RA/SLE Flashcards
What is the sex bias with RA and SLE?
mostly women are affected, RA especially develops during younger years
What are some common symptoms of RA?
joint pain and stiffness in the morning with persistent swelling (bilateral and symmetrical – not on a weight bearing joint)
What is epitope spreading?
IS sees one thing initially, then it sees more epitopes
Why does smoking tend to trigger RA?
smoke citrullinates peptides via PAD2/4, so the IS sees a new Ag and produces ACPAs (anti citriullinated protein Abs)
what is a tertiary lymphoid structure?
congregation of ICs where they shouldn’t be – produce germinal centres
Where in the joint during RA is the teritiary lymphoid structure/inflammatory pannus? What are some characterisitics of IC infiltration of the joint?
in the marginal area – in the synovium
enhanced blood flow
enhanced angiogenesis
Describe how inflammation causes RA
Ab + C1q = immune complexes
Ab + C1q –> macrophages –> activates osteoclasts + RANKL
RANKL –> activates osteoclasts
What causes mortality in younger patients with RA?
CVD
What are common symptoms of SLE?
- previous clots
- ongoing joint stiffness and pain in the morning with intermittent swelling and chest pain (similar to RA expect with the addition of chest pain)
- photosensitive rash/hives –> especially the butterfly rash on face
As lupus gets more aggressive, where do you see more complement deposition?
kidneys – glomerulus
What Ab isotypes can mediate the classical complement cascade?
IgM and IgG
Describe the complement pathway for all three cascades
classical: Ag-Ab complex + C1, C4, C2 –> C3 convertase (C3 –> C3b) –> C5 convertase (C5 –> C5b) –> C5b, C6, C7, C8, C9 –> MAC
alternative: activating surfaces (e.g. LPS) –> C3b + factor B + factor D –> C3 convertase –> etc
lectin: C4, C2, MBL –> C3 convertase –> etc
What triggers the lectin pathway and the alternative pathway, respectively?
lectin = bacterial slime basically
alternative = inflammation
Besides Abs and lectins, what can trigger complement?
NETs from neutrophils
Describe the pathogenesis of SLE
- infection, UV light and drugs can trigger apoptosis
- apoptotic material, rich in lupus autoAg, promotes the activation of DCs and B cells and the production of IFN and autoAbs, respectively
- autoAgs are pesented by DCs –> T cell activation
- activated T cells help B cells to produce Abs by the secretion of IFNg, IL-17, and by cell surface molecules (e.g. CD40L and CTLS4)
- production of autoAbs is driven by the availability of endogenous Ags and is highly dependent up T cell help, mediated by cell surface interactions (CD40/CD40L) and cyotkines (IL-21)
- T cell independent mechanisms of B cell stimulation may occur via combined BCR and TCR signaling
- in lupus nephritis, pCDs infiltrate the kidney
What kind of mortality is SLE associated with?
all cause mortality
Describe two ways in which complement activation can cause thrombosis or hemolysis
- PNH: cells lack the complement inhibitors CD55 and CD59 –> chronic surface activation of complement –> hemolysis and thrombosis
- APS/CAPS: aPl-Abs bind to platlets surfaces –> activate complement –> thrombosis
why are clots common in SLE pts?
damage to endothelium from autoAbs –> complement activation + NETosis –> thrombosis
what are four autoimmune cytopenia manifestations of SLE?
- hemolytic anemia
- neutropenia
- lymphopenia (Tregs are depleted)
- thrombocytopenia (less platlets)
Why are cytopenias bad?
- infection: more restrictured TCR repertoire, more opportunistic infections, fewer PMNs
- more bleeding
- more clotting
- epitope spreading and more survival advantages of self-reactive T cells (less diverse T and B cell populations –> expansion of reactive lymphocytes)
