Abstract
Immune privilege (IP), a term introduced to explain the unpredicted acceptance of allogeneic grafts by the eye and the brain, is considered a unique property of these tissues. However, immune responses are modified by the tissue in which they occur, most of which possess IP to some degree. The eye therefore displays a spectrum of IP because it comprises several tissues. IP as originally conceived can only apply to the retina as it contains few tissue-resident bone-marrow derived myeloid cells and is immunologically shielded by a sophisticated barrier – an inner vascular and an outer epithelial barrier at the retinal pigment epithelium. The vascular barrier comprises the vascular endothelium and the glia limitans. Immune cells do not cross the blood-retinal barrier (BRB) despite two-way transport of interstitial fluid, governed by tissue oncotic pressure. The BRB, and the blood-brain barrier (BBB) mature in the neonatal period under signals from the expanding microbiome and by 18 months are fully established. However, the adult eye is susceptible to intraocular inflammation (uveitis; frequency ~200/100,000 population). Uveitis involving the retinal parenchyma (posterior uveitis, PU) breaches IP, while IP is essentially irrelevant in inflammation involving the ocular chambers, uveal tract and ocular coats (anterior/intermediate uveitis/sclerouveitis, AU). Infections cause ~50% cases of AU and PU but infection may also underlie the pathogenesis of immune-mediated “non-infectious” uveitis. Dysbiosis accompanies the commonest form, HLA-B27–associated AU, while latent infections underlie BRB breakdown in PU. This review considers the pathogenesis of uveitis in the context of IP, infection, environment, and the microbiome.
Highlights
Immune privilege (IP) was conceived as a protective response to immune challenge by tissues with limited capacity for renewal such as the eye and the brain [reviewed in [1]]
The uveal tract and meninges display levels of IP little different from other vascular tissues [reviewed in [11]], and so it is no surprise that the anterior segment is susceptible to inflammation and that anterior uveitis (AU) is the most common brand of uveitis [12]
Many cases of presumed non-infectious uveitis have recently been shown to be linked to infection and may be due to persistent/latent infections delivered to the eye and other tissues via latently infected bone marrow precursors [85,86,87,88]
Summary
Immune privilege (IP) was conceived as a protective response to immune challenge by tissues with limited capacity for renewal such as the eye and the brain [reviewed in [1]]. These external barriers are strong and display a level of IP whereby they quench potentially damaging immune responses [60] This is important for the skin and mucosal surfaces, the gut mucosa, since they are exposed to a vast panoply (trillions) of commensal microorganisms in the microbiome. The microbiome actively participates in barrier homeostasis by secreting anti-inflammatory molecules such as short-chain fatty acids (SCFA), small molecules which can pass through the gut barrier into the system and influence immune cell function [61] In this regard, the intestinal and presumably other mucosal barriers share properties with CNS barriers which promote T cell tolerance and the generation of Treg cells (see below) [reviewed in [60]]. The immunological component of the IP-dependent CNS barrier comes into play in which Treg sustain latency by suppressing potential Teff and TRM cells, thereby preventing damaging immune responses in essential tissues and organs. Many cases of presumed non-infectious uveitis have recently been shown to be linked to infection and may be due to persistent/latent infections delivered to the eye and other tissues via latently infected bone marrow precursors [85,86,87,88]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
