>Contents>Ocular Immune Privilege
Niederkorn and his associate Apte demonstrated that AqH from normal eyes can prevent the lysis of susceptible target cells by NK cells in vitro. Apte determined that at least two factors in normal AqH mitigate NK cell killing: TGF-beta and macrophage migration inhibitory factor (MIF). TGF-beta's inhibitory activity on NK cells is delayed in time, whereas MIF acts quickly to disarm NK cells. These are the factors in the ocular microenvironment that permit tumor cells to grow progressively in the anterior chamber of mice with an intact innate immune system. Immigration of neutrophils and macrophages into the ocular microenvironment from the blood is inhibited by the presence of alpha-MSH and TGF-beta, and both of these factors interfere with the activation of these inflammatory cells within the anterior chamber. In addition, the ability of activated macrophages to produce NO is inhibited by calcitonin gene-related peptide (CGRP), another normal constituent of AqH. Soluble factors in AqH also inhibit the activation of complement via the alternative pathway. As of yet, the identity of the inhibiting molecule is unknown. Undoubtedly, other factors exist in AqH that contribute to the suppression of innate immune cells and molecules; so much remains to be learned.
Molecules expressed on cells lining the anterior chamber also inhibit innate immune effectors. Several membrane-associated inhibitors of complement activation (CD55, CD59, CD46) are constitutively expressed, and act to inhibit complement-dependent inflammation. Very recently, Kaplan and his associates have discovered that a fourth membrane complement inhibitor (Scrry) that is expressed in the normal eye plays a key role in inhibiting LPS-induced inflammation in the eye. Mice in which the gene for this inhibitor has been transgenically knocked out have a heightened susceptibility to LPS-induced uveitis.
The Eye's Dilemma
Immune Privilege
Anterior Chamber of the Eye as an Immune- Privileged Site
Inflammation of Relation to Innate and Adaptive Immune Responses
Ocular Factors That Promote Immune Tolerance of Eye-Derived Antigens
Factors That Modify Expression of Ocular Adaptive Immunity
Innate Immune Privilege in the Eye
Factors That Modify Expression of Innate Ocular Immunity
Clinical Meaning of Ocular Immune Privilege
Selected Reading
Biography
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