A Biosemiotic Analysis of Serotonin

1
A Biosemiotic Analysis of Serotonins 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

2
Framework of study

• Serotonins functionality in the immune system is
  quite complex
• Complexity
• Self-organisation
• T-cell memory formation and activation
• Serotonin
• Dendritic cells maturation

3
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

4
Serotonin signalling

• Key concepts
• Receptor sensitivity
• Synaptic plasticity
• Gene manipulation

5
Reasons for biosemiotic analysis

• Homeopathic medicines are prepared by serial
  dilution and agitation (SDA)
• SDA effects depends on signal reception rather
  than their dose

• Traditional pharmacology assumes a dose-effect
  relationship
• However, many biological processes depend on
  signals rather than doses.

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Complexity and biosemiotics

• Adaptation to microbes trauma by
• immune memorization
• Multifactorial process with systemic features
  feedback, receptor sensitivity
• Functionality by signal transduction

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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

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Serotonin production

• Sources
• Antibodies and IgE --gt mastcell degranulation
  histmamin serotonin
• Platelets platelet activating factor --gtgt
  serotonin
• Complement activation factor
• Sympathetic nerves (neurotransmitter)

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Sequestration

• ATP Ca2
• Serotonin

• Measurements
• LAMP-1
• Amperometry of transmitters
• Mono oxidase A B

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DC maturation

• ATP Ca2
• Serotonin

• Exocytosis of 5 HT
• by lysosomes

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T cell activation

• cAMP
• Receptor
• TPH-1

• Indicator
• Tryptophan -1
• Feedback to DC
• Ligand -gt
• CD 40 and CD 152

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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.

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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.

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Defining the relevant semiotic levels
Macro Antigen-antibody formation and memorization of immune system
Focal Dendritic Cell maturation through 5HT uptake and release and T cell activation
Micro CD 40 and CD 152 production by ligands as negative and positive feedback triggers for DC maturation
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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).

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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.

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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.

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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.

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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.

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T cell memorization
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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.

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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.