Immunoregulatory Systems
Relatively mild degrees of inflammation that would be harmless in the skin, for example, can cause severe vision loss if they occur in the eye. A variety of immunoregulatory mechanisms have thus evolved to modulate intraocular immune responses (eg, immune privilege).
Ocular immune privilege has been observed with various antigens, including alloantigens (eg, transplantation antigens), tumor antigens, haptens, soluble proteins, autoantigens, bacteria, and viruses. The best-studied model of immune privilege in the eye is called anterior chamber–associated immune deviation (ACAID). Whereas subcutaneous immunization with antigen elicits a strong, delayed-type sensitivity, immunization into the anterior chamber with the identical antigen results in a robust antibody response but a virtual absence of delayed-type hypersensitivity. In fact, preexisting delayed-type hypersensitivity (DH) can be suppressed by the ACAID response.
The ACAID response represents an attenuated effector arc. There are other regulators that contribute to immune privilege of the eye. The eye is further protected from severe inflammation by another modulating system termed effector blockade, by which Th1 lymphocytes, cytotoxic T lymphocytes, natural killer cells, and complement activation appear to function less effectively in the anterior uvea than elsewhere. For instance, the anterior uvea is relatively resistant to induction of a secondary purified protein derivative DH response after primary immunization with mycobacteria in the skin. There are several mechanisms of effector blockade, but one of the most important and best studied involves the Fas ligand (FasL, or CD95 ligand). The FasL is constitutively expressed on the iris and corneal endothelium. It is a potent trigger of programmed cell death, or apoptosis, of lymphocytes expressing the Fas receptor. Thus, even if an immune response develops to an ocular antigen, the inflammation can be downregulated by this mechanism of effector blockade.
Note that the immunoregulatory environment can, however, be overcome by sufficient immune stimulation.
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Skeie JM, Roybal CN, Mahajan VB. Proteomic insight into the molecular function of the vitreous. PLoS One. 2015;10(5):e0127567.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.