Common features of immune privileged sites

Distinctive anatomic, cellular and molecular features are commonly found at privileged sites: 1) a blood: tissue barrier (continuous capillaries with endothelial cells united by tight junctions) across which passage of blood cells and plasma only occurs as a facilitated process; 2) absence of a lymphatic drainage pathway, necessitating that tissue fluids drain directly into the blood vascular compartment; 3) reduced or even absent expression of molecules encoded by class I and class II genes of the major histocompatibility complex; 4) constitutive local expression of Fas ligand for (FasL) which can induce apoptosis among activated Fas1 (CD95) lymphocytes; 5) paucity of bone marrow-derived MHC class II positive cells that function conventionally as professional antigen-presenting cells; 6) deficit in the local microenvironment of molecular mediators of inflammation, such as complement factors and clotting factors, along with specific inhibitors of these tissue-threatening enzyme cascades; 7) constitutive presence of a distinctive array of molecules within the local immunosuppressive microenvironment (growth factors, cytokines and mediators) that inhibit conventional antigen processing and presentation, suppress antigen-driven lymphocyte activation, and/or down-regulate cellular and molecular mediators of inflammation. Not all of these features are found at any single immune privileged site, indicating that privilege is multifactorial in origin.

Recently it has been discovered that antigens can escape from grafts placed in privileged sites, and, as a consequence, evoke an unusual systemic immune response. Typically, delayed hypersensitivity and complement fixing antibodies are not elicited by such privileged allografts, although other immune effector modalities, such as precursor cytotoxic T cells, non-IL-4-secreting T helper cells, and non complement fixing antibodies (especially IgGl in mice) are regularly elicited. Animals bearing foreign tissue grafts in privileged sites often (but not always) display concomitant immunity: the graft in the privileged site remains healthy, even though genetically identical grafts are rejected when placed at conventional body sites.

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