytes cannot be activated by antigens previously processed by macrophages. Once activated, lymphocytes can no longer be blocked. Considering the kinetics of these simultaneous processes of phagocytosis and blocking reactions, the phenomena of high and low zone tolerance as well as partial tolerance can be explained.

Zusammenfassung

Unter Immuntoleranz versteht man spezifische immunologische Nichtreaktivität aufgrund einer Unterbrechung des immunologischen Reaktionsablaufes auf cellulärer Ebene. Demnach geht der Entstehung von Immuntoleranz die immunologische Erkennung des Antigens voraus.

Toleranzinduktion ist sowohl bei immun-immaturen als auch bei immun-maturen Individuen möglich. Hinsichtlich des Toleranzerfolges läßt sich eine umgekehrte Abhängigkeit von der Komplexität der Antigene beobachten. Für biologische Antigene bedeutet eine Zunahme der genetischen Antigenspender-Antigenempfängerdifferenz stets auch eine Erhöhung der antigenen Komplexität. So kann gegenüber Zellen eines anderen Individuums beim immunologisch ausgereiften Individuum lediglich dann Toleranz erzeugt werden, wenn ein hoher Grad an Kompatibilität vorhanden ist.

Bei immunologisch unreifen Individuen erscheint das Tolerogenspektrum breiter. Daraus muß geschlossen werden, daß in dieser Entwicklungsphase die Immuntoleranz unter quantitativ und/oder qualitativ anderen Bedingungen entsteht als beim erwachsenen Individuum.

Die Dauer einer induzierten Immuntoleranz scheint von der Persistenz des Tolerogens abhängig zu sein.

Neben der kritischen Darstellung der wichtigsten Hypothesen über die Entstehung von Toleranz wird eine Theorie vorgestellt, die auf folgenden Voraussetzungen basiert: a) Zur Immunantwort ist die Antigen-aufbereitende Funktion der Makrophagen erforderlich. b) Antigene mit geringer oder fehlender Adjuvantizität können direkt mit Lymphocyten reagieren und diese blockieren, während eine Aufbereitung solcher Antigene durch Makrophagen nicht oder nur in geringem Umfang stattfindet. c) Blockierte Lymphocyten sind durch aufbereitetes Antigen nicht aktivierbar und umgekehrt können aktivierte Lymphocyten nicht mehr blockiert werden.

Unter Berücksichtigung der aus den gleichzeitig ablaufenden Prozessen resultierenden Immunkinetik lassen sich die Phänomene der high- und low-zone Toleranz sowie der partiellen Toleranz zwanglos erklären.

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  1. Institut für Experimentelle Chirurgie an der Chirurgischen Universitätsklinik München, Germany

    U. Hopf

  2. II. Medizinische Klinik der Universität Mainz, Langenbeckstr. 1, BRD-6500, Mainz, Deutschland

    U. Hopf

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Frühere Übersichten über immunologische Toleranz erschienen in Klin. Wschr.36, 245 (1958);39, 404 (1961).

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Hopf, U. Immunologische Toleranz. Klin Wochenschr 49, 177–193 (1971). https://doi.org/10.1007/BF01495980

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