Rheumatoid Arthritis

Cure Arthritis Naturally

Cure Arthritis Naturally

Get Instant Access

Rheumatoid arthritis (RA) is an inflammatory disease involving small and large joints of the extremities, including fingers, shoulders, elbows, knees, and ankles. The

Susceptibility genes

External triggers (e.g., UV radiation)

Apoptosis

Apoptosis

Defective clearance of apoptotic bodies

Increased burden of nuclear antigens

B and T cells specific for self nuclear antigens ■

Antinuclear antibody, antigen-antibody

Endocytosis of antigen-antibody complexes i_i i-1

TLR engagement of nuclear antigen in endosomes

Stimulation of B cells and DCs

Antinuclear antibody, antigen-antibody

Stimulation of B cells and DCs

Rheumatoid Arthritis Immunology

FIGURE 18-9 A model for the pathogenesis of systemic lupus erythematosus (SLE). In this hypothetical model, various susceptibility genes interfere with the maintenance of self-tolerance, and external triggers lead to persistence of nuclear antigens. The result is an antibody response against self nuclear antigens, which is amplified by the TLR-dependent activation of dendritic cells and B cells by nucleic acids, and the production of type I interferons.

FIGURE 18-9 A model for the pathogenesis of systemic lupus erythematosus (SLE). In this hypothetical model, various susceptibility genes interfere with the maintenance of self-tolerance, and external triggers lead to persistence of nuclear antigens. The result is an antibody response against self nuclear antigens, which is amplified by the TLR-dependent activation of dendritic cells and B cells by nucleic acids, and the production of type I interferons.

disease is characterized by inflammation of the synovium associated with destruction of the joint cartilage and bone, with a morphologic picture indicative of a local immune response. Both cell-mediated and humoral immune responses may contribute to development of synovitis. CD4+ TH1 and TH17 cells, activated B lymphocytes, plasma cells, and macrophages as well as other inflammatory cells are found in the inflamed synovium, and in severe cases, well-formed lymphoid follicles with germinal centers may be present. Numerous cytokines, including IL-1, IL-8, TNF, IL-6, IL-17, and IFN-y, have been detected in the synovial (joint) fluid. Cytokines are believed to recruit leukocytes whose products cause tissue injury and also to activate resident synovial cells to produce proteolytic enzymes, such as collagenase, that mediate destruction of the cartilage, ligaments, and tendons of the joints. Increased osteoclast activity in the joints contributes to the bone destruction in RA, and this may be caused by the production of the TNF family cytokine RANK (receptor activator of nuclear factor kB) ligand by activated T cells. RANK ligand binds to RANK, a member of the TNF receptor family that is expressed on osteoclast precursors, and induces their differentiation and activation. Systemic complications of RA include vas-culitis, presumably caused by immune complexes, and lung injury.

Although much of the emphasis in studies of RA has been on the role of T cells, antibodies may also contribute to the joint destruction. Activated B cells and plasma cells are often present in the synovia of affected joints. Patients frequently have circulating IgM or IgG antibodies that react with the Fc (and rarely Fab) portions of their own IgG molecules. These autoantibodies are called rheumatoid factors, and their presence is used as a diagnostic test for RA. Rheumatoid factors may participate in the formation of injurious immune complexes, but their pathogenic role is not established. Another type of antibody that has been detected in at least 70% of patients is specific for cyclic citrullinated peptides (CCP), which are derived from certain proteins that are modified in an inflammatory environment by the enzymatic conversion of arginine residues to citrulline. These so-called anti-CCP antibodies are a diagnostic marker for the disease and may be involved in tissue injury.

Was this article helpful?

0 0
Osteoarthritis

Osteoarthritis

Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.

Get My Free Ebook


Post a comment