Natural and

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Natural and Artificial Immune Systems

This is lecture 19 of Biologically Inspired
Computing about Natural and Artificial Immune
Systems. It borrows much from a tutorial
presentation by Jon Timmis, now at York.
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Overview

• What are Artificial Immune Systems?
• Background immunology
• Why use the immune system as a metaphor for
  computation
• Immune System Inspired algorithms

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Artificial Immune Systems

• Relatively new branch of computer science
• Using natural immune system as a metaphor for
  solving computational problems
• Not modelling the immune system too hard
• What the IS does is detect invading/unusual
  things
• What AISs (usually) do is detect rare/suspicious
  events, by borrowing computational ideas from the
  IS
• Variety of applications so far
• Fault detection (Taylor, Corne)
• Computer security (Forrest, Kim)
• Novelty detection (Dasgupta)
• Robot behaviour (Lee)
• Machine learning (Hunt, Timmis, de Castro)

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Basic Immunology I
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The Role of the Immune System

• It protects our bodies from infection, operating
  via
• - A first line nonspecific line of defence
  barriers
• - A second nonspecific line of defence
  general attack.
• Then comes specific (i.e. targeted) defence,
  comprising
• Primary immune response
• Launches a response to invading pathogens
• Secondary immune response
• Remembers past encounters, leading to
• Faster response the second time around

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Basics and Terms

• A Pathogen is any agent (bacterium, virus, etc)
  that can cause us trouble
• THE IMMUNE SYSTEM IS OUR PRIMARY DEFENSE AGAINST
  PATHOGENS
• IT CONSISTS OF NONSPECIFIC AND SPECIFIC DEFENSES.
• NONSPECIFIC DEFENSES ARE THE BODY'S FIRST LINE
  AGAINST DISEASE. THEY ARE NOT DIRECTED AGAINST A
  PARTICULAR PATHOGEN. THEY GUARD AGAINST ALL
  INFECTIONS, REGARDLESS OF THEIR CAUSE.
• SPECIFIC DEFENSES ARE ATTEMPTS BY THE BODY TO
  DEFEND ITSELF AGAINST PARTICULAR PATHOGENS.
• Since Pathogens must enter the body in order to
  cause disease, the body's first line of defense
  is to keep pathogens out. So, what organ is used
  for this?

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Basics II

• The Body's MOST IMPORTANT Nonspecific Defense is
  the SKIN.  UNBROKEN Skin provides a continuous
  layer that protects almost the whole body.  Very
  Few Pathogens can penetrate the layers of dead
  cells at the skin's surface.
• Oil and sweat glands at the surface of the skin
  produce a salty an acidic environment that kills
  many bacteria and other microorganisms.
• The importance of the Skin as a Barrier against
  Infections becomes obvious when a small portion
  of skin is broken or scraped off Infection
  almost always follows.
• Infections are a result of the penetration of the
  broken skin by microorganisms normally present on
  the unbroken skin.
• Pathogens also enter the body through the Mouth
  and Nose, but the body has Nonspecific Defenses
  that protect those openings.

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• MUCOUS MEMBRANES are Tissues that protect the
  interior surfaces of the body that may be exposed
  to pathogens.
• They serve as a barrier and secret MUCUS, a
  sticky fluid that traps pathogens.
• MUCUS, CILIA, and HAIRS in the Nose and Throat
  trap Viruses and Bacteria. Pathogens that make it
  to the Stomach are destroyed by Stomach Acid and
  Digestive Enzymes.
• Many Secretions of the Body, including MUCUS,
  SALIVA, SWEAT, and TEARS, CONTAIN LYSOZYME, AN
  ENZYME THAT BREAKS DOWN THE CELL WALL OF MANY
  BACTERIA.

But what happens if something gets past all that ?
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The Inflammatory Response

• This is the SECOND LINE OF DEFENCE
• When Pathogens get past skin and mucous
  membranes, and enter the Body, this Second Line
  of Defence comes into play, triggered by injury
  to tissues in the body.
• The injured cells release a protein called
  HISTAMINE, which starts the a series of changes
  called the Inflammatory Response.

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• THE INFLAMMATORY RESPONSE IS A NONSPECIFIC
  DEFENSE REACTION OF THE BODY TO TISSUE DAMAGE.
• Histamine increases blood flow to the injured
  area and increases the permeability of the
  surrounding capillaries, as a result,  Fluid and
  White Blood Cells (WBC) leak from blood vessels
  into nearby tissue.
• Pathogens are attacked by PHAGOCYTES, WHICH ARE
  White Blood Cells THAT ENGULF AND DESTROY
  PATHOGENS

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• The most common Phagocyte, 50 to 70 percent of
  the White Blood Cells in the body, is the
  NEUTROPHIL.
• Neutrophils circulate freely through blood
  vessels, and they can squeeze between cells in
  the walls of a capillary to reach the site of
  infection.  They then engulf and destroy any
  pathogens they encounter

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• Another type of Phagocyte (also a White Blood
  Cell) is the MACROPHAGE they consume and destroy
  any pathogens they encounter, they also rid the
  body of worn out cells and cellular debris.
• Some Macrophages are stationed in the tissues of
  the body, awaiting pathogens, while others move
  through the tissues and seek out pathogens.

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• NATURAL KILLER CELLS are large white blood cells
  that, unlike phagocytes, attack cells that have
  been infected by pathogens, Not the Pathogen
  Themselves. They are particularly effective in
  killing Cancer Cells and Cells Infected with
  Viruses.
• A Natural Killer Cell punctures the cell membrane
  of its target cell, allowing water to rush into
  the cell, causing the cell to burst

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But if all that is not enough

• IF A PATHOGEN IS ABLE TO GET PAST THE BODY'S
  NONSPECIFIC DEFENSES, THE IMMUNE SYSTEM REACTS
  WITH A SERIES OF SPECIFIC DEFENSES THAT ATTACK
  THE DISEASE CAUSING AGENT.
• This is called the IMMUNE RESPONSE
• A SUBSTANCE THAT TRIGGERS THE SPECIFIC DEFENSES
  OF THE IMMUNE SYSTEM IS KNOWN AS AN ANTIGEN.
• AN ANTIGEN IS A SUBSTANCE THAT A MACROPHAGE (WBC)
  IDENTIFIES AS NOT BELONGING TO THE BODY.

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• The Immune Response involves several organs, as
  well as White Blood Cells in the Blood and Lymph.
  These include the BONE MARROW, THYMUS, LYMPH
  NODES, TONSILS, ADENOIDS, AND SPLEEN.
• Each organ of the immune system plays a different
  role in defending the body against pathogens.
• Bone Marrow manufactures the billions of WBC
  needed by the body every day.  Some newly
  produced WBC remain in the bone marrow to Mature
  and Specialize, while others travel to the Thymus
  to Mature.
• Lymph Nodes Filter Pathogens from the Lymph and
  expose them to White Blood Cells
• The Spleen, a fist-sized organ located behind the
  stomach, Filters Pathogens from the Blood.  It is
  stocked with WBC that respond to the trapped
  pathogens.

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Where is it?
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Lymphocytes
THE WHITE BLOOD CELLS OF THE IMMUNE SYSTEM ARE
KNOWN AS LYMPHOCYTES.  These WBC accumulate in
the Lymph and Lymph Nodes, but Lymphocytes are
also found in the Spleen and Blood. LYMPHOCYTES
ARE WBCs THAT ACTIVATE THE IMMUNE RESPONSE. 
There are TWO Main Types of Lymphocytes B Cells
and T Cells. 10.  B-LYMPHOCYTES (B Cells), WHICH
ARE PRODUCED AND MATURED IN THE BONE MARROW, ARE
RESPONSIBLE FOR PRODUCING ANTIBODIES. 11. 
ANTIBODIES ARE SPECIAL PROTEINS THAT CAN BIND TO
THE ANTIGEN ON THE SURFACE OF A PATHOGEN AND
HELP DESTROY IT.
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Self/Nonself distinction
In order to Respond to Pathogens, but to avoid
responding to and destroying cells from its own
body, Lymphocytes MUST BE ABLE TO RECOGNIZE A
PATHOGEN AS A FOREIGN INVADER AND DISTINGUISH IT
FROM CELLS OF THE BODY. This is the key to it
all, and where most of the inspiration comes for
computational systems.
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The Immune ResponseThe last line of defence

• The general idea is this
• Something has got through the first lines of
  defence, and entered the body in force.
• If the body has been invaded by this particular
  nasty thing before, then special Lymphocytes
  called B-Cells and T-Cells are able to recognise
  these specific pathogens, and overwhelm them
  (thanks to the immune system memory
• If this is a new invasion, then the B-Cells will
  learn how to fight this invader. (and then
  remember for next time).

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Specific Antigen Recognition
Nasty thing
This lymphocyte recognises the red pathogen

B-cell or T-cell
Surface receptor molecule
This one doesnt
B-cell or T-cell
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Generating variety
The receptor molecule is a protein, encoded by a
highly variable gene. There is essentially a
combinatorial library of parts in the genome
Each B or T cell makes up its receptor by
choosing
and one of these, etc
one of these
and one of these

dna
The result is that an enormous variety of
possible surface receptors could be chosen. This
is effectively a method for generating
random receptors. Since recognition need not be
exact, it is possible in practice for a B or T
cell to generate a receptor which matches
any given antigen.
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Generating variety II
In addition, B-Cells (but not so much T cells)
also undergo somatic hypermutation. Somatic just
means in the body, during ones lifetime. Hyper
just means a lot. In a nutshell 1.
A B-cell recognises an antigen 2. A
complex chain of events then leads to this B-cell
dividing, creating daughters who
produce the same receptor. 3. But these
daughter cells may have mutations in their
library. 4. Some of the daughters may
recognise the antigen even better. 5.
Back to 1.

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Clonal Selection and Negative Selection
The whole process (antigen recognition,
consequent production of new B-cells with similar
receptors, repeated ) is called Clonal
selection. In AIS paralance it is also called
positive selection (youll soon see why). But
how come the immune system doesnt generate
receptors which cause it to recognise (and hence
then try to destroy) bits and pieces which are
valid and necessary parts of the body? It does!
But B or T cells with such self receptors get
destroyed by a Process called negative
selection. The standard picture (from the book
by Timmis and de Castro) is on the next slide.

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Clonal and Negative Selection
1
2

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4
5
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Clonal and Negative Selection

• In the picture, we see the fate of five different
  B-cells, each with
• A different receptor molecule. Note, these are
  also called antibodies.
• Much simplified
• 1 5. These ones find themselves recognising a
  self-antigen. This leads to them
• getting killed off (clonal deletion).
  This happens as part of the cells schooling.
• Before release into the blood (lymph),
  B-cells (T-cells) are exposed to a full
• range of self-antigens in the bone marrow
  (Thymus). They are killed if they
• recognise anything. Hence, those that
  graduate and enter the system are only
• those that will recognise foreign invaders.
• 2 4. These find themselves going round the body
  a few times without recognising
• anything. Thus, they are never stimulated to
  divide and multiply, and soon die.
• Clonal expansion/positive selection this B-Cell
  recognises something the
• recognition process causes it to divide,
  producing daughters who will have
• similar, possibly higher affinity,
  receptors (and those with better affinity will
• have more offspring, etc ). They dont
  divide forever. Some become stable as
• memory cells (ready to fight if infected
  with the same pathogen again), others
• become plasma cells, which secrete lots of
  the recognising antobody into the blood.

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Interim Summary

• A pathogen comes along
• If it gets through the barriers (skin, etc),
  nonspecific lymphocytes kill it, as part of the
  inflammation response in reaction to injury.
• If it gets past that (I.e. theres so much of it,
  it gets into the bloodstream anyway), then the
  Immune Response comes into play, as follows
• If weve seen this one before, there are
  antibodies in the blood (secreted by memory
  cells) these antibodies disable and/or tag the
  invader. The tagging attracts killer cells to
  make sure it is destroyed.
• If we havent seen this before, B-cells and
  T-cells are floating around with a great variety
  of surface receptors. One of these will at least
  recognise it a bit. Clonal expansion then
  happens, and with gene variability and somatic
  hypermutation we eventually get some B or T cells
  which are capable of recognising it. The
  associated antobodies then disable and tag the
  invaders.

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Some interesting related points
Some ailments are beyond the immune system,
since they either directly disable it, or work
faster than it, or both (or something
else). Cancer the problem here is uncontrolled
growth and multiplication of normal cells. If
caused by any specific pathogen (controversial)
then it could be that just a tiny amount needs
to go unattacked for a short time, and the
problem starts. Leukaemia a cancer of the
bone marrow it (and its treatment) throw an
enormous spanner into the heart of B-cell
production. Vaccination this is where we
deliberately provoke an immune response to small
levels of a pathogen (or something similar to
it), so that our IS is ready if there is a real
infection. AIDS some T-cells (called Helper T
Cells) are the main players in most of the things
we have looked at. E.g. via special messenger
molecules, they activate the clonal expansion of
B cells! The HIV virus directly attacks Helper
T-cells, essentially disabling the immune system.

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AIS Algorithms
The IS is the inspiration for a whole new field
of computer science which is building systems,
for various purposes, which borrow ideas from the
workings of the IS. The basic ideas and
algorithms are less easy to pin down (than with
EAs, or NNs, e.g.). However, the most easily
abstracted algorithms (which are also most
frequently borrowed, are negative selection
and positive selection. The scenario is
typically this We need to detect anomalous
patterns (network attacks, bank card fraud,
unusual temperature/vibration/pressure patterns
in machinery, etc) The space of normal patterns
is very large and variable (we cant just say
anything which doesnt look like X is
bad.) We have little or no idea about what
anomalous patterns will look like. So, we use IS
ideas The overwhelmingly common approach is
Negative selection generate random
detectors (receptors), but filter them by
testing their affinity to known self patterns.
Each new pattern / window of data is
then matched against these detectors.

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Anomaly Detection the most common application of
AIS

• The normal behavior of a system is often
  characterized by a series of observations over
  time.
• The problem of detecting novelties, or anomalies,
  can be viewed as finding deviations of a
  characteristic property in the system. (I.e.
  non-self)
• For computer scientists, the identification of
  computer viruses and network intrusions is
  considered one of the most important anomaly
  detection tasks

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Negative Selection Algorithms

Developing the detector set
Using the detector set
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Basic Notes on Negative Selection Algorithms

• A robust system should detect any foreign/strange
  activity rather than looking for specific known
  patterns of intrusion.
• No prior knowledge of anomaly (non-self) is
  required
• This lack of prior knowledge is useful, because
  we normally have very few, or no, example data
  sets of intruders (e.g. attacking patterns of
  telnet packets, fraudulent credit card use
  patterns), so standard classification by (e.g. )
  NNs cant be done.

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Thats all Use google to find out more about
Artificial Immune Systems, if you
wish. Generally it has not yet been a clearly
successful research area, since it is not clear
that successes so far could not have been
achieved just as well by conventional methods.
However (my personal opinion), the more complex
the system that we need to protect, and the more
complex and varied the potential threats, perhaps
the more like natural immune systems the
protection approach needs to be.