The guards are hunting down an invader. The guards have no idea what the invader looks like, but they pick up clues. They take these clues to the Captain of the Guard, who helps determine if the clues were left by an invader or are from residents in the palace. If the Captain determines the evidence was left by an invader, they will command the guards to destroy the culprit connected to the clue. However, this Captain is poorly trained. They are presented with a clue and erroneously claim it’s from an invader when in fact it was from a resident. Too late, the guards have been ordered to attack the offender connected to the clue–but it is an innocent resident! The palace is in chaos and the rogue guards assault the very thing they’re supposed to be protecting! Our bodies act in a similar manner; the immune system protects our bodies from foreign invaders like bacteria and viruses, and a way it can do this is through the production of antibodies. That is what is supposed to happen at least, but there are times when the immune system will attack the host in a bout of friendly fire: and so autoimmune diseases start. One mechanism of self-destruction is when the immune system makes antibodies against the host–known as autoantibodies. Antibodies are our immune system’s guards and sometimes the immune system will get confused and generate autoantibodies leading to an attack on other parts of the body. But why does this happen? And what can we do to prevent this? 

B cells are like the palace guards of the body, patrolling for clues and fighting off invaders. They are a type of white blood cell made in the bone marrow that secrete antibodies to fight off infections. Each B cell is unique and has a receptor that binds to a specific antigen, like a lock to a key. Antigens are typically made of proteins or carbohydrates from foreign microbes, such as pieces of bacteria, viruses, parasites and fungi. These antigens are like the clues that guards are patrolling for. 

Let’s give a common scenario: someone is infected with E. coli. The E. coli swims around the body, but eventually a piece of the E. coli will come into contact with a pool of B cells. One of those B cells will have a receptor that binds to an antigen from E. coli (like in the above image panel A). Once the antigen and receptor come into contact, the B cell will bring the antigen inside the cell where it can be cut into smaller pieces (panel B) and presented to a helper T cell (panel C). This helper T cell will inspect the antigen that the B cell is presenting and determine whether this B cell is carrying a foreign object. If so, the helper T cell will stimulate the B cell to secrete antibodies towards that specific antigen (panel D). What’s particularly cool is that those antibodies that are secreted, started out as the receptors that initially recognized the antigens. That stimulation from the helper T cell turns those receptors into antibodies which are then free to kill the pathogen or recruit other white blood cells to do so. 

E. coli and other foreign microbes are common sources of antigens, but anything can be an antigen, even pieces of human cells, and these are specifically called self-antigens. Unfortunately, there are B cells that have receptors to these too which can be stimulated to make antibodies that subsequently attack the host. Then, how does the immune system prevent making antibodies against the host? Let’s go back to the palace metaphor: guards will show their Captain a clue and the Captain will ascertain whether the clue is from a resident or invader. A helper T cell is like the Captain of the Guard differentiating between antigens and self-antigens. In a healthy person, when the B cell presents a self-antigen to a helper T cell, the helper T cell ignores this B cell. This prevents the B cell from making antibodies. T cells are trained to ignore self-antigens during development in the thymus. If there are any T cells that recognize self-antigens, they are destroyed via the Aire (autoimmune regulatory) system. 

However, there are times when the Aire system fails to destroy helper T cells that recognize self-antigens. This leads to B cells making antibodies against these self-antigens, which are specifically referred to as autoantibodies. Instances of Aire system failure are usually genetic, where genes involved are not expressed properly. For example, the Aire system will have a cell present a self-antigen like insulin to a T cell at various frequencies which is genetically determined. In people where the Aire system presents insulin at higher frequencies, they are less likely to develop Type 1 diabetes because those T cells that react to insulin have been discarded. Likewise, in people where the Aire system presents insulin at lower frequencies or not at all, they are more likely to develop Type 1 diabetes; the T cells that would have been cast off in the thymus are now in circulation.

Today, 8% of the US population suffers from an autoimmune disease. While not every autoimmune disease has autoantibodies in play, the seven most common autoimmune diseases involve autoantibodies. For now, let’s focus on three of these autoimmune diseases: Type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. In Type 1 diabetes, the patient’s immune system generates autoantibodies against cells in the pancreas (panel A). When the autoantibodies bind to the pancreatic cells, white blood cells are recruited and they destroy the pancreatic cells. In rheumatoid arthritis, the autoantibodies are directed towards the joints leading to swelling (panel B). In multiple sclerosis, autoantibodies are directed towards the nerves and destroy nerve conductivity (panel C). 

The specific reasons as to why autoantibodies are generated is unknown. Research shows that there is a strong genetic component, but that alone does not indicate if an autoimmune disease develops. Usually, there is an environmental trigger, like a potent infection, that sends the immune system into chaos. In one scenario, a virus will infect a cell and cause that cell to die, which in turn leads to the spread of self-antigens from the dead cell. On a personal note, there was one winter where a particularly nasty flu strain was spreading in the school system, and my brother got sick with it. He recovered from the flu, but then a couple months later his blood turned acidic, in a process called ketoacidosis, was hospitalized, and was diagnosed with Type 1 diabetes. There are treatments to help manage the disease, but there are no known cures. He simply cannot get a pancreas transplant because his immune system will start generating autoantibodies again.

My brother and many other people rely on biomedical research to not only survive, but to thrive in spite of their autoimmune diseases. Researchers at the National Institutes of Health (NIH) work to develop more effective treatment for autoimmune diseases and discover the environmental factors that trigger the development of autoantibodies. Additionally, universities’ researchers are also studying autoimmune diseases, but these are funded through grants provided by institutions like the NIH, which recently had its budget reduced. If you are interested in contributing to progress in medical research targeting autoimmune disease and other conditions, there are a couple of different methods. There have been recent movements like “Stand Up for Science”  where advocates spread scientific policy awareness. Furthermore, there are petitions to reverse the NIH funding cuts to universities. You can even participate in medical studies yourself! Medical researchers are always looking for a variety of populations to make their research more robust. Finally, you can vote and encourage others to vote for representatives that support scientific pursuits.