lack of intratechal class-switch recombination from IgM
to IgG
cytokines are expressed in areas of the brain, e.g. glia, neurons, and
macrophages, and play a role in both neuronal cell death and survival.
CNS
to blood efflux of cytokines has also been shown to occur, but the
mechanism of passage is unclear.
peripheral blood-borne cytokines can ...
pass the blood-brain barrier (BBB) at leaky points, for example at the
organum vasculosum lamina terminalis (OVLT) or median eminence. They may
be actively transported across the BBB in small amounts. Saturable transport
systems from blood to the CNS have been described for IL-1a,
IL-1b,
IL-1ra,
IL-6,
and TNF-a.
Blood-borne cytokines have been shown to cross the BBB to enter cerebrospinal
fluid and interstitial fluid spaces of the brain and spinal cord. IL-2
does not cross the BBB by a saturable transport system. The blood-to-brain
uptakes of IL-1a,
IL-1b,
and IL-1ra
are interrelated for most brain sites, but the posterior division of the
septum shows selective uptake of blood-borne IL-1a.
The saturable transport systems for IL-6
and TNF-a
are distinguishable from each other and from the IL-1 systems. The amount
of blood-borne cytokines entering the brain is modest but comparable to
that of other water-soluble compounds, such as morphine, known to cross
the BBB in sufficient amounts to affect brain function.
rapidly signal the CNS through the vagus nerve.
They can influence the brain by activation of second messengers, such as
nitric oxide and prostaglandins, after binding to receptors on endothelial
cells
Neuroendocrine
regulation of immune function : is essential for survival during stress
or infection and to modulate immune responses in inflammatory disease.
noradrenergic sympathetic nerve fibers run from the CNS to primary
and secondary lymphoid organs, such as the thymus, spleen, and lymph nodes.
These nerve terminals make synaptic like connections with neighboring immune
cells releasing noradrenalin. The most important receptor receptor in terms
of the immune system is the b2-AR.
Expression of a- and b-ARs
on T and B lymphocytes, neutrophils, mononuclear cells, and NK cells has
been described.
HPA axis
short bursts of stress (such as public speaking, which induce the 'flight
or fight’ response, enhanced natural immunity) boost the immune system,
and only chronic stress (such as becoming permanently disabled) is associated
with global immunosuppression. These stress-related changes in immune function
are more likely to affect the elderly and sick.
acute (2h) stress experienced before primary or secondary antigen exposure
induces a significant mobilization of leukocytes from the blood to the
skin, significantly enhancing skin DTH. Just as an acute stress response
prepares the cardiovascular and musculoskeletal systems for fight or flight,
it may also prepare the immune system for challenges which may be imposed
by a stressor. Adrenalectomy
eliminates the stress-induced enhancement of DTH.
chronic stimulation of the hormonal stress response (e.g. caregivers of
Alzheimer's patients, students taking exams, couples during marital conflict,
Army Rangers undergoing extreme exercise and stress) is associated with
significant suppression of leukocyte mobilization, suppressing skin DTH.
enhanced susceptibility to viral infection
prolonged wound healing
decreased antibody production after vaccination
angry men are 70% more likely to develop gum disease than chilled-out ones.
Anger prompts the release of stress hormones, which dampen the immune system
and can encourage gum inflammation. Guys with one or more close friends
are less stressed and lower their risk of the diseaseref.
many animal models exist in which a blunted HPA axis response has been
associated with susceptibility to autoimmune/inflammatory disease
obese strain (OS) chicken as a model for autoimmune thyroiditis
certain mouse SLE models
the inbred rat strains
Lewis (LEW/N), with a hypoactive HPA axis
Fischer (F344/N), with a hyperactive HPA axis
in situations where there is an excess of glucocorticoid production, e.g.
animals models with a hyperactive HPA axis or in women in the third trimester
of pregnancy, there is a relative resistence to Th1-associated
autoimmune
diseases.
psychoneuroimmunology (PNI)
individuals with high comparative levels of activation of the right-hand
side of the prefrontal cortex of the brain (at baseline and in response
to a negative-emotion-inducing task) experience more intense negative emotions
and are more likely to suffer from depression.
These individuals produce lower antibody titres in response to an influenza
vaccination. Antibody titres are also correlated with the eye-blink response
to a task that induces negative emotions. Individuals with a larger eye-blink
response (which indicates stronger negative emotion) produce lower antibody
titres in response to vaccination.
and normal CSF constituents
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