Pathoma - Autoimmune disorders Flashcards
What is the role of the AIRE gene
It allow medullary epithelial cells of the thymus to display self-antigens during negative selection
Mutation will prevent developing lymphocytes from being tested against self-antigens, and allowed to be released, leading to autoimmunity
What are the 2 methods of peripheral tolerance of lymphocytes?
(1) Anergy: T-cells bind to MHC/antigen complex, and if there is no second activation signal (CD28 binding B7) the cell will shut down
(2) Apoptosis: if the T-cell keeps binding the MHC/antigen without a 2nd signal, the T-cell will begin to express FasL which will bind to death receptors
What cytokines to regulatory T-cells produce?
IL-10 and TGF-B
What molecules to Treg cells express/are positive for?
CD4+
CD25+
FOXP3+
What is Autoimmune lymphoproliferative syndrome (ALPS) caused by?
Mutation in the Fas apoptosis pathway, allowing self-reactive lymphocytes to continue proliferating and produce antibodies against normal cells
Describe bystander activation in the setting of autoimmunity
Patient makes a few self-reactive lymphocytes, but then gets an infection which ramps up the immune system causing self-reactive lymphs to multiply
Describe molecular mimicry in the setting of autoimmunity
Patient is infected with something similar to self-antigen, so self-reactive lymphocytes are increased because they are similar
What type of hypersensitivity reaction is SLE?
Type III
Describe the mechanism behind the development of SLE
Poorly cleared apoptotic debris (e.g. from UV damage) activates self-reactive lymphocytes, which then produce antibodies to host nuclear antigens
How is complement deficiency a cause of SLE
If complement cannot clear the apoptotic debris, it will remain around for cells to make antibodies against them
What are the 11 criteria of SLE:
RASH OR PAIN
Rash (malar or discoid)
Arthritis
Serositis
Hematologic disorders (e.g. anemia, thrombocytopenia, leukopenia)
Oral/nasopharyngeal ulcers
Renal disease
Photosensitivity
Antinuclear antibodies (ANA)
Immunologic disorder (anti-dsDNA, anti-Sm, anti-phospholipid)
Neurologic disorders (psychosis or seizures)
What are the 2 types of renal damage associated with SLE?
Nephrotic: membranous nephropathy
Nephritis: diffuse proliferative glomerulonephritis
What type of hypersensitivity reaction is there against blood cells in lupus
Type II (antibody directly against cells)
What is Libman-Sacks endocarditis (associated with SLE)
Small vegetations on BOTH SIDES (top and bottom) of mitral valve
What are anti-Smith antibodies directed against?
snRNPs
What complements will be decreased in SLE?
CH50, C4, and C3
What type of antibody is anticardiolipin and what can it cause false positives in?
It is an antiphospholipid in SLE
Can cause false-positive for syphilis
What type of antibody is lupus anticoagulant and what can it falsely elevate?
It is an anti-phospholipid
Can falsely elevate PTT
What are the diagnostic criteria of antiphospholipid antibody syndrome (APA)
Hypercoagulable state with + antiphospholipids( e.g. lupus anticoagulant, anticardiolipin, anti-B2-glycoprotein)
What is paradoxical about antiphospholipid antibody syndrome
Lupus anticoagulant can lead to increased PTT, but the syndrome actually causes HYPERcoagulability
What is the characteristic antibody in drug-induced lupus
Antihistone antibody
ANA is also positive by definition
What drugs are common causes of drug-induced lupus
SHIPP-E: ♣ S – sulfa drugs ♣ H – Hydralazine ♣ I – Isoniazid ♣ P – Procainamide ♣ P – Phenytoin ♣ E – Etanercept
What clinical findings are usually absent in Drug-induced lupus that are present in SLE
Renal and CNS involvment
Most common cause of death in SLE?
Renal failure, infection, and accelerated coronary atherosclerosis
