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A house divided cannot stand

-by Dr. Alan Laird, Chief Medical Officer

-by Dr. Alan Laird, Chief Medical Officer

Whether you know this statement from its scripture reference or Lincoln’s speech, these have long been held as words of wisdom. This is also true in biology. An organism that attacks itself will not do well and possibly not survive. An attack on one’s self is the essence of autoimmune disease.

Autoimmunity occurs when the human body turns on itself and directs it defense system (the immune system) at certain organs or types of cells in the body. This often causes the death of those cells or organs and results in illness for the individual. Often times that illness can become deadly if not treated. 

For at least a millennium, medical professionals had noted a disease that caused increased thirst and urination. In the eighteenth century, it was found that the urine of most of these individuals contained sugar. In the late nineteenth and early twentieth century, scientists discovered it was due to a disorder of the pancreas.  Finally in the 1920s we understood that this was a disorder of insulin. Today we know there are at least 2 subsets of this disease: Type 1 diabetes mellitus, where the body cannot make adequate insulin and Type 2 diabetes mellitus, where the body cannot respond to the more than adequate supply of insulin. For many years we thought Type 1 was an inherited disorder.  But as we discovered autoimmunity in the middle of the last century, we eventual found that Type 1 occurred as the body destroyed the insulin making cells in the pancreas.  And so today we understand that Type 1 and type 2 diabetes occur for different reasons even if the clinical presentation is similar (increased thirst and urination).

But why would the body destroy the cells that make insulin? In fact, why would the body turn on itself for any reason?  We are only beginning to understand this.  In part, it has to do with the divisions in our immune or defense system. Although there are other names for them, in general the immune system is divided into two parts or types.  The innate immune system is always “on guard” and ready to protect our bodies.  It is our first line of defense.  Then there is the adaptive immune system.  As its name implies, this system responds in a very specific way to a specific threat.  It takes time to construct this response. Therefore, unlike the innate system, the adaptive system responds later after the agent causing the attack has been analyzed and an attack plan made. The innate system would be somewhat analogous to those forces always guarding our homeland (National Guard, Coat Guard, Homeland Security, Police, and others) who respond quickly to an emergency. Then after analysis of an attack, the adaptive system goes to work (Army, Navy, Air force, Marines) as well as those previous forces to repel the enemy and attack its source. For the purposes of biology, when we talk about immunity, we are referring to adaptive immunity, or that response that is programmed and specific to a single agent. For the most part, when immunity goes wrong and begins a sustained attack on the human body, it is due to a mis-programing of the adaptive immune system.

In battle, we see mistakes made and we inadvertently attack our own people. Usually, this is quickly realized, and the attack is stopped. But with our bodies, once the immune system is “convinced” that this cell type or organ does not belong as part of the body, the attack continues until the tissue or organ is destroyed. Once programed, the immune system is not about to “second think” the war, especially when it has advanced to the adaptive stage.

Again, how does this happen? There are three major theories as to what goes wrong to cause autoimmunity. This gets very technical and often there are things we do not yet understand.   

The first theory is that the process by which our immune system knows what is our body (self) as opposed to an outside substance (called an antigen), becomes deranged. This can occur because some infectious agents may “look” very similar to our cells, and in clearing the infection, our immune system also attacks our own cells.

The second theory is that our body cells may change the way they “look” to our immune system due to injury, infection or aging. The immune system then sees those “changed” cells as foreign to our body and begins attacking them.

The third theory is that the damage caused by the innate immune system to fight a foreign agent may trigger the adaptive immune system to fight not only the foreign agent, but also the body itself.

The also appears to be a genetic component to this as persons with a specific variation in their DNA are more prone to autoimmune diseases. That does not mean that those who have those variations will get an immune disorder, but they do have more risk to develop one.

However it happens, the immune system begins attacking the body and keeps up the attack causing not only short term, but also long-term damage. The cell or organ attacked can include most any type. If it happens to be blood vessels, the patient may end up with lupus (systemic lupus erythematous). If it is joints, then rheumatoid arthritis may result.  And, as in the example above, if it is the beta cells of the pancreas, then diabetes mellitus type 1 occurs. If there is any good news, it is that we are understanding more of the disease process and the disease triggers. As we do, new and powerful treatments have been crafted that improve people’s lives and control these diseases even if they cannot be cured. It is often devastating to deal with a life long illness that attacks your own body. If the progress we have seen in the past 30 years can continue, we may reach a day when these disorders can be effectively controlled, possibly cured, and hopefully prevented.