Download Immune system

In the Name of God
Neuroimmunoendocrinology
PharmD Class, 25-Ordibehesht-95
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Longest name for a field!
Neuroimmunoendocrinology
PsychoNeuroImmunoEndocrinology!
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Longest English Word!
PsychoNeuroImmunoEndocrinology
+ a bit of Pharmacology
Pneumonoultramicroscopicsilicovolcanoconiosis
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Immune
system
Endocrine
system
Nervous
system
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Immune
system
Endocrine
system
Nervous
system
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Immune
system
Endocrine
system
Nervous
system
Dr F Noorbakhsh, Dept. of Immunology, TUMS
OK! Let’s open this up!
Immune
infiltration of CNS
Immune
system
Endocrine
system
Nervous
system
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Neuroimmune
interactions
OK! Let’s open this up!
Immune infiltration
of endocrine glands
Immunoendocrine
interactions
Immune
system
Endocrine
system
Nervous
system
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Immune infiltration
of endocrine glands
Immune
infiltration of CNS
Immune
system
Immunoendocrine
interactions
Endocrine
system
These
Nervous
system
Dr F Noorbakhsh, Dept. of Immunology,
TUMS categorizations!
are approximate
Neuroimmune
interactions
Main questions about the interactions
between NE and Immune systems
• Why are they connected?
• How are they connected?
• What are the effects of these connections?
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
1- Why are they connected?
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
The two-dimensional response chart
Self
Autologous
molecules
Neoplasms,
injured cells
Safe
Microbial flora,
Food, pollens
Nonsafe
Infectious agents
Non-self
There is a similarity in function!
Immune system
•
Safe-nonsafe recognition
•
Self-nonself recognition
•
Regulates relationship with the
Microbial world
•
Sensory-effector system
Dr F Noorbakhsh, Dept. of Immunology, TUMS
There is a similarity in function!
Nervous system
•
Safe-nonsafe recognition
•
Self-nonself recognition
•
Regulates relationship with the
Physical world
•
Sensory-effector system
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Physical world
sensor-effector
Microbial world
sensor-effector
Dr F Noorbakhsh, Dept. of Immunology, TUMS
2- How are they connected?
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Cytokines
Hormones
Neurotransmitters
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Cytokines
Hormones
Neurotransmitters
Dr F Noorbakhsh, Dept. of Immunology, TUMS
From the NE to Immune system
• Leukocytes have adrenoceptors
– (mainly beta2 AR)
• Leukocytes have glucocorticoid receptors
• Leukocytes have receptors for other
neuroendocrine factors (ACTH, FSH, LH, GH,
prolactin, catecholamines, neuropeptide-Y, and
enkephalins)
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
From the NE to Immune system
• Leukocytes have adrenoceptors
• Leukocytes have glucocorticoid receptors
• Leukocytes have receptors for other
neuroendocrine factors (ACTH, FSH, LH, GH,
prolactin, catecholamines, neuropeptide-Y,
and enkephalins)
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Leukocytes listen to adrenal (both
cortex and medulla)
B
Cell
CD4T
Cortex
Cathecolamines
Mφ
CD8T
medulla
NK
Glucocorticoids
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
From the NE to Immune system
• Leukocytes have adrenoceptors
• Leukocytes have Glucocorticoid receptors
• Leukocytes have receptors for other
neuroendocrine factors (ACTH, FSH, LH, GH,
prolactin, catecholamines, neuropeptide-Y,
and enkephalins)
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Leukocytes listen to hypophysis!
CRH
GH
B Cell
CD4
T
TSH
Mφ
CD8T
PRL
NK
ACTH
LH/FSH
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
From Immune system to the NE
• Cytokine receptors are present on the surface
of astrocytes and neurons
• The cytokines IL-1, TNF- α and INF-α can
change the function of the HPA axis.
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Cytokines
hormones
neurotransmitters
hormones
neurotransmitters
cytokines
Dr F Noorbakhsh, Dept. of Immunology, TUMS
• What are the effects of
these interconnections?
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Some major neuroimmune phenomena
• Sickness behavior
• Stress and immune system
• Depression and immune system
• Schizophernia and
immune system
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Sickness behavior
•
•
•
•
•
Depressed mood,
Fatigue, Psychomotor slowing,
Anorexia, fever
Sleep disturbances,
Cognitive dysfunction.
Proinflammatory cytokines (IL-1, TNF-α)
Anything else?
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Genetic studies on obese mice
The discovery of leptin (1994)!
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Leptin; what does it do?
Food intake
Adipose tissue
Arc .N
PVN
Leptin
Appetite
Satiety
Neuropeptide Y
Leptin; what does it do?
Food intake
Adipose tissue
Arc .N
PVN
Leptin
Appetite
Satiety
Neuropeptide Y
db/db mice
Ob/Ob mice
Male: 1-5
ng/dl
Sexually
dimorphic:
Female:
7-13fold
ng/dl
F/M: 2-3
Leptin levels
Overweight
Full
Hungry
Full
Hungry
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Normal
Hungry
Leptin; can we use it as a drug?
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Adipokines!
Stress and Immune system
STRESS:
A specific response by the body to a stimulus
that disturbs or interferes with normal
physiological equilibrium/homeostasis
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Stress and immune system
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Stress and immune system
 Shifts the Th1/Th2 balance towards Th2.
 Decreases cytotoxic T-cell and NK-cell activities.
 Impairs cellular immune response.
 Increases IL-1, IL-6, TNF-α
 Decreases IL-2, IFN-γ
 Decreases MHC I and II expression
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Risk of
cancers
Intracellular
bacterial
infections
Viral
infections
Stress
Allergy/
atopy
Th1-mediated
autoimmunities?
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Stress enhances Th1-related autoimmunities!
Multiple sclerosis
Rheumatoid arthritis
Stress
Type 1 Diabetes
Autoimmune thyroid disease
Crohn’s disease
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
A multiple-dimensional immunohomeostasis
Dr F Noorbakhsh, Dept Immunology, TUMS
Stress and immune system
Cathecolamines
Glucocorticoides
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Depression and immune system
• An increase in plasma concentration of
proinflammatory cytokines IL-1, IL-2 & IL-6
• Concentrations of proinflammatory cytokines
in patients with major depression correlate
with disease severity and HPA activity.
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
TCAs
Antidepressants
Imipramine
Clomipramine
Amitriptyline
Nortriptyline
…
TCAs
Imipramine
Clomipramine
Amitriptyline
Nortriptyline
…
Brain adrenergic
pathways’ involvement
in depression
Antidepressants
MAOI
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Phenelzine
TCAs
Antidepressants
MAOI
Imipramine
Clomipramine
Amitriptyline
Nortriptyline
…
Phenelzine
Fluoxetine
Paroxetine
Serteraline
Citalopram
…
SSRI
Brain serotonergic
pathways’ imbalance
causes depression
Venlafaxine
SNRI
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Desvenlafaxine…
Serotonin synthesis pathway
Tryptophan
TPH
5-HT
IDO
degradation
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Serotonin
Immune system and depression?
Proinflammatory cytokines
Indolamine dioxygenase
(IDO)
Tryptophan
5HT precursors
Depression
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
KYNA
Low grade
inflammation
QUIN
Overt inflammation
(neuroinflammatory
disorders)
Neuropsychopharmacology Reviews 2012
Any other mechanisms?
Immune activity
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
Depression
BH4
Tryptophan
Phe
TPH
BH4
BH4
PAH
TH
Tyr
5-HT
Serotonin
DOPA
Dopamine
Norepinephrine
BH4
Arginine
NOS
Nitric oxide
Dr F Noorbakhsh, Dept. of Immunology, TUMS
Another mechanism!
Neuropsychopharmacology Reviews 2012
Questions and comments
Dr F Noorbakhsh, Dept. of Immunology,
TUMS
‫فال اقسم بمواقع النجوم ‪...‬‬
Quiz!
‫ کدام یک از سایتوکاین های زیر با تاثیر بر سیستم عصبی‬-1
‫ میشود؟‬Sickness behavior ‫باعث ایجاد عالئم‬
TNF-a -‫الف‬
TGF-b -‫ب‬
IFN-gamma -‫ج‬
IL-2 -‫د‬
Dr F Noorbakhsh, Dept. of Immunology,
TUMS