Neuroimmunology I: Immunoregulation in neurological disease

Abstract

Aberrations in immune function that ultimately result in disease states may involve three aspects of immune regulation: (1) regulatory T cells, which both suppress and induce immune responses; (2) idiotype-antiidiotype networks, which serve as internal regulatory networks during generation of an immune response; and (3) immune response genes, which determine genetic differences in an individual's immune response. Three major diseases of the nervous system, multiple sclerosis, myasthenia gravis, and acute inflammatory polyneuropathy (Guillain-Barré syndrome), are classified as "autoimmune" in nature and may be due to underlying disorders of immunoregulation. In multiple sclerosis there is a loss of suppressor T cells in the peripheral blood during attacks, in myasthenia gravis there are thymic abnormalities and antibodies against the acetylcholine receptor, and in acute inflammatory polyneuropathy, macrophage-mediated destruction of peripheral nerve myelin occurs in the context of sensitized T cells and is usually associated with a preceding viral illness. In each of these diseases the following central questions must be answered: (1) against what antigen (or antigens) of the nervous system is the autoimmune response directed? (2) what is the mechanism of immune damage? and (3) what initiates, or triggers, the autoimmune response?

Murine monoclonal antibodies to the myelin-associated glycoprotein react with large granular lymphocytes of human blood.

“…Since natural killer and T suppressor cells are important in immune regulation, a further imbalance in the immune system could result. A similar situation has been described for myasthenia gravis in which acetylcholine receptor-like antigens have been found in the human thymus and on lymphocytes (3,4).…”

“…Evidence has been accumulating for shared antigenic determinants between the nervous system and the immune system (1)(2)(3)(4)(5). This crossreactivity may be involved in the etiopathology of such neurological diseases as multiple sclerosis (5) and myasthenia gravis (3,4).…”

“…This crossreactivity may be involved in the etiopathology of such neurological diseases as multiple sclerosis (5) and myasthenia gravis (3,4). It recently has been demonstrated that Leu 7 (or HNK-1)-a mouse monoclonal antibody, raised to a human lymphoblastoma, that recognizes human natural killer cells-reacts with components of nervous tissue (6,7).…”

Selective loss of a subset of T helper cells in active multiple sclerosis.

“…Recent studies have suggested that multiple sclerosis (MS) may be a disorder of immune regulation in which effector and regulatory T-cell populations are altered (1)(2)(3)(4)(5). Several studies have found a reduction in both the number and activity of T suppressor/cytotoxic (Tj) cells in MS patients that may correlate with disease activity (6,7).…”

Pathogenesis of Multiple Sclerosis: Implications Based on Its Multifactorial Etiology

“…The hypothesis that a decrease in Ts cell function plays a cause-effect role in clinically active MS [51] is very attractive. One way to evaluate a cause-effect relationship is to de termine if it applies to other autoimmune or immunoregulatory diseases.…”