Psycho-Immunology: Patient Heal Thyself.

Author: Bob Orndoff
Published on: April 3, 2000

The immune response can invoke action from many different parts of the body, including the blood and hempoetic (blood-forming) organs such as the thymus gland, spleen and marrow, the liver, adrenal glands and the nervous system. The main job of this immune “system” is to recognize self and alien, know which is which and reject the alien. By doing so properly, the immune response protects us from disease.

White blood cells (lymphocytes), for example can surround, engulf, immobilize and inactivate invading bacteria in a wound. Pus is the result, a combined lymphocyte-captive-bacteria conglomerate. Proteins in blood serum make up the so-called “humoral” immune system and can selectively bind with other proteins and render them non-reactive. A virus, for example, has a protein shell--normally used to bind itself to the cell it infects-- that can be detected, then bound by these serum antibodies, and, since the virus cannot lock onto cells, it is neutralized. Often the serum (humoral) response works in conjunction with the lymphocytes and the two, cellular and humoral, augment each other’s effectiveness.

The liver synthesizes various serum components--globulins for example--which are recruited in the humoral immunoresponse.

Adrenal glands come in two parts: the inner, medulla, that secretes the flight or fight hormone, adrenalin, and an outer shell, the cortex, that makes various steroids, many of which, e.g., cortisone, reduce inflammation.

What the nervous system does in immunoresponsiveness is a brand new chapter in the annals of medicine. This relatively new branch of medicine, Psycho-Immunology, began with bits and pieces of research around the mid-to-late 1970’s.

In 1974, I recall, a close friend of mine, “Peter,” who was then a pre-doctoral student in physiological psychology had been assigned to assist his major professor in reviewing a research grant proposal that had been submitted to the National Institutes of Health. He was so astounded by what he had been reading, that he called me long distance for the sole purpose of telling me about this. “...strange and almost bizarre...” (his words) research program.

In the normal course of submitting proposals for research grants, preliminary research has already been done, and the proposal is a request for additional money with which to pursue more intensive research along the same lines. Contained within the proposal is the complete description, with methods and findings, of the preliminary research itself.

My friend divulged only the essence of the preliminary research findings for a research program with the working title: “Learned Immuno-Responses in the Laboratory Rat.” The title alone gave it away--rats could be trained to make their immune system respond.

“No way, Pete!” I shouted skeptically over the phone, but nonetheless eager to hear more.

“Oh yeah, it’s true!” Pete yelled excitedly, “I didn’t believe it either. But I kept reading and reading. I went over this with a fine tooth comb...wait’ll hear what they did.”

Rats have a keen sense of taste and prefer mildly sweet water, they also don’t like water made bitter with quinine, but will drink it they have to. These two flavors, sweet and bitter, were used as discrimination cues. For some rats sweet water made them sick because it was radioactive, for others it was the bitter water that was contaminated.

After ingestion of the water the rats became very sick and their immune systems reacted appropriately. (That the invader was radiation and not a typical pathogen, e.g., bacteria, is irrelevant--the immune system still tries to fight the disease and its increased activity can be measured by a change in ratios and amounts of different types of white cells and increases in serum levels of certain proteins.) Eventually the rats recovered to normal health, although the illness was lengthy.

The test of whether rats learn to augment their immunoresposiveness came when the recovered rats were again given water with the same flavor the once made them sick--this time, the water had no radiation, it was safe. nevertheless, the rats showed the immune responses they had shown upon their initial exposure to the radiated water. The conclusion was that the brain had learned that a specific flavor heralded illness and, moreover, as a result, signaled the immune system to get to work.

As a result of Peter’s phone call and his exuberance, I paid close attention thereafter to the releases of new research in the literature having anything to do psychology and autonomic responses. I never found one that was exactly like that described to me by Peter, maybe the research proposal was not funded--I don’t know.

In 1975, however, there it was: the research that formally established psychoneuroimmunology (PNI) was a now-famous report by Robert Ader of learned Psycho-Immunology using Pavlovian conditioning in rats.

Recall that in the Classical or Pavlovian conditioning, dogs were given food (e.g., meat powder) immediately after a bell was rung. The biologically salient stimulus, food, caused the dogs to salivate. The neutral stimulus was the bell’s ringing. After repeated pairings of the bell with the food, the dogs in this Pavlov’s experiment salivated when they heard the bell, even with no food given.

In Ader’s experiment immune responsiveness was conditioned just like the behavior salivation in Pavlov’s experiment. Ader used a drug called Cyclophosphamide, which irritates the stomach, as the biologically-salient stimulus, and paired it with flavored water as the neutral stimulus. But to Ader’s surprise, many of the experimental rats died--not being an immunologist, Ader failed to realize that Cyclophosphamide was an Immuno-suppressor, and a powerful one at that.

Ader then gave the surviving rats an “antigenic challenge” by injecting them with sheep red blood cells (erythrocytes), that caused the rats to make antibodies against the sheep’s “foreign cells.” Upon measuring the antibody response Ader found that rats fed the Cyclophosphamide produced less antibodies to sheep erythrocytes. The rats given sheep erythrocytes and flavored water--without Cyclophosphamide--also produced less antibodies. The once-neutral flavored water by itself suppressed the immune system because of its past association with the Cyclophosphamide--just like Pavlov's dogs did when they salivated to the bell. It seemed obvious to Ader that something in the rats' brain caused this response...it was learned and remembered.

These accounts are intentionally overly simplified for the purposes of this brief article. For example, I left out the discussion of various control groups and other details. But, the main findings have been replicated in this and other paradigms over and over since the 1970’s and, as a result of Ader’s and other prototypical studies, Psycho-Immunology as a distinct field of medical science, is on the map, so to speak.

For those of you who have taken Introductory Psychology, you may recognize the form of learning as “Classical” or “Pavlovian” conditioning. In this case a neutral stimulus (the flavor) takes on the power of a biologically-salient stimulus (the radiation) as a result of the paired association of the two stimuli.

And those of you familiar with the more modern advances in psychology may see that it’s only short epistemological hop from the Classical Conditioning paradigm to the more advanced, and potentially useful, “Instrumental Training” to make Psycho-Immunology a therapeutic tool.

Biofeedback, a procedure wherein the patient (or trainee) is given a perceptible external signal that corresponds with an internal (normally imperceptible) event and then is trained to modify the external stimulus and, thereby, modifying the internal event. The simplest to demonstrate is heart rate, for just one of many examples of internal events subject to modification via biofeedback training.

Imagine sitting, with electrodes attached to your fingers, in front of a computer screen with a moving, squiggly line that goes up when your heart accelerates and goes down when your heart slows. There could even be a pre-determined (and adjustable) threshold set by you or the trainer, one that sounds a faintly audible tone when your heart rate descends below, say 70 beats per minute. The trainer tells you, “Your job is to make the tone sound for as long as you can.”

At first, you try to relax--which is difficult for most without practice and some training (to be in another article to come)---and after five or so minutes you hear a short “beep.”

“That’s it,” your trainer encourages. “Now just make the tone make the stay on for longer and longer periods.”

You wonder what it is that you are doing to make the machine (and hence your heart rate) responsive, and you might even ask. Most do. Your trainer will typically say, “Just keep relaxing...you’ll see.”

And see, you will. In no time, maybe one or two one-hour sessions you’ll be able to forthrightly turn on the tone and keep it on for as long as you like. But what have you really done?

You have accomplished something that was thought a mere 40 years ago, and before, to be impossible: you have learned instrumental control over an autonomic (read: automatic) response. Not unlike working for a paycheck, you have learned how to perform a response in order to achieve something. What is unusual is that you have learned to exert voluntary control over an involuntary system.

You can do this for blood pressure, temperature for the body as a whole or specific body parts such as the hands and feet, general arousal--or the opposite: relaxation (via the galvanic skin response), muscle tension for general musculature or specific muscles (e.g. tension headaches), brain waves and many, many more physiologic, autonomic responses.

Now the real leap: Can humans train their immune system and prevent or lessen disease? They can train their heart rate, blood pressure, gastrointestinal motility, muscle tension, vasodilatation, temperature, brain waves, and so on. Most clinicians and researchers who are involved in some way with Psycho-Immunology say yes. The research is in its beginning stages and effort and time will tell. The prognosis is excellent.