Name the two main types of tolerance?
- Central: thymus
- Peripheral: BM
What is the significance of the AIRE gene?
- Responsible for creating central tolerance
- Allows for the expression of the autoimmune antigens in the thymus so that de-sensitization of T cells and exposure of autoreactive T cells
- only T cells non sensitive to self are allowed to proliferate
What is the disorder associated with the absence of AIRE gene?
Autoimmune polyendocrinopathy candiadiasis ectodermal dystrophy (APECED)
some symptoms:
- calcification of the tympanic membrane
- enamel hypoplasia
- hypothyroidism and hypoparathyroidism
- chronic mucocutaneous candidiasis
What are the four types of peripheral tolerance?
- Anergy: decrease the autoimmune T cell response by deactivating cofactors needed for T cell activation
- T reg suppression
- activation of apoptosis
- antigen sequestration: some areas of the body are not exposed to antigens under normal conditions
How do the B cells participate in tolerance?
- They are involved with B cell receptor editing
- Only receptors that aren’t self reactive are allowed to proliferate
What are the two ways that infections may lead to expression of immune phenomena?
1. molecular mimicry: some antigens from pathogens are structurally similar to some normal structures/auto antigens in our body. During infection, IS attacks both pathogen and normal structures.
ex: rheumatic heart disease with M proteins and myosin
2. exposure of antigens to cryptic sites: in order to get a systemic t-cell response, parts of the body that aren’t usually exposed to antigen become exposed and the destruction of pathogens leads to increase antigen around
What are the two autoimmune diseases discussed in the lecture?
- Systemic lupus erythematous (SLE)
- Systemic scleroderma
- diffuse
- limited
DEPCT: SLE
D: low complement & IF deposits of ICs in the glomerulus; Smith antigen; anti SSA {neonates and skin}
D: multi-systemic autoimmune disroder
E: Black women; common
P: genetic susceptibility + triggering factors + abnorma immune response
C: butterfly rash on face; discoid rash, oral ulcers, arthritis, kidney disease, photosensitivity
T: suppress immune system—-NSAIDs, corticosteroids, anti B cell agents
Symptoms of SLE?
RASH OR PAIN
R: rash—malar or discoid
A: arthritis
S: soft tissues inflammation/serositis
H: hematological: prone to thrombosis due to anti-phospholipid autoantiboddies
O: oral ulcers
R: Renal disease or Raynaud’s
P: photosensitivity; positive VDRL
A: antinuclear antibodies
I: immunosuppressant
N: neurological disorders
Which drugs cause lupus?
PPHID ME
Procainamide
Phenytoin
Hydralazine
Isoniazid
D-penicillamine
Minocycline
Ethosuximide
Which autoantibodies are associated with lupus?
- Smith: specific for lupus diagnosis
- Anti SSA: skin and neonatal
- anitphospholipid: thrombotic state
What are the two types of: systemic sclerosis?
Two types:
diffuse cutaneous: rapid skin thickening > leads to more severe symptoms (visceral disease); cardiac issues + pulm fibrosus + HTN + renal failure > death
limited cutaneous: CREST syndrome; less skin thickening, + anticentromere antibody
What is the CREST syndrome? Which disease are they associated with?
C: calcinosis: may be visible through the skin
R: Raynaud’s: painful vasoconstriction in hands > red fingers
E: esophageal dysmotility:
S: sclerodactyly: fibrosus that leads to decreased mobility of joints
T: telangeictasis: constriction of blood vessls such that they have a spiderweb like appearance
Associated with limited cutaneous sclerosis
Which disease is associated with the anticentomere antibody?
limited cutanous sclerosis
What can we use to diagnose sclerosis?
- ECG
- CXR
- Barium swallow: determine motlity of esophagus
- urinalysis
- skin biposy
How to treat sclerosis?
Cannot be cured; treat symptoms
- antiacids: prevent reflux
- CCB: prevent heart stuff
- ACEi/ARB: prevent kidney stuff and htn
- immunosuppressives
