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 OrgansLymph 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 responseTonsils• 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 OrgansBone marrow• The site of origin of all types of blood cells• Including all white blood cellsThymus• Located in the upper thoracic cavity• A site of lymphocyte maturation• Secretes thymosin which aids the maturation of T-cellsSpleen• 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 & InfectionAntigens• 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• 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 birthResults 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 ImmunityMemory• 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 ImmunityT-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 ImmunityActivation 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

Humoral ImmunityB-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

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 ResponsePrimary 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 reappearsSecondary 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 processesMeasuring immunocompetenceEnumerative 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• 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 illnessEx: 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., 1993Social 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)• 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