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Psychoneuroimmunology
Josée L. Jarry, Ph.D.
Health Psychology, psy333
Department of Psychology
University of Toronto
September 30, 2002
Psychoneuroimmunology - Definition
• The study of the link between psychological states
and the functioning of the immune system
• The link between the two is provided by the
Central Nervous System (CNS)
• Our psychology affects our nervous system, which
in turn affects our immunity
The Immune System
• Designed to monitor the invasion of
microorganisms in the body
• Prevent their spread and growth by eliminating
them
• Prevents infection: the growth of cells associated
with disease
• Also patrols for mutant T-cells
• Made of specific and nonspecific immunity
• It is spread throughout the body in the form of the
lymphatic system
The Lymphatic System
• Consists of lymphatic vessels and lymphatic
organs
• Closely associated with the cardiovascular
system
• Contributes to the body’s immune response
• One-way system that begins with lymphatic
capillaries
• Ends with a return of the lymph to the blood
circulation
Lymphatic Capillaries & Vessels
• Take up fluid that has diffused from and has
not been absorbed by the blood capillaries
• Once fluid has entered the lymphatic
vessels, it is called lymph
• The lymphatic capillaries join to form the
lymphatic vessels
The Lymphoid Organs
Lymph nodes
• Small, round or ovoid structures
• Found at specific points along the lymph vessels
• They clean the lymph
• Antigens leaking into the lymph nodes activate
lymphocytes to mount an immune response
Tonsils
• Located in a ring around the pharynx
• Functions similar to that of lymph nodes
• They are the first to encounter pathogens that enter
the body by the nose or mouth
The Lymphoid Organs
Bone marrow
• The site of origin of all types of blood cells
• Including all white blood cells
Thymus
• Located in the upper thoracic cavity
• A site of lymphocyte maturation
• Secretes thymosin which aids the maturation of T-cells
Spleen
• Upper left region of the abdomen
• Cleans blood, disposes of worn-out blood cells
• Removes bacteria
Lymph
• Called lymph because it contains lymphocytes
• Comes from capillary diffusion & fluids secreted
from the body cells
Lymphocytes
• A type of white blood cell, or leukocyte, found in
lymph
Several types of lymphocytes:
• T-lymphocytes or T-cells
• B-lymphocytes or B-cells
• Natural killer (NK) cells
Antigens & Infection
Antigens
• invading microbes such as bacteria, viruses, parasites, or fungi
• any microorganism that is foreign to our physiology
Pathogens
• antigens that have the potential to cause disease
Localized infection
• the infection is confined to a defined site
Focal infection
• the infection remains localized but sends toxins to other parts of
the body
Systemic infection
• the infection spreads to a number of areas of the body at once
Nonspecific Immunity
Barriers to entry
• Skin secretes oil that kills bacteria on skin
• Upper respiratory tract is lined with ciliated
cells that sweep mucus and trapped particles
up into the throat to be swallowed or
expectorated
• Stomach has acid pH that kills bacteria
• Bacteria in the intestine prevent the
development of pathogens
Nonspecific Immunity (cont’d)
Inflammatory reaction
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Injured tissue releases inflammatory chemicals
Capillaries dilate and become more permeable
This allows proteins and fluids to escape
The rise in temperature increases phagocytosis by
white blood cells
• Results in redness, heat, swelling
• The swelling stimulates free nerve endings, pain
• Blood vessel rupture results in the formation of a
clot that seals the break
Nonspecific Immunity
Natural Killer Cells
• Large granular lymphocytes
• Kill virus-infected cells and tumour cells by
cell to cell contact (next slide)
Specific Immunity
• Protection against particular antigens
• Results from prior exposure to a specific antigen
• Acquired sometime after birth
Results from the action of:
• B lymphocytes or B-cells
– These mature in bone marrow
– Produce antibodies that combine with, and neutralize
antigens
• T lymphocytes or T-cells
– Mature in the thymus gland
– Directly attack antigen-bearing cells
– Regulate the immune response
Specific Immunity
Memory
• Certain immune system cells adapt to an antigen
• Also remember it when they encounter it again
• The immune system cells react to antigens more strongly
when they encounter it again
Specificity
• Specific immune system cells respond to specific antigens
only
Tolerance
• The immune system cells do not react to the body’s own
cells, or “self”
Cell-mediated Immunity
T-lymphocytes (T-cells)
Cytotoxic T-cells
Responsible for cell-mediated immunity
• Destroy specific antigen-bearing cells such as
virus-infected or cancer cells
• Contain perforin molecules
• Form a pore in the membrane of the infected cell
• This allows water and salts to enter
• The cell swells and bursts
Cell-mediated Immunity
Activation of T-cells
• T-cells have receptors
• Macrophages present fragments of broken down
pathogens to T-cells through a HLA antigen
• This sensitizes the T-cell, which acquires specific
receptors on its surface that enables them to recognize
the invader
• The T-cell undergoes clonal expansion
• Cytotoxic T-cells secrete chemicals that kill infected
cells
• Helper T-cells produce cytokines that stimulate Bcells
• Some T-cells become memory T-cells
Humoral Immunity
B-lymphocytes (B-cells)
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Have antigen specific receptors on their surface
Antigen binds with receptor
This stimulates the B-cell to undergo clonal expansion
B-cells divide into plasma cells
Plasma cells mass-produce antibodies
Antibodies circulate, find antigens, bind to them, and mark
them for latter destruction
• The destruction is then carried out by phagocytes
• Some B-cells become memory cells
• Memory cells are responsible for long-term immunity
Humoral Immunity
T-lymphocytes (T-cells)
Helper T-cells (CD4)
• produce substances called interleukins that
speed the division of B-cells and T-cells
Suppressor T-cells (CD8)
• suppress the production of antibodies after
the antigen has been destroyed
Primary & Secondary Immune Response
Primary immune response
• Occurs during the initial exposure to an invader
• Some of the sensitized B-cells and T-cells replicate
but do not go into action
• They become memory lymphocytes
• Memory B- and T-cells become activated only if the
antigen reappears
Secondary immune response
• Occurs during subsequent exposure to antigen
• Memory lymphocytes initiate the immune response
• Direct and indirect attack on the antigen
• Occurs much faster
Immunocompetence (1)
The degree to which an antigen is identified, destroyed, and
disposed of by the immune system processes
Measuring immunocompetence
Enumerative assay
• Consists of counting NK, T-cells, and B-cells.
• Cannot count them directly in bone marrow or the spleen;
therefore count them in the bloodstream and mucous
secretions (often saliva)
Competence is determined by:
• A minimum number of cells for adequate immune
function
• A balance between various cell types
• In general, the higher the count, the better the immune
system functions
Immunocompetence (2)
Functional tests of immunocompetence
• Consists of combining blood sample with a mitogen
• Then measure the production of lymphocytes
Mitogens
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A mitogen stimulates immune cell activity like an antigen
Concanavalin (Con A)
Phytohemagglutinin (PHA)
Pokeweed mitogen (PWM)
For NK cells:
NK cell cytotoxic activity assay
• Cell count after introduction of tumour cells
• Measuring the destruction of the tumour cells or NK cell
lysis
The effects of psychological
factors on the immune system:
Stress, Mood, Personality, and
Social Support
Stress & Immune Functioning (1)
• The nervous system and the immune system interact closely
• The nervous system affects the endocrine system by controlling
the secretion of hormones via the pituitary gland
• It also affects the immune system via the autonomic nervous
system’s action on the thymus gland, the spleen and bone
marrow
• Hormones from the pituitary and adrenal gland modulate the
immune system cells
• Immune cells secrete cytokines and antibodies that fight foreign
invaders
• Cytokines are blood born messengers that regulate the
development of immune cells and also influence the central
nervous system
Stress & Immune Functioning (1)
• Aversive condition in which the demands of a situation are
perceived to be greater than our ability to cope with them
(Lazarus & Folkman, 1984)
Laboratory studies (e.g., Cohen et al. 1991)
• Volunteers are exposed to acute, short-term stressors (e.g.,
making speeches)
• Immune functioning is simultaneously measured
• Shows that it takes as little as five minutes for a stressor to
inhibit the ability of the immune system to respond effectively
• Also exposure to antigens
• Record illness occurrences
Stress & Immune Functioning (2)
Longitudinal studies (e.g., Irwin et al 1987)
• Involves following-up individuals who have
suffered significant stresses at one point over long
period of time after the stressful event or time
period
• Shows that strong stresses lead to significantly
more illness over time
• This effect remains after controlling for factors
that may account for increased illness such as
smoking and substance abuse
• Also shows that the immune system can remain
suppressed in the long term
Stress & Immune Functioning (3)
Field studies
• Involves measuring immune functions following stress
occurring in a natural setting
• Not necessarily long term
Main effect versus interaction
• Stress is often investigated in the spirit of being a main
effect
• In fact, it may interact with other factors to produce
immunosuppression and illness
• Studies have shown that stress combines with factors such
as personality style to affect illness
Ex: Tice and Baumeister (1997)
Mood and Immunity
• Stressful life events often induce significant
negative emotions such sadness, grief and
helplessness
• Stress often brings on depression
• Depression has a strong impact on illness and
death
• Sick people with depression are three times as
likely to die from their illness as those who are not
depressed
• Studies also show that negative mood suppresses
immune function
Mood and Cancer
• Two ways of measuring the impact of mood on cancer
• Both are longitudinal
Begin with cancer-free people
• Measure their mood
• Then monitor for cancer onset
Begin with people who have cancer
• Assess their mood
• Then monitor cancer progression
Cancer mediated by suppressed immunity?
• Depressed people have lower natural killer cell activity
(NKCA) than non-depressed matched people
• Antidepressants increase NKCA
Personality, Social Support, and Immunity
Personality
• A person’s collection of attributes and behavioural
tendencies that are consistent over time and across
a variety of situations
Ex: Esterling et al., 1993
Social support
• Interpersonal resources that help avoid or cope
with difficult times. Can be emotional support or
instrumental support (tangible)
Ex: Theorell et al (1995)
Conditioning and Immunity
Ader & Cohen (1975)
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Study paradigm
Pairing of saccharine with cyclophosphamide (CY)
CY is a drug with immunosuppressive properties
CY is the unconditioned stimulus to suppress immune
functions
Saccharine is the conditioned stimulus
Exposure to antigen
Measurement of antibodies after exposure to saccharine
alone
Reduced production of antibodies after saccharine alone