The Sickening Mind: Brain, Behaviour, Immunity and Disease. Paul Martin

fails for some reason and the immune system starts attacking ‘self’. B-lymphocytes manufacture antibodies against other cells in the body and these autoantibodies start to attack healthy tissue. The result is an autoimmune disorder. Those who liken the immune system to an army repelling foreign invaders have used the illuminating metaphor of ‘friendly fire’ to describe the phenomenon of autoimmunity.

      Autoimmunity is thought to play a role in at least twenty (and perhaps in excess of forty) diseases, and the list is growing. Among those included are rheumatoid arthritis; various thyroid disorders such as Graves’s disease and Hashimoto’s disease; primary biliary cirrhosis of the liver; systemic lupus erythematosus; Guillain-Barré syndrome; multiple sclerosis; diabetes mellitus; uveitis; pernicious anaemia; myasthenia gravis; and inflammatory bowel disorders such as celiac disease, ulcerative colitis and Crohn’s disease.

      The mechanisms of autoimmunity are not fully understood. Certain autoimmune diseases appear to arise because cells become altered in various ways – perhaps by viral infection or mutation – so that the immune system no longer recognizes them as ‘self’. In other cases, autoimmunity results from a failure in the complex and delicately balanced mechanisms that regulate the immune system.

      Genetic factors are known to play an important role in some autoimmune disorders. For example, insulin-dependent diabetes mellitus (otherwise known as childhood-onset diabetes) results from the autoimmune destruction of cells in the pancreas, the organ responsible for producing the blood sugar-regulating hormone insulin. Diabetics have a genetic predisposition to develop the disease. But environmental factors, including stress, also play their part in determining whether a genetically predisposed individual actually develops the disease. Even if one of a pair of genetically identical twins has diabetes there is still a 50–70 per cent chance that the other twin will not get the disease. Chronic psychological stress significantly increases the risk that those who are genetically predisposed will advance to full-blown diabetes.

      Females are much more susceptible than males to a number of autoimmune diseases, and this is true both in humans and other species. Women are three times more likely than men to suffer rheumatoid arthritis, six times more likely to develop autoimmune thyroiditis, and at least ten times more likely to suffer from systemic lupus erythematosus. This sex difference in disease susceptibility is at least partly a consequence of hormonal differences; male and female sex hormones, such as testosterone, progesterone and oestradiol, influence the immune system in various ways.

      Autoimmune diseases result from excessive or inappropriate immune activity. Accordingly, they may be ameliorated by drugs that suppress the immune system – the opposite of what happens in normal infectious diseases. This is why doctors use immune-suppressive drugs to treat autoimmune diseases.

MEASURING IMMUNITY

      A prerequisite for any research into the relationships between mind, immunity and health is the ability to measure how well (or how badly) the immune system is doing its job. But as we know all too well, the immune system is not a simple entity whose activity can be readily described by a single index, any more than the multifaceted complexities of human intelligence can be fully encapsulated in a single number called IQ. So how do scientists measure immunity?

      The functioning of a highly complex system such as a national economy can be quantified, albeit rather crudely, but only by using a diverse range of measures to describe various aspects of the system. Thus economists have come up with a variety of indices for quantifying economic activity, including the gross domestic product and gross national product; the headline and underlying rates of inflation; assorted interest rates; indices of money supply; the trade balance between imports and exports; exchange rates against foreign currencies; various measures of unemployment (most of them controversial); foreign debt; government borrowing; gold and currency reserves; measures of consumer spending, and so on. Each measure says something different about the economy and no single one gives a complete picture of the whole system.

      Your immune system is far more complex than any national economy. Therefore if it is simplistic to talk of a national economy going up or down, it is even more simplistic to talk of an immune system going up or down. Fortunately immunologists, like economists, have at their disposal a number of informative ways of assessing certain basic aspects of this complex system.

      Much of the research on how psychological and emotional factors affect immune function has focused on the white blood cells, primarily because they are the easiest to get at. Studying what is going on inside the thymus or spleen is difficult and intrusive, but taking a blood sample is quick and painless. Modern techniques also allow scientists to measure antibodies in saliva, one of the most readily accessible bodily fluids.

      Scientists assess the immune function of white blood cells in two basic ways: by counting particular types of cells to see how many there are circulating in the bloodstream, or by measuring how well those cells perform their immunological functions.

      The simplest approach is to count the total number of white blood cells in a given volume of blood, although this produces a crude index of limited use. An improvement on this is to count a specific type of white blood cell, such as T-lymphocytes or natural killer cells, or to gauge the amount of a particular class of antibody. But the biological and medical meaning of these measures is not always clear. A drop in the number of circulating lymphocytes may simply mean that lymphocytes have been shunted elsewhere in the body, probably into the spleen. At any one time only about 10 per cent of all lymphocytes are circulating in the bloodstream; the rest are stored in lymphoid organs such as the spleen and lymph nodes. Further information is provided by calculating the relative proportions of various cells, such as the ratio of helper T-cells to suppressor T-cells, since these proportions must be about right for the immune system to function properly.

      The second, more revealing, approach relies on what are known as functional measures. These assess how well the various cells are performing their immunological functions. Research into the relationships between psychological factors and immunity has tended to rely on two particular functional measures of immune activity: the responsiveness of lymphocytes to stimulation and the cell-killing activity of natural killer cells. Because these two measures are so central to research in this field they warrant closer inspection.

      As we have already seen, lymphocytes will respond to antigens by proliferating or producing multiple copies of themselves. This response can also be triggered in a non-specific way (that is, in the absence of the specific antigen) by chemicals known as mitogens. Lymphocyte function can thus be measured in a test tube simply by introducing mitogens to the sample.⁷ Responsive lymphocytes will proliferate wildly when stimulated with the appropriate mitogen (a Good Thing), while unresponsive lymphocytes will be sluggish (a Bad Thing). Assume this is what I mean when henceforth I refer to lymphocyte responsiveness.

      The prime function of natural killer cells is to destroy certain types of virus-infected cells and cancer cells. The obvious method of assessment in this case is to see how effective they are at destroying suitable target cells in the test tube. This is what is meant by natural killer cell activity, the second workhorse measure of immune function that will crop up repeatedly in subsequent chapters.⁸

      It has to be admitted that lymphocyte responsiveness, natural killer cell activity and most of the other measures commonly used to assess immune function are flawed, allowing only a partial glimpse into the complexities of the immune system. Scientists can no more encapsulate the state of an individual’s immune system in a few numbers than they can sum up that person’s behaviour or emotional state with a few numbers.

      It is a curious and regrettable fact that scientists tend to place greater faith in measurements of reassuringly physical entities, like the responsiveness of lymphocytes or the activity of natural killer cells, than they do in measurements of supposedly abstract entities like thoughts, emotions or behaviour. There is no rational basis for this prejudice, which is yet another reflection of our propensity to regard mind and body as two fundamentally