Immunology Flashcards
What are the 3 groups of immune mediated diseases which affect the joints?
1) Rheumatoid arthritis
2) Juveline arthritis
3) Spondyloarthritis
What is Rheumatoid arthritis?
chronic, inflammatory disorder
Which tissues does Rheumatoid arthritis target?
1) synovial lining of joints
2) bursae
3) tendon cheaths
4) cartilage
5) bone
What are the characteristic antibodies for Rheumatoid arthritis?
1) RF (Rheumatoid factor)
2) ACPA (anti-cyclic citrullinated peptide)
Are males or females more susceptible to Rheumatoid arthritis?
females
What is the role of HLA in Rheumatoid arthritis?
DR4 subtypes of DRB1 alleles may bind pathogenic epitopes (particualrly thsoe containing citrulline) and alter negative selection in the thymus
What is PTPN22?
Protein Tyrosine Phophatase Lyp in RA; active in hematopoetic tissues
What is PADI4?
Peptidyl Arginine Deiminase type IV in RA; enzyme whcih converts arganine to citrulline
What is the series of events in the immunobiology of RA?
- acute initiating events (tissue damaeg)
- synovial fibroblasts stimulated by damage
- innate immune system activated
- stimulation of adaptive immune responsive
Which types of T-cells are activated in the adaptive immunity of RA?
CD4+ Th1 and Th17
CD8+
How do Th17 cells enhance inflammation in RA?
produce cytokines which suppress Treg cells
Which bacterium are Th17 cells important in providing defense against intracellular bacteria?
M. tuberculosis
What is the Rheumatoid factor?
IgM anti-IgG with specificity to the Fc region of IgG
What is citrullination?
post-translational modification of arganine
What is the purpose of citrullination?
HLA-DR4 molecules preferentially bind to citrullinated peptides
What is the anti-cyclic citrullinated peptide (ACPA)?
measures IgG antibodies in RA
What does a positive ACPA test in early RA predict?
more severe disease with development of erosive arthritis sooner
What is the role of IL-1 in RA?
activates monocytes/macrophages to cause inflammation
What is IL-1Ra?
IL-1 receptor antagonist; produced constitutively and during inflammation and binds but does not activate IL-1 receptor
What is the role of TNF-alpha in RA?
inflammation; fever and macrophage activation
Which factors do monoclonal antibodies target in RA therapies?
1) TNK-alpha
2) IL-6 receptor
3) B cells
Which factors do TNF-receptors target in RA therapies?
TNF-alpha
Which factors do receptor antagonists target in RA therapies?
IL-1
Which factors do CTLa4-Ig fusion proteins target in RA therapies?
CD80/86
What is Juvenile Idiopathic Arthritis?
chronic arthritis occurring before 16 yo; unknown cause
Is there a gender preference in Juvenile Idiopathic Arthritis?
NO
What is the pathogenesis of Juvenile Idiopathic Arthritis?
Th1 mediate inflammation
What are the autoantibodies in Juvenile Idiopathic Arthritis?
1) RA
2) ACPA
3) ANA
What is the synovial inflammation of Juvenile Idiopathic Arthritis?
1) mononuclear cells (B, T, macrophages, dendritic cells)
2) T cells (CD4+ Th1)
Which cytokines are released in Juvenile Idiopathic Arthritis?
1) IL-1
2) IL-6
3) TNF-alpha
What is spondyloarthritis?
heterogenous group of inflammatory diseases which include spinal and peripheral joint arthritis
Why do only a subset of HLA-B27 positive individuals (5%) develop disease?
HLA-B27 is a class I HLA molecule . While most individuals with SpA are B27 positive, not all B27 positive individuals develop disease
What are the immune abnormalities in SpA?
1) increased macrophages/monocytes
2) upregulation of TLR2 and TLR4
3) infiltration of synovium with CD8+ T cells
4) presence of TNF-alpha, IL-1
5) responsive to anti-TNF treatment
What serve as targets for immune based therapy?
inflammatory cytokines
