Psychoneuroimmunology

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Psychoneuroimmunology

• Josée L. Jarry, Ph.D.
• Health Psychology, psy333
• Department of Psychology
• University of Toronto
• September 30, 2002

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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

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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

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The Lymphatic System

• Consists of lymphatic vessels and lymphatic
  organs
• Closely associated with the cardiovascular system
• Contributes to the bodys immune response
• One-way system that begins with lymphatic
  capillaries
• Ends with a return of the lymph to the blood
  circulation

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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

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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

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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

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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

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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

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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

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Nonspecific Immunity (contd)

• Inflammatory reaction
• 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

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Nonspecific Immunity

• Natural Killer Cells
• Large granular lymphocytes
• Kill virus-infected cells and tumour cells by
  cell to cell contact (next slide)

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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

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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
  bodys own cells, or self

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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

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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
  B-cells
• Some T-cells become memory T-cells

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Humoral Immunity

• B-lymphocytes (B-cells)
• 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

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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

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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

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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

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Immunocompetence (2)

• Functional tests of immunocompetence
• Consists of combining blood sample with a mitogen
• Then measure the production of lymphocytes
• Mitogens
• 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

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The effects of psychological factors on the
immune system Stress, Mood, Personality, and
Social Support
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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 systems 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

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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

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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

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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)

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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

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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

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Personality, Social Support, and Immunity

• Personality
• A persons 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)

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Conditioning and Immunity

• Ader Cohen (1975)
• 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

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