Neuroimmune system

Neuroimmune system
This diagram depicts the neuroimmune mechanisms that mediate methamphetamine-induced neurodegeneration in the human brain. The NF-κB-mediated neuroimmune response to methamphetamine use which results in the increased permeability of the blood–brain barrier arises through its binding at and activation of sigma-1 receptors, the increased production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and damage-associated molecular pattern molecules (DAMPs), the dysregulation of glutamate transporters (specifically, EAAT1 and EAAT2) and glucose metabolism, and excessive calcium influx in glial cells and dopamine neurons.
Details
System	Neuroimmune
Identifiers
TA
TH	{{#property:P1694}}
TE	{{#property:P1693}}
FMA	{{#property:P1402}}
Anatomical terminology [[[d:|edit on Wikidata]]]

The neuroimmune system is a system of structures and processes involving the biochemical and electrophysiological interactions between the nervous system and immune system which protect neurons from pathogens. It serves to protect neurons against disease by maintaining selectively permeable barriers (e.g., the blood-brain barrier and blood-cerebrospinal fluid barrier), mediating neuroinflammation and wound healing, and mobilizing host defenses against pathogens.

The neuroimmune system and peripheral immune system are structurally distinct. Unlike the peripheral system, the neuroimmune system is composed primarily of glial cells; among all the hematopoietic cells of the immune system, only mast cells are normally present in the neuroimmune system. However, during a neuroimmune response, certain peripheral immune cells are able to cross various fluid–brain barriers in order to respond to pathogens that have entered the brain.

Structure

The key cellular components of the neuroimmune system are glial cells, including astrocytes, microglia, and oligodendrocytes. Unlike other hematopoietic cells of the peripheral immune system, mast cells naturally occur in the brain where they mediate interactions between gut microbes, the immune system, and the central nervous system as part of the microbiota-gut-brain axis.

G protein-coupled receptors that are present in both CNS and immune cell types and which are responsible for a neuroimmune signaling process include:

• Chemokine receptors: CXCR4
• Cannabinoid receptors: CB1, CB2, GPR55
• Trace amine-associated receptors: TAAR1
• μ-Opioid receptors – all subtypes

Cellular physiology

The neuro-immune system, and study of, comprises an understanding of the immune and neurological systems and the cross-regulatory impacts of their functions. Cytokines regulate immune responses, possibly through activation of the hypothalamic-pituitary-adrenal (HPA) axis. There is growing evidence that auto-immune T-cells are involved in neurogenesis. Studies have shown that during times of adaptive immune system response, hyppocampal neurogenesis is increased, and conversely that auto-immune T-cells and microglia are important for neurogenesis (and so memory and learning) in healthy adults.

Clinical significance

It has been demonstrated that prolonged psychological stress could be linked with increased risk of infection via viral respiratory infection. Studies, in animals, indicate that psychological stress raises glucocorticoid levels and eventually, an increase in susceptibility to streptococcal skin infections.

The neuroimmune system plays a role in Alzheimer's disease. In particular, microglia may be protective by promoting phagocytosis and removal of amyloid-β (Aβ) deposits, but also become dysfunctional as disease progresses, producing neurotoxins, ceasing to clear Aβ deposits, and producing cytokines that further promote Aβ deposition. It has been shown that in Alzheimer's disease, amyloid-β directly activates microglia and other monocytes to produce neurotoxins.

See also

2

External links

• Figure7.1: Neuroimmune mechanisms of methamphetamine-induced CNS toxicity