A biosemiotic Analysis of Serotonin’s Complex Functionality Argyris Arnellos+, Martien Brands++, Thomas Spyrou+, John Darzentas+

A Biosemiotic Analysis of Serotonin’s Complex Functionality

• Argyris Arnellos+, Martien Brands++, Thomas Spyrou+, John Darzentas+

• +Dept of Product & Systems Design Engineering, University of the Aegean, Syros, Greece

• ++University of Liverpool, Division of Primary Care

Framework of study

• Serotonin’s functionality in the immune system is quite complex

• Complexity

• Self-organisation

• T-cell memory formation and activation

• Serotonin

• Dendritic cells maturation

Serotonin: an example of a self- organization of a complex system

• Key process:

• Memorization of immune system through T cell activation by

• Serotonin signalling on Dendritic cells and T cells

Serotonin signalling

• Key concepts:

• Receptor sensitivity

• Synaptic plasticity

• Gene manipulation

Reasons for biosemiotic analysis

• Traditional pharmacology assumes a dose-effect relationship

• However, many biological processes depend on signals rather than doses.

Complexity and biosemiotics

• Adaptation to microbes & trauma by

• immune memorization

• Multifactorial process with systemic features: feedback, receptor sensitivity

• Functionality by signal transduction

Steps to the path of T-cell memory formation

• Inflammation:

• Platelets activation: Serotonin (5 HT) production

• Dendritic cells (DC): 5 HT sequestration

• DC maturation: exocytosis of 5 HT

• T cell activation: uptake of 5HT

Serotonin production

• Sources :

• Antibodies and IgE --> mastcell degranulation histmamin & serotonin

• Platelets: platelet activating factor -->> serotonin

• Complement activation factor

• Sympathetic nerves (neurotransmitter)

Sequestration

• ATP Ca2+

• Serotonin

DC maturation

• ATP Ca2+

• Serotonin

T cell activation

• cAMP

• Receptor

• TPH-1

The modeling of T-cell formation under a biosemiotic framework

• Dynamic Object (DO): an activated and fully-functional T cell.

• Immediate Object (IO):

• The DO in its semiotically available form.
• Indicates a range of possible DOs.
• Establishes conditions of possibility to the DO. It is not the IO. It is an IO.

• Immediate Interpretant (II):

• The range of interpretability.
• It is the possible IOs.

• Dynamic Interpretant (DI):

• The actual effect of the sign.
• The realization of one of all the possibilities that are denoted by the range of interpretability.
• The effective reconstruction of an IO.

The modeling of T-cell formation under the biosemiotic framework

• Interpretant: the reconstruction of a form (habit) which was embodied in an Object.

• Reconstruction: Communication of the form of an activated and fully-functional T cell through Signs in CD by ligands in potency to the next generation of the immune system.

• The activated T-cell constrains the behavior of the immune system as an interpreter.

Defining the relevant semiotic levels

The modeling of T-cell formation under the biosemiotic framework

• Sign: activated platelets (platelets that sequester 5-HT)

• IO: The CD ligands.

• The CD ligands is the object expressed (represented) in the specific Sign.
• The ligands is the DO (the activated and fully-functional T-cell) in its semiotically available form.
• A CD ligand can indicate a range of possible functional DOs, as a CD ligand will be interpreted in different ways in different contexts.

• II: The range of interpretability (the set of different instances) of DC maturation.

• The set of possible mature DCs that can be mediated by the specific activated platelets (platelets + 5-HT).

The modeling of T-cell formation under the biosemiotic framework

• Sign: The ligands as feedback on sequestration.

• IO: DC maturation as an IO of the activated and fully-functional T cell.

• DC can modulate T cell proliferation and/or differentiation, then, this IO can indicate a range of possible functional DOs.

• II: The range of SERT expression in the DC.

• Interpretant constraints the interpreter in further interactions.

• DI: The realisation of one of the possible IOs, a DC with a certain degree of maturation.

• DI will play the role of the Sign in the next semiosis.

The modeling of T-cell formation under the biosemiotic framework

• Sign: The DC mature_SERT_expression via 5-HT release. It is the DI of the previous semiosis.

• IO: An activated and ready for interaction T cell.

• II: The range of possibilities of IOs, that is, a set of T-cells with a certain level of cAMP.

• DI: It will be a T cell from the set denoted by the II. This T-cell will be the Sign of the next semiosis.

The modeling of T-cell formation under the biosemiotic framework

• Sign: A T-cell with a specific level of cAMP.

• IO: A T-cell with a level of TPH-1.

• II: The range of possibilities of the IO.

• DI: A T-cell with a specific range of TPH-1.

The modeling T-cell formation under the biosemiotic framework

• Sign: A T-cell with a specific range of TPH-1

• IO: Antigen – Antibody formation

• II: T-cell derived signals – CD ligands

• DI: A specific CD ligand.

T cell memorization

Results and Comments

• An explanatory tool which models the complex phenomenon at the level of emergence.

• It seems that serotonin is just a sign (not-dependent on dose).

• It is a signal that triggers the self-organisation of a very complex system that is being respectively informed under the proper context.

• It engages in information processes based on the presented analysis.

• Modeling of the phenomenon under semiotic terms abstracted from the level of biochemistry could help us ask different questions to complex problems.

• Other tools are missing that should be integrated to the biosemiotic framework.

• Applying biosemiotics modeling to homeopathy gives us the chance to embody biosemiotics in a very diverse and complex testbed.

Further work

• Integrate with theories and frameworks of self-organisation and general systemic and evolutionary thinking.

• A detailed biosemiotic analysis of T cell memory formation.

• Integration with other works of biosemiotics in intra- and extra-cellular signaling.

• Experimental designs in SDA research, which will provide a way to test and refine certain aspects of the theory.