Autoimmunity Flashcards
What is tolerance, what is central tolerance?
tolerance = state of immunological unresponsiveness to self
central tolerance = deletion of lymphocytes in primary lymphoid organs before they mature
What is autoimmunity?
failure of tolerance
What where the three clues to the importance of tolerance?
- CSS
- one copy of a defective Fas gene. auto-Abs against RBCs, large number of lymphocytes - APECED
- dysfunctional AIRE gene - IPEX
- mutated Foxp3 genes
What are organ specific autoimmune disorders? Name three examples
Organ specific = target Ags unique to a specific organ or gland
examples:
- DM 1
- Graves disease
- Myasthenia gravis
What are systemic autoimmune disorders? name 1 example
systemic = Ag expression and damage is widespread
example = MS
What is DM1? What is the immune effector, the affected tissue, how damage occurs?
affected tissue = insulin-producing beta cells in the pancrease
immune effector = Th1 cells, auto-Abs
damage:
- CTLs infiltrate the pancreas and activate macrophages
- cytokine release and production of auto-Abs –> complement and ADCC activities
- eventful DTH response releases destructive enzymes
Describe the edmonton protocol and a possible cure for DM1 (new)
edmonton protocol:
- islet cells isolated from donated pancreases are transplanted into DM1 pts
- temporary relief from insulin injections. but need anti-rejection drugs
new study:
- reprogram blood cells to become pluripotent SCs using hormones and GFs
- stimulate those cells to become insulin producing cells
- mouse model is promising
Describe the animal model for DM1
- non-obese diabetic mouse (NOD)
- natural mutations
- spontaneously develop IDDM
- females are more at risk
Describe Graves disease. What tissue is affected, what is the immune effector, how is damage caused? Treatments?
tissue = thyroid
immune effector = auto-Abs (stimulating)
damage:
1. auto Abs block TSHR
2. triggers +ve response
3. overproduction of thyroid hormones
treatments:
- medications to inhibit thryroid hormone synthesis
- radioactive iodine to kill thyroid cells
- removal of the thymus
What is myasthenia graves? What tissue is affected, what is the immune effector, how is damage caused?
tissue = skeletal muscles
immune effector = auto-Ab (blocking)
damage:
1. Ab’s bind to AChR
2. block ACh binding
3. no muscle activation
What is the animal model of myasthenia gravis, how is it made?
model = EAMG
made = inject rabbits with AChR
What is MS? What tissues is affected, what is the immune effector, what are the risk factors, how is damage delt?
tissue = CNS/myelin
effector = Th1 cells, Tc cells. autoAbs
risk factors = genetic and environment
damage:
- unknown trigger sets up initial focus of inflammation in brain and BBB becomes locally permeable to leukocytes and blood proteins
- T cells specific for CNS Ag and activated in peripheral lymphoid tissues reencounter Ag presented on microglia or DCs in brain
- inflammatory reaction in brain due to mast cell activation, complement activation, Abs, and cytokines
- demyelination of neurons
What is the animal model of MS, how is it made?
animal model = EAE
made:
- immunize with MBP in strong adjuvant
What are the three main factors that make you susceptible to autoimmune diseases?
- release of sequestered Ags
- MBP
- sperm Ag
- trauma - environ factors
- diet
- geographical
- lifestyle
- stress
- infections - genetic predisposition
How can molecular mimicry cause autoimmune disorders, name some examples of mimicry
- epitopes in pathogen trigger the initial response and then it cross reacts with self proteins to cause disease
examples:
- HPV E2 –> insulin R
- measles P3 –> MBP
