Tolerance and Autoimmunity Flashcards
What is the difference between central tolerance and peripheral tolerance?
Central tolerance is where the T/B-cells with high avidity to self-antigens are killed via apoptosis.
Peripheral Tolerance - has multiple modes of inactivation:
- Apoptosis - when constant stimulation, it’s killed
- Anergy - no co-stimulation
- Suppression via Treg
A patient presents with frequent candiasis infections of his mouth and nails and also known hypothyroidism. What could be the cause of all of his symptoms?
APECED - Defect in the AIRE gene, causing the thymus to release T-cells that are self reactive to epithelial and glandular cells in the body.
Autoimmunity towards adrenal, parathyroid, and most epithelial cells.
Defective Central Tolerance
A child comes into the office with diffuse lymphadenopathy and lab test find hypergammaglobulinemia. What could be the cause?
ALPS - Autonomic lymphoproliferative syndrome
- Widespread lymphadenopathy and splenomegaly
- *Dysfunctional Fas ligand preventing normal apoptosis of double negative T-cells
A young 3 month old male with weight loss and failure to thrive, diffuse rash, and hypergammaglobulinemia with very high IgE levels. What could be causing these symptoms?
IPEX, Immune dysregulation.
X-linked mutation in Foxp3, loss of Treg cells.
Presents with IBS, DM, Hemolytic anemia, and diffuse eczema rash.
What dictates if you develop an autoimmune syndrome or not?
Two parts: Depends on what HLA versions you have, then environmental factors can induce the autoimmune syndomes
What kind of CD4+ cells need to be activated in order to develop a Type 1 hypersensativity to a stimuli?
TH2 Help T-cell needs to induce a IgE response to the stimuli.
A patient develops a sore throat and fever that lasts for several days before resolving, then 3 weeks later knee and ankle swelling with a diffuse rash. What could be the cause?
Acute Rheumatic Fever, antibodies from the Strep cross react with tissues in the body especially joints and heart.
- Heart Murmur develops too
Greaves Disease, Myastenia Gravis, Goodpasteur Syndrome, and hemolytic anemia are all examples of what kind of hypersensativity?
Type II Hypersensativity
A patient develops a facial butterfly rash, stiff and aching joints, and oral ulcers. Upon lab exam she has elevated Creatinine, proteinuria, low serum complement levels. What could be causing these symptoms?
Acute Systemic Lupus Erythematosus
- Caused by development of antibodies that are soluble and cause complexes that get stuck in low flow areas like joints and kidney causing local inflammation and damage.
What are the possible symptoms of Lupus and criteria for diagnosis?
Mucosal - Malar Rash, Discoid Rash, Photosensivity, oral ulcers
Organs - Arthritis, Serositis, Cerebritis, Nephritis
Lab: ANA, Immune against dsDNA, and autoimmune cytopenia
** Need 4/11 to diagnose**
What can cause early onset Lupus?
Complement defects can lead to early onset SLE due to complement being use to get rid of the complexes, so if there is less functional complement, then they can build up more easily.
A patient has had ongoing joint stiffness and swelling with intermittent low fevers for several months. What could be causing these symptoms?
Rheumatoid Arthritis
- T-cells react to tissue in joints and release cytokines and recruit B-cells, Macros, causing the inflammation.
How can RA be treated to prevent the symptoms?
- NSAIDS
- Anti-metabolites, preventing proliferation of lymphocytes
- Glucocorticoids
- Antibodies against inflammatory cytokines
A patient presents with generalized fatigue, proximal muscle weakness, scaley rash on skin of joints (Gottron’s Papules), heliotrophic rash, base of nails have skin changes. LFTs elevated and very high CK.
What could be causing these symptoms?
Dermatomyositis -
Diffuse muscle death in groups next to normal fibers in wedge shapes similar to ischemia
Primarily mediated by CD8+ destroying self tissues
