Immu-KnowledgeWhat Can the Immune System Teach us

About Cognition?

Marieke RohdeReading Group DyStURB (Dynamical Structures to Understand Real Brains)

1.) DyStURB

Structure

1. DyStURB • Past, present, future.• Next Sessions

2. Immu-Knowledge• Summary of Varela’s paper• Discussion

DyStURB• Dynamical Structures to Understand Real Brains

A new dynamical framework to understand (neuro)cognitive phenomena is progressively substituting traditional computational and representational frameworks. More specificially a dynamical approach provides better methodologies to analyse real brain activity (where representations aren't just there to be measured), a better ontology which does not presuppose an a priori distinction between brain, body and world and better synthetic tools to produce adaptive and cognitive agents in the real world.

This new framework is still in the process of being built and a new transdisciplinary re-ensemble looks necessary to redefine some of the fundamental conceptual and empirical tools dealing with cognitive phenomena. Although not really that new (see Ashby, Freeman and other pioneers) the dynamical approach challenges traditional concepts and offer a new range of phenomena and tools.

DyStURB

• Topics covered in the past– Neural dynamics– Neurophenomenology– Dynamical Methods– Dynamical Theories of …

• A forum to discuss interesting work you came across or your work (in progress).

DyStURB Wiki

• Credit to Sampsa!

• Alife bibliography – needs developing.

• You could do so many things….

I would be glad about support!

2.) Immu-Knowledge

Varela and Immunology

• Next to so many other things, Francisco Varela had been active in the field of immunology for many years.

• Together with Coutinho and Stewart, he promoted the network theory in immunology.

Metaphors

• Military vs. Cognitive– Defense, invasion,

protect self from foreign…

– Cognitive: recognition, learning, memory

(reservation: cognitive in a vague sense, same as military)

Cognititive Networks

• Immune system like brain– Network of processes: populations of lymphocytes,

dynamically interacting, stimulating/inhibiting each other…

– Like brain: in structure and emergent cognitive phenomena it creates.

• Promethean: response to unpredictable (man made, never seen) antigens no genetically “preprogrammed” GPS

• Same dead end as computer metaphor

Immu-knowledge in History

• Instructionist: Antibodies as playdough, the antigens work as heteronomous instructors to form antibodies against them.

• Problem: Self/Non-self discrimination

• Solution: Information processing view, correct response to correct input.

Heteronomy, faithfully followed ever since

Immu-knowledge in History

• Problem: Who perceives, who recognises? No sensory organs or homunculi (“higher brain areas”)

• Realisation: Antigens bind to several antibodies. Gain: route to generality. Loss: Simplicity, Bijectivity.

• “Recognition” by antigen: Neutralisation by chemical binding. Danger of “Horror Autotoxicus”

Immu-knowledge in History

• Conclusion: Only antigens that recognise antibodies are produced, only non-self is recognised.

Paradox: One cannot defend without recognising self and non-self, one cannot recognise without destroying.

Current Doctrine: Clonal Selection

• Jerne, Burnet: fixed repertoire of antibodies. • Question: Initially random, how does it “learn”?• Burnet: Binding promotes production of antigen

(Carrying lymphocyte proliferates) Darwinian selection, antigenic determination rather than genetic determination

• Problem (remains): Self-Tolerance• Solution: Repertoire misses self components

(deleted during embryogenesis) • (First recognise self, then non-self)

Autonomous Immune Networks

• Give up horror autotoxicus:

There are antigens binding to self, and they do not at normal levels lead to autoimmune diseases.

• Important: antibodies part of self antibodies recognising antibodies

• Jerne: Network with an internal dynamics.

Autonomous Immune Networks

• Recognition no longer a private encounter between antigen and antibody:– There is multiple “partners”– They have “prey” and “predators”– Antigen resembles something already present

• Not an offense but a small perturbation of an ongoing homeodynamics.

Interpretation

• Reaction not determined by antigen but by network• “Immune Response” to antigen specific case, laboratory

condition. Normally all sorts of modulations and behaviours take place

• Antigen free animals have quite a functional immune system

• Not defense, but self-assertion. identity• Mutual dance between immune system and body: rich

interconnected network shapes body and is shaped by body

• Learning through ongoing replacement

Paradigm shift

• Simplified: Different cell types and molecular/ genetic controls (“somatic hypermutations”)

• This is about a Fundamental conceptual outline.• Significance of anti-antibodies (anti-idiotypic):

Autonomy vs. Heteronomy, creation of identity vs. Defense.

• No discrimination, non-self is like self, possibly reflexive response to unrecognised.

• (self/nonsense, rather than self/non-self)

Dropping Defense

• Normally: low numbers of antigens lead to creation of low levels of antibodies - same with self recognisers

• Immune network not “attractor” but more like wheather: in constant change, but never going over certain limits.

• Defense (inflammation etc.) takes place, but is a limiting case of something more fundamental: molecular identity. (reflex independent of network)

• Defense/avoidance secondary acquisitions, like neural network: avoidance secondary to motion.

• Immune system is not about defense as little as brains are about reflexes. They are about being alive in the first place.

• (Invertebraes: multicellular life without immune system.)

Future

1. Research questions: network dynamics, connectivity, population dynamics, emergent nonlinearities…

2. Medical problems (e.g. autoimmunity) seen in a new light. Focus on vaccination?

3. Modelling: Networks other than neural instantiate learning, memory etc.

3.) Discussion

Questions

• In how far are brain and immune system analogues?

• In particular: can the distributed cognitive capacities be assumed to work analogously?

• How plausible is clonal selection?• Wheather or stationary/periodic attractor?• Could there be reflex without the complex

system?• Ecology analogue?• What is it to create an identity? • Self – nonsense?