2.4 Autoimmune disorders Flashcards
1
Q
Autoimmune disease prevalence in USA
A
1-2%
2
Q
Central tolerance
A
-B and T cells that react to self-antigen are destroyed
3
Q
AIRE
A
- “autoimmune regulator”
- A transcription factor inside medullary thymic epithelial cells
- Allows variety of self-antigens to be presented to T-cell precursor during negative selection
- Defect in AIRE leads to Autoimmune polyendocrine syndrome
4
Q
autoimmune polyendocrine syndrome candidiasis ectodermal dystrophy (APECED)
- mech
- clinical findings
A
- defect in AIRE gene in thymus leads to defective negative selection of T cells
- T cells attack endocrine glands, with classic triad:
1. Hypoparathyroidism
2. Adrenal failure
3. Chronic candida infections (thrush)
5
Q
Peripheral tolerance, mechs
A
- Anergy
- lack of costimulation (B7/CD28) - Apoptosis
- Fas apoptosis pathway (defect is ALPS) - Suppression (T Reg cells):
- IL10, TGF-B
- CTLA4-induced Anergy
6
Q
What do T Reg cells do in peripheral tolerance?
A
- IL10, TGF B to reduce inflammatory response
- CTLA4-induced Anergy
- CTLA4 competes with CD28 to bind B7.
- FOXP3 gene
- defect in gene is IPEX syndrome
7
Q
Diseases of T Reg cells
A
- CD25 polymorphisms
- CD25 is IL2 receptor, so lack of T cell stimulation - IPEX syndrome
- FOXP3 mutation, lack of CTLA4
8
Q
IPEX syndrome:
- mech
- acronym
A
- lack of peripheral tolerance from lack of CTLA4 (binds B7) from FOXP3 gene mutation in T Reg cells
- Autoimmune attack, esp endocrine cells.
- Immune dysregulation
- polyendocrinopathy
- enteropathy
- X-linked, affects boys in infancy
9
Q
CD25
-what problems associated with this
A
- IL2 receptor
- CD25 polymorphisms for T Reg cells are associated with autoimmunity:
1. MS
2. DM1
10
Q
Why autoimmune diseases more common in women?
A
-Estrogen may reduce apoptosis of self-reactive B Cells
11
Q
Epitope spreading
A
- mechanism of autoimmunity
- Exposure of self-antigens released by tissue destruction may trigger immune system to recognize as foreign.
12
Q
Autoimmune lymphoproliferative syndrome (ALPS)
- mech
- clinical findings
A
- defect in peripheral tolerance
- defect in Fas apoptosis pathway of CD4 T cells that are self-reactive
- lymphadenopathy
- hepatosplenomegaly
- lymphoma
13
Q
HLA-B27
A
HLA type that makes someone much more likely to get ankylising spondylitis
14
Q
Lupus:
- mech
- steps of pathophysiology
A
- Ag/Ab complexes deposit in body and activate complement (Type III HSR)
1. apoptosis of cells (eg UV damage) cause nuclear contents to leak
2. Macrophages phagocytize nuclear components and present to B cell, which makes Ab to nuclear antigens
3. The next time there is apoptosis (eg UV), the Ab reacts with nuclear antigens, forming complexes.
4. Dendritic cells phagocytize complexes and amplify immune response, leading to more Ab produced.
15
Q
Lupus:
-classic symptoms (11)
A
- Fever, weight loss, fatigue, lymphadenopathy, Raynaud
- Malar butterfly rash, discoid rash (wolf bite)
- Oral/nasopharyngeal ulcers
- Arthritis
- Serositis (pleuritis, pericarditis)
- CNS:psychosis, seizures
- Renal damage (diffuse proliferative glomerulonephritis, membranous glomerulonephritis)
- Ab against blood cells (Type II HSR)–anemia, thrombocytopenia, leukopenia
- Libman-Sacks endocarditis
- ANA (antinuclear Ab)
- Anti-dsDNA or anti-Sm antibodies
