Psychoneuroimmunology

Epi 6181, University of OttawaMonika Goetz

Monday March 9th, 2015

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Outline

Defining PNI

Defining stress

The Nervous System

The Immune System

PNI Response

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Defining PNIPsychoneuroimmunology: aka PNI, the study of the

relationship between the nervous system and the immune system

Nervous system: the network of nerve cells and fibers that transmits nerve impulses between parts of the body

Immune system: the network of immune cells that protect the body through immune responses

Stress causes the nervous system to activate the immune system

The two systems communicate via the endocrine system (hormones)

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Defining Stress“Nonspecific response of the body to any

demand made upon it” (Hans Selye, 1979)

1. Sympathetic NS 2. HPA Axis

“Events that are interpreted as threatening to an individual and which elicit physiological and behavioural responses” (Bruce McEwen, 2000)

Alarm• High energy

Resistance• Alertness and healing

Exhaustion• Low energy

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The Nervous SystemNervous

System (NS)

Central NS

Brain Spinal Cord

Peripheral NS

Autonomic NS

Sympathetic NS

Parasympathetic NS

Somatic NS

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1. Sympathetic NS (SNS): “Fight or Flight”

Brain sends signals to the sympathetic ganglion in the spinal cord

Presynaptic neurons secrete acetylcholine (ACh), which binds to postsynaptic neurons, signaling release of catecholamines (epinephrine, norepinephrine)

Innervation found in blood vessels, liver, kidney, intestines, lung, heart, and brain

Results in pupil dilation, increased sweating, blood sugar, heart rate, and blood pressure

If stressor is prolonged, adrenal gland also secretes epinephrine and norepinephrine

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Parasympathetic NS (PNS):

“Rest and Digest”

Innervation in postrema (part of medulla in the brainstem, controls vomiting) which connects to HPA axis and activates sympathetic NS

Operates via vagus nerve, partially reponsible for control of the heart and digestive system

Main neurotransmitter is acetylcholine (ACh)

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2. The HPA Axis: Chronic Stress

CRF: corticotrophin-releasing factor (or hormone)

ACTH: adrenocorticotropic hormone

Cortisol: “stress hormone” elevates blood sugar and boosts metabolism

Hypothalamus: signals pituitary gland

Pituitary gland: endocrine gland

(secretes hormones)

Adrenal cortex: endocrine gland

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The Brain and the HPA Axis

Hippocampus: critical for memory storage

Amygdala: important for emotion

processing

Paraventricular nucleus: a part of the

hypothalamus

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Key Stress MessengersCatecholamines

Epinephrine (E), norepinephrine (NE)

Produced by adrenal gland as well as postsynaptic sympathetic neurons

Act on adrenic receptors

Response to acute stressors

Promotes production of pro-inflammatory cytokines

Glucocorticoids

Cortisol

Produced by adrenal gland in response to ACTH (part of HPA Axis)

Act on glucocorticoid receptors

For adaptive purposes

Regulates production of pro-inflammatory cytokines

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The Immune SystemInnate Immunity

Rapid response (hours)

Reacts the same way for every kind of infection

Uses physical and chemical barriers

Phagocytic cells, blood proteins

Adaptive Immunity

Slower response (days)

Increases strength and specificity with each repeated infection

Uses white blood cells, macrophage cells, antibodies

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Immune ResponseCertain immune cells produce cytokines: small

proteins that combat infections and communicate with brain

Trigger hypothalamus to produce fever, sleepiness, lack of energy, lack of appetite, and lack of sex drive

Ways of conserving energy, immune response is very energy consumptive

Inflammation result of response, good for drawing immune cells to site of infection but can be harmful if chronic or systemic

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Receptor-Mediated Immune Response

Adrenergic receptors (E and NE, SNS) Expressed in white blood cells Pro-inflammatory (alertness and healing)

ACh receptors (PNS) Expressed in some immune cells Anti-inflammatory cytokine production

CRH receptors (HPA Axis) Expressed in immune cells Pro-inflammatory cytokines

Glucocorticoid receptors (Cortisol, HPA Axis) Expressed in immune cells Regulates inflammatory response by acting as a negative

regulator

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Chronic StressSymptoms of illness often from own body fighting

off infection, body perceives “stress” as an infection

Overstimulation of HPA Axis shown to be immunosuppressive

Brief release of cortisol improves memory, attention, and immune response – good

Prolonged release impairs memory and immune activity – not good

Exhaustion – energetically expensive

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ConclusionsTemporary or acute stress can be important in

driving our behaviours and contributing to our survival (SNS, fight or flight)

Chronic stress can lead to exhaustion and immunosuppression, threatening our survival (HPA Axis)

Stress-related inflammation may be a significant contributor to inflammatory diseases and risk factor for other health problems

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PNI

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Stress ManagementPharmaceutical agents

Sleep medication Antidepressants Drugs that reduce inflammation and oxidative stress

Physical activity Increases neurotrophin (neuron growth factor) expression

in cortex and hippocampus Increases neurogenesis in dendate gyrus of hippocampus

Social support

Eliminating stress!

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References1. Black, Paul H., 2002. “Stress and the inflammatory response: A review of neurogenic

inflammation”, Brain, Behavior, and Immunity 16, 622–653

2. Hamer, M., Endrighi, R., and L. Poole, 2012. “Physical Activity, Stress Reduction, and Mood: Insight into Immunological Mechanisms” Psychoneuroimmunology: Methods and Protocols, Methods in Molecular Biology, vol. 934

3. Jones, Harlan P., 2012. “Immune Cells Listen to What Stress is Saying: Neuroendocrine Receptors Orchestrate Immune Function”, Psychoneuroimmunology: Methods and Protocols, Methods in Molecular Biology, vol. 934

4. Kalat, James W., 2009. “Biological Psychology 10th Edition”, Wadsworth, Cengage Learning

5. McEwen, Bruce S., 2007. “Physiology and Neurobology of Stress and Adaptation: Central Role of the Brain” Physiol Rev 87: 873–904

6. McCorry, Laurie K., 2007. ”Teacher’s Topics: Physiology of the Autonomic Nervous System” American Journal of Pharmaceutical Education; 71 (4) Article 78

7. Smith, Sean M., and Wylie W.. Vale, 2006. ”The role of the hypothalamic-pituitary-adrenal axis in the neuroendocrine reponses to stress”, Dialogues Clin Neurosci. 2006;8:383-395.

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