2.4 - Autoimmune disorders Flashcards
central tolerance in the thymus leads to either T cell apoptosis or ____________
generation of Treg cells
what is the result of an AIRE mutation? what is the normal function of AIRE?
- autoimmune polyendocrine syndrome
- controls the mechanisms that prevent the body from attacking itself
autoimmune polyendocrine syndrome is due to a mutation in _______
AIRE
what is the pathogenesis of autoimmune polyendocrine syndrome?
- mutation in AIRE
- failure of central tolerance (
where does positive selection of T cells occur?
cortex of thymus
where does negative selection of T cells occur?
medulla of thymus
the cortex of the thymus is where _______ selection of T cells occurs
positive
the medulla of the thymus is where __________ selection of T cells occurs
negative
what are the manifestations of autoimmune polyendocrine syndrome?
- hypoparathyroidism
- adrenal failure
- chronic candida infection
is autoimmune polyendocrine syndrome a failure of positive or negative selection?
negative (normally prevents body from making self reactive T cells)
peripheral tolerance leads to what two outcomes?
- anergy
- apoptosis of T and B cells
what condition results from a mutation in the Fas apoptosis pathway?
autoimmune lymphoproliferative syndrome (ALPS)
ALPS is a result of a mutation in what process?
Fas apoptosis pathway
what is the pathogenesis of autoimmune lymphoproliferative syndrome (ALPS)? what is the result?
- mutation in Fas apoptosis pathway
- self reactive lymphocytes cant undergo apoptosis and can generate IgG against blood cells, leading to lymphopenia
Treg cells block T cell activation and suppress autoimmunity by producing what cytokines?
IL-10 and TGFB
polymorphisms in what CD are associated with autoimmunity?
CD25
mutations in what gene lead to IPEX syndrome?
FOXP3
what is IPEX syndrome? what is cause?
- Immune dysregulation
- Polyendocrinopathy
- Enteropathy
- X linked
- due to FOXP3 mutation
what is the normal function of FOXP3?
“forkhead box P3”
involved in the development and function of Treg cells
what is the pathogeneis / cause of anti-nuclear antibodies seen in SLE? how does damage ensue?
- poorly cleared apoptotic debris (from UV light) activates self reactive lymphocytes, which then produce the antibodies
- DNA antigens activate TLRs, amplifying immune response (IFNa)
deficiencies of what complement proteins is associated with SLE?
C1q, C4, C2
what are the important antiphosphlipid antibodies seen in SLE?
- anticardioplipin
- anti-B2 micrglobulin I
- lupus anticoagulant
what antibody can lead to a falsely elevated PTT in SLE?
lupus anticoagulant (anti phospholipid Ab)
does antiphospholipid Ab syndrome lead to a hyper- or hypo- coagulable state?
hypercoagulable
which drugs can cause drug-induced SLE? which antibody is seen in DIL?
- procainamide, hydralazine, INH
- anti-histone
sjogren syndrome is mediated by type ____ hypersensitivity?
IV
what antibodies are seen in sjogren syndrome?
- ANA
- antiribonucleoprotein (anti-SSA / Ro, anti-SSB / La)
which antibodies are responsible for the extraglandular manifestations seen in sjogren syndrome?
SSA and SSB
which sjogren syndrome autoantibody can cross the placenta in and cause neonatal lupus?
SSA
what is the greatest adverse effect of neonatal lupus?
congenital heart block
what are the diagnostic criteria for sjogren syndrome?
- dry eyes
- ANA plus SSA / SSB / RF
- sialadenitis
need 2/3
patients with sjogren syndrome are at increased risk for what type of cancer? how does it present?
- B cell (marginal zone) lymphoma
- unilateral enlargement of the parotid gland (late)
what are the components of CREST syndrome?
- calcinosis / anti-centromere antibodies
- raynaud phenomenon
- esophageal dysmotility
- scelerodatyly
- telangiectasias
diffuse scleroderma is associated with what autoantibody?
anti-Scl-70 (anti-DNA topoisomerase I)
mixed CT disease is associated with what two autoantibodies?
ANA plus anti-U1 ribonucleoprotein
anti-U1 ribonucleoprotein is associated with:
MCTD
anti-Scl-70 (anti-DNA topoisomerase I) is associated with:
diffuse scleroderma
