Final (SLE AND MS) Flashcards
SLE is different than RA because its a ___________ autoimmune disease
systemic
SLE affects what population more?
women
ethic
What are 5 common themes of SLE?
- auto-reactive B cells
- anti-nucleic acid auto-Ab
- pDCs
- TLR7/9
- IFN-a
where are auto-reactive B cells made in SLE?
extra-follicular B cell activation
How are anti-nucleic acid auto-Ab made in SLE?
cell damage from mutations exposes nucleic acids
How are pDCs involved in SLE?
DNA/RNA released from damaged cells is recognized by pDCs TLR7/9 activating them
How is TLR-7/9 involved in SLE?
recognizes released DNA/RNA from cell damage
How is IFN-a involved in SLE?
produced by activated pDCs when their TLRs recognize RNA/DNA from damaged cells
**all nucleated cells have IFN-a receptors
What is the SLE loop?
production IFN-a from activated pDCs activates formation of auto-reactive B cells and anti-nucleic acid auto-Abs
What induces the formation of auto-reactive B cells and anti-nucleic acid auto-Abs in SLE?
secretion of IFN-a
What is the entry criteria for SLE?
positive ANA
What is ANA?
antibodies against nuclear material
What are 3 ANAs in SLE?
- anti-dsDNA
- anti-histamine
- anti-Smith (RNA)
What is the clinical criteria for SLE?
fever
nephritis
seizures
What is the SLE flare?
waxing and waning of SLE symptoms
During the SLE flare what is elevated?
anti-DNA Ab
TLR-9 activated pDCs
IFN-a
* increased risk of nephritis and cardiac events
What is the immunological criteria for SLE?
decreased C3 and C4
increased anti-dsDNA & anti-Smith Ab
What does it mean when C3 and C4 is low?
less complement activation = less tagging and clearance = more chance for B cells to encounter DNA/RNA and produce auto-Ab
What is the best immunological marker for SLE?
anti-Smith Ab
What are 3 possible sources of DNA/RNA that activates pDCs in SLE?
- cell damage + LL37 + TLR-7 + pDCs
- RNA/DNA Ab internalized by pDCs
- loss of function of DNASE1L3
What is the regular function of DNASE1L3?
breaks down DNA/RNA from apoptosed cells
How does the loss of function of DNASE1L3 play a role in SLE?
large DNA/RNA from apoptosed cells cannot be broken down resulting in activation of pDCs (TLR-9/7) = IFN-a secretion
What gene makes SLE a monogenic disease?
DNASE1L3
Belimumab is an anti-BAFF treatment for SLE. How does it work?
prevents auto-reactive B cells from leaving the spleen
(BAFF is a B cell survivial signal)
Anifrolumab is a ant-IFNRA treatment for SLE. How does it work?
prevents mDCs from signaling to B cells to create auto-reactive B cells
Vocolsporin is a anti-Cal & synaptopin protecting drug. How does it work?
prevents transcription of NFAT = decreased T cells and cytokine production
protects podocytes (kidney filatration cells) *stabalizes cytoskeleton
What is multiple sclerosis?
neuroinflammatory disease caused by immune complexes infiltrating the blood brain barrier
What is the clinical manifestation of MS?
lesions on CNS caused by immune complex mediated inflammation
What cells cause damage to the myelin sheath in MS?
CD8+ T cells and Ab attach to attract other immune cells
What are the 3 types of MS?
- relapsing-remitting
- secondary progressive
- primary progressive
What is relapsing-remitting MS?
waxing and waning of symptoms
* increased inflammation and demylenation when waxing
Where are lesions on brains seen and by what imaging?
NMR
white matter
What is secondary progressive MS?
waxing and waning but overtime recovery is eventually not possible
What is primary progressive MS?
never experience remission (directly to progressive disease)
What does it mean that the brain is immune privileged?
there is typically not immune responses there
Where does immune response initiate in MS?
outside of CNS CD8+ T cells are activated then cross BBB
Natalizumab is an anti-alpha4-beta1 integrin binding drug for MS. How does it work?
blocks CD8+ T cells from crossing the BBB = improved RR MS
What are B cell’s role in MS?
make auto-Ab that bind to myelin to make macrophages eat mylein
Ocrelizumab is an anti-CD20 therapy. How does it work for MS?
absence of CD20 induces B cell death = less auto-B cells and Ab
S1P Modulators are drugs for MS. How?
prevents auto-reactive T cells from leaving the thymus
Anti-IFN-B is a drug for MS. How?
limits inflammatory response
What is EBV role in MS?
creates auto-reactive B cells against myelin which then presents to T cells making then auto-CD8+ T cells against myelin
What is EBVs role in MS via molecular mimicry?
EBV viral protein sequences mimic human myelin proteins and thereby induce autoimmunity against myelin and CNS antigens
What is a unique way auto-Ab are made in SLE?
B cell activation occurs outside of SLT (thanks to increased pDCs and IFN)
