Lecture 20 - Psychoneuroimmunology Flashcards
What are the two connections of the CNS to the immune system?
What is released in response to stress? (6)
Is the response different for physical vs. Psychological?
- Direct (neuronal)
- Indirect (neuroendocrine)
- Catecholamines
- epinephrine (EPI)
- norepinephrine (NE)
- Gamma amino benzoic (GABA)
- Acetylcholine (ACH)
- Serotonin
RESPONSE IS SAME FOR BOTH
What organs are involved in the direct response to stress? (3)
- Primary lymphoid
- Secondary lymphoid
- Adrenal Medulla
Indirect –> CNS communicates hormonally with immune system
Where is the stress response initiated by GABA, ACh, Serotonin, etc?
What is released into portal blood system of the pituitary?
What is then released from anterior pituitary?
What is then released form the adrenal cortex?
- PVN of hypothalamus
- CRH is released
- ACTH
- Cortisol release from Adrenal Cortex
Peripheral Nerves can also stimulate Primary and Secondary Lymphoid Tissue:
1.Bone marrow is primarily stimulated by ______ fibers
(secreting norepinephrine)
- Thymus is stimulated by what 3 fibers?
- The spleen is strongly _______
- Lymph nodes received _________ and _______ stimulation.
- noradrenergic
- Thymus:
- noradrenergic
- cholinergic (secreting ACH)
- peptidergic fibers (secreting neuropeptides) - noradrenergic
- noradrenergic, peptidergic
Adrenal medulla is innervated directly by what fibers?
When stimulated, hypothalamus activates the ______ nerves, which in turn trigger _____ cells of the adrenal medulla to secrete catecholamines.
T and B lymphocytes, neutrophils, mononuclear cells, and NK cells posses receptors for what 3 things?
- Sympathetic nerve
- Splanchnic
- CHROMAFFIN
a) Catecholamines
b) Ach
c) Neuropeptides
What is the effect of the following on the immune system (in regards to T/B cell function and NK cell activity, cytokine production, leukocyte mobilization):
- Cortisol (3)
- Epinephrine/Ne (2)
- Beta Endorphins and Enkephalins (2)
1. Cortisol: anti-inflammatory **reduces: 1)cytokine production 2)T and B cell reactivity 3) NK cell activity
- Epinephrine and NE:
a) increase leukocyte mobilization
b) Increase NK cell activity
- Beta endorphins and Enkephalins:
increase: - T cell reactivity
- NK cell activity
Where are NE and E released from?
What do endorphins originate from? Function?
Enkephalins are produced in what 3 areas?
What do endorphins and enkephalins increase?
- Adrenal medulla
- Endorphins: POMC synthesized in pituitary after CRH stimulation
- analgesia and happiness - Brain, pituitary, adrenal gland
- analgesia (bind same opiod receptors as endorphins) - Increase T cell reactivity and NK cell activity
(endorphins = hormones, enkephalins = NTs)
What are the 2 types of stress?
- Acute controllable (emotional/mental)
2. Chronic uncontrollable negative stress
taking care of Alzheimer’s patients
What increases in acute stress?
jumping out of a parachute
- increase circulating leukocytes, NK cells **
- CD3
CD4
CD8
CD16 (monocytes)
CD56 (NK) - Increased catecholamine levels
(HR, cortisol, NE and E)
What is the increase in NK cell activity with acute stress like parachute jumping, associated with?
What happens one hour after parachute jumping to the levels of mononuclear cell populations? Why?
INCREASED circulating NK cells
Levels decrease because the cells have localized to regional lymph nodes
–> mimicked by the administration of Catecholamines and Cortisol
Immediate leukocyte mobilization in the circulation is due to what?
Redistribution to the lymph nodes is a consequence of what?
Catecholamines (NE and E)
- Under influence of catecholamines and cortisol, leukocytes redistribute to the lymph nodes where they can respond quickly to antigenic challenge
Redistribution to the lymph nodes is a consequence of what?
Hormonal modification of adhesion molecules on the surface of leukocytes (CD11a) and ICAM-1 on endothelial cells
- levels return to normal after the stressful event
What two factors are increased by NE/E and facilitate mobilization of leukocytes to the lymph nodes?
- CD11 a on leukocytes
- ICAM-1 on endothelium
- squeeze through HIGH Endothelial Venues
What is the acute affect of stress (cortisol in low dose of 5mg/kg) on DHT response
vs. Chronic stressed (high cortisol at 40mg/kg)?
What about chronic stress over a period of days?
DICHOTOMOUS EFFECT (test)
ACUTE:
INCREASE delayed hypersensitivity to tuberculin
CHRONIC:
-decreased response
NO RESPONSE after a period of days
What are the results of chronic stress as seen in the experiment with caregivers for Alzheimer’s patients? (2)
What about the high stress group in particular?
- Decreased cytokine production (IL-1).
- Decreased antibody production.
HIGH STRESS:
1. Decreased cytokine response to influenza vaccine (IL-2)
- Increase in the number of colds
What cytokines are produced as a consequence of an on-going immune or inflammatory process?
Cytokines change the ____ of nerve cells in the CNS and influence the secretion of neuroendocrine factors, especially______
IL-1
TNF
IL-6
- Firing frequency
- ACTH production
Leukocytes are capable of neuropeptide and neurotransmitter production of what 3 things (specifically)?
- ACTH
- Beta- endorphins
- Enkephalins
- endorphins and enkephalins may produce an analgesic effect in infected tissue
What is the result of the production of IL -1,6, and TNF?
What are the 2 ways that cytokines produce this behavior?
BEHAVIOR –> “sickness behavior”
fever, headache, muscle and joint pain diminished appetite, lethargy.
- Circulation
- Afferent neurons (vagal)
- alert brain to infection or injury
Where do cytokines cross the BBB via the circulation?
What is produced after the neural system is activated by cytokines?
Circumventricular Organs (CVO)
- and begin to express receptors for IL-1, TNF, and IL-6
PROSTAGLANDINS!!!
What is the result of excessive production of IL-1,6,and TNF?
CNS interacts with the immune system to regulate excessive inflammation via ____ and ____ nerve
systemic inflammation that can result in organ failure and death.
- Efferent vagus
- Splenic nerve
Action potentials transit the splenic nerve releasing __1___, which stimulates the production of __2___ by T lymphocytes (via surface beta 2 adrenergic receptors).
- What does this interact with? What receptors?
- WHERE?
- What is inhibited?
- NE
- ACh
- Interacts with MACROPHAGES (via surface Alpha 7 ACh receptors)
- In the SPLEEN
- inhibts transcription of Il-1,6, and TNF a
What is the controlling mechanism for pro-inflammatory cytokines?
CHOLINERGIC anti-inflammatory pathway
Stress, (fight or flight response) immediately releases what?
What 3 things occur?
Since immune function and fight or flight cannot occur simultaneously, what is SLOWLY released?
This is an adaptive response for short term or long term stressors?
CATECHOLAMINES
- Energy diverted to muscles
- HR increases
- Body is ready for physical action
CORTISOL (maximizes energy for fight or flight)
SHORT - TERM
- Disadvantageous only when stress is chronic.
What is important when considering the stressor? (3)
What does this determine?
- Duration
- Timing
- Nature
DETERMINES the magnitude of the immune response
The result would be enhanced immunological protection from the infectious agent and more rapid healing of the wound
(prepare immune system for impending danger)
