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Friday, 14 January 2011 19:37

Immunological Reactions

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When a human being or an animal is subjected to a psychological stress situation, there is a general response involving psychological as well as somatic (bodily) responses. This is a general alarm response, or general activation or wake-up call, which affects all physiological responses, including the musculoskeletal system, the vegetative system (the autonomic system), the hormones and also the immune system.

Since the 1960s, we have been learning how the brain, and through it, psychological factors, regulates and influences all physiological processes, whether directly or indirectly. Previously it was held that large and essential parts of our physiology were regulated “unconsciously,” or not by brain processes at all. The nerves that regulate the gut, glands and the cardiovascular system were “autonomic”, or independent of the central nervous system (CNS); similarly, the hormones and the immune system were beyond central nervous control. However, the autonomic nervous system is regulated by the limbic structures of the brain, and may be brought under direct instrumental control through classical and instrumental learning procedures. The fact that the central nervous system controls endocrinological processes is also well established.

The last development to undercut the view that the CNS was isolated from many physiological processes was the evolution of psychoimmunology. It has now been demonstrated that the interaction of the brain (and psychological processes), may influence immune processes, either via the endocrine system or by direct innervation of lymphoid tissue. The white blood cells themselves may also be influenced directly by signal molecules from nervous tissue. Depressed lymphocyte function has been demonstrated to follow bereavement (Bartrop et al. 1977), and conditioning of the immune-suppressive response in animals (Cohen et al. 1979) and psychological processes were shown to have effects bearing on animal survival (Riley 1981); these discoveries were milestones in the development of psychoimmunology.

It is now well established that psychological stress produces changes in the level of antibodies in the blood, and in the level of many of the white blood cells. A brief stress period of 30 minutes may produce significant increases in lymphocytes and natural killer (NK) cells. Following more long-lasting stress situations, changes are also found in the other components of the immune system. Changes have been reported in the counts of almost all types of white blood cell and in the levels of immunoglobulins and their complements; the changes also affect important elements of the total immune response and the “immune cascade” as well. These changes are complex and seem to be bidirectional. Both increases and decreases have been reported. The changes seem to depend not only on the stress-inducing situation, but on also what type of coping and defence mechanisms the individual is using to handle this situation. This is particularly clear when the effects of real long-lasting stress situations are studied, for instance those associated with the job or with difficult life situations (“life stressors”). Highly specific relationships between coping and defence styles and several subsets of immune cells (number of lympho-, leuko- and monocytes; total T cells and NK cells) have been described (Olff et al. 1993).

The search for immune parameters as markers for long-lasting, sustained stress has not been all that successful. Since the relationships between immunoglobulins and stress factors have been demonstrated to be so complex, there is, understandably, no simple marker available. Such relationships as have been found are sometimes positive, sometimes negative. As far as psycho-logical profiles are concerned, to some extent the correlation matrix with one and the same psychological battery shows different patterns, varying from one occupational group to another (Endresen et al. 1991). Within each group, the patterns seem stable over long periods of time, up to three years. It is not known whether there are genetic factors that influence the highly specific relationships between coping styles and immune responses; if so, the manifestions of these factors must be highly dependent on interaction with life stressors. Also, it is not known whether it is possible to follow an individual’s stress level over a long period, given that the individual’s coping, defence and immune response style is known. This type of research is being pursued with highly selected personnel, for instance astronauts.

There may be a major flaw in the basic argument that immunoglobulins can be used as valid health risk markers. The original hypothesis was that low levels of circulating immunoglobulins might signal a low resistance and low immune competence. However, low values may not signal low resistance: they may only signal that this particular individual has not been challenged by infectious agents for a while—in fact, they may signal an extraordinary degree of health. The low values sometimes reported from returning astronauts and Antarctic personnel may not be a signal of stress, but only of the low levels of bacterial and viral challenge in the environment they have left.

There are many anecdotes in the clinical literature suggesting that psychological stress or critical life events can have an impact on the course of serious and non-serious illness. In the opinion of some, placebos and “alternative medicine” may exert their effects through psychoimmunological mechanisms. There are claims that reduced (and sometimes increased) immune competence should lead to increased susceptibility to infections in animals and in humans, and to inflammatory states like rheumatoid arthritis as well. It has been demonstrated convincingly that psychological stress affects the immune response to various types of inoculations. Students under examination stress report more symptoms of infectious illness in this period, which coincides with poorer cellular immune control (Glaser et al. 1992). There are also some claims that psychotherapy, in particular cognitive stress-management training, together with physical training, may affect the antibody response to viral infection.

There are also some positive findings with regard to cancer development, but only a few. The controversy over the claimed relationship between personality and cancer susceptibility has not been solved. Replications should be extended to include measures of immune responses to other factors, including lifestyle factors, which may be related to psychology, but the cancer effect may be a direct consequence of the lifestyle.

There is ample evidence that acute stress alters immune functions in human subjects and that chronic stress may also affect these functions. But to what extent are these changes valid and useful indicators of job stress? To what extent are immune changes—if they occur—a real health risk factor? There is no consensus in the field as of the time of this writing (1995).

Sound clinical trials and sound epidemiological research are required to advance in this field. But this type of research requires more funds than are available to the researchers. This work also requires an understanding of the psychology of stress, which is not always available to immunologists, and a profound understanding of how the immune system operates, which is not always available to psychologists.

 

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