The Danger Theory and Its Application to Artificial Immune Systems


The Danger Theory and Its Application to
Artificial Immune Systems
Uwe Aickelin1, Steve Cayzer
Information Infrastructure Laboratory
HP Laboratories Bristol
HPL-2002-244
September 4th , 2002*
E-mail: u.aickelin@bradford.ac.uk, Steve_Cayzer@hp.com
artificial Over the last decade, a new idea challenging the classical self-non-
immune self viewpoint has become popular amongst immunologists. It is
systems, called the Danger Theory. In this conceptual paper, we look at this
danger theory theory from the perspective of Artificial Immune System
practitioners. An overview of the Danger Theory is presented with
particular emphasis on analogies in the Artificial Immune Systems
world. A number of potential application areas are then used to
provide a framing for a critical assessment of the concept, and its
relevance for Artificial Immune Systems.
* Internal Accession Date Only Approved for External Publication
1st International Conference on Artificial Immune Systems, Canterbury, UK. 2002
1
Department of Computing, University of Bradford, Bradford, BD7 1DP
© Copyright Hewlett-Packard Company 2002
The Danger Theory and Its Application to Artificial Immune
Systems
Uwe Aickelin Steve Cayzer
Department of Computing Hewlett-Packard Laboratories
University of Bradford Filton Road
Bradford Bristol
BD7 1DP BS12 6QZ
u.aickelin@bradford.ac.uk Steve_Cayzer@hp.com
Abstract In the next section, we provide an overview of the Danger
Theory, pointing out, where appropriate, some analogies
in current Artificial Immune System models. We then
Over the last decade, a new idea challenging the
assess the relevance of the theory for Artificial Immune
classical self-non-self viewpoint has become
System security applications, which is probably the most
popular amongst immunologists. It is called the
obvious application area for the danger model. Other
Danger Theory. In this conceptual paper, we
Artificial Immune System application areas are also
look at this theory from the perspective of
considered. Finally, we draw some preliminary
Artificial Immune System practitioners. An
conclusions about the potential of the Danger concept.
overview of the Danger Theory is presented with
particular emphasis on analogies in the Artificial
2 THE DANGER THEORY
Immune Systems world. A number of potential
application areas are then used to provide a
The immune system is commonly thought to work at
framing for a critical assessment of the concept,
three levels: External barriers (skin, mucus), innate
and its relevance for Artificial Immune Systems.
immunity and the acquired or adaptive immune system.
As part of the third and most complex level, B-
Lymphocytes secrete specific antibodies that recognise
1 INTRODUCTION
and react to stimuli. It is this pattern matching between
Over the last decade, a new theory has become popular
antibodies and antigens that lies at the heart of most
amongst immunologists. It is called the Danger Theory,
Artificial Immune System implementations. Another type
and its chief advocate is Matzinger [18], [19] and [20]. A
of cell, the T (killer) lymphocyte, is also important in
number of advantages are claimed for this theory; not
different types of immune reactions. Although not usually
least that it provides a method of  grounding the immune
present in Artificial Immune System models, the
response. The theory is not complete, and there are some
behaviour of this cell is implicated in the Danger model
doubts about how much it actually changes behaviour and
and so it is included here. From the Artificial Immune
/ or structure. Nevertheless, the theory contains enough
System practitioner s point of view, the T killer cells
potentially interesting ideas to make it worth assessing its
match stimuli in much the same way as antibodies do.
relevance to Artificial Immune Systems.
However, it is not simply a question of matching in the
It should be noted that we do not intend to defend this
humoral immune system. It is fundamental that only the
theory, which is still controversial [21]. Rather we are
 correct cells are matched as otherwise this could lead to
interested in its merits for Artificial Immune System
a self-destructive autoimmune reaction. Classical
applications and hence its actual existence in the humoral
immunology [12] stipulates that an immune response is
immune system is of little importance to us. Our question
triggered when the body encounters something non-self or
is: Can it help us build better Artificial Immune Systems?
foreign. It is not yet fully understood how this self-non-
self discrimination is achieved, but many immunologists
Few other Artificial Immune System practitioners are
believe that the difference between them is learnt early in
aware of the Danger Theory, notable exceptions being
life. In particular it is thought that the maturation process
Burgess [5] and Willamson [22]. Hence, this is the first
plays an important role to achieve self-tolerance by
paper that deals directly with the Danger Theory, and it is
eliminating those T and B cells that react to self. In
the authors intention that this paper stimulates discussion
addition, a  confirmation signal is required; that is, for
in our research community.
either B cell or T (killer) cell activation, a T (helper)
lymphocyte must also be activated. This dual activation is
further protection against the chance of accidentally non-self, and thus provides grounding for the immune
reacting to self. response. If we accept the Danger Theory as valid we can
take care of  non-self but harmless and of  self but
Matzinger s Danger Theory debates this point of view
harmful invaders into our system. To see how this is
(for a good introduction, see Matzinger [18]). Technical
possible, we will have to examine the theory in more
overviews can be found in Matzinger [19] and Matzinger
detail.
[20]. She points out that there must be discrimination
happening that goes beyond the self-non-self distinction The central idea in the Danger Theory is that the immune
described above. For instance: system does not respond to non-self but to danger. Thus,
just like the self-non-self theories, it fundamentally
" There is no immune reaction to foreign bacteria in the
supports the need for discrimination. However, it differs
gut or to the food we eat although both are foreign
in the answer to what should be responded to. Instead of
entities.
responding to foreignness, the immune system reacts to
" Conversely, some auto-reactive processes are useful,
danger.
for example against self molecules expressed by
This theory is borne out of the observation that there is no
stressed cells.
need to attack everything that is foreign, something that
" The definition of self is problematic  realistically,
seems to be supported by the counter examples above. In
self is confined to the subset actually seen by the
this theory, danger is measured by damage to cells
lymphocytes during maturation.
indicated by distress signals that are sent out when cells
die an unnatural death (cell stress or lytic cell death, as
" The human body changes over its lifetime and thus
opposed to programmed cell death, or apoptosis).
self changes as well. Therefore, the question arises
whether defences against non-self learned early in
Figure 1 depicts how we might picture an immune
life might be autoreactive later.
response according to the Danger Theory. A cell that is in
distress sends out an alarm signal, whereupon antigens in
" Other aspects that seem to be at odds with the
the neighbourhood are captured by antigen-presenting
traditional viewpoint are autoimmune diseases and
cells such as macrophages, which then travel to the local
certain types of tumours that are fought by the
lymph node and present the antigens to lymphocytes.
immune system (both attacks against self) and
Essentially, the danger signal establishes a danger zone
successful transplants (no attack against non-self).
around itself. Thus B cells producing antibodies that
Matzinger concludes that the immune system actually
match antigens within the danger zone get stimulated and
discriminates  some self from some non-self . She asserts
undergo the clonal expansion process. Those that do not
that the Danger Theory introduces not just new labels, but
match or are too far away do not get stimulated.
a way of escaping the semantic difficulties with self and
Stimulation
Match, but
too far
No match
away
Danger
Zone
Antibodies
Antigens
Cells
Damaged Cell
Danger Signal
Figure 1: Danger Theory Model.
Matzinger admits that the exact nature of the danger generation (particularly B cells, which produce
signal is unclear. It may be a  positive signal (for hypermutated clones during activation).
example heat shock protein release) or a  negative signal
A problem is posed by the antigen-presenting cell itself,
(for example lack of synaptic contact with a dendritic
whose (innocuous) antigens are by definition always in
antigen-presenting cell). This is where the Danger Theory
the danger zone. Lymphocytes reacting to these antigens
shares some of the problems associated with traditional
might destroy the antigen-presenting cell and thus
self-non-self discrimination (i.e. how to discriminate
interfere with the immune response. The negative
danger from non-danger). However, in this case, the
selection of immature lymphocytes protects against this
signal is grounded rather than being some abstract
possibility.
representation of danger.
Figure 2 shows a more detailed picture of how the Danger
Another way of looking at the danger model is to see it as
Theory can be viewed as an extension of immune signals.
an extension of the Two-Signal model by Bretscher and
These diagrams are adapted from those presented in
Cohn [4]. In this model, the two signals are antigen
Matzinger [19] except for the sixth, which incorporates
recognition (signal one) and co-stimulation (signal two).
suggestions made in Matzinger [20].
Co-stimulation is a signal that means  this antigen really
In the original view of the world by Burnet [6], only
is foreign or, in the Danger Theory,  this antigen really
signal one is considered. This is shown in the first
is dangerous . How the signal arises will be explained
diagram, where the only signal shown is that between
later. The Danger Theory then operates by applying three
infectious agents and lymphocytes (B cells, marked B,
laws to lymphocyte behaviour (the laws of lymphotics
and T killer, marked Tk). Signal two (second diagram)
[20]):
was introduced by Bretscher and Cohn [4]. This helper
" Law 1. Become activated if you receive signals one
signal comes from a T helper cell (marked Th), on receipt
and two together. Die if you receive signal one in the
of signal one from the B cell. That is, the B cell presents
absence of signal two. Ignore signal two without
antigens to the T helper cell and awaits the T cell s
signal one.
confirmation signal. If the T cell recognises the antigen
" Law 2. Accept signal two from antigen-presenting (which, if negative selection has worked, should mean the
cells only (or, for B cells, from T helper cells). B antigen is non-self) then the immune response can
cells can act as antigen-presenting cells only for commence. It was Lafferty and Cuningham [17] who
experienced (memory) T cells. Note that signal one proposed that the T helper cells themselves also need to
can come from any cells, not just antigen-presenting be  switched on by signals one and two, both from
cells. antigen-presenting cells. This process is depicted in the
third diagram.
" Law 3. After activation (activated cells do not need
signal two) revert to resting state after a short time. Note that the T helper cell gets signal one from two
sources  the B cell and the antigen-presenting cell. In the
For the mature lymphocyte, (whether virgin or
former case the antigens are not chosen randomly  the
experienced) these rules are adhered to. However, there
very opposite, since B cells are highly selective for a
are two exceptions in the lymphocyte lifecycle. Firstly,
range of (hopefully non-self) antigens. In the latter case,
immature cells are unable to accept signal two from any
the antigens are chosen randomly (the antigen-presenting
source. This enables an initial negative selection
cell simply presents any antigen it picks up) but signal
screening to occur. Secondly, activated (effector) cells
two should only be provided to the T helper cell for non-
respond only to signal one (ignoring signal two), but
self antigens. It is not necessarily clear how the antigen-
revert to the resting state shortly afterwards.
presenting cell  knows the antigen is non-self. Janeway
An implication of this theory is that autoreactive effects
[14] introduced the idea of infectious non-self (for
are not necessarily harmful, and are in fact expected
example bacteria), which  primes antigen presenting
during an infection. This is because any lymphocyte
cells, i.e. causing signal two to be produced (fourth
reacting to an antigen in the  danger zone will be
diagram). This priming signal is labelled as signal 0 in the
activated. These antigens are not necessarily the culprits
figures.
for the danger signal. If they are, then the reacting
Matzinger proposes to allow priming of antigen-
lymphocytes will continue to be restimulated until the
presenting cells by a danger signal (fifth diagram). She
antigens (and therefore the danger signal) are removed.
also proposes to extend the efficacy of T helper cells by
After this, they will rest, receiving neither signal one nor
routing signal two through antigen presenting cells [20].
signal two.
We have marked this as  signal 3 in the sixth diagram
On the other hand, lymphocytes reacting to innocuous
(although Matzinger does not use that term, the intention
(self) antigens will continue to receive signal one from
is clear). In Matzinger s words  the antigen seen by the
these antigens, even after the danger (and therefore signal
killer need not be the same as the helper; the only
two) has vanished. Therefore these lymphocytes will be
requirement is that they must both be presented by the
deleted, and tolerance will be achieved. However, further
same antigen-presenting cell . This arrangement allows T
autoreactive effects can be expected, partly because  self
helper cells to prime many more T killer cells than they
changes over time, and partly because of new lymphocyte
would otherwise have been able to.
1. Antigen in Control (Burnet) 2. Helper in Control (Bretscher & Cohn)
Virus Infected Cell
Virus Infected Cell Virus Infected Cell
Virus Infected Cell Virus Infected Cell
Bacterium
Bacterium Bacterium
Bacterium Bacterium
Tk
Tk Tk
Tk Tk
(non-random)
(non-random)
B
B B
B B
Signal 1
Signal 1 Signal 1
Signal 1 Signal 1
Th Signal 2
Th Signal 2
Signal 2
3. APC in control (Lafferty & Cunningham) 4. Infectious non self in control (Janeway)
Virus Infected Cell Virus Infected Cell
Virus Infected Cell Virus Infected Cell
Virus Infected Cell Virus Infected Cell
Virus Infected Cell Virus Infected Cell
Virus Infected Cell
Bacterium Bacterium
Bacterium Bacterium
Bacterium Bacterium
Bacterium Bacterium
Bacterium
Tk Tk
Tk Tk
Tk Tk
Tk Tk
Tk
(non-random) (non-random)
(non-random) (non-random)
(non-random) (non-random)
(non-random)
B B
B B
B B
B B
B
Signal 0
Signal 0
Signal 0
Signal 1 Signal 1
Signal 1 Signal 1
Signal 1 Signal 1
Th Signal 2 Th Signal 2
Th Signal 2 Th Signal 2
Th Signal 2 Th Signal 2
Th
(random) (random)
(random) (random)
(random)
APC APC
APC APC
APC
Bacteria
Bacteria
5. Danger in Control (Matzinger) 6. Multiplication of effect (Matzinger)
Virus Infected Cell
Virus Infected Cell
Virus Infected Cell
Virus Infected Cell
Virus Infected Cell
Virus Infected Cell Virus Infected Cell
Bacterium
Bacterium
Bacterium
Bacterium
Bacterium
Bacterium Bacterium
Tk
Tk
Tk
Tk
Tk
Tk Tk
(non-random)
(non-random)
(non-random)
(non-random)
(non-random) (non-random)
B
B
B
B
B
B B
Signal 0 Signal 0
Signal 0 Signal 0
Signal 0 Signal 0
Signal 1 Signal 1
Signal 1 Signal 1
Signal 1 Signal 1
Th
Th
Th Signal 2 Signal 2
Th Signal 2 Signal 2
Th Signal 2 Th APC Signal 2
Signal 3
Signal 3
Signal 3
(random)
(random)
(random)
(random) (random)
Virus?
APC
APC
APC
APC APC
Distress
Distress Distress
Bacteria
Bacteria
Bacteria Bacteria
Figure 2: Danger Theory viewed as immune signals.
3 THE DANGER THEORY AND SOME
The Danger Theory is not without its limitations. As
mentioned, the exact nature of the danger signal is still
ANALOGIES TO ARTIFICIAL
unclear. Also, there is sometimes danger that should not
IMMUNE SYSTEMS
be responded to (cuts, transplants). In fact, in the case of
transplants it is often necessary to remove the antigen- Danger theory clearly has many facets and intricacies, and
we have touched on only a few. It might be instructive to
presenting cells from the transplanted organ. Finally, the
list a number of considerations for an Artificial Immune
fact that autoimmune diseases do still, if rarely, happen,
System practitioner regarding the suitability of the danger
has yet to be fully reconciled with the Danger Theory.
model for their application. The basic consideration is
whether negative selection is important. If so, then these
4 THE DANGER THEORY AND
points may be relevant:
ANOMALY DETECTION
" Negative selection is bound to be imperfect, and
An intriguing area for the application of Artificial
therefore autoreactions (false positives) are
Immune Systems is the detection of anomalies such as
inevitable.
computer viruses, fraudulent transactions or hardware
" The self/non-self boundary is blurred since self and
faults. The underlying metaphor seems to fit particularly
non-self antigens often share common regions.
nicely here, as there is a system (self) that has to be
protected against intruders (non-self). Thus if natural
" Self changes over time. Therefore, one can expect
immune systems have enabled biological species to
problems with memory cells, which later turn out to
survive, can we not create Artificial Immune Systems to
be inaccurate or even autoreactive.
do the same to our computers, machines etc? Presumably
If these points are sufficient to make a practitioner
those systems would then have the same beneficial
consider incorporating the Danger theory into their model,
properties as natural immune systems like error tolerance,
then the following considerations may be instructive:
distribution, adaptation and self-monitoring. A recent
overview of biologically inspired approaches to this area
1. A danger model requires an antigen-presenting cell,
can be found in Williamson [22].
which can present an appropriate danger signal.
In this section we will present indicative examples of such
2.  Danger is an emotive term. The signal may have
artificial systems, explain their current shortcomings and
nothing to do with danger (see, for example, our
show how the Danger Theory might help overcome some
discussion on data mining applications in section 5).
of these.
3. The appropriate danger signal can be positive
One of the first such approaches is presented by Forrest et
(presence of signal) or negative (absence).
al [11] and extended by Hofmeyr and Forrest [13]. This
4. The danger zone in biology is spatial. In Artificial
work is concerned with building an Artificial Immune
Immune System applications, some other measure of
System that is able to detect non-self in the area of
proximity (for instance temporal) may be used.
network security where non-self is defined as an
undesired connection. All connections are modelled as
5. If there is an analogue of an immune response, it
binary strings and there is a set of known good and bad
should not lead to further danger signals. In biology,
connections, which is used to train and evaluate the
killer cells cause a normal cell death, not danger.
algorithm. To build the Artificial Immune System,
6. Matzinger proposes priming killer cells via antigen-
random binary strings are created called detectors.
presenting cells for greater effect. Depending on the
These detectors then undergo a maturation phase where
immune system used (it only makes sense for
they are presented with good, i.e. self, connections. If they
spatially distributed models) this proposal may be
match any of these they are eliminated otherwise they
relevant.
become mature, but not activated. If during their further
7. There are a variety of considerations that are less
lifetime these mature detectors match anything else,
directly related to the danger model. For example,
exceeding a certain threshold value, they become
migration  how many antibodies receive signal
activated. This is then reported to a human operator who
one/two from a given antigen-presenting cell? In
decides whether there is a true anomaly. If so the
addition, the danger theory relies on concentrations,
detectors are promoted to memory detectors with an
i.e. continuous not binary matching.
indefinite life span and minimum activation threshold.
There are also a couple of points that might tempt a Thus, this is similar to the secondary response in the
practitioner to alter the danger model as presented here. natural immune system, for instance after immunisation.
For example, the danger model has quite a number of
An approach such as the above is known in Artificial
elements. Given that the antigen-presenting cell mediates
Immune Systems as negative selection as only those
the danger signal, we might be able to simplify the model
detectors (antibodies) that do not match live on. It is
 for example, do we still need a T helper cell? In
thought that T cells mature in similar fashion in the
addition, there are some danger signals that might in some
thymus such that only those survive and mature that do
sense be  appropriate and thus should not trigger an
not match any self cells after a certain amount of time.
immune response. In such cases, a method for avoiding
An alternative approach to negative selection is that of
the danger pathway must be found. A biological example
positive selection as used for instance by Forrest et al [9]
is transplanted organs, in which antigen-presenting cells
and by Somayaji and Forrest [22]. These systems are a
are removed.
reversal of the negative selection algorithm described
above with the difference that detectors for self are
evolved. From a performance point of view there are
advantages and disadvantages for both methods. A
suspect non-self string would have to be compared with
all self-detectors to establish that it is non-self, whilst with
negative selection the first matching detector would stop or non-self. To achieve this self-non-self discrimination
the comparison. On the other hand, for a self-string this is will still be useful but it is no longer essential. This is
reversed giving positive selection the upper hand. Thus, because non-self no longer causes an immune response.
performance depends on the self to non-self ratio, which Instead, it will be danger signals that trigger a reaction.
should generally favour positive selection.
What could such danger signals be? They should show up
However, there is another difference between the two after limited infection to minimise damage and hence
approaches: the nature of false alarms. With negative have to be quickly and automatically measurable. Suitable
selection inadequate detectors will result in false signals could include:
negatives (missed intrusions) whilst with positive
" Too low or too high memory usage.
selection there will be false positives (false alarms). The
" Inappropriate disk activity.
preference between the two in this case is likely to be
problem specific.
" Unexpected frequency of file changes as measured
for example by checksums or file size.
Both approaches have been extended further [10]
including better co-stimulation methods and activation
" SIGABRT signal from abnormally terminated UNIX
thresholds to reduce the number of false alarms, multiple
processes.
antibody sub-populations for improved diversity and
" Presence of non-self.
coverage and improved partial matching rules. Recently,
similar approaches have also been used to detect hardware
Of course, it would also be possible to use  positive
faults (Bradley and Tyrrell [1]), network intrusion (Kim
signals, as discussed in the previous section, such as the
and Bentley [16]) and fault tolerance (Burgess [5]).
absence of some normal  health signals.
What are the remaining challenges for a successful use of
Once the danger signal has been transmitted, the immune
Artificial Immune Systems for anomaly detection?
system can then react to those antigens, for example,
Firstly, self and non-self will usually evolve and change
executables or connections, which are  near the emitter
during the lifetime of the system. Hence, to be effective,
of the danger signal. Note that  near does not necessarily
any system used must be robust and flexible enough to
mean geographical or physical closeness, something that
cope with changing circumstances. Based on the
might make sense for connections and their IP addresses
performance of their natural counterparts, Artificial
but probably not for computer executables in general. In
Immune Systems should be well suited to provide these
essence, the physical  near that the Danger Theory
qualities. Secondly, appropriate representations of self
requires for the immune system is a proxy measure for
and good matching rules have to be developed. Most
causality. Hence, we can substitute it with more
research so far has been concentrated in these two areas
appropriate causality measures such as similar execution
and good advances have been made so far [8].
start times, concurrent runtimes or access of the same
resources.
However, as pointed out by Kim and Bentley [15], scaling
is a problem with negative selection. As the systems to be
Consequently, those antibodies or detectors that match
protected grow larger and larger so does self and non-self
(first signal) those antigens within a radius, defined by a
and it becomes more and more problematic to find a set of
measure such as the above (second signal), will
detectors that provides adequate coverage whilst being
proliferate. Having thereby identified the dangerous
computationally efficient. It is inefficient, if not
components, further confirmation could then be sought by
impossible, to map the entire non-self universe,
sending it to a special part of the system simulating
particularly as it will be changing over time. The same
another attack. This would have the further advantage of
applies to positive selection and trying to map all of self.
not having to send all detectors to confirm danger. In
conclusion, using these ideas from the Danger Theory has
Moreover, the approaches so far have another
provided a better grounding of danger labels in
disadvantage: A response requires infection beyond a
comparison to self / non-self, whilst at the same time
certain threshold and human intervention confirming this.
relying less on human competence.
Although one might argue that the operator sees fewer
alarms than in an unaided system, this clearly is not yet
the ideal situation of an autonomous system preventing all
5 THE DANGER THEORY AND OTHER
damage. Apart from the resource implication of a human
ARTIFICIAL IMMUNE SYSTEM
component, an unduly long delay might be caused by this
necessity prolonging the time the system is exposed. This
APPLICATIONS
situation might be further aggravated by the fact that the
It is not immediately obvious how the Danger Theory
labels self and non-self are often ambiguous and expert
could be of use to data mining problems such as the
knowledge might be required to apply them correctly.
movie prediction problem described in Cayzer and
How can these problems be overcome? We believe that
Aickelin [7], because the notions of self and non-self are
applying ideas from the Danger Theory can help building
not used. In essence, in data mining all of the system is
better Artificial Immune Systems by providing a different
self. More precisely, it is not an issue what is self or non-
way of grounding and removing the necessity to map self
self as the designer of the database has complete control domains where the relevance of  danger is far from
over this aspect. obvious.
However, if the labels self and non-self were to be
replaced by interesting and non-interesting data for
6 CONCLUSIONS
example, a distinction would prove beneficial. In this
To conclude, the Danger Theory is not about the way
case, the immune system is being applied as a classifier. If
Artificial Immune Systems represent data. Instead, it
one can then further assume that interesting data is
provides ideas about which data the Artificial Immune
located  close or  near to other interesting data, ideas
Systems should represent and deal with. They should
from the Danger Theory can come into play again. To do
focus on dangerous, i.e. interesting data.
so, it is necessary to define  close /  near . We could use:
It could be argued that the shift from non-self to danger is
" Physical closeness, for instance distance in the
merely a symbolic label change that achieves nothing. We
database as measured by an appropriate metric.
do not believe this to be the case, since danger is a
" Correlation of data, as measured by statistical tools.
grounded signal, and non-self is (typically) a set of feature
" Similar entry times into the database. vectors with no further information about their meaning.
The danger signal helps us to identify which subset of
" File size.
feature vectors is of interest. A suitably defined danger
A danger signal could thus be interpreted as a valuable
signal thus overcomes many of the limitations of self-non-
piece of information that has been uncovered. Hence,
self selection. It restricts the domain of non-self to a
those antibodies are stimulated that match data that is
manageable size, removes the need to screen against all
 close this valuable piece of information.
self, and deals adaptively with scenarios where self (or
non-self) changes over time.
Taking this idea further, we might define the danger
signal as an indication of user interest. Given this
The challenge is clearly to define a suitable danger signal,
definition, we can speculate about various scenarios in
a choice that might prove as critical as the choice of
which the danger signal could be of use. One such
fitness function for an evolutionary algorithm. In addition,
scenario is outlined below for illustrative purposes.
the physical distance in the biological system should be
translated into a suitable proxy measure for similarity or
Imagine a user browsing a set of documents. Each
causality in an Artificial Immune System. We have made
document has a set of features (for instance keywords,
some suggestions in this paper about how to tackle these
title, author, date etc). Imagine further that there is an
challenges in a variety of domains, but the process is not
immune system implemented as a  watcher , whose
likely to be trivial. Nevertheless, if these challenges are
antibodies match document features.  Interesting
met, then future Artificial Immune System applications
documents are those, whose features are matched by the
might derive considerable benefit, and new insights, from
immune system.
the Danger Theory.
When a user either explicitly or implicitly indicates
interest in the current document, a  danger signal is
Acknowledgements
raised. This causes signal two to be passed, along with
signal one, to antibodies matching any antigen, i.e. We would like to thank the two anonymous reviewers,
document feature, in the danger zone, i.e. this document. whose comments greatly improved this paper.
Stimulated antibodies become effectors, and thus the
immune system learns to become a good filter when References
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Hardware Immune System, Proceedings of the 2002
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[2] Forrest H. Bennett III, John R. Koza, Jessen Yu,
may change over time and so it is important that the
William Mydlowec, Automatic Synthesis,
immune system adapts in a timely way to such a changing
Placement, and Routing of an Amplifier Circuit by
definition of (non-) self.
Means of Genetic Programming. Evolvable Systems:
Meanwhile, every document browsed by the user
From Biology to Hardware, Third International
(whether interesting or not) will be presented to the
Conference, ICES 2000: 1-10, 2000
antibodies as  signal one . Uninteresting document
[3] D. W. Bradley, Andrew M. Tyrrell, Immunotronics:
features will therefore give rise to signal one without
Hardware Fault Tolerance Inspired by the Immune
signal two, which will tolerate the autoreactive antibodies.
System. Evolvable Systems: From Biology to
The net effect is to produce a set of antibodies that match
Hardware, Third International Conference, ICES
only interesting document features.
2000: 11-20, 2000
As mentioned, this example is purely illustrative but it
[4] Bretscher P, Cohn M, A theory of self-nonself
does show that ideas from the Danger theory may have
discrimination, Science 169, 1042-1049, 1970
implications for Artificial Immune System applications in
[5] Burgess M: Computer Immunology, Proceedings of [21] Langman R (editor), Self non-self discrimination
LISA XII, 283-297, 1998. revisited, Seminars in Immunology 12, Issue 3,
2000.
[6] Burnet F, The Clonal Selection Theory of Acquired
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TN, 1959. system-call delays, Proceedings of the ninth
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[7] Cayzer S, Aickelin U, A Recommender System
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2002 Congress on Evolutionary Computation, 2002. computer security, HP Labs Technical Reports
HPL-2002-131, 2000 (available from
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http://www.hpl.hp.com/techreports/2002/HPL-
Immune Systems: A Bibliography, Computer
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Science Division, University of Memphis, Technical
Report No. CS-02-001, 2001.
[9] Forrest S, Hofmeyr S, Somayaji A, Longstaff T, A
sense of self for Unix processes, Proceedings of the
1996 IEEE Symposium on Research in Security and
Privacy, 120-128, 1996.
[10] Forrest S, http://www.cs.unm.edu/~immsec/, 2002.
[11] Forrest S, Perelson A, Allen L, Cherukuri R, Self-
non-self discrimination in a computer, Proceedings
of the 1994 IEEE Symposium on Research in
Security and Privacy, 202-212, 1994.
[12] Goldsby R, Kindt T, Osborne B, Kuby Immunology,
Fourth Edition, W H Freeman, 2000.
[13] Hofmeyr S, Forrest S, Architecture for an Artificial
Immune System, Evolutionary Computation 8(4),
443-473, 2000.
[14] Janeway C, The immune System evolved to
discriminated infectious nonself from noninfectious
self, Immunology Today 13, 11-16, 1992.
[15] Kim J, Bentley P, An evaluation of negative
selection in an artificial immune for network
intrusion detection, Proceedings of the 2001 Genetic
and Evolutionary Computation Conference, 1330-
1337, 2001.
[16] Kim J, Bentley P, Towards an Artificial Immune
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[17] Lafferty K, Cunningham A, A new analysis of
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42, 1975
[18] Matzinger P, http://cmmg.biosci.wayne.edu/asg/
polly.html
[19] Matzinger P, The Danger Model in Its Historical
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[20] Matzinger P, Tolerance, Danger and the Extended
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