tolerance and autoimmune diseases Flashcards
(35 cards)
T cell tolerance: Positive selection
double positive
Interact with MHC + self = survive
(MHC restriction)
T cell tolerance: Negative selection
Single positive
high affinity with TCR - MHC + self = death
intermediate affinity with MHC + self =survive
AIRE gene
autoimmune regulator gene in the thymus
role in negative selection
Defect in AIRE
results in incomplete deletion of auto reactive T cells
APECED Syndrome
Autoimmune PolyEndocrinopathy Candidiasis Ectodermal Dystrophy syndrome
(polyglandular autoimmune syndrome)
Central Tolerance
Deletion of immature self reacting lymphocytes, receptor editing B cells Negative selection T cells
Peripheral Tolerance Due to:
- Sequestration,
- Treg
- Anergy: Lack of costimulatory signal,
- Too high conc. Of self antigens
peripheral tolerance T regulatory cells
CD4+
CD25+
*** Foxp3+
FoxP3+
master regulator gene
Mutation in FOXP3 gene
IPEX syndrome
IPEX syndrome
• Immune dysregulation
Polyendocrinopathy
Enteropathy
• X linked causes early death
– Watery diarrhea
– Eczematous dermatitis
– Polyendocrinopathy
– Coob’s test +
What causes Breakdown of Immune Tolerance?
Infection: molecular mimicry (cross reactivity)
Mutation in FOXP3, and AIRE genes
Organ-specific
Response is against antigens in localized particular organ
Systemic
gens
Mechanism of tissue injury
Hypersensitivity type II, III, IV
Autoimmune Hemolytic Anemia
Rh blood group antigens ->
destruction of RBCs
- ** –Coombs test: +
- ** –Spherocytes in blood smear
Autoimmune Thrombocytopenia Purpura
platelet intrgrin -> abnormal bleeding
*** Goodpasture’s Syndrome
basement membrane collagen type 4 ->
glomerulonephritis, pulmonary hemorrhage
Diagnosis: anti human IgG labelled with fluorescence: Smooth or linear pattern using Direct fluorescent staining
Pemphigus Vulgaris
epidermal cadherin, desmoglein 1 and 3, desmosomal adhesion molecules ->
Oral and dermal blisters as a result of intra-epidermal splitting (acantholysis), and erosion
High frequency in Ashkenazi Jews
Acute Rheumatic Fever
streptococcal call wall antigens, antibodies cross-react with cardiac muscle ->
arthritis, myocarditis, late scarring of heart valves
- Grave’s Disease
TSH receptor -> ->
over production of thyroid hormone (T4 thyroxine and T3 triiodothyronine)
hyperthyroidism
*** HLA DR 3 association
- Myasthenia Gravis
Ach receptor ->
progressive weakness
*** DR3
SLE (systemic lupus erythematosus)
dsDNA ->
butterfly rash on the face, glomerulonephritis, vasculitis, arthritis
type III hypersensitivity
** Risk gene HLA-DR2 or DR3
Type 1 diabetes (insulin-dependent DM)
glutamic decarboxylase, cross-reactive with Coxsackie virus proteins
destruction of insulin due to specific autoantibody and T CD8 cell
** HLA DR3/DR4 association
