Innate Immunity and Autoimmune Diseases

Abstract

The innate immune response is responsible for the initial defense against invading pathogens and signs of damage; in turn, it activates the adaptive immune response to result in highly specific and lasting immunity, mediated by the clonal expansion of antigen-specific B and T lymphocytes. Inflammation is the acute response to infection and tissue damage to limit aggression to the body. It is a complex reaction of vascularized tissues to infection, toxin exposure or cell injury that includes extravasation of plasma proteins and leukocytes. Paradoxically, uncontrolled and prolonged inflammation can result in secondary damage and the development of immune pathology in the host. The components of the innate immune system have recently been studied as responsible mechanisms in various chronic diseases such as diabetes mellitus, atherosclerosis, asthma and allergies, among others. Autoimmune disease is an attack on auto tissues by the adaptation of the immune system. In general, such diseases are characterized by autoantibodies and/or autoreactive lymphocytes directed at antigens against themselves. The innate immune system is often considered an effector of self-reactive lymphocytes, but also provides protection. Studies in mice with specific gene-directed mutations show that defects in innate immune system proteins may predispose to the development of a systemic lupus erythematosus-like syndrome (lupus) characterized by autoantibodies against double-stranded DNA (ds DNA) or nuclear components. This seems to be due to a failure in the removal of apoptotic cells or nuclear waste. These observations imply that the innate immune system has a general protective role against autoimmune disease. For example, in systemic diseases such as lupus, innate immunity is important in the elimination of nuclear antigens and, therefore, in the improvement of tolerance to B lymphocytes. Alternatively, in specific organ disorders such as type diabetes 1 o Crohn’s disease, the innate immune system can be protective by eliminating pathogens that trigger or exacerbate the disease or regulate the presentation of antigens for T lymphocytes. Discuss various disease models in which the innate immune system could provide a protective role, deficiencies in the regulation of B lymphocyte signaling through the antigen/receptor or in the clearance of lupus antigens, (dsDNA and nuclear proteins), can lead to a disease similar to lupus. The repertoire of B cells seems to be very biased toward self-activity, as, possibly, that of the T-cell. This tendency toward self-activity is not surprising because B and T cells are positively selected against highly conserved autoantigens.