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SBRN 2000
(VI-Brazilian Symposium on Neural Networks)
Presentation Topics (I)
Motivation
Research Background
Immune Engineering
Introduction to the Biological Immune System
A Brief History of Immunology
Basic Principles
A General Overview of the Defense Mechanisms
Anatomy and Properties
Innate Immune System
Adaptive Immune System
The Antibody Molecule and Immune Diversity
Cell Receptors
APC
B cell
T cell
(V)
( II ) B cell ( IV )
T cell
( III )
( VI )
Nossal, 1993
Skin
Biochemical
barriers
Phagocyte
Innate
immune
response
Lymphocyte
Adaptive
immune
response
Antigen First
Antibody (Ab) complement
protein
Granules
Binding sites
VH VH
VL VL
CH CH
CL CL
CH CH
B Lymphocyte
SBRN 2000 - Brazilian Symposium on Neural Networks 15
PART II
Information Processing Within
the Immune System
Information Processing
Clonal Selection
Affinity Maturation
Hypermutation
Receptor Editing
Diversity
Reinforcement Learning
Pattern Recognition
Self/Non-Self Discrimination
Immune Network Theory
Antigen
OR Receptor editing
Antigen-binding sites
George & Gray, 1999
SBRN 2000 - Brazilian Symposium on Neural Networks 20
Repertoire Diversity (I)
Problem:
The amount of different pathogens is much
larger than the number of cells and molecules
available for combat
Solution:
Capability of producing an enormous amount
of different cell receptors
Question:
How is it possible to generate millions of
antibody types in an organism with a finite
(105) number of genes?
Antibody concentration
lag
and affinity
lag
Response to
antigen A
Response
to antigen B
(I)
APC
Peptide
p2
Foreign stimulus
i2
Ag p1
(epitope) Internal image
i1
S uppre s s ion Recognizing p3
Ag set
i3
1 Anti-idiotypic set
2
Jerne, 1974
3
Activa tion
SBRN 2000 - Brazilian Symposium on Neural Networks 27
Immune Network Theory (III)
General features
structure;
dynamics; and
metadynamics.
Existing models
Dynamic equations representation.
Receptors
Cytokines
IS Production
Blalock, 1994
SBRN 2000 - Brazilian Symposium on Neural Networks 33
Cognition!? (I)
Cognition: symbolic manipulation of the mental
representations that compose knowledge, defining
the behavior of an individual (Edelman, 1992).
Cognitive system: capable of extracting
information and experience from input data
through the manipulation of information already
contained in the system; it is intentional (Cohen,
1992a,b).
Immune Cognition: N. K. Jerne, I. Cohen, A.
Coutinho, F. Varela, A. Tauber, etc.
Self/Non-Self recognition, learning and memory;
Internal images (network theory).
SBRN 2000 - Brazilian Symposium on Neural Networks 34
Cognition!? (II)
Cognition (psychology): the superior functions of
the brain, like pattern recognition, self recognition
and intention:
related to stimuli like physical, chemical, emotional, etc.
Sensorial activity of the IS (Blalock, 1994)
The sensorial aspects of the IS complement the
cognitive capabilities of the brain through the
recognition (perception) of stimuli that can not be
smelt, tasted, seen, etc., to cause physiological
responses
Intentionality Personality
Axon
(pre-synaptic neuron) Epitopes
Post-synaptic
neuron
Vesicles containing
neurotransmitters Lymphocytes
Neurotransmitters receptors
(Post-synaptic neuron)
Self Strings
(S)
Generate
Random Match Detector Set
Strings (R0) No (R0)
Yes
Reject
Protected
Match No
Strings (S)
Yes
Nonself
Detected
Send signals to
neighbor machines
Segregate Algorithmic
code/data Virus Analysis
Extract Signature(s)
010011100010.....001101
Immature
No match during
tolerization
Death Memory
Immune Engineering:
Basic Theory
Immune Engineering
Engineering consists of designing basic
systems for solving specific tasks (Wolfram,
1986)
Traditional Engineering
detailed specification of the behavior of each
component of the system (step-by-step procedure)
Immune Engineering (IE)
general, or approximate, specification of some
aspects of the global behavior of the system, like a
performance or adaptability (fitness) measure
extraction of information from the problems
themselves
SBRN 2000 - Brazilian Symposium on Neural Networks 54
Pattern Recognition
Shape-Space S
V
Ve
Complementarity
e
Representations
Distance measures
m=<m1, m2,..., mL>,
m SL L e
MHC/peptide complex or epitope
(Ligand)
Ab or TCR
(Biding site of a B or T cell) SBRN 2000 - Brazilian Symposium on Neural Networks 55
Immune Engineering
Definition: meta-synthesis process that will define
the solution tool to a given problem, based upon its
own characteristics and immunological principles
(de Castro, 2001).
Focus on a single cell type: B cell
Pictorial representation:
Paratope mj identification
Idiotope
(epitope)
mi,1 v1 vl1+1 mi ,l1+1 mj1
mi,2 v2 vl1+ 2
... ... mi,i ... mi ,l1+ 2 mj mj2
... ...
mi , l1 vl 1 vL mi,L mjl
Antibody Antigen
SBRN 2000 - Brazilian Symposium on Neural Networks 56
AIS & IE
AIS taxonomy:
Structures and hybrid algorithms based on
immunological mechanisms and/or metaphors;
Computational algorithms inspired by immunological
principles;
Immunological computation; and
Immune engineering.
Potential applications of the immune engineering:
pattern recognition, optimization, function
approximation and data analysis (clustering).
Hamming Shape-Spaces:
L
1 if Ab i Ag i
D = / where / = Hamming distance
i =1 0 otherwise
0 0 1 1 0 0 1 1 0 0 1 1 0 0 1 1
1 1 1 0 1 1 0 1 1 1 1 0 1 1 0 1
XOR : 1 1 0 1 1 1 1 0 XOR : 1 1 0 1 1 1 1 0
D = Affinity: 4 D = Affinity: 6+24=22
Forrest et al., 1994 Hunt et al., 1995
SBRN 2000 - Brazilian Symposium on Neural Networks 58
PART VI
Immune Engineering:
Tools & Applications
General Aspects (I)
Algorithms:
SAND: A Simulated Annealing Model of Diversity
CLONALG: The Clonal Selection Algorithm
ABNET: An Antibody Network
aiNet: An Artificial Immune Network
The Clonal Selection Principle (CSP):
Used by the IS to describe the adaptive immune
response to an antigenic stimulus;
Most stimulated cells will reproduce under a
hypermutation scheme (B cell);
Low affinity clones are eliminated; and
Self-reactive clones will be purged from the repertoire.
SBRN 2000 - Brazilian Symposium on Neural Networks 60
General Aspects (II)
SAND
Generation of a well-distributed initial repertoire.
CLONALG
Pattern recognition and optimization via CSP
ABNET
The CSP is used to control network size, and affinity
maturation is responsible for learning (adaptation)
aiNet
CLONALG is used to control network learning, and the
immune network theory specifies cell-cell affinities
N N
4
F (%) = 100. 2
HD(i, j ) Percentage HD (affinity)
L.N i =1 j =i +1
1 N
D(%) = 100. s (i ) Percentage of different
N i =1
antibodies
F (%) + D(%)
E (%) = Percentage energy
2
SBRN 2000 - Brazilian Symposium on Neural Networks 63
SAND: Euclidean Shape-Space
L
Affinity measure: ED = i i
( x y ) 2
i =1
( )
R = IT I 1/ 2 Resultant vector (distance from the
origin of the coordinate system)
AbT
E (2) yes
AbT
T = .T rand < P ?
Mutate
ct = 0 (3)
ct = 0 AbT ct = 0, P
(1)
(8) Abd Abr
Abm
Ab
f (2)
(7)
Re-select
Select
(3)
(6) f
Abn
C* Clone
(5)
(4)
Maturate C
Abn
f (2)
(7)
Re-select
Select
(3)
(6) f
Abn
C* Clone
(5)
(4)
Maturate C
(1)
Ab
f (2)
(7) Clone and prune
Select
(6) (3)
vj = k
Abk
(5) k = k + 1
Maturate
(4)
Abk*
0 1 0 2 w2=[0,0,0], 2=1
0 1 0 3 w3=[1,0,0], 3=0
v1=1 v2=2 v3=1
Ag1 Ag2 Ag3
0 1 1
1 w1=[1,1,1]
0 1 0
2 w2=[0,0,0]
0 1 0
1 0 0 0 1 0 1 1 Ag
0 0 1 1 1 1 1 0 Ab k (Affinity: 5)
Updating ( = 2)
1 0 0 0 1 0 1 1 Ag
0 1 1 1 0 1 1 0 Ab k (Affinity: 7)
SBRN 2000 - Brazilian Symposium on Neural Networks 73
aiNet: Basic Principles (I)
Definition:
The evolutionary artificial immune network, named
aiNet, is an edge-weighted graph, not necessarily fully
connected, composed of a set of nodes, called cells, and
sets of node pairs called edges with a number assigned
called weight, or connection strength, specified to each
connected edge.
0.4
3
1 0.1
0.15 2 4
0.3 0.32
Discussion
Discussion (I)
Growing interest for the AIS
Biological Inspiration
utility and extension
improved comprehension of natural phenomena
Example-based learning, where different
pattern categories are represented by adaptive
memories of the system
Strongly related to other intelligent approaches,
like ANN, EC, FS, DNA Computation, etc.
http://www.dca.fee.unicamp.br/~lnunes
or
lnunes@dca.fee.unicamp.br