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Psychoneuroimmunology
Margot Shields
December 2006
Core References:
Cohen S, Herbert TB. Health psychology: Psychological
factors and physical disease from the perspective of human
psychoneuroimmunology. Annual Review of Psychology
1996; 47: 113-42.
Kiecolt-Glaser J, McGuire L, Robles TF, Glaser R.
Psychoneuroimmunology: Psychological influences on the
immune function and health. Journal of Consulting and
Clinical Psychology 2002; 70: 537-47
Psychoneuroimmunology
• Definition - the study of interrelations between the central
nervous system and the immune system.
• Interrelations → association is bidirectional.
• Animal studies advanced the understanding of PNI
• showed evidence for nerves connecting the CNS and the
immune system
• existence if chemicals called cytokines that are produced by the
immune system, cross the blood-brain barrier and alter how the
CNS functions.
Psychoneuroimmunology
•
Term first coined in 1964 by George F. Solomon (suggested that personality
factors and emotions played a role in autoimmune disease).
•
There were only a handful of human studies prior to the 80’s.
•
The main focus of PNI human studies is to see if psychological factors
affect states of immunity, and whether or not psychologically induced
changes in immunity alter susceptibility to immune system-mediated
disease.
•
1981 book by Ader, Felten and Cohen called Psychoneuroimmunology
reviewed the role of the CNS in the relationship between behaviour and the
immune system.
•
In 2001 the third edition of the book used two volumes to cover the growing
number of research contributions.
Tests of Immune Function
• Most immune system cells are located in bone marrow, thymus,
lymph node, spleen, tonsils and appendix.
• Because there is no easy way to access the cells of these organs,
PNI work with humans is primarily limited to the study of immune
components in circulating peripheral blood.
• Circulating blood transports immune components between the
organs of the immune system and sites of inflammation.
• Components of the immune system that circulate in the blood (e.g.,
some types of white blood cells and antibodies) work to combat
against invading antigens.
Tests of Immune Function
(1) Enumerative tests
• Enumerative tests count the number or percentages of different
kinds of white blood cells in the peripheral blood (neutrophils,
monocytes and lymphocytes).
• The body cannot respond adequately to invading antigens without a
minimum number of each type of immune cell. An optimum
response requires a proper balance of the various types of cells.
• However, changes found in the PNI literature are usually quite small
and whether these changes indicate compromised immune function
is theoretically unclear.
Tests of Immune Function
(2) Functional tests
In vitro tests
• Cells are removed from the body and their function is studied in the lab.
•
Lymphocyte proliferation
 test of cellular immunity that examines how effectively stimulated lymphocytes
divide.
 It is assumed greater proliferation indicates more effective cell function.
 Lymphocytes are the key cells controlling the immune response.
 The ability of these cells to proliferate rapidly in the fact of an antigenic challenge
is essential to an adequate response.
•
NK (natural killer) cell cytotoxic activity test
 used to determine how effectively NK cells kill transformed cells
 NK cells can be thought of as serving a surveillance function (NK natural killer
cells).
Tests of Immune function
(3) Functional tests
In vivo tests - asses the function of cells in living organisms
1. Quantification of antibodies (Ab) to herpes viruses
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used to indirectly assess cellular immune competence.
almost everyone has been exposed to common herpes viruses.
these viruses differ from most other known viruses in that after
exposure, they are present in the body all the time, although often in
latent states.
when the immune system is suppressed, the latent virus replicates.
Ab is produced in response to the herpes viral replication and the
amount of Ab produced fluctuates in relation to the amount of the virus
produced.
therefore higher levels of herpes virus Ab are interpreted as indirect
evidence of compromised cellular immune function.
Tests of Immune function
In vivo tests - Continued
2. Delayed-type hypersensitivity response
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a more direct test of cellular immunity.
small amounts of an antigen are introduced by injection into the skin.
a hypersensitivity response is one in which swelling and redness occurs at the
site of injection.
inflammation is expected in response to the antigens and the larger the
inflammation, the more competent the cellular immune system is assumed to be.
3. Competence of the humoral arm of the immune system
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assessed by measuring the amount of Ab produced in response to inoculation by
an antigen.
the more Ab produced in response to the antigen the more competent the
humoral system is assumed to be.
can be measured in the blood, saliva or nasal discharge.
Immunity and disease
• other pathways by which psychological states could have impact
on the immune system and susceptibility to disease.
Stress
Laboratory studies
• Assess the effects of acute stressors (5-20 minutes) on immune
response.
• Associated with declines in the functional aspects of immunity.
• Immune changes in both cell numbers and functions occur as soon
as 5 minutes after the onset of a stressor.
• Most immune indicators return to baseline measures by one hour
following cessation of the stressor, but there is some evidence that
NK activity remains depressed for as long as 48 hours.
• High SNS activation in face of acute stressors is associated with
larger immune changes.
Stress
Short-term or acute stressors
• Series of studies looked at the impact of exams on cellular
immune function among medical students.
• During exams, students showed a decrease in the function of a
range of indicators of cellular immune response (decreased NK
activity, lymphocyte proliferation, increases in production of
antibody to herpes virus).
• Immune response to a vaccination (Hep B) was associated with
stress levels. Those experiencing stress were less likely to
produce and antibody after the first vaccination.
• It was also found that exam stress was related to delays in
healing of wounds.
Stress
Chronic stress
• Caregivers of Alzheimer’s patients found to have prolonged
endocrine and immune dysregulation, alterations in vaccine
response and delayed wound healing.
• Immunological changes have been documented for weeks or
months following natural disasters such as hurricanes or
earthquakes. Intrusive thoughts among victims of a hurricane
were found to be associated with lower levels of natural killer
cells (NK).
• Studies were conducted to assess stress effects on residents of
the area surrounding the Three Mile Island nuclear power plant.
Almost 10 years after the accident higher levels of the antibody
to herpes virus was found in TMI residents compared with
marched control group residents.
Affect and personality
• Findings from a daily diary study showed that antibodies
to an orally ingested antigen were higher in saliva on
days when participants reported more positive moods.
• Negative mood has been shown to be associated with
reduced NK cells.
• Among healthy older adults, a sense of coherence
moderated the association between anticipation of
moving and reduced levels of NK cells.
• In a sample of HIV-infected men, situational optimism
about health outcomes was liked to a slower immune
decline, later symptom onset and longer survival.
Interpersonal Relationships
• Among women whose husbands were undergoing cancer treatment,
those reporting higher levels of social support had higher NK cell
activity and higher levels of lymphocyte proliferation.
• Medical students who reported higher levels of social support had a
stronger immune response to a Hep B vaccination.
• People with fewer social ties are more susceptible to respiratory
viruses.
• Spousal caregivers of dementia patients who had lower levels of
social support had the greatest negative changes in the immune
function one year later.
• However, relationships that are negative are also associated with
immune dysregulation. Marital conflict is associated with lower
levels of endocrine and immune function.
Health consequences
• Studies have shown that psychosocial factors are associated with
immune related health outcomes including infectious disease,
cancer, wound healing, autoimmune disease and HIV.
• However there is limited evidence for direct immune pathways for
these links, and the studies have methodological problems.
• Currently PNI studies use a battery of vitro tests and for humans
these tests are limited to peripheral blood samples.
• This likely does not reflect important immunological processes
occurring in lymphoid organs or other regions such as the skin.