Pathophysiologie der Entzündung

Zusammenfassung

Entzündung ist das Resultat einer Aktivierung des Immunsystems aus unterschiedlichen Ursachen. Das Immunsystem ist ein hochkomplexes, evolutionär optimiertes Verteidigungssystem aus zellulären und humoralen Komponenten. Die Immunsituation des Wirtes, die Art und Virulenz des entzündlichen Agens und die (teilweise genetisch determinierte) Feinjustierung der Entzündungsreaktion entscheiden über den Ausgang einer Entzündungsreaktion. Probleme entstehen u. a. durch entzündungsbedingte Gewebedefekte (z.B. Fibrose) sowie durch ungenügende (Immundefizienz) oder überschießende Immunantworten (Autoimmunität). Das dynamische Gleichgewicht zwischen Immundefizienz und Autoimmunität wird durch stringente Selektionsmechanismen in Knochenmark und Thymus und durch Kontrollmechanismen (Checkpoints) in den peripheren lymphatischen Geweben sichergestellt. Viele Tumoren haben Eigenschaften, die zu einer Immunsuppression in ihrem Mikromilieu führen und umgehen dadurch ihre Zerstörung durch das Immunsystem.

In den vergangenen Jahren ist es gelungen, diese lokale Immunsuppression durch den Tumor teilweise zu durchbrechen. Erste klinische Studien haben sehr ermutigende Indizien dafür geliefert, dass die Nutzung des Immunsystems für therapeutische Zwecke eine sehr effektive Waffe bei der Bekämpfung von Tumorerkrankungen sein kann.

Summary

Inflammation results from activation of the immune system in response to a broad range of different stimuli. The immune system is a highly complex and evolutionary optimized defense system with cellular and humoral components. The course of an inflammatory response is influenced by the immune condition of the host, the virulence e. g. of an infectious agent, and the fine tuning of the local tissue reaction, which may be influenced by individual genetic factors. Immunity is a compromise between insufficient (immunodeficiency) or exaggerated (auto-immunity) immune reactions. The dynamic balance between these two extremes is achieved through stringent T- and B-cell selection in the bone marrow and thymus on the one hand and through „checkpoint control” in peripheral lymphatic tissues. Many tumors have ways to suppress local immune responses and to escape destruction through the immune system (one of the so-called „hallmarks of cancer”).

In recent years, different approaches have successfully been able to reverse this local immunosuppression. First clinical trials using these strategies have shown highly promising results indicating that the therapeutic use of the immune system will be a very effective instrument in the arsenal of cancer treatment agents.

Schlüsselwörter

T-Zelle - B-Zelle - Antigenpräsentation - Immunsuppression - Immundefekt - Autoimmunität - Checkpoint - Inhibitor - Tumor - Therapie

Keywords

T-cell - B-cell - antigen presentation - immunsuppression - immunodeficiency - autoimmunity - checkpoint - inhibitor - tumor - therapy

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