Rheumatoid Arthritis Immunology

Rheumatoid Arthritis Immunology

Cellular and chemical mechanism involved in development of rheumatoid arthritis and study ways for blocking disease causing agent or induce tolerance

Human sample – synovial fluid and blood

Animal model -mice

Purpose discusses pathways and methodology to examine;

• Cellular interaction – expansion of fibroblast-like cells

-Immune cell infiltration and activation

• Antibodies – RF and Citrulinated Abs
• Cytokines

Introduction

Rheumatoid arthritis (RA) is an autoimmune infection characterised by joint inflammations though not restricted to the joint, the disease affects equally other body organs and tissues. The principle diagnosis is through the skin or joint serum screening or diagnosis. The infection attacks through a precise cause of the irreparable damage to the affected body parts due to the inflammation of the synovial membrane, which formed the tendon sheath and joint lining. Besides, the disease destroys the joint tissues and reduces the joint mobility through erosion and tethering of the tendons. Hence, it makes the muscles to become fixed to the adjacent tissues, which in the process restrain movement of the patient. The condition accelerates the loss of the functional characteristic of the affected limb or organ hence accelerate the emergence of deformity.

Furthermore, the existence of monocytes chemoattractant protein- 1 generated from the osteoclasts involved in the production of the cytokines alongside the life of supper families like the IL-10, IL-28, and IL -29 accelerate anti inflammatory contributions of the arthritis. The progress in the bone degradation and bone erosion induces radiographic progression attached to the induced cytokines available in the RA linked to the signal transducer and activator to the transcription pathway. Hence, it activates protein kinase B for the extracellular signal regulated through the mitogen-activated protein kinase.

Mechanism of RA Development

The existence of anti-citrullinated protein antibody from the catalysed calcium dependent enzyme peptidtlarginine deiminase facilitated post translational modifications enhances detection of the RA in patients with different genetic association. However, the immune response to the RA infection tend to advance in severity thus, it impede the performance certainty of the prominent pathophysiological differences. The concept of gene mutation accelerates the frequency with which the infection survives through the immune system of the patient. Besides, the multistage diagnosis attached to the elevated levels of the RA specificity accelerate detection through a range of citrullinated protein associated with gene encoding attributed to the stronger genetic risk factors. The steady consideration of gene performance of an individual to the antitrypsin deficiency accelerates the impact of the RA in a patient with protein inhibitor genes. The interpretation of epigenetic conditions affects gene interaction and accelerates the severity with which the RA takes place within the patient. However, the constant exposure to dangerous environmental condition s that affect average body functions like the dusty place, smoking, among others weaken the immune system of an individual creating room for the emergence of opportunistic infections.

The suppression of the antigen by the toxic environmental conditions triggers the transformation of the genes in a manner that accelerate mutation and future occurrence of the RA among different people. The progressive development of the mutation stages on the secondary lymphoid tissues that suffer from the release of self-antigen that endangers the immune response to the epitopes. The tendency affects the microbial resistant that, in turn, jeopardizes the neoantigen tolerance of the ACPA, thus elevate the levels of inflammation development on the patient’s soft tissues and the joints.  The presence of-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA) promote the extent of immunity with an autoimmune response to the activity of the enzymes within the body. The progressive in microvascular and biomechanical accelerate the implication of chemical mechanisms attached to the development of RA among the vulnerable individuals in the society.

The steady interaction of the fibroblasts accelerates the inertia immune through the monocyte interpolation that steadily affects the progress and performance of the T-lymphocytes. The consistency with which the deterioration of the membranes affects the monocytes advances the immune decay in expense of the inflammatory infections. The alternative pathway involve neutrophil NETosis, nature killer cell activation, the approach operate on the antigen driven and cytokines released by the specific cells as the principle diver to the abnormal immunity in the RA through sustained chronic synovitis. Hence, it boosts the proinflamatory cell metabolism anchored on the immune complex-mediated compliment activation, for the adaptive immune response against self antigen and the abnormal response to the immunologic homeostasis.

However, the condition on the skin accelerates formation of nodules and vesculitis that steadily accelerate destruction process of the blood vessels. Constant cartilage destruction regenerates into pain, fever, swelling and tenderness of the affected body parts. For the RA infection, the joint involvement remains symmetrical. The focus on rheumatic factors and diagnostic elements facilitate precise diagnosis for the infection to accelerate better medication initiation. The antibody erythrocyte sedimentation rates alongside the C-reactive protein (CRP) antibodies and erythrocyte sedimentation remains viable diagnostic approach of the infection. However, the RF sensitivity report provided significant information on its prevalent in the region. The increased levels of RF in the body advance the chances of developing the rheumatic arthritis among the population. The infection tent to affect female figure more compared to the similar cases in males. The focus on biological makers in the RA patients like the rheumatoid factor (RF) and antibodies circulation facilitate the process of radiographic tests that reflect the potential risk level attached to the process.  The adoption of unregulated tests for the RF test that leads the false positive data while the adoption of RF tests for the RA diagnosis may incorporate the RF approach that analyses the synovium made up of calls called the fibroblast like synoviocytes (FLS) cells that are significant for the performance e of the RA pathogenesis.  Thus, it triggers the known RA supported by few theories that explains the emergence of the immune systems that explains the migration process of the cells to the affected jointed.

The development of RA infections  span from the genetic, epigenetic modification, where the rise is on the monozygotic  up to 15% compared to the case of dizygotic twin of about 3%. The increasing frequency for the first degree of the patient with joint infection involved the synovial injury and hyperplasia. The progressive infection on the joints triggers the release of a cytokines that causes the inflammations of the joint. However, steady modifications of the antigen through citrullination make the immune system to recognise an antigen as a foreign body. consecutively, the antigen presenting cell (APC)  will recognizes the adjusted antigen in the system thus enhances activation and migration to the limp nodes leading to the formation of the germinal centres locate and centred at the B. Cells. Besides, the activated T cells in the lymph nodes generate the CD4+ T Cell activations. The adoption of stimulation process accelerates the formation of the B calls in the G C that proliferate and form the plasma cells that produces the auto-antibody against the modified antigen that migrates through the receptors to join the body tissues.

Hyperplastic synovium

The condition emanate from a mixture of bone marrowsderived microphages and the specialised FLS. The synovial cells helps in maintaining the steady

Cytokines

The cytokines constitute specific receptors in the immune cells of the patient alongside the epithelial cell and fibroblasts coordinate the body immune response to perceived genotypic infections.  The rheumatic diseases depending on the unbalanced production of inhibitory cytokines accelerate the production of pro-inflammatory cytokines that advances the chronic inflammatory conditions among the diverse patient base. The existence of pleiotropic cytokine that accelerate immune regulation through the binding process to the receptor TNR-RI and the TNF-RII produced through multiple cell types and the inert immune cells. The collective contribution of the cells generates chronic inflammation of the RA type among different patient as accelerated through antigen presentation or the co-stimulation. The consistencies with which the patient displays the respectability to the antigen receptor accelerate the endothelial cell junction and inversion of the inflamed tissues due to the presence of the interferon in the cells.

Furthermore, the adaptive immune response in the RA incorporate auto reactive of the B-cell and the production of the rheumatoid factor (RF) auto antibodies and anti-cyclic citrinullated peptides (CCP) antibodies. The presence of a two-sided immune response, for example the immunity that provides protective response, deregulation of the inflammatory response leading to chronic inflammations plays a major role in the propagation of the infection and for an extended period regenerate to age related RA infections.  The presence of microphages constitutes the first line of defence that plays the pivotal roles in the induction and progression of the inflammatory progress as in the prolonged activation of the cells leading to the pro-inflammatory cytokines and inflammatory mediators. Consequently, the deregulated inflammatory responses accelerate emergence of the cycle of chronic inflammations. The present cytokines and matrix metalloproteinase’s secreted by infiltrating macrophages facilitate the T-cell activation proliferation and cell to cell interactions that accelerate tissue damages leading to inflammation propagation and joint damages.