Immune privilege

Certain sites of the mammalian body have immune privilege (no immunity), meaning they are able to tolerate the introduction of

• the eyes
• the placenta and fetus
• the
  testicles
• the central nervous system

Immune privilege is also believed to occur to some extent or able to be induced in

Immune privilege is thought to be an evolutionary adaptation to protect vital structures from the potentially damaging effects of an inflammatory immune response. Inflammation in the brain or eye can lead to loss of organ function, while immune responses directed against a fetus can lead to miscarriage.^[6]

Medically, a

Antigens from immune privileged regions have been found to interact with T cells in an unusual way: inducing tolerance of normally rejected stimuli.^[9] Immune privilege has emerged as an active rather than a passive process.^{[citation needed]}

Physical structures surrounding privileged sites cause a lack of lymphatic drainage, limiting the immune system's ability to enter the site. Other factors that contribute to the maintenance of immune privilege include:

• low expression of classical MHC class Ia molecules
• expression of immunoregulatory nonclassical, low polymorphic class Ib MHC molecules
• increased expression of surface molecules that inhibit complement activation
• local production of
  TGF-β^[10]
• presence of neuropeptides
• constitutive expression of Fas ligand that controls the entry of Fas-expressing lymphoid cells.^[1][11]

The nature of isolation of immunologically privileged sites from the rest of the body's immune system can cause them to become targets of

As well as the mechanisms that limit immune cell entry and induce immune suppression, the eye contains active immune cells that act upon the detection of foreign antigens. These cells interact with the immune system to induce unusual suppression of the systemic immune system response to an antigen introduced into the eye. This is known as anterior chamber associated immune deviation (ACAID).^[12][13]

Placenta and fetus

The mother's immune system is able to provide protection from microbial infections without mounting an immune response against fetal tissues expressing

A number of theories exist as to the exact mechanism by which fetal tolerance is maintained. It has been proposed in recent literature[16] that a tolerant microenvironment is created at the interface between the mother and fetus by regulatory T-cells producing "tolerant molecules". These molecules including heme oxygenase 1 (HO-1), leukaemia inhibitory factor (LIF), transforming growth factor β (TGF-β) and interleukin 10 (IL-10) have all been implicated in the induction of immune tolerance. Foxp3 and neuropillin are markers expressed by the regulatory T-cells by which they are identified.^{[citation needed]}

Testes

Sperm are immunogenic – that is they will cause an autoimmune reaction if transplanted from the testis into a different part of the body. This has been demonstrated in experiments using rats by Lansteiner (1899) and Metchinikoff (1900),

The central nervous system (CNS), which includes the brain and spinal cord, is a sensitive system with limited capacity for regeneration. In that regard, the concept of "immune privilege" within the CNS was once thought to be critical in limiting inflammation. The blood–brain barrier plays an important role in maintaining the separation of CNS from the systemic immune system but the presence of the blood–brain barrier, does not, on its own, provide immune privilege.^[26] It is thought that immune privilege within the CNS varies throughout the different compartments of the system, being most pronounced in the parenchyma tissue or "white matter".^[26]

The concept of CNS as an "immune-privileged" organ system, however, has been overwhelmingly challenged and re-evaluated over the last two decades. Current data not only indicate the presence of resident CNS

Although there is no conventional lymphatic system in the CNS, the drainage of antigens from CNS tissue into the cervical lymph nodes has been demonstrated. The response elicited in the lymph nodes to CNS antigens is skewed towards B-cells. Dendritic cells from cerebrospinal fluid have been found to migrate to B-cell follicles of cervical lymph nodes.^[29] The skewing of the response to antigen from the CNS towards a humoral response means that a more dangerous inflammatory T-cell response can be avoided.

The induction of systemic tolerance to an antigen introduced into the CNS has been previously shown.^[30] This was seen in the absence of the T-cell mediated inflammatory "delayed type hypersensitivity reaction" (DTH) when the antigen was reintroduced in another part of the body. This response is analogous to ACAID in the eye.^{[citation needed]}

Clinical applications

There is great potential for use of molecular mechanisms present in immune privileged sites in transplantations, especially allotransplantations. Compared to skin allografts, which are rejected in almost 100% of cases, corneal allografts survive long-term in 50–90% of cases. Immune privileged allografts survive even without immunosuppression, which is routinely applied to different tissue/organ recipients.^[31] Research suggests that the exploitation of anterior chamber-associated immune deviation (ACAID), aqueous humor and its anti-inflammatory properties and the induction of regulatory T cells (Treg) may lead to increased survival of allotransplants.^[32]

Another option of exploitation of immune privilege is

The existence of immune privileged regions of the eye was recognized as early as the late 19th century and investigated by Peter Medawar.^[36] The original explanation of this phenomenon was that physical barriers around the immune privileged site enabled it to avoid detection from the immune system altogether, preventing the immune system from responding to any antigens present. More recent investigations have revealed a number of different mechanisms by which immune privileged sites interact with the immune system.

References