Thanks everyone for your helpful answers.
Just thought I'd post what your answers have led me to...
Immune privilege = Part of the body not attacked by the immune system
Medawars (1948) original explanation for this phenomenon that immune privilege was just immune ignorance, with privileged sites isolated behind blood-tissue barriers lacking lymphatic drainage, and with antigenic material (trapped within these isolated sites) remaining invisible to the immune system is now known to be incorrect. It has since been found that foreign tissues in privileged sites could eventually evoke antigen-specific systemic immunity and that certain privileged sites (such as the testis) had extensive efferent lymphatic pathways. Rather than immune ignorance, the systemic immune apparatus recognizes antigens in privileged sites and cooperates to create and sustain a graft-friendly environment. Infectious organisms or tumor cells inserted into immune-privileged sites do not elicit destructive or protective immunity.
Within such immune privileged organs immune responses are suppressed:
(1) MHC-mismatched (the half-paternal placenta)
(2) harbor germ-line cells (ovary and testis)
(3) contain bradytrophic tissues with poor regenerative capacity (lens and cornea in the anterior chamber of the eye)
(4) their function crucially depends on highly specialized, interconnected, postmitotic cells (the CNS)
One might speculate that for all these reasons, inflammation-induced cell loss must be limited to a minimum, and as a consequence, many antigens that elicit strong immune responses elsewhere in the body are tolerated in immune privileged sites. For example, certain viruses are removed at those sites of the body where neighboring cells can divide and replace lost cells, but persist within the CNS. From an evolutionary point of view, it is obviously less detrimental for an individual to live with such viruses in the brain than losing all infected neurons as a result of an adaptive immune response.
At least four pathways are known by which immune privilege can lead to T-cell tolerance:
(1) clonal deletion
(2) clonal anergy
(3) immune deviation
(4) T-cell suppression
Privileged tissues also are often characterized by:
(1) intratissue structural barriers such as extensive tight junctions among parenchymal cells (Sertoli cells, retinal pigment epithelium)
(2) elaborate surface _expression of hyaluronic acid (placenta, trabecular meshwork of the eye)
(3) reduced or absent _expression of MHC class I and class II molecules (brain, eye, placenta)
(4) _expression of class Ib molecules (placenta)
(5) release of class I molecules (liver)
(6) secretion of immunosuppressive cytokines (eye) and corticosteroids (gonads)
(7) fetal-like fibroblasts (gingival oral mucosa)
As summarized by Streilein (1997), privileged sites incorporate multiple additional features allowing them to accept foreign grafts:
(1) blood-tissue barriers (for eye, brain)
(2) absence of efferent lymphatics (eye)
(3) direct tissue fluid drainage into the blood (eye, brain)
(4) functional integrity of the spleen (eye)
(5) establishment of a potent immunosuppressive microenvironment containing growth factors such as TGF-beta (eye, brain, placenta, testis) and neuropeptides (eye)
(6) soluble and membrane-bound inhibitors of complement activation and fixation (anterior chamber of eye)
There are two distinct loci of immune privilege:
privileged sites (the best example being the fetus)
privileged tissues....
(1) EYE (anterior chamber, cornea, and retina) (blood-retina barrier) critical to avoidance of stromal keratitis, blinding disease of cornea accompanying ocular infection with HSV-1. Existence of ocular immune privilege is believed to serve the purpose of limiting the extent to which innate and adaptive immunity can cause intraocular inflammation. By limiting intraocular inflammation, immune privilege preserves the integrity of the visual axis and thereby prevents blindness. Ocular inflammation, whether expressed within the cornea or within the uveal tract, is a frequent cause of visual impairment. The eye is relatively protected from the vision-damaging effects of intraocular inflammation.
Orthotopic corneal allografts are the most successful of all solid-organ transplants in humans because the eye is a privileged site and the cornea is a privileged tissue (acute rejection if immune privilege lost)
(2) BRAIN (blood-brain barrier)
Endothelial cells are packed much tighter together in the brain, due to the existence of zonula occludentes (tight junctions) between them, blocking the passage of most molecules. The blood-brain barrier blocks all molecules except those that cross cell membranes by means of lipid solubility (such as oxygen, carbon dioxide, and ethanol) and those which are allowed in by specific transport systems (such as sugars and some amino acids). It is generally accepted that substances with a molecular weight higher than 500 Daltons can not cross the blood-brain barrier, while the lighter ones can.
(3) GRAVID UTERUS & PLACENTA & EMBRYO & AMNIOTIC MEMBRANE (blood-placenta barrier) biologically necessary for success of pregnancy so normal immune function does not occur. In order that the fetus is not attacked by the mother's immune system, the uterus/ uterine endometrium is an immune-privileged site during pregnancy. That makes sense; what is the implanting conceptus but something chimerically foreign (xenograft)?
The Rh factor marker is a protein, so there is no incidental preexposure. One either has the factor, Rh+, or one doesnt, Rh-. (Yes,oversimplifying.) For transfusions, it is important to get it right. But there is another case where it can be a problem, and that concerns maternity. Suppose mother is Rh-, and father is Rh+. If he is homozygous Rh+/Rh+, then all conception will be phenotypically Rh+; if he is heterozygous Rh+/Rh-, then half the conceptions will be of Rh+ phenotype. The first pregnancy with an Rh+ conceptus is generally not a problem. At parturition, however, there is no way to avoid fetal blood mixing with maternal blood, and so mother will be exposed to the Rh-antigen, and generate circulating anti-Rh IgG molecules. If the next pregnancy is an Rh+ conceptus, these anti-Rh IgG molecules will cross the placenta, destroying the fetal erythrocytes, resulting in erythroblastosis fetalis or hemolytic disease of the newborn. The drug RhoGam® is essentially an anti-(anti-Rh IgG) IgG.
(4) TESTES / SERTOLI CELLS (blood-testes barrier)
The junctions of Sertoli cells form the blood-testis barrier (between the blood vessels & the seminiferous tubules of the testes), a structure that partitions the interstitial blood compartment of the testis from the adluminal compartment of the seminiferous tubules. Sertoli cells control the entry and exit of nutrients, hormones and other chemicals into the tubules of the testis.
The seminiferous tubules have a basement membrane that, together with Sertoli cells, forms a blood-testis barrier. Because blood does not penetrate the seminiferous tubules:
1. The developing spermatozoa receive nutrients indirectly, from Sertoli cells, rather than from capillaries.
2. The interior of the tubules are 'immunologically privileged' - no immune reactions. This is important because sperm become haploid (by meiosis) beginning at puberty long after the immune system develops so haploid sperm are considered nonself by the immune system.
A male will produce antibodies that attack his own sperm, if the sperm are exposed to circulation (lymphocytes).
(5) OVARY
(6) PROSTATE
(7) TUMORS
(8) HAIR FOLLICLES
(9) CARTILAGES
(10) LIVER
(11) ADRENAL CORTEX
