When the immune system functions normally, it produces a response intended to protect against harmful or foreign substances like bacteria, parasites, and cancerous cells. The response may include specific immune cells and/or antibodies. Autoimmune diseases arise when the immune system produces a response against one or more of the body's normal constituents as if they are harmful. When the immune system fails to distinguish between "self" and "non-self", it may produce immune cells or antibodies (called autoantibodies) that target its own cells, tissues, and/or organs. Those attacks cause inflammation and tissue damage that lead to autoimmune disorders. There are more than 80 diseases that occur as a result of autoimmune responses and researchers suspect at least 40 additional diseases have an autoimmune basis. The National Institutes of Health (NIH) estimates that 23.5 million Americans are affected. Most autoimmune disorders are rare. However, the overall number of cases of autoimmune diseases is rising for unknown reasons. Women are disproportionately affected compared to men. Some diseases such as lupus affect 10 times more women than men. The cause of most autoimmune diseases is unknown, but it appears that there is an inherited (genetic) predisposition in many cases. In a few types of autoimmune disease (such as rheumatic fever), a virus or infection with bacteria triggers an immune response. The antibodies or immune cells called T-cells attack normal cells because some part of their structure resembles a part of the infecting microbe. Autoimmune disorders fall into two general types: those that damage many organs (systemic autoimmune diseases) and those where only a single organ or tissue is directly damaged by the autoimmune process (localized). However, the distinctions become blurred as the effect of localized autoimmune disorders frequently extends beyond the targeted tissues, indirectly affecting other body organs and systems.