University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

423

Pages:

1
Author:

Mariam A. A.

RHEUMATOID ARTHRITIS Triggers & Genetics (Top Left): broad suseptibility davlont -> PTPN22 Genetics: HLA DR-1 & HLA DR4, CTLA-4, STAT 4 environmental: e.g. smoking, silcon, lights' dust, peridontis some injury: e.g. microbial, mechanical Pathogen: I pathogen with PAD Amps -> arginine de-aminase enzyme people in smokes -> converts arginine into citrulline Citrullination Process: Type II collagen & other proteins -> arginine -> (Post-translational modification) -> citrulline Immune Response Activation (Center/Right): Foreign recognition T-cells -> Th1-Th17, IL-17 -> Synovial Cell Activation Synovial cells release -> TNF-α, IL-1, IL-6 This leads to auto antibodies -> proliferation OS, macrophage, mast cell bind with FcγR -> degranulation -> IL-1, TNF-α Interaction between T-cells and Antigen Presenting Cells involves: TCR, MHCII, CD28, CO-STIM anti-citrullinated protein antibody [CRP] is present. osteoclast -> RANK-L synovial cells -> VEGF & PMKL Also involved: IL-1, IL-6, TNFα, MPSI Pannus Formation (Top Right): Results in -> thick & swollen synovial membrane with granulation or scar tissue. This forms a Pannus made out of -> myofibroblasts and inflammatory cells composed of -> immune cells + synovial cells Leads to Fibrosis -> cartilage, soft tissue damage + bone erosion Cells in the pannus become activated -> Protease release -> break down cartilage tissue -> underlying bone exposed Inflammatory Cascade (Bottom): immune complexes -> accumulate in synovial fluid -> complement system -> pain, proinflammatory, bradykinin, oedema chronic inflammation -> VEGF -> angiogenesis -> φ inflammatory cell migration Vasodilation (caused by IL-1, TNF-α) -> leads to leukocyte recruitment (neutrophils, macrophages) -> Fluid move to synovial strium -> inflammatory exudate + swelling -> synovitis Antibody Production (Bottom Right): plasma cell produces antibodies against citrullinated protein in joints new antibody -> anticitrullinated fibrinogen antibodies -> bind to citrullinated fibrinogen -> [Qch-I] -> immune complexes