CONDITIONAL IMMUNE RESPONSE
A potentially important application of Pavlovian conditioning involves the body's immune system.
Like other body systems, it can be activated or suppressed through classical conditioning. This
has exciting implications. If learning can stimulate immune system activity, people should be able
to arrange conditions to improve health or healing. Perhaps humans have already been doing this
for thousands of years. Classical conditioning may shed a light on healing rituals and trances
practiced by pre-modern cultures.
An early experiment reported by Schmeck (1985) involved a team of researchers at the University
of Alabama medical school. They studied effects of classical conditioning on activity of natural
killer cells (NK cells) that destroy germs and other invaders in the body. In the experiment, mice
were exposed for three hours at a time to a powerful odor (camphor ). Exposure to this odor, by
itself, had no effect on the mice.
Next, the odor was made to predict a significant biological event. After exposure to the odor, mice
in an experimental group were given injections of a synthetic chemical called poly I:C (for
polyinosinic-polycytidilic acid) that stimulates activity of natural killer cells. Mice in the control
group did not receive the poly I:C.
How did researchers demonstrate a conditional immune response in mice?
For the experimental group, the odor of camphor was paired with exposure to Poly I:C nine times.
In the 10th session, the mice were exposed only to the odor of camphor. Every mouse in the
experimental group showed large increases in natural killer cell activity. Their bodies were
"predicting" the injection of poly I:C and responding with immune system activity. In the control
group, which was exposed only to the odor of camphor, no such response occurred.
This is typical of research on classical conditioning. It is capable of demonstrating remarkable,
subtle biological effects. However, analyzing the exact mechanism can be difficult. How exactly
does a mouse's "knowledge" that poly I:C is about to be delivered to its bloodstream stimulate the
production of NK cells? If researchers knew that, perhaps they could help human patients boost
production of NK cells when needed, as well.
Researchers suspect that neuroimmunomodulation takes place at every level of the nervous
system. The word neuroimmunomodulationcontains the word roots for nerve (neuro)
and immune (immuno). So neuroimmunomodulation means modulating immune system activity
with nervous system activity. The discipline of psychoneuroimmunology-arose in the 1970s and
1980s to study psychological influences on immune system functioning. However, research in this
area has produced disappointing results. The positive effects of psychological intervention on
health are easy to document, but evidence relating these benefits to immune system changes
has been elusive (see the section on psychoneuroimmunology in Chapter 14).
Pavlovian conditioning of immune function: animal investigation
and the challenge of human application
Michael S. Exton , , a, Anne Kristin von Auerb, Angelika Buske-Kirschbaumb, Ursula Stockhorstc,
Ulrich Göbeld and Manfred Schedlowskia
a Institute for Medical Psychology, University of Essen, Hufelandstraße 55, 45122, Essen, Germany
b Center for Psychobiological and Psychosomatic Research, University of Trier, Dietrichstraße 10-11, 54290,
Trier, Germany
c Institute of Medical Psychology, Heinrich-Heine-University Düsseldorf, PO Box 101007, 40001, Düsseldorf,
Germany
d Clinic of Pediatric Hematology and Oncology, Heinrich-Heine-University Düsseldorf, PO Box 101007,
40001, Düsseldorf, Germany
Accepted 25 November 1999.
Available online 15 May 2000.
Abstract
Pavlovian conditioning of immune functions provided early impetus to the rapidly expanding knowledge of bidirectional
communication among the immune, endocrine, and central nervous systems. Since these early
investigations, the phenomenology of this response has been well characterized. However the neural
mechanisms and biological relevance of conditioned immunomodulation remain unclear. To this end, we
present here data from our laboratories that have: (1) revealed some of the neural mechanisms and
biological relevance of an animal model of conditioned immunomodulation; (2) demonstrated the
conditionability and potential mechanisms of conditioned immune responses in healthy humans, and (3)
investigated conditioned immunomodulation in a clinical sample. Together, these data demonstrate that
animal models provide a basis for investigating mechanisms whereby conditioned changes in immune
function may modulate health status in a clinical realm.
Author Keywords: Behavioral conditioning; Psychoneuroimmunology; Rat; Human; Sympathetic nervous
system
Article Outline
1. Introduction
2. Conditioned immunomodulation in the rat: mechanisms and biological relevance
2.1. Conditioned immunomodulation in the rat
2.2. Neuroendocrine mechanisms of conditioned immunomodulation
2.3. Biological relevance of conditioned immunomodulation
2.4. Conclusions
3. Conditioned immunomodulation in healthy humans: phenomenon and neuroendocrine mediators
3.1. Conditioned increase of NK cell activity in blood
3.2. Conditioned increase of NK cell numbers in blood
3.3. Conditioned NK cell numbers and activity: neuroendocrine mechanisms
4. Conditioned immunomodulation in humans: clinical application
5. Conclusions
References
Corresponding author. Tel.: +49-201-7234505; fax: +49-201-7235948; email: michael.exton@uniessen.
de
The learned immune response: Pavlov and beyond
Manfred Schedlowskia, , and Gustavo Pacheco-Lópezb
aInstitute of Medical Psychology and Behavioral Immunobiology, University of Duisburg-Essen, Medical
Faculty, 45122 Essen, Germany
bPhysiology and Behaviour Group, Swiss Federal Institute of Technology (ETH-Zurich), 8603
Schwerzenbach, Switzerland
Received 19 June 2009;
revised 10 August 2009;
accepted 14 August 2009.
Available online 19 August 2009.
Abstract
The ability to associate physiological changes with a specific flavor was most likely acquired during evolution
as an adaptive strategy aimed at protecting the organism while preparing it for danger. The behaviorally
conditioned or learned immune response is an exquisite example of the bidirectional communication
between the central nervous system (CNS) and the peripheral immune system. How is it possible that
specific immuno-modulating properties of a drug or substance (unconditioned stimulus) can be re-enlisted
just by the mere re-exposure to a particular taste, odor or environment (conditioned stimulus)? To answer
this key question, we review the neurobiological mechanism mediating this type of associative learning, as
well as the pathways and mechanisms employed by the brain to harness the immune system during the
execution of the conditioned immune response. Finally, we focus on the potential therapeutic relevance of
such learned immune responses, and their re-conceptualization within the framework of “learned placebo
effects”.
Keywords: Behavioral conditioning; Conditioned taste aversion; Placebo; Cyclosporine A; Noradrenaline; β-
Adrenoceptors; Lymphocytes; Interleukin-2; Spleen
Article Outline
1. Introduction
1.1. Conditioned taste aversion
1.2. One single experimental model for the bidirectional CNS–immune interaction
1.3. Cyclosporin A as an unconditioned stimulus
2. How the CNS receives the signals: Afferent pathways
3. Conditioning takes place: Relevant brain structures and neurotransmitters
4. The conditioned immune response: Efferent pathways
5. The clinical relevance of the learned immune response
5.1. Animal models
5.2. Human studies
6. The learned immune response: Summary, open questions and future perspectives
6.1. Open questions
Acknowledgements
References
Corresponding author. Address: Division of Medical Psychology, Institute of Medical Psychology and
Behavioral Immunobiology, University of Duisburg-Essen, Medical Faculty, Hufelandstr. 55, 45122 Essen,
Germany. Fax: +49 201 723 5948.
Note to users: The section "Articles in Press" contains peer reviewed accepted
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Classical conditioning: the new hegemony
Article Abstract:
Data from different disciplines show that classical conditioning is involved in
more human and animal behavior than was once thought. (Classical
conditioning, exemplified in Pavlov's experiments on dogs, involves training an
organism to produce a given response to a stimulus by always associating a given
stimulus with that response.) Previous views that considered classical
conditioning to involve only bodily secretions, reflexive actions, or emotions have
been replaced. It is now thought that classical conditioning can be involved in
problem-solving and other rule-governed processes. This new view has been
accompanied by changes in how classical conditioning is conducted and
evaluated. Such seemingly unrelated phenomena as the placebo effect, relapse to
drug abuse by postaddicts, and the disease-fighting immune response appear to
involve classical conditioning. Classical conditioning has been found in smaller
and smaller organisms and has even been found in brain slices and in fetuses in
the womb. Several research areas that use classical conditioning to explain
phenomena can now be integrated, challenging traditional teleological
interpretations of classical conditioning and offering some basic principles for
testing conditioning in various areas.
author: Turkkan, Jaylan Sheila
Publisher:Cambridge University Press
Publication Name:Behavioral and Brain Science
Subject:Psychology and mental health
ISSN:0140-525X
Year:1989
Psychological aspects, Evaluation, Immunity, Immunity (Physiology), Drug abuse, Conditioned
response, Conditioned responses, Behavior modification, Placebos, Classical conditioning,
Conditioning (Psychology), Behaviorism (Psychology), Behaviorism
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