Autotoxicity and Alzheimer disease

Immunological responses are considered to be either humoral, resulting from cloning of B lymphocytes, or cell mediated, resulting from cloning of T ly mphocytes. Autoimmune diseases occur when the cloned products attack host t issue. Inflammation is considered a nonspecific response to injury, charact erized by exudation of serum into damaged tissue, and identified by the car dinal signs of rubor, calor, dolor, and tumor. However, these classic mecha nisms do not fit pathological observations of Alzheimer disease (AD)-affect ed brain tissue. Although many of the components prominently associated wit h peripheral immunological and inflammatory states are present in AD lesion s, there are no identifiable B lymphocytes or antibodies, and T cells are s parse. Furthermore, the blood-brain barrier is intact, excluding exudation of exogenous serum proteins. Although "neuroinflammation" is the term commo nly used to describe the pathological changes, it fails to define adequatel y the process that is taking place. The reaction is neither a nonspecific r esponse to injury, as classically implied for inflammatory reactions, nor a n autoimmune reaction, despite the directed attack against plaques and extr acellular tangles. It is most appropriately defined as an innate immunoreac tion. The fact that such a reaction can be mounted by brain, an organ frequ ently described as being immunologically privileged, suggests that a reeval uation is required of the dimensions of the innate immune system, including how it operates at the tissue level. The innate immune system is primitive , while the adaptive immune system, which is directed by peripheral immune organs, is an invention of vertebrates. Even in vertebrates, however, the i nnate immune system is the first line of defense. Much more needs to be lea rned about the operation of the innate immune system in health and disease.