The immune system is the body's surveillance and defense system that protects us against invasion by organisms such as bacteria and viruses. Normally a critical part of immune system function is the ability to differentiate between the body, or self, from foreign invaders, or non-self. This function is accomplished by the immune system's ability to identify portions of proteins, called antigens.

Before birth, immune cells that may potentially recognize the tissues of the body are deleted so that they will not be around later to damage normal tissues. The state of not reacting to one's own body is called tolerance. It is thought that in conditions such as rheumatoid arthritis as well as other autoimmune diseases, some immune cells that mistake normal parts of the body for foreign organisms may somehow escape the deletion process. As a result, later in life they recognize parts of the joint as something that should be attacked and eliminated. Alternatively, infectious agents such as viruses may be able to fool the immune system into thinking that a part of the body is foreign, thus breaking tolerance and leading the immune system to attack the body instead of the inciting infection. The inclination to lose tolerance to one's own body is probably determined by the genetics of the immune system.

To understand why tolerance breaks down in autoimmune diseases, it is first necessary to understand the process by which the immune system finds and attacks foreign substances. Within the ranks of the immune system, there are three primary types of cells that mount the detection response.

Macrophages

The macrophage is the first cell type to act as a sentinel to detect and report about what it finds in the environment around it. Macrophage means "big eater." The macrophage is constantly eating up a little bit of whatever surrounds it, cutting the ingested proteins up into small pieces (the antigens mentioned above), and then displaying these pieces of protein on its surface.

T cells

The macrophage is said to present these antigens to the T cell, which is the next cell in the chain and the primary decision maker in the immune process. T cells are highly specialized. In fact, each of the thousands of T cells within your body is different from every other one. On their surface, T cells express a protein called the T cell receptor, which will bind to only one or a few antigens out of the thousands that are possible. When a macrophage and a T cell encounter one another, they see whether any of the antigens on the surface of the macrophage fit into the T cell receptor. Most of the time the antigens don't fit. But if the antigens do match the T cell receptor, then the cells stick to one another. Through the action of chemical messengers, the T cell becomes turned on, or activated.

B cells

Activated T cells then call in the last cell in the chain, which is the B cell. Like T cells, each B cell is unique. Instead of making specific surface proteins, though, B cells make proteins called antibodies that can be released from the B cell into the bloodstream where they travel until they bind to the antigen that fits. After an infecting organism is coated with antibodies, it is tagged for recognition by the immune cells that destroy foreign substances.

One complication of this system is that the macrophage eats and presents everything that it encounters, whether friend or foe. So the interaction between the macrophage and the T cell is an especially critical encounter since the body needs to ensure that no T cells bind to and become activated in response to self antigens. There are two safety mechanisms that help to prevent the activation of T cells by self antigens.

• The first occurs very early in life, when the T cells are first being born. Each T cell passes through a specialized organ at the base of the neck called the thymus. In the thymus, T cells are given the opportunity to bind to antigens made from the body's own proteins. Any T cells that bind too strongly are killed. This process is called the development of tolerance and is a critical part of the process by which the immune system learns to ignore its host's own proteins.
• The second safety mechanism occurs at the time of the encounter between the macrophage and the T cell. Other proteins are important regulators of the immune response and are called the HLA group proteins. It is these proteins that must be matched between a tissue donor and recipient to ensure that an organ transplant will be successful and not attacked by the recipient's immune system.