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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.
                Overview
• What are Artificial Immune Systems?
• Background immunology
  – Why use the immune system as a metaphor for
    computation
• Immune System Inspired algorithms
       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)
Basic Immunology I
   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
                 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?
                           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.
                       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 ?
   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.
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
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
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.
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
  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.
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.
              Where is it?
  Primary lymphoid       Secondary lymphoid
       organs                 organs

                             Tonsils and
                               adenoids


   Thymus

                                Spleen



                              Peyer’s patches

                                 Appendix

Bone marrow                      Lymph nodes

                                 Lymphatic vessels
            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.
         The Immune Response:
         The 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).
       Specific Antigen Recognition
Nasty thing
                                           This lymphocyte
                         B-cell or         recognises the
                         T-cell            red pathogen


               Surface receptor molecule


                                           This one doesn’t
                           B-cell or
                           T-cell
                      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:
         one of these       and one of these     and one of these, etc…


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.
                Generating variety II
In addition, B-Cells (but not so much T cells) also undergo somatic
hypermutation. Somatic just means in the body, during one’s 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.
     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 (you’ll
soon see why).

But how come the immune system doesn’t 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.
    Clonal and Negative Selection
1                        Clonal deletion
                       (negative selection)


        Self-antigen                      Proliferation
                                           (Cloning)                            M


2
                                                                                M

     Antibody
                                                                            Memory cells
                       Selection
                                                          Differentiation
3                                                                           Plasma cells




                       Foreign antigens
4
      Self-antigen


                         Clonal deletion
5                      (negative selection)
         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 cell’s `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.

3.     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 don’t 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.
                   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. there’s so much of it, it gets into the
    bloodstream anyway), then the Immune Response comes into
    play, as follows:
If we’ve 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 haven’t 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.
        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, the
activate the clonal expansion of B cells! The HIV virus directly attacks
Helper T-cells, essentially disabling the immune system.
                        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 can’t just say `anything
 which doesn’t 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.
   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
         Negative Selection Algorithms
                      Self
                  strings (S)




    Generate
 random strings     Match            Detector
      (R0)                      No   Set (R)

                        Yes


                   Reject                                    Detector Set
                                                                 (R)


Developing the
detector set                               Strings (e.g.
                                                               Match        No
                                           credit card use
                                           patterns)
                                                                    Yes


                  Using the                                   Non-self
                                                              Detected
                  detector set
        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 can’t be done.
That’s 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.

				
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posted:8/7/2011
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