Dynamic Foundations of Disease — Paper IX examines several long-recognized paradoxes in autoimmune immunology and interprets them within a systems-oriented framework. Classical models of autoimmune disease emphasized immune complex formation and complement activation as central mechanisms of tissue injury, particularly in systemic lupus erythematosus (SLE). While these models explained many clinical observations, subsequent research has revealed additional layers of complexity involving innate immune activation, interferon signaling, inflammatory mediators, and interacting regulatory loops. This conceptual article links classical immune-complex theory with modern insights into neutrophil extracellular traps (NETs), complement pathways, interferon signaling, and autoantibody networks. Through a series of immunological paradoxes—including CRP responses, apoptotic clearance mechanisms, NET formation, interferon signaling, and complement deficiencies—it illustrates how immune mechanisms evolved for host protection may under certain conditions contribute to sustained immune activation. Taken together, these observations support the interpretation of autoimmune disease as a dynamically evolving immune network rather than a static pathological state. Within the broader Dynamic Foundations of Disease series, these paradoxes are discussed as potential manifestations of instability within interacting regulatory systems and as indicators of dynamic transitions in immune network behavior. This article forms part of the Dynamic Foundations of Disease series, which explores disease mechanisms as dynamic processes within interacting biological systems.
Anita Domargård (Mon,) studied this question.
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