Psychoneuroimmunology

1
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

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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.

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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 80s.
• 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.

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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.

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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.

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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).

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Tests of Immune function

• (3) Functional tests
• In vivo tests - asses the function of cells in
  living organisms
• Quantification of antibodies (Ab) to herpes
  viruses
• 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.

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Tests of Immune function

• In vivo tests - Continued
• Delayed-type hypersensitivity response
• 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.
• Competence of the humoral arm of the immune
  system
• 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.

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Immunity and disease

• other pathways by which psychological states
  could have impact on the immune system and
  susceptibility to disease.

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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.

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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.

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Stress

• Chronic stress
• Caregivers of Alzheimers 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.

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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.

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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.

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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.