View source for Immune response in central nervous system

In addition to the protection conferred by [[bone]], [[meninges]], and CSF, the Central Nervous System, comprised of the [[brain]] and [[spinal cord]], is protected by the [[blood-brain barrier]] (BBB). The blood brain barrier provides neurons with a relatively constant metabolic environment, protection against toxins and infectious agents, and other humoral agents such as antibodies and large proteins.  The BBB is not perfectly impermeable, however, and does allow communication through circumventricular organs such as the [[pituitary gland]], [[pineal gland]], and [[area postrema]]. These areas present potential paths for the spreading of infection into brain tissue and triggering of inflammation and immune response-like processes mediated principally by [[microglia]], the resident macrophages of the CNS. Microglias, the key immune mediators of the brain, are in charge of the phagocytosis of cellular debris and secretion of neurotrophic factors and cytokines upon damage or infection. 

Although the brain is considered an immune privileged site, extensive research has demonstrated that bi-directional communication takes place between the nervous and the immune system in both healthy and diseased individuals. Immune cells cross the BBB by means of diapedesis. The binding and internalization phases of this process are initiated by interactions between [[glycoprotein]]s on the endothelial surface with glycoproteins on the immune cell surface.  Activation of the immune system results in the elaboration of [[cytokine]]s and inflammatory mediators that induce hypothalamic CRF, which stimulates the release of the same immunosuppressive molecules that mediate the response to stress

The immune system and the central nervous system interact with each other by way of cell signaling. Cytokines, growth factors and chemokines produced by [[macrophage]]s and [[lymphocyte]]s can modulate brain functions.  Pro-inflammatory cytokines, such as interleukin-1, interleukin-6, interferons, and tumor necrosis factor alpha induce weakness, malaise, listlessness, inability to concentrate, feelings of depression, lethargy, anhedonia and loss of appetite (sickness behavior). Studies in animals and humans have shown that infusion of systemic or central cytokines induces sickness behavior symptoms. Cytokines and chemokines are capable of regulating neurotrophins and other molecules critical to neurodevelopmental and other neural processes (i.e. synaptic plasticity).  TNF-alpha plays a facilitatory role in glutamate excitotoxicity by inhibiting glial glutamate transporters on [[astrocytes]], increasing expression of AMPA receptors on synapses and can inhibit long-term potentiation.  IFN-γ is capable of inhibiting remyelination in demyelinated lesions of the CNS.  Elevated levels of IL-6 in the CNS primes developing neurons to NMDA neurotoxicity by affecting intracellular Ca2+ homeostasis.  Lymphocytes can synthesize neurotransmitters like substance P, [[norepinephrine]]

Central Nervous System can modulate immune response directly the release of [[neurotransmitter]]s and other molecules.  Reported evidence shows that lesions of the left cortex produced pronounced immune deficits in spleen cell number, lymphocyte proliferation, and natural killer cell activity.  Lymphocytes express neurotransmitter receptors on their cell surface.  [[Somatostatin]], neuropeptide Y, [[dopamine]] and substance P can directly induce cytokine secretion of T CD4+ cells in vitro.  Neuropeptides can activate immune cells (for example, Substance P signaling via NK1R enhances NK cell response against Herpes Simplex Virus type2).  Substance P has the ability to inhibit T cell adhesion by closing T cell voltage-gated K+ channels

== References: ==
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*Rust RS. Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions. Semin Pediatr Neurol. Jun 2000;7(2):66-90
*Ishizu T, Minohara M, Ichiyama T, et al. CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis. J Neuroimmunol. Jun 2006;175(1-2):52-8
*Bartels, Christie, MD. Systemic Lupus Erythematosus. 2009. Medscape http://emedicine.medscape.com/article/332244-overview. 
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*Lupus Foundation of America. Nervous System. http://www.lupus.org/webmodules/webarticlesnet/templates/new_aboutaffects.aspx?articleid=102&zoneid=17
*F. G. I. Jennekens and L. Kater. The central nervous system in systemic lupus erythematosus. Part 1. Clinical syndromes: a literature investigation. Rheumatology 2002; 41: 605-618

==See also==
* [[Immunology]]

[[Category:Immunology]]