Systemic versus organ-specific autoimmune disease
Autoimmune disease also can be classified as systemic or organ specific. Systemic autoimmune diseases, such as SLE, involve multiple organs or tissues, whereas organ-specific autoimmune diseases involve a single organ or tissue, such as the thyroid gland in autoimmune thyroiditis or the islet of Langerhans in type I diabetes (TID).
Autoantibody-mediated autoimmune diseases sometimes can be transmitted transplacentally, as in the case of neonatal Grave’s disease or congenital complete heart block and neonatal lupus. IgG antibodies/autoantibodies can cross the placenta, whereas IgM cannot. Thus, neonatal autoimmune diseases are invariably caused by IgG, not IgM, autoantibodies. In view of the half-life of IgG (twenty-one to twenty-eight days), nearly all maternal IgG disappears from the circulation of the baby by six to twelve months postpartum. Thus, in most cases, neonatal autoimmune disease is transient. One exception is congenital complete heart block, which is thought to be mediated by the transplacental passage of anti-Ro or anti-La autoantibodies that cross-react with cardiac antigens, causing permanent inflammation-mediated damage to the cardiac conduction system.
T-cell versus B-cell-mediated autoimmune disease
Autoimmune disease may be mediated primarily by T cells, as in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis (EAE). In that case, disease can be transmitted from one animal to another by transfering antigen-specific T lymphocytes. Alternatively, autoimmune disease may be caused by B cells that produce autoantibodies, as in the case of systemic lupus erythematosus (SLE). Autoantibodies bind to self antigen (proteins, nucleic acids, or other molecules from one’s own body, also known as autoantigens) and can damage cells either by binding directly to a cell surface or extracellular matrix antigen or through the formation of immune complexes.
DEFINITIONS AND TYPES OF AUTOIMMUNITY
AUTOIMMUNITY VERSUS AUTOIMMUNE DISEASE
The classical studies of Paul Ehrlich in the early twentieth century laid the foundation for our current notions of the concept of autoimmunity. Ehrlich used the term autoimmunity to signify an immune response against self and introduced the phrase horror autotoxicus, suggesting that there are mechanisms to protect against autoimmunity. Over the years, autoimmunity has been recognized as not uncommon and not necessarily detrimental. Thus, an important distinction must be drawn between autoimmunity, which may be asymptomatic, and autoimmune disease, which occurs when autoimmunity leads to an inflammatory response, resulting in tissue injury. An autoimmune response does not necessarily imply the existence of autoimmune disease.
The past two decades have seen the development of novel treatment modalities for PIDs. These include the use of Ig replacement therapy (for antibody deficiency), bone marrow tramsplantation (for SCID), and gene therapy (for the treatment of X-linked SCID and SCID due to ADA deficiency). In X-linked SCID and in ADA-deficiency gene, corrected bone marrow cells have a selective advantage over unmodified stem cells, contributing to successful engraftment by gene-reconstituted cells. The correction of genetic defects in conditions where the expression of the normal molecule does not provide a selective survival advantage will be more difficult and will require the development of more effective genetic vectors. The elucidation of molecular defects underlying PIDs helps in the development of better methods of diagnosing these disorders and genetic counseling of affected families. The contribution of new genetic techniques for elucidating molecular defects underlying PIDs have been described elsewhere.
In this review, we have highlighted how defects in individuals components of the immune system can leas to the susceptibility to different categories of pathogens. Such analyses help us to understand which components of immunity are non-redundant for protection against different microorganisms. This knowledge also helps us to be guided by the pattern of microbial infections in an individual patient in devising a rational approach to have the investigation of patients with suspected the immunodeficiency.
In the past decade, we have realized that defects in some components of the innate and adaptive immunity may result in susceptibility to a narrow range of microbial pathogens. This indicates that some immune mechanisms have evolved to deal with specific pathogens but are redundant for immunity against other microorganisms. Such knowledge may lead to the development of novel treatment strategies targeted against specific microbes.