IMMUNE PRIVILEGE: THE EYES HAVE IT

HOW DOES YOUR IMMUNE SYSTEM PROTECT VULNERABLE PARTS OF YOUR BODY LIKE YOUR EYES? IT GIVES THESE SPECIAL PARTS IMMUNE PRIVILEGE.

What do you picture when you think of your immune system? One picture could be your own personal army, courageously defending you against foreign bodily threats. While a strong immune system provides you with protection from infections and diseases, this robust protection comes with a price, collateral damage to your body (1, 2).

Much like the siren on a fire truck, the inflammation that accompanies immune responses serves a dual purpose (1). First, the siren, or inflammation, clears a path for help to get to the site of trouble as quickly as possible. Second, it also indicates that something is wrong; that there’s a threat that needs to be contained and neutralized. Despite its helpfulness to a fast and strong immune response, inflammation can damage bystander (uninfected or uninjured) cells (2, 3).

IMMUNE PRIVILEGE: PROTECT BYSTANDER CELLS

Most of your body is capable of regenerating itself. Your stomach lining replaces itself every 2-9 days, your skin replaces itself every month, and you recycle red blood cells every 4 months (4). However, certain parts of your body, like your eyes, brain, and central nervous system are unable to regenerate themselves or take a very long time to regenerate (3, 4). Since the eyes’ and brains’ regeneration capacity is limited and their purposes (vision and thinking) are very advantageous to life (without either of these functions, you’d have a hard time reading this blog article), these parts of your body can’t experience the collateral damage that usually occurs during a strong, protective immune response (3). These parts of your body need special treatment, or “immune privilege”(2).

Another part of the body that gets special treatment is the pregnant uterus containing a fragile fetus (2). A fetus is foreign to the mother’s body and while the fetus develops, it is very vulnerable. So, a fetus also gets “immune privilege” within the mother's womb (a very good thing for our species survival) (2).

Immune privilege is an adaptation by our immune system that enables different immune defenses and additional protection that avoid damaging and killing bystander cells (5). This article will focus specifically on the immune privilege of your eyes.

MECHANISMS OF IMMUNE PRIVILEGE

Your eyes’ immune privilege status is maintained by three mechanisms (6):

1. Physical and Chemical Barriers

2. Suppressive Environment

3. Limited Adaptive Immune Response

PHYSICAL AND CHEMICAL BARRIERS THAT PROTECT YOUR EYES

Tears are the first barrier a pathogen must face if it wants to infect and damage your eyes (7). When you blink, tears coat your eyes and wash pathogens out (7). Besides physically washing out pathogens, tears also contain antimicrobial peptides and lysozyme to quickly kill pathogens (7). Antimicrobial peptides are a diverse group of proteins that kill pathogens but not your own cells and are one of the earliest defenses of your immune system (8). Lysozyme is an enzyme found in your tears that kills pathogens (7). Your tears also contain IgA, a specific type of antibody (7). An antibody is a special type of molecule made by B cells (a type of immune cell that helps to kill infected cells) that acts like a Wanted Ad that’s stuck to a criminal (9). In your eyes, the IgA antibody binds to pathogens before they enter your eye cells, preventing your eye cells from infection (7). Your tears both physically and chemically protect your eyes from pathogen invasion and infection.

Your iris (the colored part of your eye) is a another kind of physical barrier that T cells (a type of immune cell) must face in your eyes (5). The iris barrier doesn’t prevent immune cells from entering your eye but it does limit their aggression (5). T cells that pass through this physical barrier lose their aggression and are neutralized, like soldiers who put the safety on their guns and are told to stand down. The cornea barrier is even more strict, it limits activation of immune cells, suppresses inflammation, and even kills some immune cells to stop them from crossing into the eye (5). In other words, the cornea barriers forces soldiers to put the safety back on their guns, turns off the alarm signal and even forces some immune soldiers to sacracfice themselves to protect your eyes.

These physical and chemical barriers protect your eyes from infection and support its immune privilege.

A SUPPRESSIVE ENVIRONMENT LIMITS INFLAMMATION TO PROTECT YOUR EYES

The vitreous humor and aqueous humor in your eyes are like soup, but instead of being filled with chicken and noodles, they’re filled with molecules that suppress inflammation and its dangerous destruction (5). These suppressive molecules limit different immune cells’ activation and their production of inflammatory molecules (3). The humors of the eye muzzle weapons and muffle or stop alarm signals to prevent bystander destruction, controlling the immune response.

Besides the suppressive humor soup, the cells of your eyes also have some molecules on their surfaces to limit inflammation (3). They have surface markers called FasL and TRAIL that kill activated immune cells like T cells (3). Your eye cells also have the surface marker, CRP, that stops the cascade of inflammation in its tracks to prevent your eye cells from being damaged during an infection (3).

In addition to those suppressive surface markers, your cells have unique MHC1 identifiers (3). Almost every cell in your body has MHC1 surface molecules that constantly say “I am you, I belong here!”(1). When you get infected with a virus, the MHC1 surface molecule changes its tune to “I’m infected, help me, kill the invader!” by showing the virus to passing immune cells or disappearing so no message is said and your immune system gets suspicious of the silent treatment and investigates (1). Your eyes don’t express the typical MHC1 molecules and thus they won’t say, “I’m infected, help me, kill the invader!” and get killed (3). Instead, your eyes have unique MCH1 molecules, HLA-G and HLA-E, that say, “I am you, I belong here . . . Don’t kill me!” and HLA-G and HLA-E don’t disappear during an infection so no investigation by your immune cells takes place (3). The cell surface markers on your eyes’ cells prevent bystander cell death and suppress inflammation.

Your eyes live in a suppressive environment that controls and reduces the amount of inflammation to protect your eyes and support their immune privilege.

LIMITED ADAPTIVE IMMUNE RESPONSE PROTECTS YOUR EYES

An adaptive immune response is an immune response to a specific threat and is carried out by T and B cells (1). There are two main cell types involved in adaptive immune responses: T cells and B cells (1). In other parts of your body that are not immune privileged, B and T cells are free to act to protect you during an infection or threat. In your eyes, only B cells (and even then, only a certain type of B cell) are free to protect your eye with its antibodies (2). If your eyes were a command operation, only one type of sniper would be allowed to shoot and even then, only with a semi-automatic gun to limit the damage and to ensure the right threats are neutralized. Both barriers and the suppressive eye environment inhibit T cells from acting by ordering them to stand down and sometimes disarming them.

The eye also interacts with your immune system to generate a special kind of T cell, a regulatory T cell (T-reg) to further protect your eye from inflammation and damage (2). Regulatory T cells act like the military police. They keep soldiers in line and curb disobedience to orders. In your eyes, regulatory T cells keep the other T cells under control and stop them from causing inflammation or from killing your eye cells (2). The limited adaptive response also allows for your eyes to better accept foreign tissue, like with cornea transplants( 5, 6). Cornea transplants have the highest success rate of acceptance out of all the organ transplants and don’t require matching (unlike bone marrow donations) or additional medication to suppress your immune system (6). Part of the reasons for the success in cornea transplant is the modified adaptive immune response helping to protect the transplant tissue.

CONCLUSION

If the eyes are the window to the soul, then your immune system ensures this window is protected from smears and shattering. Immune privilege is an evolutionary adaptation by our immune system that allows for modified immune responses to avoid causing damage and death of vital bystander cells (5).

Your eyes have immune privilege because your eyes’ cells are unable to regenerate and they carry out a very advantageous function: sight! This immune privilege is rarely overwhelmed except to avoid the death of the individual when the case of blindness or vision impaired would be the lesser risk (2).

Overall, immune privilege shows how well your immune system protects all parts of your body, even parts that can’t afford collateral damage and thus need special treatment, like your eyes.

REFERENCES

1. M. Murphy, Kenneth, Janeway, Charles A. Jr., Travers, Paul, and Walport, Janeway’s Immunobiology, 8th Edition (Garland Science, New York City, ed. 8th, 2012).

2. I. Benhar, A. London, M. Schwartz, The privileged immunity of immune privileged organs: the case of the eye. Front. Immunol. 3, 296 (2012).

3. J. Y. Niederkorn, See no evil, hear no evil, do no evil: the lessons of immune privilege. Nat. Immunol. 7, 354–359 (2006).

4. R. Milo, Ron, Phillis, » How quickly do different cells in the body replace themselves? (2015), (available at http://book.bionumbers.org/how-quickly-do-different-cells-in-the-body-replace-themselves/).

5. J. W. Streilein, Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J. Leukoc. Biol. 74, 179–185 (2003).

6. R. Zhou, R. R. Caspi, Ocular immune privilege. F1000 Biol. Rep. 2 (2010), doi:10.3410/B2-3.

7. A. M. McDermott, Antimicrobial compounds in tears. Exp. Eye Res. 117, 53–61 (2013).

8. K. McGill, Antimicrobial Peptides: Your Body’s Homeland Security | The Dish on Science. TheDishOnScience (2017), (available at https://thedishonscience.stanford.edu/posts/amp-immune-foot-soldiers/).

9. K. Mcgill, "Seasonal Flu Virus: Why Vaccines Never Go Out of Style" | The Dish on Science. TheDishOnScience (2017), (available at https://thedishonscience.stanford.edu/posts/seasonalfluvaccine/).