Certain sites of the body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response.
Immune privilege refers to specific sites in the body where immune responses are limited or actively suppressed to prevent inflammation or tissue damage that could impair function.
Immune privilege is an adaptation to protect vital structures from the potentially lethal effects of an inflammatory immune response in those regions.
Inflammation in the brain or eye could cause the loss of organ functions, while immune responses directed against a fetus could cause miscarriage.
Immune-privileged sites are areas where foreign antigens like transplanted tissue or pathogens can persist for long periods without eliciting a strong immune response.
Tissue grafts are normally recognized as foreign antigens by the body and attacked by the immune system.
In immune privileged sites, tissue grafts can survive for extended periods of time without rejection occurring.
Immunologically privileged sites include:
Brain / Central Nervous System (CNS) The blood–brain barrier restricts entry of immune cells and molecules. Microglia act as specialized immune cells with regulated activity.
Eyes-The cornea and anterior chamber maintain immune privilege to preserve vision.
Mechanisms of immune privelege include local production of TGF-β and Fas ligand (FasL) to suppress inflammation.
Testes-The blood–testis barrier protects developing sperm from immune attack.
Sertoli cells secrete immunosuppressive factors (e.g., TGF-β, IL-10).
Placenta and Fetus
It is thought that immune privilege also occurs to some extent,or is able to be induced in articular cartilage.
Immune privilege allows doctors to perform cornea transplants and knee meniscal transplantation.
Antigens from immune privileged regions have been found to interact with T cells inducing tolerance of normally rejected stimuli.
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 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 immunosuppressive cytokines such as TGF-β
The nature of isolation of immunologically privileged sites from the rest of the body’s immune system can cause them to become targets of autoimmune diseases or conditions, including sympathetic ophthalmia in the eye.
The eye contains active immune cells that act upon the detection of foreign antigens, limiting cell entry and induce immune suppression.
These cells interact with the immune system to induce unusual suppression of the systemic immune system response to an antigen introduced into the eye (anterior chamber associated immune deviation (ACAID).
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 macrophages 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.
The immune-privileged property has served to work against the eye instead.
T cells normally encounter self-antigens during their development, when they move to the tissue draining lymph nodes.
Anergy is induced in T cells which bind to self-antigens, deactivating them and preventing an autoimmune response in the future.
Immune tolerance in pregnancy:The mother’s immune system is able to provide protection from microbial infections without mounting an immune response against fetal tissues expressing paternally inherited alloantigens.
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, and humans diminished numbers of Tregs are associated with immunological rejection of the fetus and miscarriage:This confirm the importance of these
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, 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.
Sperm are immunogenic, and cause an autoimmune reaction if transplanted from the testis into a different part of the body.
The likely reason for their immunogenicity or rather antigenicity is that sperm first mature at puberty, after central tolerance has been established, therefore the body recognizes them as foreign and mounts an immune reaction against them.
Mechanisms for their protection must exist in this organ to prevent any autoimmune reaction.
The blood–testis barrier is likely to contribute to the survival of sperm.
The blood–testis barrier cannot account for all immune suppression in the testis, due to its incompleteness at a region called the rete testis and the presence of immunogenic molecules outside the blood–testis barrier, on the surface of spermatogonia.
The Sertoli cells play a crucial role in the protection of sperm from the immune system.
A Sertoli cell barrier, which complements the blood-testis barrier, protects by tight junctions, which appear between two neighboring Sertoli cells.
Another mechanism which is likely to protect sperm is the suppression of immune responses in the testis.
The central nervous system (CNS), which includes the brain and spinal cord, is a sensitive system with limited capacity for regeneration.
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.
Immune privilege within the CNS varies throughout the different compartments of the system, being most pronounced in the parenchyma tissue or white matter.
The presence of resident CNS macrophages, also known as microglia within the CNS actively interact with peripheral immune cells challenging the the concept of immune privilege.
Generally, in normal (uninjured) tissue, antigens are taken up by antigen presenting cells (dendritic cells), and subsequently transported to the lymph nodes. Alternatively, soluble antigens can drain into the lymph nodes. In contrast,
In the CNS, dendritic cells are not thought to be present in normal parenchymal tissue or perivascular space although they are present in the meninges and choroids plexus.
Thus, the CNS is thought to be limited in its capacity to deliver antigens to local lymph nodes and cause T-cell activation.
There is no conventional lymphatic system in the CNS.
The drainage of antigens from CNS tissue occurs into the cervical lymph nodes, and 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.
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.
Sertoli cells have immunosuppressive function, and can protect and nurture islets producing insulin to treat type I diabetes.
The maternal immune system is actively regulated to tolerate the semi-allogeneic fetus: Expression of non-classical MHC molecules (HLA-G) helps prevent maternal immune attack.
Limited immune surveillance supports reproduction and implantation.
Mechanisms of Immune privilege include: Physical barriers: Tight junctions-blood–brain, blood–testis barriers.
Lack of lymphatic drainage: Reduces antigen presentation.
Local immunosuppressive environment: Cytokines (TGF-β, IL-10), neuropeptides, and expression of FasL induce apoptosis of activated T cells.
Regulatory T cells (Tregs): Help maintain tolerance locally.
Corneal transplants often succeed without immunosuppression due to ocular immune privilege.
Immune privilege breakdown can lead to autoimmune disease — e.g., autoimmune orchitis, uveitis, or multiple sclerosis.
Tumors may exploit immune-privileged–like mechanisms to evade immune detection.