The main culprit of RA, autoreactive B-cells also play role in autoantibody production, T-cell activation and pro-inflammatory cytokine production that ultimately contribute to RA pathogenesis [11].
B lymphocytes play several critical roles in the pathogenesis of rheumatoid arthritis. They are the source of the rheumatoid factors and anticitrullinated protein antibodies, which contribute to immune complex formation and complement activation in the joints.
In rheumatoid arthritis (RA), T cells infiltrate into the synovial membrane where they initiate and maintain activation of macrophages and synovial fibroblasts, transforming them into tissue-destructive effector cells.
Some studies have been performed to evaluate the role of Treg cells in RA, and there is controversy regarding the relative number and function of CD4+CD25+ Treg cells in RA [79, 80]. Treg cells have been identified in peripheral blood and synovial tissue of patients with RA [80–82].
RA was classically considered a type 1 T helper (Th1)-mediated disease, but today data indicate that type 17 T helper cells (Th17) are more important in its promotion. Evidence shows that type 22 T helper cells (Th22) also contribute to RA pathogenesis.
During the onset of RA, B cells can promote the activation, proliferation, and differentiation of other cells such as T cells, monocytes, and osteoclasts in the synovium by providing cytokines, autoantibodies and other mediators.
TNF (tumor necrosis factor) is both a pro-inflammatory and anti-inflammatory cytokine that is central to the development of autoimmune disease, cancer, and protection against infectious pathogens. As well as a myriad other activities, TNF can be a product of T cells and can act on T cells.
Based on the concept that activated T cells are the key mediators of chronic autoimmune inflammation, various T-cell directed therapeutic interventions have been introduced for the treatment of RA. Comprehensive reviews have discussed the concepts and the clinical efficacy of T-cell directed therapy in RA [79-82].
Although effector and memory T cells coordinate cutaneous immune responses against microorganisms and cancer, aberrant or inappropriate T cell activation against innocuous or auto-antigens can lead to chronic inflammatory disorders of skin.
In the susceptible host, additional T cells are recruited to sites of inflammation through bystander activation, or by stimulation with self antigens released from inflamed tissues. As the inflammatory process progresses, chronic cytokine production induces profound nondeletional T-cell hyporesponsiveness.
The Epstein-Barr virus isn't the only virus suspected as an infectious agent in RA. Other examples include retroviruses and parvovirus B19, which causes fifth disease.
People born with specific genes are more likely to develop RA. These genes, called HLA (human leukocyte antigen) class II genotypes, can also make your arthritis worse. The risk of RA may be highest when people with these genes are exposed to environmental factors like smoking or when a person is obese. Smoking.
A number of hormonal abnormalities are present in RA patients. A major theme of these abnormalities seems to be that deficiencies in the production or action of gonadal (estrogens and androgens) and adrenal (corticosteroids and DHEA) hormones may be involved in regulating the onset, severity, and progression of RA.
Abstract. CD4+ helper T type 1 (Th1) and Th2 cells are critical mediators of inflammatory diseases. Although T cells represent only a fraction of the leukocytes that are found in the lung during inflammation, they play a critical role in coordinating the immune response to infectious agents and allergens.
A large body of human and murine studies has established multiple mechanisms by which T cell dysfunction promotes systemic autoimmunity in a variety of common rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), myositis, psoriasis/psoriatic arthritis, and vasculitis (15).
Activated macrophages, monocytes, and other cells mediate local responses to tissue damage and infection. At sites of tissue injury, damaged epithelial and endothelial cells release factors that trigger the inflammatory cascade, along with chemokines and growth factors, which attract neutrophils and monocytes.
B cells have protective functions through the provision of anti-inflammatory cytokines in autoimmune diseases, [29], [30].
IL-10-secreting regulatory B-cells have an anti-inflammatory role in murine obesity [114]. Nishimura, et al. recently identified a distinct set of IL-10 secreting B-cells, which negatively regulate adipose tissue inflammation [115].
TNF (a.k.a. cachectin or cachexin, and formerly known as TNF-α) is predominantly produced by macrophages, but can also be secreted in limited quantities by B cells, natural killer cells, endothelial and muscle cells, fibroblasts, and osteoclasts.
Naive CD8 T cells produce both membrane-bound and soluble TNF-α TNF-α exists in two active forms, a membrane-bound form and a soluble form (30). We examined the ability of naive CD8 T cells to produce both forms of TNF-α during the first 4 h of TCR engagement.
There are 3 main types of T cells: cytotoxic, helper, and regulatory. Each of them has a different role in the immune response. Cytotoxic T cells (Tc cells) have a co-receptor called CD8 on their cell surface.
Each B cell produces a single species of antibody, each with a unique antigen-binding site. When a naïve or memory B cell is activated by antigen (with the aid of a helper T cell), it proliferates and differentiates into an antibody-secreting effector cell.
B-cells are the type of cells that produce antibodies to fight bacteria and viruses. These antibodies are Y-shaped proteins that are specific to each pathogen and are able to lock onto the surface of an invading cell and mark it for destruction by other immune cells.
B cells differentiate to plasma cells and secrete autoantibodies (4). These autoantibodies form autoantigen-autoantibody complexes that bind to the FcγR on other APCs (5). This enhanced antigen presentation eventually triggers both natural killer cells and CD8+ T cells to attack the pancreatic beta cell.