Brain and immunity

by Hinal Kharva :

In the time of the pandemic, we are hearing a lot about immunity. I was wondering whether our brain plays any role in the modulation of immunity.  How do emotions affect our immunity? The interdisciplinary field of science that studies interactions among brain, behavior, and the immune system, is called “Psychoneuroimmunology”.  

To understand the link between the brain and the immune system, let us look at the functional similarities. Both the brain and the immune system can recognize “self” and “non-self”.  Both systems show an innate response and could also respond to external environmental stimuli using learning and memory (adaptive response).  To conclude, they both can be considered as sensory organs. 

Psychoneuroimmunology research suggests that communication between the brain and the immune system is bidirectional. The nervous system mediates the regulation of immunity and the immune system mediates regulation of nervous system function.  The mechanism of communication has been extensively studied where communication between immune cells and nerve endings happens through messengers like neuroendocrine hormones, neurotransmitters, cytokines, and their respective receptors (Carr & Blalock, 1991).

Let’s look at two different psychological phenomena to understand the connections between brain, behavior, and immune system.

1. Learning and immune response:

Learning is a primary function of the brain through which an organism can adapt to the environment. One learning process is known as classical conditioning where two stimuli are paired together resulting in a learned response. An example is Pavlov’s experiment where a stimulus (food) was paired with a neutral signal (bell ringing) and presented to a hungry dog.  After a repetition of the stimuli, the dog started salivation as a response to the bell rings even in the absence of food.

Do we know such examples of classical conditioning in the immune system, where a seemingly neutral stimulus can produce an immune response?  Researchers have shown that immune functions could also be classically conditioned (Ader & Cohen, 1975). There are three different models used as a method to condition alterations in immune function: taste aversion learning, odor conditioning, and fear conditioning. These experiments have utilized various chemicals/drugs. In these experiments, animals, as well as humans, are exposed to substances that either stimulate or suppress immune function.

In the 1970s, a taste-aversion experiment was performed using a saccharine-flavored drinking solution as the conditioned stimulus paired with a tasteless nausea-inducing (and immunosuppressive) agent (cyclophosphamide). They observed that some of the animals died when subsequently presented with the saccharine-flavored solution alone.  This led to the hypothesis that due to conditioning, the dosage of a simple saccharine solution might have resulted in an immunosuppressive effect, which was also tested in subsequent experiments (Ader & Cohen, 1975).  It is also possible that this alteration in immune function is due to the side effects of other changes in organisms.  Another limitation of classical conditioning of the immune system in humans is that these results are not easy to reproduce. The placebo effect (treatment which is designed to have no therapeutic value but still shows some effect) plays a role. Placebo effects are not elicited in animals.

2) Emotions and immune response:

We know emotions are important psychological mechanisms for the regulation of behavior.  Here, the question is whether any changes in emotion show any alteration in immune response?  What kind of emotions could be beneficial for our immunity? 

One of the studies showed that the histamine-induced inflammatory skin response was exaggerated after a negative mood and suppressed after a positive mood (Zachariae, Jorgensen, Egekvist & Bjerring, 2001). In another study, a positive mood was associated with enhanced chemotaxis (attraction towards certain biochemical signals) of immune cells (Zachariae, Bjerring, Zachariae, et al., 1991).  However, it is worth noting that the mood valence might not directly result in the modulation of the immune response. As an example, the negative mood could be associated with impaired sleep quality (Thomsen, Mehlsen, Christensen & Zachariae, 2003), which in turn is known to affect immune function (Born, 1999).  

There have been several experiments and therapeutic trials to understand whether psychosocial intervention like relaxation and stress management can improve the immune system and course of the disease.  Indeed, documented case studies show that regular relaxation training, such as progressive muscle relaxation, biofeedback, hypnosis, or meditation, lead to a reduction in physical tension that can be measured as decreased heart rate, blood pressure, muscle tension, and skin conductance. In parallel, negative feelings such as anxiety and depression are reduced too. 

As a whole, we still do not have a clear picture of how behavior manipulation affects the immune response and ultimately survival.  Further experimental studies are required to understand brain, behavior, and immune system interactions.


Zachariae, R. (2009). Psychoneuroimmunology: A bio-psycho-social approach to health and disease. Scandinavian Journal of Psychology, 50, 645–651

Book: M. Schedlowski & U Tewes (1999).  Psychoneuroimmunology, an Interdisciplinary Introduction, 

Institute of Medical Psychology, University of Essen, Hannover Medical School, Germany

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