Frontiers in Immunology (Nov 2012)
Good news – bad news: the Yin and Yang of immune privilege in the eye
Abstract
The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialised function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because of its natural defences are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and can restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumour-related IP can combine to permit extensive tumour growth and increased risk of metastasis thus threatening the survival of the host.
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