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From Fetus to Brain: How Immune Privilege Protects Our Source of Life?
In the mammalian body, certain parts of the body are immune-privileged, meaning they can tolerate the introduction of antigens without triggering an inflammatory immune response. This privilege not only protects sensitive tissue but also contributes to the success of organ transplants. Research shows that immune privilege is an adaptive response in biological evolution to protect important structures from potential damage.
Immune-privileged sites include the eyes, placenta and fetus, testicles, and central nervous system.
Organ transplants are often viewed as foreign antigens and are subject to attack by the immune system. However, in immune-privileged sites, tissue transplants can survive for long periods of time without rejection. This phenomenon is particularly evident in areas such as the eyes and placenta, where the special structure and immune environment enable them to avoid inflammatory responses. Particularly in the eye, when foreign antigens enter, the immune system's response is weakened, allowing successful eye transplants.
Mechanism of immune privilege
The process of immune privilege is not passive but active. Antigens in these immune-privileged regions interact with T cells in unusual ways, promoting tolerance to stimuli that would normally be rejected. Some specific mechanisms include:
- Low expression of classical MHC class Ia molecules
- Express immunomodulatory non-classical, low polytypic class Ib MHC molecules
- Increase the expression of surface molecules that inhibit complement activation
- Local production of immunosuppressive cytokines, such as TGF-β
- Presence of neuropeptides
- Continuous expression of Fas ligand controls the entry of Fas-expressing lymphocytes
The presence of these mechanisms not only protects immune-privileged sites, but may also make them targets for autoimmune diseases or disease conditions.
Immune privileged parts
Eyes
The immune privilege of the eye lies not only in the structural restriction of immune cell entry, but also in the suppression of systemic immune responses by active immune cells upon detection of foreign antigens. When external events cause foreign antigens to enter the eye, these antigens are sent to the lymph nodes and mobilize the system's immune response. In some cases, this may trigger an autoimmune response, even though under normal circumstances such a response should be suppressed.
Placenta and fetus
The maternal immune system provides protection against microbial infection without mounting an immune response against fetal tissue expressing paternally inherited antigens. Research shows that regulatory T cells play a key role in maintaining tolerance to fetal antigens. Experiments have shown that during normal pregnancy, the number of Tregs increases, which is directly related to miscarriage.
Testicles
Sperm is considered immunogenic, meaning it will cause an autoimmune reaction if transplanted from the testicles to other parts of the body. To protect these immunogens, structures and mechanisms within the testicle, such as the blood-testis barrier and the role of Sertoli cells, are critical to preventing immune system attack.
Central nervous system
The concept of immune privilege of the central nervous system, including the brain and spinal cord, was once thought to be critical for limiting inflammation, but this concept has been re-evaluated over the past two decades. New research shows that interactions between microglia and other immune cells exist in the central nervous system and are not completely isolated from the peripheral immune system as previously thought.
Clinical Application
Molecular mechanisms of immune privilege have great potential in transplant medicine. Corneal transplantation has a much higher success rate than skin transplantation, and immune-privileged allografts can survive even without the imposition of immunosuppression. Research suggests that harnessing anterior chamber-associated immune bias (ACAID) and its anti-inflammatory properties may improve organ transplant survival.
Under certain circumstances, cell therapy using the immunosuppressive properties of Sertoli cells also shows some promise, but this also requires further experiments to confirm its practicality in humans.
Research on immune privilege has revealed how many undiscovered mechanisms in our bodies protect us from autoimmune attack, while potentially providing new treatment ideas for future medical treatments. As we think about how to further leverage this knowledge, can we come up with new ways to change the way we treat disease?
