Everything about Immune Privilege totally explained
Immune privilege is a term used to describe certain sites in the body which are able to tolerate the introduction of
antigen without eliciting an
inflammatory immune response.
Tissue grafts are normally recognised as foreign antigen by the body and attacked by the
immune system. However in immune privileged sites, tissue grafts can survive for extended periods of time without
rejection occurring. Known immunologically privileged sites include:
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 the loss of the child.
The existence of immune privileged regions of the eye was recognised as early as the late
19th century and investigated by
Medawar. 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. Antigens from immune privileged regions have been found to interact with
T cells in an unusual way inducing tolerance as opposed to a destructive response . Immune privilege has emerged as an active rather than a passive process.
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 MHC molecules
increased expression of surface molecules that inhibit complement activation
local production of immunosuppressive cytokines such as TGF-β
presence of neuropeptides
constitutive expression of Fas ligand that controls the entry of Fas-expressing lymphoid cells.
Sympathetic ophthalmia is a rare disease which results from the isolation of the eye from the systemic immune system. Usually, trauma to one eye induces the release of eye antigens which are recognized and picked up by local antigen presenting cells (APC) such as neutrophils and dendritic cells. These APC carry the antigen to local lymph nodes to be sampled by T cells and B cells. Entering the systemic immune system, these antigens are recognized as foreign and an immune response is mounted against them. The result is the sensitization of immune cells against a self-protein, causing an autoimmune attack on both the damaged eye and the non-damaged eye.
Pregnant uterus
A mother’s uterus is able to provide protection from microbial infections without mounting an immune response against fetal tissues expressing paternally inherited alloantigens. A better understanding of the immunology of pregnancy may lead to the discovery of reasons for miscarriage.
Regulatory T cells (Tregs) appear to be important in the maintenance of tolerance to fetal antigen. Increased numbers of Tregs are found during normal pregnancy. In both mouse models and humans diminished numbers of Tregs were associated with immunological rejection of the fetus and miscarriage. Experiments in mice involving the transfer of CD4+/CD25+ Treg cells from normal pregnant mice into abortion-prone animals resulted in the prevention of abortion. This confirmed the importance of these cells in maintaining immune privilege in the womb.
A number of theories exist as to the exact mechanism by which fetal tolerance is maintained. It has been proposed in recent literature 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're identified.
Brain
The brain is a sensitive organ with a limited capacity for regeneration. This makes immune privilege in the brain essential for the limitation of inflammation and maintenance of function.
The blood-brain barrier is important in maintaining the brains separation from the systemic immune system but it isn't on its own responsible for the maintenance of immune privilege. Immune privilege of the brain varies throughout different compartments being most pronounced in the parenchyma tissue or "white matter". In normal tissues antigen is taken up by antigen presenting cells (dendritic cells), which migrate to the lymph nodes, or soluble antigen can drain by itself into the lymph node. Dendritic cells have not been found in normal parenchyma tissue or perivascular space although they're present in the meninges and choroids plexus. The skewing of the response to antigen from the brain 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 brain has been proven. 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.
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