ARTICLE IN PRESS

Neurocomputing 73 (2010) 1244–1255

Contents lists available at ScienceDirect

Neurocomputing
journal homepage: www.elsevier.com/locate/neucom

A danger theory inspired artificial immune algorithm for on-line supervised

two-class classification problem
Chenggong Zhang a,, Zhang Yi b
a
The Computational Intelligence Laboratory, School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, PR China
b
The Machine Intelligence Laboratory, College of Computer Science, Sichuan University, Chengdu 610054, PR China

a r t i c l e in f o a b s t r a c t

Article history: Self–nonself discrimination has long been the fundamental model of modern theoretical immunology.
Received 12 January 2009 Based on this principle, some effective and efficient artificial immune algorithms have been proposed
Received in revised form and applied to a wide range of engineering applications. Over the last few years, a new model called
6 January 2010
‘‘danger theory’’ has been developed to challenge the classical self–nonself model. In this paper, a novel
Accepted 9 January 2010
immune algorithm inspired by danger theory is proposed for solving on-line supervised two-class
Communicated by T. Heskes
Available online 28 January 2010 classification problems. The general framework of the proposed algorithm is described, and several
essential issues related to the learning process are also discussed. Experiments based on both artificial
Keywords: data sets and real-world problems are carried out to visualize the learning process, as well as to
Artificial immune system
evaluate the classification performance of our method. It is shown empirically by the experimental
Danger theory
results that the proposed algorithm exhibits competitive classification accuracy and generalization
Supervised classification
Computational intelligence capability.
& 2010 Elsevier B.V. All rights reserved.

1. Introduction
Over the past 50 years, it was widely believed that the immune
system functions by discriminating between the self and the
nonself. This simple and straightforward thought became one of
the foundations of modern immunology, which we call the SNS
(Self–NonSelf) model. However, recently a different viewpoint has
appeared, and it attracts much interest in both the theoretical
immunology and artificial immunology communities. This new
model is the ‘‘danger model’’ proposed by Matzinger in
1994 [11,13]. The essential difference between the danger model
and the SNS model is that the danger model does not suggest that
the discrimination between self and nonself is the key factor in
triggering the immune response. Although to what extent
the danger model factually reflects the inner mechanisms of the
immune system remains controversial [20], it is uncontroversial
to extract the promising mechanisms from this new theory
to help us design new bionic techniques. From the point of view of
artificial immunology, we are actually interested in applying
the metaphors behind the danger model—especially those that
the former models cannot offer us—to design novel artificial
immune algorithms.
The danger theory assumes that cells that undergo unnatural
deaths may release danger signals to a small area around that cell.
 Corresponding author.
E-mail addresses: zhchgo@gmail.com, cgzh@hotmail.com (C. Zhang).
zhangyi@scu.edu.cn (Z. Yi).
This area is called the ‘‘danger zone’’ [3]. On the other hand, the
danger signal should not be sent by healthy cells or by cells
undergoing normal physiological deaths [13]. The APCs (antigen-
presenting cells) that receive the danger signal within the danger
zone are activated and co-stimulate the B-cells or helper T-cells that
have already captured the antigen, i.e., received the nonself signal.
Under the effect of these two types of signals, the B-cells undergo the
clonal selection process. Even if a B-cell or helper T-cell outside the
danger zone captures an antigen, it cannot be stimulated because it
does not receive a danger signal from a APC. The danger zone
establishes a way to locally develop an antibody population, thereby
preventing the interference from antigens in distant areas.
In this paper, we present a new immune algorithm inspired by
the danger theory and apply it to solve two-class classification
problems. The concept of ‘‘danger zone’’—derived from danger
theory—is incorporated into our model in order to effectively
develop an antibody population. The danger zone in the proposed
model is defined as an area in the shape-space that is caused by
antigenic stimulation. The size of the danger zone is gradually
decreased while the accumulated intensity of the antibody response
increased. This strategy, as far as we know, is the first attempt of
introducing time-varying antigen status into artificial immunology.
In addition, based on the concept of danger zones, two kinds of
signals, i.e., nonself and danger signals, are adopted in the proposed
model. The precondition for triggering the antibody response is that
the antibody receives both nonself signals and danger signals
simultaneously. Although the signal mechanisms in our model are
somewhat different from that of Matzinger’s model, the model is
effective in terms of both classification accuracy and computational

0925-2312/$ - see front matter & 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.neucom.2010.01.005
 ARTICLE IN PRESS
C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255
complexity. A suppression mechanism is also implemented to
prevent the antibody population from growing too fast. Further-
more, a clonal selection mechanism based on the historical
performance records of antibodies is used to guarantee that the
antibodies capable of recognizing antigens more effectively will
proliferate and survive longer.
The rest of the paper is organized as follows. In Section 2, we
present a brief review of the danger theory, especially of those
mechanisms directly related to our model, and summarize some
related work in the artificial immune community that share a
common inspiration with our model. In Section 3, we outline the
framework of the proposed algorithm and detail several essential
issues related to its learning procedure. In Section 4, experimental
results based on artificial data sets as well as on real-world
problems are presented to show the effectiveness of our
algorithm. We draw conclusions and give directions for future
research in Section 5.
2. Background and related work
Because danger theory is a relatively new field in both theoretical
immunology and artificial immunology, it is necessary to give a brief
review. For simplicity, we focus our description mainly on the
mechanisms directly related to our model. The reader can refer to
[11–13,7] for a comprehensive understanding of this theory.
An easy way of understanding the danger theory is to point out
the similarities between it and the SNS model. As Matzinger stated
[12], both types of models agree that there is a need for some sort of
discrimination at the effector stage of the immune response and that
this critical need to discriminate is the evolutionary selection pressure
behind the mechanisms that endow T-cell receptors and antibodies
with their enormous range and exquisite degrees of specificity. There
are differences between the danger model and the SNS model. The
danger model suggests that the immune system is more concerned
with damage than with foreignness, and is called into action by alarm
signals from injured tissues, rather than by the recognition of the
nonself. In a word, the immune system responds to dangers, but not
always to foreigners. This description might seem to be a renaming of
SNS model. If all self cells are benign and all nonself substances are
dangerous, the danger model is unwanted. However, there indeed
exist some kinds of dangerous self entities (e.g., some mutations) and
benign, even beneficial nonself entities (e.g., fetuses). It is these special
self and nonself entities that provide some phenomena that the
classic SNS model cannot explain very well. For example, there are a
number of harmless viruses in our body and, more specifically, in the
food that we ingest and in our gut, but why then does the immune
system not respond to them? Why do mothers not reject their
fetuses? Why are tumors not rejected, even though they are carrying
‘‘foreign’’ tumor-specific antigens? These observations that do not fit
well with the SNS model become the driving behind the creation of
the danger theory.
The danger theory assumes that cells that undergo unnatural
death may release danger signals that cover a small area around
that cell. This area is called the ‘‘danger zone’’ [3]. However, the
danger signal should not be sent by healthy cells or by
cells undergoing normal physiological deaths [13]. The APCs
(antigen-presenting cells) that receive the danger signal within
the danger zone are activated and co-stimulate the B-cells or
helper T-cells that have already captured the antigen, i.e., received
the nonself signal. Under the effect of these two types of signals,
the B-cells undergo the clonal selection process. Even if B-cells or
helper T-cells out of the danger zone capture the antigen, they
cannot be stimulated because they do not receive danger signals
from an APC. The above mechanisms, especially the concept of the
danger zone and the two types of signals, become the primary
1245
metaphors that we take from the danger theory. It should be
pointed out that in our model, the process of immune response is
simplified. The co-stimulation signal is directly detected by
antibodies rather than relayed by APCs and helper T-cells.
Moreover, it is the antibodies rather than the B-cells that undergo
clonal selection to produce offspring.
The danger theory has attracted many researchers in
recent years and is showing its potential in various areas such
as data mining [3,17] and anomaly detection [2,3,9]. The
first paper directly concerning the application of danger theory
in artificial immune systems is [3]. In this conceptual paper, the
authors propose that the classic negative selection algorithm
for artificial immune system is bound to be imperfect (We think
the imperfection of negative selection is due to the imperfection
of the SNS model, e.g., the lack of reasonable explanation for some
phenomena with respect to a changing self.). They also propose
that because of the deficiency of previous algorithms, there may
be some potential application areas such as anomaly detection
and data mining that can accommodate this new theory.
The authors pointed out that the principal problem in applying
danger theory to engineering applications is to suitably define the
danger signal. Based on their work, an idea of designing a danger
theory inspired IDS (Intrusion Detection System) was proposed by
Aickelin et al. [2]. They use two metaphors, apoptosis (natural
cell death) and necrosis (anomaly cell death), as the basic of the
danger signal. The IDS responds quickly when it detects any
danger signal. The self–nonself discrimination is still important in
the system, though may not able to trigger a response. In [9],
a danger model based algorithm that uses the functionality of
dendritic cells is proposed and applied to anomaly detection.
The authors claim that their algorithm illustrates a prediction
from the danger theory that is also a crucial element in designing
anomaly detection: ‘‘self-reaction killers should be found
during the early phases of most response to foreign antigens,
and they should disappear with time’’. Another conceptual paper
[17] utilizes the context dependent response, which is an
important property of danger theory, to build a web mining
system.
3. The proposed method
In this section, we first outline the general framework of our
proposed model, and then explain in detail several key issues
related to the learning process.
3.1. Overview of the proposed model
Before we begin the description, we will give a brief summary
of the notations and operators used in learning process detailed
later.
The notations are listed as follows:
 S: shape-space where the immune recognition takes place,
S DRn ;
 ab: an individual antibody, ab A S;
 AB: antibody population, ABD S;
 mAB: memory antibody population;
 gAB: general antibody population, mAB \ gAB ¼ |; mAB[
gAB ¼ AB;
 sAB: stimulated antibodies, sAB D AB;
 ag: an individual antigen, ag A S;
 AG: antigen population, AG D S;
 DZ: current danger zone;
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1246 C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255

The operators are listed as follows: 22: end while

23: Output mAB;
 ChangeStatus(ab): operator used to change the status of
antibody ab. When the learning algorithm is finished, the obtained memory
 ClonalSelection(ab): clonal selection operator; antibodies can be used to classify previously unknown antigens.
 Suppress(AB): suppression operator; This is a simple process in which an unknown antigen will be
 React(ab,ag): antibody ab reacts to danger caused by antigen classified as the same class as the antibody with which it has the
ag; lowest affinity.
 UpdateDanger(ag): operator used to update the size of the
danger zone caused by antigen ag;
3.2. Details of the learning algorithm

Every cell (antigen or antibody) has a label indicating its class. In the following subsections, we will detail several key issues
The value of the label is taken from f0; 1g because we deal with related to the learning process of our proposed algorithm, from
two-class classification problems. which we can obtain a clear view of the interaction between
The status of an individual antibody is defined by a antibodies and the immune memory development mechanisms.
triple (sti,rel,cr), where sti indicates the antibody’s accumulated (1) Initialization: The algorithm begins with a random gAB
stimulation level, rel indicates the antibody’s accumulated population initialization of antibodies in the shape-space. The
reliability in terms of classification accuracy, cr indicates whether label of each antibody is randomly assigned. The status of each
or not the antibody belongs to the same class as current antigen. antibody, i.e., sti, rel and cr, is set to zero. The mAB is initialized as
Among these attributes, sti and rel are determined by the an empty set. An important parameter in this phase is iniSize, the
antibody’s historical records. Every time an antigen is presented initial size of gAB. We found that the final size of the antibody
to the antibody population and causes an immune response, the population and the classification performance are fairly insensi-
status of each antibody may change. How the antibodies’ statuses tive to iniSize. In fact, the redundant antibodies caused by too
influence the immune memory development is a key issue in our large iniSize can be gradually cleaned out under the filtrating
work and will be discussed in Section 3.2. effect of clonal selection. On the other hand, if the iniSize is too
Based on the above notations and operators, we give a small, the algorithm is also capable of producing sufficient
framework for our proposed algorithm (see Algorithm 1). antibodies under the proliferating effect of clonal selection.
Algorithm 1. Danger theory based immune algorithm. (2) Nonself and danger—two kinds of signals: As mentioned
previously, the central idea of the danger model is that the
1: Initialize gAB,mAB’|; immune system does not react to foreigners but to dangerous
2: while Stopping criterion not satisfied do entities. However, ‘‘no reaction’’ does not means ‘‘no detection’’.
3: for i’0 to jAGj do The detection of danger serves only as a co-stimulation signal,
4: Present AG(i) as current active ag; which we call ‘‘signal 1’’. The perceiving of foreign antigens is
5: DZ created by ag; called ‘‘signal 0’’ which first triggers the immune function.
6: gAB receives signal 0 from ag; In our model, the antibody population is divided into two sub-
7: gAB receives signal 1 from DZ; populations: general antibodies and memory antibodies. Any
8: Select antibodies receives both signal 0 and signal 1 to general antibody with a sufficient accumulated stimulation level
form sAB; may be converted to a memory antibody. Memory antibodies do
9: for all ab A sAB not take part in reaction to antigens. They serve as a fixed
10: ChangeStatus(ab); memory for antigens. Once a memory antibody is generated, its
11: React(ab,ag); status will not change until being suppressed (killed) by other
12: end for memory antibodies.
13: Suppress(AB); Every time an antigen is presented, all general antibodies
14: DecreaseDanger(ag); receive the signal 0. This means that all general antibodies in the
15: for all ab A sAB shape-space can detect the stimuli of current antigen. Such
16: if the ab.sti reaches a certain threshold then detection is performed through calculating the affinity between
17: ClonalSelection(ab); each antibody and the current antigen:
18: end if
affinityðab; agÞ ¼ JabagJ: ð1Þ
19: end for
20: end for However, unlike signal 0, signal 1 is only sent to antibodies within
21: Check the stopping criterion; the danger zone created by the current antigen (see Fig. 1). The

Fig. 1. Illustration of two signals. Every general antibody can receive signal 0, but only those within the danger zone can receive signal 1. Antibodies which receive both
signal 0 and signal 1 are stimulated.
 ARTICLE IN PRESS
C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255
antibodies that receive both signal 0 and signal 1 are stimulated
by the current antigen and are allowed to change their status
(see Algorithm 2).
Algorithm 2. ChangeStatus(ab).
1: ab:sti’ab:sti þ1;
2: if ab.label = = ag.label then
3: ab.cr= 1;
4: else
5: ab.cr= 1;
6: end if
7: ab:rel’ab:rel þ ab:cr;
(3) Antibody reaction and variable danger zone: In addition to
updating their status, stimulated antibodies can also react to the
current antigen. The reaction intensity of an antibody is inversely
proportional to its affinity with the current antigen. The
antibodies closer to the current antigen have a higher reaction
intensity (see Algorithm 3). Moreover, the stimulated antibodies
that belong to the same class label as the current antigen (i.e.,
cr= 1) move toward that antigen, whereas the stimulated
antibodies that belong to a different class (i.e., cr=  1) move
away from that antigen (see Algorithm 3).
Algorithm 3. React(ab,ag).
1: var ¼ 1affinityðab; agÞ=ag:danger;
2: ab’ab þab:cr  var  ðagabÞ;
In our model, the danger values of antigens are decreased over
time. Such decrease is, like natural immune system, a result of
antibody reaction to antigen (see Fig. 2). Therefore, it is reasonable to
assume that the more antibodies stimulated by an antigen, the more
its danger value (i.e., the range of its danger zone) will be decreased.
Thereafter, the antigen will stimulate fewer antibodies when it is
presented again. In fact, from the point of view of immune response,
more stimulated antibodies means that the immune system exhibits
a stronger response to the current antigen, and hence the antigen
receives a stronger resistance. On the other hand, from the point of
view of learning, more stimulated detectors (antibodies) mean that
the current sample (antigen) contributes more to the learning
process, so it is reasonable to weaken its activity in future learning.
Fig. 2. Antibody reaction and antigen danger value decreasing. Left: before antigen presentation; Right: after antigen presentation. The stimulated antibodies with cr = 1
move toward the antigen; the stimulated antibodies with cr=  1 move away from the antigen. The decrease of the danger value of antigen ag 2 is larger than that of
antigen ag 1 since it stimulated more antibodies. Notice that we draw two antigens here to illustrate the difference of antibody reaction mechanism under different
situations. In real implementation there would be only one antigen presented in each generation.
1247
Based on these considerations, we designed Algorithm 4 to gradually
decrease the danger value of antigens.
Algorithm 4. DecreaseDanger(ag).
1: var’ðjsABjþ 1Þk1 ;
2: ag:danger’ag:danger=var;
The introducing of a variable danger value has an additional benefit
of simplifying the criterion for checking whether or not to stop the
algorithm. In fact, by properly setting a value of k1 in Algorithm 4, we
can guarantee that the decreasing rate of danger values always
remains larger than the increasing rate of the number of antibodies
stimulated by the antigen. Hence, there must be a time at which the
antigens have such a small danger value that they cannot stimulate
any antibody. Thus, we define the stopping criterion as follows: stop if
beyond a predefined number of iterations there is no antibody
stimulated by any antigen. However, there may be an exception to
this criterion. When there are a large number of antigens concen-
trated in a relatively small area, it may take a long time to satisfy the
stopping criterion, even if the antibody population has already
matured. In this situation, we may predefine a maximum generation
number (usually a certain proportion of original antigen population
size). The learning process must be terminated at that time even if the
stopping criterion has not yet been satisfied.
(4) Suppression between antibodies: Like other classification or data
analysis methods, obtaining effective classifiers of appropriate size is
an essential issue in designing bio-inspired algorithms. In our
proposed model, we control the size of the antibody population by
implementing suppression among the antibody population. The
intensity of suppression between any two antibodies is inversely
proportional to their affinity against current antigen.
The suppression is divided into two independent processes. One is
the suppression between stimulated antibodies (they are general
antibodies within the current danger zone). The other is the
suppression between memory antibodies within the current danger
zone.
For any two stimulated antibodies abi and abj, the one with the
higher affinity to the current antigen will be deleted with probability
p1 which is calculated by following equation:
 k
affinityðabi ; abj Þ 2
p1 ¼ 1 ; ð2Þ
2  ag:danger
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1248 C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255

where k2 is a parameter that controls the suppression intensity. 13: end if

Similarly, for any two memory antibodies Mabi and Mabj within the 14: end for
current danger zone, the one with the higher affinity to the current
antigen will be deleted with probability p2 which is calculated by
following equation: (5) Clonal selection: The clonal selection is adopted in the
 k proposed model to aid in the reproduction of superior antibodies
affinityðMabi ; Mabj Þ 3 that have good performance in classification accuracy and
p2 ¼ 1 ; ð3Þ
2  ag:danger deletion of antibodies that often make mistakes. We need to
where k3 is a parameter that controls the suppression intensity. define a measurement to determine whether an antibody is
Algorithm 5 depicts the suppression process (see also Fig. 3). superior or inferior. We achieve this by introducing two positive
threshold values, namely THR 1 and THR 2 ðTHR2r THR1Þ. Only
Algorithm 5. Suppress(sAB). when the sti of a general antibody reaches THR 1 can it enter the
clonal selection process. Then, according to the rel value of that
1: randomly group the stimulated antibodies into pairs (if antibody, one of the following operations will be implemented:
the size is odd, ignore any single one.);
2: for all pairs do
(1) If rel Z THR2, convert the antibody to a memory antibody,
3: calculate probability p1 according to Eq. (2);
clone it, and then mutate the clones.
4: if random op1 then
(2) If rel rTHR2, invert the label of the antibody, reset its status
5: delete the antibody with higher affinity to current
to zero.
antigen;
(3) If jrelj oTHR2, delete the antibody with probability p, where
6: end if
p ¼ 1ðjrelj=THR2Þ2 .
7: end for
8: randomly group the memory antibodies within the danger
zone into pairs (if the size is odd, ignore any single one); Such clonal selection mechanisms make us measure the
9: for all pairs do potential of an antibody from the point of view of its historical
10: calculate probability p2 according to Eq. (3); record of performance in classification. If the sti reaches THR 1
11: if random op2 then while the rel is still lower than THR 2, then the antibody was
12: delete the memory antibody with higher affinity to alternately stimulated by antigens with different class labels. In
current antigen; other words, the antibody has a low reliability in terms of

Fig. 3. Suppression between antibodies. Left: before the suppression. Right: after the suppression. Four antibodies ab 1, ab 2, ab 3, and ab 4 are randomly grouped into two
pairs (ab 1,ab 2) and (ab 3,ab 4), with affinityðab1; ab2Þ 4 affinityðab3; ab4Þ and affinityðab3; agÞ 4affinityðab4; agÞ. Hence the intensity of suppression between ab 1 and ab 2 is
smaller than that of ab 3 and ab 4. After the suppression both ab 1 and ab 2 may survive, whereas ab 3 will be suppressed by ab 4 due to its larger affinity with
current antigen.

Fig. 4. Clonal selection. Left: before the clonal selection. Right: after the clonal selection. There are four antibodies ab 1, ab 2, ab 3, and ab 4 whose sti reach THR 1. ab 3 was
alternately stimulated by antigens in different class, so it will be deleted due to its unreliability in terms of classification accuracy. The ab 4 was continually stimulated by
opposite class antigens, so its label will be inverted. ab 1 and ab 2 are both go through proliferation. The rel of ab 1 is larger than that of ab 2. This makes the offspring size of
ab 1 larger than that of ab2, and the mutation rate of ab 2 larger than that of ab1.
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C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255 1249

classification, and it is reasonable to force it to forgo reproduction. represent the distribution of antigens in each class. The parameter
Algorithm 6 depicts the process of clonal selection (see also settings used in the experiment are listed in Table 1, where
Fig. 4). iniSize indicates the initial antibody population size and iniDV
indicates the initial danger value of each antigen. The
Algorithm 6. ClonalSelection(ab). stopping criterion is defined as follows: stop when after 4500
1: if jab:reljo THR2 and random o1ðjrelj=THR2Þ then generations (a quarter of antigen population size) no antibody is
2: delete ab; stimulated.
3: else if ab:rel r THR2 then (2) Results: Fig. 6(a) shows the final memory antibody
4: ab:label’1  ab:label; population. The learning process lasts 634 263 generations. The
5: ab:sti’0; final memory antibody population contains 1419 antibodies,
6: among which 730 antibodies belong to class 1 and 689 antibodies
ab:rel’0;
belong to class 2. Hence, the compression ratio is 4.06%. From
7: else
Fig. 6(a), we can find that the evolved antibodies can effectively
8: Clone ab;
represent the overlapping regions and that the boundary
9: Each offspring of ab goes through mutation;
separating the two classes is clear.
10: Convert ab to memory antibody;
Next we will quantitatively validate that the proposed model
11: end if
has promising data representation capability. For each class i
ði A f1; 2gÞ, we will test the vector quantization error EQ(Agi,Abi),
The size of clones is calculated by following formula: which is defined as
 
ab:relTHR2
size ¼ ðmc1Þ  þ1 ; ð4Þ 1 X X 1
THR1THR2 EQ ðAg i ; Abi Þ ¼ affinityðab; agÞ; ð5Þ
2 ab A Ab ag A NðabÞ jNðabÞj
i
where the integer mc represents the maximum size of clones.
Notice that for any antibody ab that can take part in cloning, the where Agi and Abi represent the antigen population and the final
following relation must hold: THR2 rab:relr THR1. From Eq. (4), antibody population of class i, respectively. The neighborhood
we have 0 rsize rmc. (receptive field) N(ab) of an antibody ab is defined as

0
NðabÞ ¼ ag A Ag i jab ¼ arg min
0
affinityðag; ab Þg: ð6Þ
4. Simulations ab A Abi

To obtain comparative results, we used another two artificial

In this section, we present experiments that have been
performed to illustrate the learning process, as well as to evaluate
the classification performance of our proposed method.
4.1. Artificial data
immune algorithms to learn the artificial data set. They are aiNet
[4,5] and RLAIS [19], which have proved to be very efficient for
data representation. For each algorithm including the proposed
model, we performed 50 independent trials and the final

(1) Experimental setup: The artificial data set contains 18 000 Table 1
antigens in a two-dimensional unit square. The antigens are evenly Parameter settings of our model used in experiment based on artificial data set.
divided into two classes that are highly not linearly separable (see
THR 1 THR 2 iniSize iniDV mc k1 k2 k3
Fig. 5(a)). As shown in Fig. 5(b) and (c), extensive overlapping
regions exist in the border of each class. Our objective is to obtain an 6 4 10 0.02 4 1.5 0.5 1.5
antibody population of appropriate size that can effectively

1
area 2
0.9

0.8

0.7

0.6
area 1
0.5 0.65
0.62
0.4 0.615
0.61 0.6
0.3 0.605
0.6
0.2 0.595
0.59 0.55
0.1 0.585
0.58
0 0.575 0.5
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0. 3
0. 4
0. 5
66

0. 7
0. 8
69
7
71
72

0. 5
0. 3
0. 5
0. 4
0. 5
0. 5
0. 5
0. 6
0. 5
0. 7
5
6
6
6

6
6

0.

82
8
83
8
84
8
85
8
86
8
87
0.

0.

0.
0.

0.

Fig. 5. (a) Antigen population. The dots represent class 1 antigens; the circles represent class 2 antigens. Each class contains 9000 antigens. The two classes are highly not
linearly separable. (b) and (c) Zoomed area 1 and zoomed area 2 in (a) where the overlapping regions exist.
 ARTICLE IN PRESS
1250 C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255

Generation = 25000 Generation = 50000 Generation = 75000

1 1 1

1
0.5 0.5 0.5
0.9
0 0 0
0.8 0 0.5 1 0 0.5 1 0 0.5 1
Generation = 100000 Generation = 125000 Generation = 150000
0.7 1 1 1

0.6
0.5 0.5 0.5
0.5

0.4 0 0 0
0 0.5 1 0 0.5 1 0 0.5 1
Generation = 200000 Generation = 400000 Generation = 600000
0.3
1 1 1
0.2
0.5 0.5 0.5
0.1

0 0 0 0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 0.5 1 0 0.5 1 0 0.5 1

Fig. 6. Evolutionary process of the memory antibody population. (a) Final memory antibody population. The dots and circles represent class 1 and class 2 antibodies,
respectively. (b) Memory antibody population in different generations.

Results on class 1 antigens Results on class 2 antigens

0.15 0.14

0.14
0.13
Vector quantization error

Vector quantization error

0.13
0.12
0.12
0.11
0.11

0.1
0.1

0.09 0.09

0.08
The model aiNet RLAIS The model aiNet RLAIS

Fig. 7. Vector quantization error on artificial data set. (a) Results on class 1 antigens. (b) Results on class 2 antigens.

quantization error is averaged over these 50 trials. Fig. 7 shows
the results and their statistical properties. From Fig. 7, we can find
that the proposed model has obtained the lowest mean
quantization error on both class 1 and class 2 antigens, which
are 0.095 (with standard deviation 0.0054) and 0.090 (with
standard deviation 0.0034), respectively. The RLAIS performed
worst on both class 1 and class 2 antigens. It obtained a mean
quantization error 0.144 (with standard deviation 0.0024) and
0.131 (with standard deviation 0.0040), respectively. The aiNet
performed better than RLAIS, but worse than the proposed model.
Moreover, we used the original data set to test the classifica-
tion performance of our algorithm. The final classification
accuracy is 87.24%. Considering that the data set is highly not
linearly separable and that there are a large number of antigens
within the overlapping regions (see Fig. 5), the proposed model
can be thought of as exhibiting good classification capability on
the artificial data set.
Fig. 6(b) shows the memory antibody population in different
generations. The algorithm behaves like incremental learning:
gradually stimulation by different antigens causes the randomly
initialized antibodies to undergo reaction, suppression, and clonal
selection, and makes it eventually grow into matured antibodies.
As shown in Figs. 6(b) and 8(a), the learning process can be
divided into two distinct phases: the shaping phase and the
maturing phase. In the previous 200 000 generations, the memory
antibody population is gradually shaped as a rough distribution of
antigen population. The population grows quickly in this phase.
When the shaping is finished, the learning process enters the
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C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255
4500
general antibody
memory antibody
4000
number of stimulated antibodies
3500
3000
population size
2500
2000
1500
1000
500
0 0
0 100000 200000 300000 400000 500000 600000 700000
generation number
Fig. 8. Size of memory antibody population and number of stimulated antibodies during the on-line learning. The sampling frequency is 50 generations. (a) Antibody
population size. (b) Number of stimulated antibodies.
maturing phase. This phase lasts about 400 000 generations in
which the population grows slowly. Fig. 8(b) shows the number of
stimulated antibodies in different generations. We can find that
the number of stimulated antibodies decreases along the learning
process. In the shaping phase, the danger values of antigens are
relatively large, and hence there are more antibodies stimulated
by their danger zones. Consequently, both the clonal selection and
suppression take place frequently. The skeleton topology of the
antibody population is formed in this phase. In the maturing
phase, the danger values of antigens are relatively small, and
hence there are fewer antibodies stimulated. Consequently, the
clonal selection and suppression take place infrequently.
4.2. Real problem
In this section, the proposed algorithm is tested on breast
cancer diagnosis, which is a widely used benchmark problem.
(1) Experimental setup: The experiment is based on the
Wisconsin Breast Cancer Database taken from the University of
California at Irvine (UCI) Machine Learning Repository [14]. The
original database contains 699 instances, and each instance has
nine numerically valued attributes. Because there are 16 instances
that contain missing attribute values, we only use the remaining
683 instances for our experiment. The instances are divided into
two classes: class 0 (tested benign) contains 444 (65.0%)
instances; class 1 (tested malignant) contains 239 (35.0%)
instances. All nine of the attributes of each instance are normal-
ized before experiment.
The breast cancer diagnosis is a widely used benchmark
problem among machine learning researchers, and several
previous algorithms have been proposed for and applied to this
problem. We studied some of these algorithms and carried out
comparative experiments to prove that our proposed model has
competitive classification capability. The involved algorithms are
C4.5 [16], RIAC [10], LDA [18], NEFCLASS [15], Optimized-LVQ [8],
Big-LVQ [8], AIRS [8], Supervised fuzzy clustering [1], ClONALG
[6], and DCA [9]. Among these algorithms, AIRS, CLONALG, and
DCA are artificial immune algorithms. In particular, DCA is
inspired from danger theory.
1251
4
3.5
3
2.5
2
1.5
1
0.5
0 100000 200000 300000 400000 500000 600000 700000
generation number
Table 2
Parameter settings of our model used in experiment based on Wisconsin Breast
Cancer Database.
THR 1 THR 2 iniSize iniDV mc k1 k2 k3
5 3 300 1.5 3 0.05 2.2 7.0
For each algorithm, we apply a 10-fold cross-validation for 20
independent runs. Strictly speaking, the original data set is randomly
divided into 10 mutually exclusive subsets. Each of the first nine
subsets contains 68 instances, while the last subset contains 71
instances. In each of the 20 runs, the tested algorithms go through
training and validating 10 times. In each trial, one of the 10 subsets
is selected as the validating set, the rest nine subsets are used as the
training sets. Table 2 lists the parameter settings of our model used
in the experiment, where iniSize indicates the initial antibody
population size and iniDV indicates the initial danger value of each
antigen. The stopping criterion is defined as follows: stop when after
615 generations (the number of antigens in the training set) no
antibody is stimulated.
(2) Results: Figs. 9 and 10 show the experimental results of the
involved algorithms on the Wisconsin breast cancer problem.
From Fig. 9 we can observe that DCA outperforms the other 10
algorithms with regard to the mean classification accuracy on the
training data sets over 20 independent runs. It achieved a mean
accuracy of 97.44%. AIRS performs the second best with a mean
accuracy of 97.14%. Among the other nine algorithms, our
proposed model performs the best with a mean accuracy of
96.88%. In order to obtain statistical information, we conducted
standard one-tailed t-tests on the mean classification accuracy,
with significant level of 95%. The corresponding results show that
the proposed model performs significantly better than C4.5, RIAC,
NEFCLASS, Supervised fuzzy clustering, and CLONALG; the
difference between our model and the other five algorithms
have no statistical significance. From Fig. 10, we can observe that
the proposed model outperforms the other 10 algorithms with
regard to the mean classification accuracy on the validating data
set over 20 independent runs. The proposed model has achieved a
mean accuracy of 96.79%. Big-LVQ performs the second best with
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1252 C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255

0.98

0.975

0.97

Classification accuracy
0.965

0.96

0.955

0.95

0.945
el

SS

VQ

A
4.

rin
LD

C
IA
od

LV

AL
LA

−L
C

AI

D
R

te
m

g−

N
us
ed
C

LO
e

Bi
EF
Th

cl
iz

C
im
N

F.
pt

S.
O

Fig. 9. Results on training data set in experiment based on Wisconsin breast cancer database.

0.97

0.965
Classification accuracy

0.96

0.955

0.95

0.945

0.94
S
el

VQ

G
A

A
4.

rin
S

R
LD

C
IA

LV

AL
od

LA

−L

AI
C

D
R

te
m

g−

N
us
ed
C

LO
e

Bi
EF

cl
Th

iz

C
im
N

F.
pt

S.
O

Fig. 10. Results on validating data set in experiment based on Wisconsin breast cancer database.

mean accuracy of 96.60%. The standard one-tailed t-tests with
significant level of 95% shows that the proposed model performs
significantly better than C4.5, RIAC, NEFCLASS, Supervised fuzzy
clustering, CLONALG, and DCA.
To summarize, the proposed model performs third best with
regard to the mean classification accuracy on the training data set,
and performs best with regard to the mean classification accuracy on
validating data set. Further, for the training data set, the proposed
model performs better than five other algorithms with significant
level of 95%; for the validating data set the proposed model performs
better than six other algorithms with significant level of 95%. These
results prove that our model exhibits competitive classification
capability and promising generalization capability.
Fig. 11 shows the size of the memory antibody population
during the first run. The evolution of the antibody population is
divided into two distinct phases. In the first 5000 generations
(10 000 generations in case of fold 4 and fold 8), the population is
shaped as a rough distribution of the antigen population;
antibodies gradually occupy the areas in which the antigens
congregate. In later generations, the learning process enters the
maturing phase. In this phase, the antibodies go through local
proliferation and suppression, and the slight difference between
clustering areas is formed in this phase.
Fig. 12 shows the number of stimulated antibodies during the
first run. The number of stimulated antibodies decreases along
with learning process due to the time-varying danger values of
antigens. Notice that there are some evident peaks in the case of
folds 2, 4 and 8. This is because of the random population
initialization mechanism. If the initial 300 general antibodies
congregate in a relatively small area, then in the shaping phase
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C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255 1253

Fold 1 Fold 2 Fold 3 Fold 4

2000 2000 1000 2000

1500 1500 1500

1000 1000 500 1000

500 500 500

0 0 0 0
0 5000 10000 0 5000 10000 0 5000 10000 15000 0 10000 20000
Fold 5 Fold 6 Fold 7 Fold 8
2000 1500 1500 2000

1500 1500
1000 1000

1000 1000

500 500
500 500

0 0 0 0
0 5000 10000 0 5000 10000 0 5000 10000 0 5000 10000 15000
Fold 9 Fold 10
1000 1500

1000

500

500

0 0
0 5000 10000 0 5000 10000

Fig. 11. Size of memory antibody population during each of the 10 learning processes in the first run. The x-axis represents generation number; the y-axis represents
population size. The red thick curves represent general antibody population; the blue thin curves represent memory antibody population. The sampling frequency is set as
10 generations. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

some areas containing a considerable number of antigens may not
be explored by antibodies. Therefore, when the newborn
antibodies eventually find these areas, the antigens may
stimulate a large number of antibodies due to their relatively
large initial danger value, and hence the peak appears.
5. Conclusion
The natural immune system is an interesting research field
because it provides an intricate model of adaptive learning
processes. Therefore, it inspires novel effective paradigms for
engineering applications. Such a model is proposed in this paper
for solving on-line two-class classification problems. Our method
is based on the mechanisms of a novel theoretical immunology
model—danger theory, e.g., danger zone and danger signals. We
evaluate our method through experiments based on an artificial
data set as well as on a real-world problem. Experimental results
show that our method exhibits good topology learning and
classification capability.
The main contribution of this paper is the introduction of a
framework of a danger theory based immune algorithm that may
become the foundation of a series of bio-inspired methods. The
concept of a time-varying antigen status provides us with more
reasons to design novel immune operators. Although the danger
theory based immune algorithm is relatively young compared to
traditional immune algorithms like negative selection and clonal
selection, this new method is showing its potential in more and
more application areas and will play more important roles in both
artificial immunology and engineering applications.
Most of the work in this paper is empirical and experimental. So,
the next step of our work is to theoretically analyze the learning
process of our method and apply it to more complicated problems.
Moreover, we have found that there may be some intricate relation-
ships between the parameters used in our model, and we believe that
it is worth studying these relationships theoretically.
Acknowledgments
The authors would like to thank the anonymous reviewers and
the Associate Editor for their helpful remarks and comments,
which have greatly improved this paper.
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1254 C. Zhang, Z. Yi / Neurocomputing 73 (2010) 1244–1255

Fold 1 Fold 2 Fold 3 Fold 4

20 20 20 20

15 15 15 15

10 10 10 10

5 5 5 5

0 0 0 0
0 5000 10000 0 5000 10000 0 10000 20000 0 10000 20000

Fold 5 Fold 6 Fold 7 Fold 8

20 20 20 20

15 15 15 15

10 10 10 10

5 5 5 5

0 0 0 0
0 5000 10000 0 5000 10000 0 5000 10000 0 5000 10000 15000
Fold 9 Fold 10
20 20

15 15

10 10

5 5

0 0
0 5000 10000 0 10000 20000

Fig. 12. Number of stimulated antibodies during each of the 10 learning processes in the first run. The x-axis represents generation number; the y-axis represents the
number of stimulated antibodies. The sampling frequency is set as 10 generations.

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Chenggong Zhang received his B.Sc. degree in Com-
puter and Information Science from Southwest Uni-
versity in 2002 and the M.Sc. degree in Computer
Science from University of Electronic Science and
Technology of China (UESTC), in 2005. He is currently
pursuing the Ph.D. degree in Computational Intelli-
gence Laboratory, School of Computer Science and
Engineering, UESTC.
1255
Zhang Yi received his B.Sc. degree in Mathematics
from Sichuan Normal University, Chengdu, China, in
1983 and his MS degree in Mathematics from Hebei
Normal University in 1986. In December 1987, he was
promoted Associate Professor in the University of
Electronic Science and Technology of China. From
1989 to 1990, he was a Senior Visiting Scholar in the
Department of Automatic Control and Systems En-
gineering in The University of Sheffield, England. In
1994, he received his Ph.D. degree in Mathematics
from the Institute of Mathematics, The Chinese
Academy of Science, Beijing, China. He was promoted
full Professor in 1994 in the University of Electronic
Science and Technology of China. From February 1999 to February 2000 and from
August 2000 to August 2001, he was a Research Associate in the Department of
Computer Science and Engineering at The Chinese University of Hong Kong. From
August 2001 to December 2002, he was a Research Fellow in the Department of
Electrical and Computer Engineering at The National University of Singapore.
Currently, he is a professor of College of Computer Science, Sichuan University.