248
Erroneous activation of many inflammatory mediators is found associated with
many autoimmune disease manifestations, suggesting the inflammatory connection
in the pathophysiology of autoimmune disease development. Autoimmunity is classified as type III hypersensitivity reactions in which the autoantibody binds to selfantigens present in tissue or in circulation. The resulting freely circulating complexes
may eventually become heavy and insoluble over time, resulting in their accumulation in the tissues and blood vessels, which ultimately triggers the activation of
complement and T cells, leading to uncontrolled inflammatory reactions. As a direct
consequence, localized cell death occurs, and the function of the tissue or even the
organ would be lost due to blockage of blood vessels by clot formation (e.g. vasculitis in systemic lupus erythematosus). T cells sensitized to self-antigens may cause
tissue damage through the release of lymphokines (e.g., TNF), which either directly
damage the tissues or attract inflammatory cells to the site. These events initiated by
self-reactive T cells result in the type of pathology typically associated with type IV
hypersensitivity. Current therapies for autoimmune diseases include treatment with
immune-compromising drugs, thymectomy, and plasmapheresis, and for diseases
involving immune complexes, T-cells-specific vaccination for a given autoantigen,
administration of synthetic blocking peptides that compete with autoantigen and,
treatment with monoclonal antibodies that react with some component specifically
involved in an autoimmune/inflammatory reaction. Autoimmune disorders are
either mediated by autoantibodies or activated TH1 cells. Goodpasture’s disease is
caused by the autoantibodies activated against basement membrane antigens of the
kidney glomeruli and lung alveoli followed by the activation of complement split
products leading to progressive nephropathy and pulmonary hemorrhage.
Etiologically, type 2 diabetes is also categorized as an autoimmune disease in which
the autoimmune attack on pancreatic β cells via activated cytotoxic T cells and autoantibodies leads to clinical complications of insulin deficiency. Local production of
many cytokines such as IFN-γ, TNF-α, and IL-1 are increased during its pathogenesis, thereby aggravating the disease complications. The systemic autoimmune diseases are directed against a broad spectrum of tissues and have manifestations in a
variety of organs resulting from cell-mediated responses and cellular damage caused
by autoantibodies or immune complexes. A number of autoimmune diseases stem
from circulating complexes of antibody with self-proteins, with glycoproteins, or
even with DNA such as in systemic lupus erythematosus. Rheumatoid arthritis (RA)
is a chronic, multiple, invasive autoimmune disease with two chief clinical manifestations, arthrosynovitis and exarthrosis, and is a long-lasting autoimmune disorder
that primarily affects joints. TNF-α and interleukins such as IL-1, IL-6, and IL-8 are
the important cytokines implicated in the RA pathophysiology. Hyperinflammation
via increased activation of these cytokines triggers hyperproliferation of synovial
tissues and infiltration of blood-derived cells, resulting in the erosion of cartilage
and bones. Inhibition of TNF-α has been attributed as a promising approach toward
its treatment. Other diseases that may present similar attributes include systemic
lupus, psoriatic arthritis, and fibromyalgia. Rheumatoid arthritis is featured by the
generation of rheumatoid factors which are reactive against the Fc region of immunoglobulin. Autoantibodies bind to circulating IgG and form IgM.IgG complexe
B.C. Bhavya and M. Haridas
Erroneous activation of many inflammatory mediators is found associated with
many autoimmune disease manifestations, suggesting the inflammatory connection
in the pathophysiology of autoimmune disease development. Autoimmunity is classified as type III hypersensitivity reactions in which the autoantibody binds to selfantigens present in tissue or in circulation. The resulting freely circulating complexes
may eventually become heavy and insoluble over time, resulting in their accumulation in the tissues and blood vessels, which ultimately triggers the activation of
complement and T cells, leading to uncontrolled inflammatory reactions. As a direct
consequence, localized cell death occurs, and the function of the tissue or even the
organ would be lost due to blockage of blood vessels by clot formation (e.g. vasculitis in systemic lupus erythematosus). T cells sensitized to self-antigens may cause
tissue damage through the release of lymphokines (e.g., TNF), which either directly
damage the tissues or attract inflammatory cells to the site. These events initiated by
self-reactive T cells result in the type of pathology typically associated with type IV
hypersensitivity. Current therapies for autoimmune diseases include treatment with
immune-compromising drugs, thymectomy, and plasmapheresis, and for diseases
involving immune complexes, T-cells-specific vaccination for a given autoantigen,
administration of synthetic blocking peptides that compete with autoantigen and,
treatment with monoclonal antibodies that react with some component specifically
involved in an autoimmune/inflammatory reaction. Autoimmune disorders are
either mediated by autoantibodies or activated TH1 cells. Goodpasture’s disease is
caused by the autoantibodies activated against basement membrane antigens of the
kidney glomeruli and lung alveoli followed by the activation of complement split
products leading to progressive nephropathy and pulmonary hemorrhage.
Etiologically, type 2 diabetes is also categorized as an autoimmune disease in which
the autoimmune attack on pancreatic β cells via activated cytotoxic T cells and autoantibodies leads to clinical complications of insulin deficiency. Local production of
many cytokines such as IFN-γ, TNF-α, and IL-1 are increased during its pathogenesis, thereby aggravating the disease complications. The systemic autoimmune diseases are directed against a broad spectrum of tissues and have manifestations in a
variety of organs resulting from cell-mediated responses and cellular damage caused
by autoantibodies or immune complexes. A number of autoimmune diseases stem
from circulating complexes of antibody with self-proteins, with glycoproteins, or
even with DNA such as in systemic lupus erythematosus. Rheumatoid arthritis (RA)
is a chronic, multiple, invasive autoimmune disease with two chief clinical manifestations, arthrosynovitis and exarthrosis, and is a long-lasting autoimmune disorder
that primarily affects joints. TNF-α and interleukins such as IL-1, IL-6, and IL-8 are
the important cytokines implicated in the RA pathophysiology. Hyperinflammation
via increased activation of these cytokines triggers hyperproliferation of synovial
tissues and infiltration of blood-derived cells, resulting in the erosion of cartilage
and bones. Inhibition of TNF-α has been attributed as a promising approach toward
its treatment. Other diseases that may present similar attributes include systemic
lupus, psoriatic arthritis, and fibromyalgia. Rheumatoid arthritis is featured by the
generation of rheumatoid factors which are reactive against the Fc region of immunoglobulin. Autoantibodies bind to circulating IgG and form IgM.IgG complexe
B.C. Bhavya and M. Haridas