Transcript C43

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
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Complexity
Self-organisation
T-cell memory formation and activation
Serotonin
Dendritic cells maturation
Serotonin: an example of a selforganization 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
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Synaptic plasticity
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Gene manipulation
Reasons for biosemiotic
analysis
Traditional pharmacology
assumes a dose-effect
relationship
Homeopathic medicines
are prepared by serial
dilution and agitation
(SDA)
However, many biological
processes depend on
signals rather than doses.
SDA effects depends on
signal reception rather
than their dose
Complexity and biosemiotics
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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
1.
ATP
Ca2+
2.
Serotonin
3.
Measurements:
LAMP-1
Amperometry of
transmitters
Mono oxidase A &
B
DC maturation
ATP
Ca2+
Serotonin
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Exocytosis of 5 HT
by lysosomes
T cell activation
Indicator:
Tryptophan -1
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cAMP
Feedback to DC
Ligand ->
CD 40 and CD 152
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Receptor
TPH-1
The modeling of T-cell formation
under a biosemiotic framework
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Dynamic Object (DO): an activated and fully-functional T
cell.
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Immediate Object (IO):
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Immediate Interpretant (II):
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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.
The range of interpretability.
It is the possible IOs.
Dynamic Interpretant (DI):
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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
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Interpretant: the reconstruction of a form (habit) which
was embodied in an Object.
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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
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
The modeling of T-cell formation
under the biosemiotic framework
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Sign: activated platelets (platelets that
sequester 5-HT)
IO: The CD ligands.
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DC
maturation
(II)
Activated
platelets
(Sign)
The CD ligands is the object expressed
(represented) in the specific Sign.
The ligands is the DO (the activated and fullyfunctional 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.
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The set of possible mature DCs that can be
mediated by the specific activated platelets
(platelets + 5-HT).
CD ligands
(IO)
The modeling of T-cell formation
under the biosemiotic framework
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Sign: The ligands as feedback on
sequestration.
IO: DC maturation as an IO of the activated
and fully-functional T cell.
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(Sign)
SERT
expression in
the DC
DC can modulate T cell proliferation and/or
differentiation, then, this IO can indicate a range of
possible functional DOs.
(II)
II: The range of SERT expression in the DC.
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CD ligands – as a
feedback on 5-HT
sequestration
Interpretant constraints the interpreter in further
interactions.
DI: The realisation of one of the possible
IOs, a DC with a certain degree of
maturation.
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DI will play the role of the Sign in the next
semiosis.
DC maturation
(IO)
The modeling of T-cell formation
under the biosemiotic framework
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Sign: The DC mature_SERT_expression
via 5-HT release. It is the DI of the previous
semiosis.
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IO: An activated and ready for interaction T
cell.
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II: The range of possibilities of IOs, that is, a
set of T-cells with a certain level of cAMP.
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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.
DC mature SERT
expression via
5-HT release
(Sign)
T cell with a
certain level
of cAMP
(II)
An activated
and ready for
interaction T
cell
(IO)
The modeling of T-cell formation
under the biosemiotic framework
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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.
T-cell with a
specific level
of cAMP
(Sign)
Possibilities of
reconstruction
of specific IOs
(II)
T-cell with a
TPH-1
(IO)
The modeling T-cell formation under
the biosemiotic framework
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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 with a
specific TPH1
(Sign)
T-cell derived
signals – CD
ligands
(II)
Antigen –
Antibody
formation
(IO)
T cell memorization
T-cell with a
specific level of
cAMP
(Sign)
DC mature - SERT
expression via 5-HT
release
(Sign)
CD ligands –
(Sign)
Possibilities of
reconstruction of
specific IOs
(II)
T-cell with a TPH1
(IO)
Activated T cell
(IO)
T-cell derived
signals – CD
ligands
(II)
Antigen –
Antibody
formation
(IO)
T cell with a
certain level of
cAMP
(II)
SERT
expression
in the DC
(II)
DC
maturation
(IO)
T-cell with a
specific TPH1
(Sign)
Results and Comments
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An explanatory tool which models the complex phenomenon at the level of
emergence.
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It seems that serotonin is just a sign (not-dependent on dose).
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It is a signal that triggers the self-organisation of a very complex system that
is being respectively informed under the proper context.
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It engages in information processes based on the presented analysis.
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Modeling of the phenomenon under semiotic terms abstracted from the
level of biochemistry could help us ask different questions to complex
problems.
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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
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Integrate with theories and frameworks of self-organisation and
general systemic and evolutionary thinking.
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A detailed biosemiotic analysis of T cell memory formation.
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Integration with other works of biosemiotics in intra- and extracellular signaling.
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Experimental designs in SDA research, which will provide a way to
test and refine certain aspects of the theory.