Immunomodulatory Actions

Intravenous immune globulin supplies anti-idiotypic antibodies that bind to and neutralize pathogenic autoantibodies, hindering their interaction with the autoantigen. Binding of the anti-idiotypic antibodies to antigenic determinants and surface IgM or IgG on B cells could also cause negative signals on B cells and could result in downregulation of antibody production

This contains high-affinity neutralizing antibodies against interleukin-lalpha, interleukin-6, and tumor necrosis factor-alpha in quantities sufficient to overpower circulating pathogenic cytokines or downregulate the synthesis of cytokines by the T cells. It also contains neutralizing antibodies against epitodes of superantigens and antibodies against the Vbeta3, Vbeta8, and Vbeta17 gene families of the T-cell receptor peptides. Since superantigens stimulate a large fraction of Vbeta chain-expressing unsensitized T cells and cytokine secretion, their inhibition restrains the activation and clonal expansion of superantigen-triggered cytotoxic T cells.

The binding of infused IgG molecules to Fc receptors on the surface of phagocytic cells that attack the target tissues of patients with various autoimmune neurologic diseases can prevent Fc receptot-mediated phagocytosis of antigen-bearing target cells or inhibit antibody-dependent cell-mediated cytotoxicity by saturating or adjusting the affinity of the Fc receptos. The formation of covalent and non-covalent complexes between IVIg and the products of complement activation, notably C3b and C4b, prevents the consolidation of C3 molecules into the C5 convertase assembly and intervenes with the formation and deposition of membranolytic attack complexes on target cells. The deposition of membranolytic attack complex mediates the destruction of myelin and axons in the Guillain-Barre syndrome, the postsynaptic region of the neuromuscular junction in myasthenia gravis, and the endomysial capillaries in dermatomyositis.

Intravenous immune globulin draws transient lymphopenia , decreases the number of natural killer cells, and seems to downregulate the expression of lymphocyte function-associated antigen-1 on activated T cells. The presence of soluble CD4, CD8 and MHC-II molecules in IVIg theoretically could interfere with antigen recognition by the T cells. The function of CD8+ T cells may also be inhibited by antibodies in IVIg administered against a preserved region of MHC-I molecules.

Medicine has its office, it does its share and does it well; but without hope back of it, its forces are crippled and only the physician's verdict can create that hope when the facts refuse to create it.

- Mark Twain -