On the origin of immunopathology

Area of Science:

• Integrative immunology
• Theoretical biology
• Systems biology

Background:

• Current immunology frameworks are limited, focusing on stimulus-response and neglecting inherent biological stability.
• Existing models fail to adequately explain interactions with commensal microbiota and dietary macromolecules (oral tolerance).
• Immunology remains disconnected from broader biological fields like evolutionary and developmental biology.

Purpose of the Study:

• To propose a new paradigm for immunology centered on dynamic and conservative physiological stability.
• To re-evaluate immunopathology, including autoimmune diseases and immunodeficiencies, as disruptions of this stability.
• To address gaps in understanding the organism-host interactions and the role of the observer in defining immunological specificity.

Main Methods:

• Conceptual re-evaluation of immunological principles.
• Integration of insights from the Biology of Cognition and Language (Autopoiesis theory).
• Analysis of T lymphocyte clonal diversity and its relation to immune stability.

Main Results:

• Immunopathology, characterized by decreased T lymphocyte diversity (oligoclonal expansions), is proposed as a consequence of lost stabilizing connectivity.
• This loss of connectivity, rather than being a marker, is presented as a fundamental pathogenic mechanism.
• The study challenges the traditional stimulus-response model, advocating for a focus on inherent biological dynamics.

Conclusions:

• A paradigm shift is needed in immunology, emphasizing dynamic stability and conservative physiological processes.
• Understanding immune system function requires considering the organism as an integrated entity and acknowledging the observer's role.
• The proposed framework, drawing from autopoiesis theory, offers a more holistic view of immunology and its pathologies.