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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Thank you for listening