PsychoNeuroImmunology
(and other stress related diseases)


Overview
The importance of PsychoNeuroImmunology

An introduction to the immune system

How immune-system Function is measured in Psychoneuroimmunology research
           Counting cells
           Function test
           Methodological issues

Research on Stress & Social Support with PNI, Cancer, HIV & CHD 
           The effect of stress on immune functioning
           
The effect of mood on  immune functioning
           Personality and Cancer
           Social Support and immune functioning

Proposed biological mechanisms to explain Psychoneuroimmunology

Future directions for Psychoneuroimmunology research


Psychoneuroimmunology
(and other stress related diseases)

Key Considerations:
Review the psychological state, health relationship, function of the immune system, the methodological issues for researchers, evidence, and possible mechanisms.


The Importance of Psychoneuroimmunology

The relationship between immunocompetence, or one's functional efficacy of immune response, and  psychological experiences and outcomes is central to this topic. 

 Psychoneuroimmunology (PNI)  involves interest in the biological mechanisms responsible to specific and general responses of the bio-psycho-social agent. This field examines both possible ways to stave off or moderate stress along with assessments of immune system functioning or state. 

As we have already considered, the field of health psychology places a great deal of stake in explanation and prediction of the relationship between mental and physiological states.  Psychological tools for 'measuring' psychological states and traits is related to physiological and behavioural measures of  immune activity and health promoting behaviours. 


            Methodological Issues

Poole et al. (2015)
Consideration of time frame is important in the study of PNI,
where both acute or short-term stressors as well as
chronic or long term effects are considered. 

As such short term changes in the immune system function
are measured in conjunction with short term stressors
(e.g., daily hassles, sudden events). 

Small fluctuations in the immune system function may be measured
 over the average day as well as over an period of months. 

Where such longer term stressors are considered
(e.g., trait anxiety, workplace stress, marital problem,
financial challenges, chronic illness or terror). 

As pointed out in Selye's research on stress, longer term
stressors lead to the GAS, including the reactive resistance
of parallel biological systems.  Because of the multiplicity of responses,
the singular effects of measurements of any specific response
 will be difficult to determine. 


Statistical issues arise when considering multiple measures or  variables.

Some of these are positive and some are negative.  The positive ones are that, generally speaking, more (relevant) variables means better prediction of the outcome or target variable.  

Multi-variable Methods typically used here are correlation, multiple regression, factor-analytical, or path analysis.

Factorial designs are also used under experimental treatments. Here the so called main and interaction effects are examined. 

The downfall of making multiple predictions in a given study is:
that the more statistical relationships examined, the greater
the likelihood that an erroneous relationship will be established.

In other words, each relationship between variables is examined
 and a decision about whether or not it is thought to be real is made
 based upon the probability that it will be true,
given known parameters, 95 times out of 100.  

Statistical significance is this  level of 05% chance of error,
sometimes placed more conservatively at 01% chance of error.
While this level may be achieved there may or may not be a
clinically significant
difference in outcome or change of symptoms or state. 

Field research offers the possibility of examining physiological
 responses to real stressors in natural situations. The challenges
here are that cohort and contamination of data by extraneous variables
 may be more likely.  These are expected in cross-sectional
studies and longitudinal studies, respectively. 

Laboratory research offers a greater degree of confidence
in making 'cause and effect' attributions about the variables
through controlled experimental studies.

However, the lack of natural situations may alter the response
 of the individual against their exposure to an known antigen.  

Limitations on researchers ability to expose healthy people to
pathogens
is an ethical issue that leads to the use of
quasi-experimental
or natural experimental studies
(e.g., natural prevalence, disaster response).


An Introduction to the Immune System

Antigens are microorganisms that are foreign to the human body
and may cause disease (e.g, viruses, bacterial, fungi, parasites). you tube

Pathogensare referred to as pathogens when they potentially cause death. 

Infections or diseases may be localized,
or situated in only one area of the body which may also
 be focalized where they send toxins out throughout the body.

They may also be systemic, affecting the entire body.
Internal systems of attack on these antigens take various forms,
 primarily through the development of specific and acquired immunity. 

Lymphocytes are a mainstay in the immune system,
including B-cells, T-cells and NK-cells (natural kills). utube

Immune system memory maintains small numbers of "B memory cells"
 that enable the body to create immunoglobulins and antibodies
when re-exposed to an antigen.

Taking about 5 days to produce a strong response the B-lymphocytes
 produce antibodies that are specific to that antigen (e.g., water parasites).  

The action of B-lymphocytes to produce antibodies is aided through
helper T-cells (CD4) which produce cytokines called interleukins
(e.g., leukin-1, interleukins-2).  Suppressor T-cells (CD8)
work as "off switches" for the immune system.  

Tolerance to one's own cells usually occurs where antibodies
 are not produced against one's own cells,
except in auto-immune disorders (e.g., arthritis). 

Nonspecific immunity operates through the general response
 of swelling and phagocytosis. 


How Immune-System Function is Measured in PNI Research

Counting cells is the primary method used for dependent variables in PNI studies.
 As such, one's  immunocompetence is measured by one or more cell type counts. 

An enumerative assay is performed to  count levels of B-cells, T-cells and NK-cells
to determine a minimal number or varied balance among these white blood cells. 

Function tests are done to asses immunocompetence in action, across time. 
These are done in vitro ( in the test tube) as well as in vivo (in the human body)
for a specified period of time. 

In vitro studies will involve the addition of a mitogen (agent to increase activity) to a blood sample (e.g., Con A, PHA, PWM), showing greater or lesser responses under various psychological states or conditions (e.g, confrontation). 

A second common approach makes use of the NK cell cytotoxic assay that shows activity of NK cells. Others like the herpesvirus or Epstein-Barr virus counts may also be used to assess immune functioning. 

Specific Ab responses may also be made at the infection or injection site. 

 


Research on Stress, Mood, Social Support & Personality
 with PNI, Cancer & HIV


In various studies, the biological has been examined against a host of psychological and social factors that have shown some impact on immune functioning. Some such variable examined include: personality traits, psychological states or moods, acute and chronic stress,  social support and coping styles. 

The Effect of Stress on Immune Functioning

Immunosuppression is often observed in association with experiences of stress. Lazarus & Folkman (1984) define stress as "an aversive condition in which the demands of a situation are perceived to be greater than our ability to cope with them (Poole at al., p. 65) .

Responses may be observed in as few a five minutes or as long as 5 days.  Some dispositional differences in physiological reactivity have been cited by Poole et al with respect to cortisol levels and URIs (upper respiratory infections). 

Boscarino (1997) reports that PTSD Viet Nam vets were more likely to have circulatory, metabolic digestive or muscular ailments. They were 2.4 times more likely to have these medical problems, effects maintained at 20 year follow-up. 

Poole et al. also cite studies on Three Mile Island residents, hurricane Andrew survivors, Gulf War vets, earthquake victims and men and women going through divorce. Here they point out that:

        Three-Mile residences had elevated herpes virus levels, 
        indicating compromised immunity after 10 years.

        Gulf war vets had clusters of symptoms associated with interleukin-1 
        apparently maintained partially through classical conditioning.

        Divorced or separated women had immune compromise on a variety of measures
         while men who initiated the break-up had better immune function than did those 
         whose partners initiated the split.

    Stress & URI

Studies have shown that colds, flu and bronchitis are more likely among those who have recently undergone traumatic life events or prolonged daily hassles.

Poole et al. report filed studies that subjective self-report measures are commonly used to measure stress in conjunction with other characteristics like situation and dispositional anxiety.

La Via et al (1996) reported that people with generalized anxiety disorder  had higher stress-intrusion scores (in vitro lymphocyte activity) as well as ( 3 times) more URI related sick days taken.

One of the challenges of field studies is the lack of control over amount or level  of antigen exposure.  In controlled experiments on URIs, antigens are often administered through nasal sprays in viral challenge studies.

On the other hand, the impactof  intact social support systems can be examined through field studies, where it has been found that larger and more diverse social support systems appear to lessen the likelihood of cold infections (Cohen et al., 1997).

Other studies cited by Poole et al. have indicated that positive life events can have a negative impact on immune functioning. 

   Stress & Autoimmune Disease
Autoimmune diseases such as rheumatoid arthritis are exacerbated by stress. They occur as a result of the body failing to maintain tolerance.

    Stress & Cancer

Stress is expected to be brought on by cancer as well as it having an effect on the prognosis of cancer. 

Spiegel et al (1988) have shown that experience of major life events is positively correlated with onset of cancer. Geyer (1991) also has shown a greater likelihood of malignancy for women experiencing major life events.

Poole et al also indicate that other studies have not demonstrated such results. While it is difficult to determine the exact relationship between stress and cancer it appears that it can potentiate cancerous growth even if it may not initiate it.  


Sergerstrom & Miller (2004) did a Meta-Analytic study of 300 studies across 30 years of study on psychological stress and the immune system found that acute stress was associate with an adaptive upregulation of immune functioning along with some specific down regulation. Chronic stresses, however were associated with cellular and humoural functioning of the immune system.


The Effect of Mood on Immune Functioning

Research on stress suggests that elevated emotional arousal is associated with compromised  immune function, while other studies have shown that depression or diminished arousal is also associated with immune compromise.

Irwin et al (1987) found that women who had higher depression scores (having lost husband to cancer) also had most compromised immune function.

Schleifer (1983) also found pre-bereavement males had better lymphocyte proliferation than men who had recently lost their wives to cancer.

Another study (Glaser et al, 2000) had found that the stress of caring for a husband  with dementia lead to more immuno-suppression than those women who had already lost their husbands

Herrmann et al. (1998) also indicate that depression at the time of admittance is correlated with mortality in a longitudinal study.

Levav et al (2003) report increased cancer incidence following bereavement due to accident or war.

Marks et al. (2015, p. 319) contest those results in the Copenhagen heart study by Nielsen et al. (2005) indicating women who expereinced higher levels of stress were less likely to be diagnosed with breast cancer.


    Negative Mood and URI

Cohen at al (1995) examined negative state vs. trait mood, finding that state or transient negative affect could predict the presence of symptoms upon a viral challenge test. 


Social Support and Immune Functioning

Social support, or the degree to which one has interpersonal resources to help in coping and providing health has been examined along with PNI & HIV 

Miyazaki et al. (2003) report a beneficial relationship between perceived social support and immune function across CD and NK functioning.

Lee et al. (2001) report benefits from Korean Qi-therapy (Qi-Gong) on psychoneuroimmunological on anxiety; mood; cortisol; melatonin; neutrophil function; NK cells; natural killer cells.


Proposed biological mechanisms

Poole et al propose four possible causes: endocrine system, sympathetic nervous system, immune system, and behaviour.

Hypothalamus and the sympathetic nervous system stimulate the immune system.

Reactivity hypothesis suggests that those whose sympathetic system is  more reactive will also have a greater immunosuppression in the face of stress and the GAS.

It appears that we are evolutionarily prepared to respond to immediate stressors “flight or fight” but less so to fighting off slower acting antigens.


Immune system function has been associated with a number of chronic conditions including: cancer, hiv-aids, arthritis, mutiple sclerosis, lupis and many other conditions and diseases whic often lead to death