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NROC61 - Eskandari article notes

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Le Boutillier

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Eskandari - Neural-Immune Interactions in Health and Disease
-immune system and CNS communicate
-CNS signals immune system via hormonal & neuronal pathways and immune sysem sig
nals CNS through similar
routes via immune mediators & cytokines
-primary hormonal pathway by which CNS regulates immune system is hypothalamic-p
ituitary-adrenal (HPA) axis,
through hormones of neuroendocrine stress response
-sympathetic NS regulates immune system function primarily via adrenergic NTs re
leased through neural routes
-neuroendocrine regulaltion of immune function is essential for survival during
stress/infection and to
modulate immune responses in inflammatory disease
-glucocorticoids are main effector endpoint of neuroendocrine response system
-numerous routes by which immune, endocrine, and CNS communicate
-CNS regulates immune system locally at sites of inflammation, regionally in imm
une organs, and systemically
through hormonal routes
-immune system regulates CNS -ex: cytokines produced at an inflammatory site sig
nal brain to produce symptoms
of sickness-related behaviour and fever
-interruptions/perturbations of these connective pathways can alter severity, co
urse, and susceptibility
and resistance to diseases
-several brain centers involved in immune regulation
-2 major mechs through which CNS regulates immune system
1) the hormonal stress response through production of glucocorticoids
2) the autonomic NS w/ release of NE
-hormonal stress response is mainly regulated via HPA axis
-corticotropin-releasing hormone (CRH) is secreted from paraventricular nucleus
of hypothalamus into
hypophyseal portal blood supply
-CRH & arginine vasopressin stimulates expression and release of adrenocorticotr
opin (ACTH) from anterior
pituitary gland
-ACTH circulates through blood stream to adrenal glands, where it induces expres
sion and release of
-HPA axis is subject to regulation from w/i CNS and from periphery
-CRH is positively regulated by serotonergic, cholinergic, and catecholaminergic
-glucocorticoids negatively feed back to suppress HPA axis at both hypothalamic
and pituitary levels
-other neuropeptides such as gamma-aminobutyric acid/benzodiazepines (GABA/BZD)
inhibit serotonin-induced
CRH secretion
-glucocorticoids regulate a wide variety of immune cell expression and functions
-glucocorticoids modulate cytokine expression, adhesion molecular expression, im
mune cell trafficking,
immune cell maturation and differentiation, expression of chemoattractants and c
ell migration, and production
of inflammatory mediators and other inflammatory molecules
-at physiologic conc, glucocorticoids are not totally immunosuppressive, but spe
cifically regulate immune
-at lower concs, glucocorticoids cause a shift in immune responses from a proinf
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