Pathogenesis of immune disease Flashcards
WHat is RA?
Chronic Synovitis-can cause damage-happens in synovium
caused my rheumathoid factor and anti-cyclic citrullinated peptide antibodie
What is ankylosing spondylitis?
Arthiritis but no rhumathoid factors
Affects the spine-and the lumbar spine (RA only affects Cspine)
Ankylosing-bone effusion Spondylytis-of the spine
NO ANTIBODIES
Inflammation of enthesitis of where fibrosum annulosus insert in the bone
can lead to calcification and stock stuck in place
What is SLE?
Systemic lupus erthyramtosus
Chronic tissue inflammation in presence of antibodies vs self antigens-nuclear AG
has a lot of immune complexes
autoantibodies-antinuclear antibodies, dsDNA antibodies (main one)-histone complexes
What are HLA molecules? Which one are associated with which autoimmune disease?
Human leukocyte antigens-form the MHC-important for recognising self and foreign AG
Class 1-HLA A/B/C
Class 2-DR/DQ/DB-present foreign AB
strong genetic association in RA, SLE and AS
RA-DR4
SLE-DR3
B27 (class 1)-AS (but like can make rats develop AS without CD8 cells-which would be activated by B27-so maybe misfold in cell and cause stress -> cytokines)
doesnt mean if you have these you have the disease-but just very common in diseases patients
WHat are the 4 main autoantibodies in rheumathology?
RA-rheumathoid factor and anti-cyclic citrulinated peptide AB
SLE-Antinuclear AB, Anti dsDNA AB
=> investigate if not obvious
in others- OA, reactive arthiritis, gout, ankylosing Spongolytis-NONE
Other connective disease have AB-and can overlap
Which rheumathoid antibodies are the most useful in SLE? What information do they give? relation between dsDNA-AB and complement
ANA-seen in ALL SLE, but not only in SLE-not specific if dont know which nuclear AG is binding too (eg: Anti-SM is for lupus)
Anti dsDNA-only in SLE -diagnostic
can use dsDNA AB to measure activity of immune complexes-indicate flaring of the disease when rise-can tell before patient–very useful
As it activate complement, it gets used up-expect complement to be LOW
immune complexes cause inflam either by binding Ig receptors
Other is complement system (recognise it)
What is the role of cytokines in causing rheumathoid disease?
TNFa-very important in RA-leukocyte accumulation, chemokine release, PGE2 production
many other cytokines in role, but TNFa main one-if inhbited everything goes down
Other is RANKL-important in bone destruction in RA
activated by NFKB-produces by T cells and activates osteoclasts
SLE-B cell hyper-reactivity-use antiBcell ABs-deplete B cells (eg Rituximab (anti CD20), or belimumab vs BLYS (B lymphocye stimulator)
What is the role of prostaglandin in autoimmune rheumathoid diseases?
Lipid mediators of inflammation
Prostaglandin inhbition can cause reduction of pain and swelling-reduce disease pain BUT not reduction of the damage
NSDAIDs-inhbit COX and production of these
