Denzin - Autoimmunity Flashcards
IPEX
FoxP3 mutation - autoimmune disease
- can have diabetes
- diarrhea
- failure to thrive
- dermatitis
What do Tregs do?
They inhibit the immune response by inhibiting T cell function
Autoimmune polyglandular syndrome (APC)
Causes susceptibility to many autoimmune diseases. Patients will often have parathyroid gland failure, susceptibility to infection, Addison’s disease etc.
- AIRE is the transcription factor responsible for this
AIRE
AIRE is a transcription factor in the thymus. It mediates the transcription of ectopic gene expression. Things that aren’t normally expressed in the thymus are turned on y AIRE in the thymus to allow the T cell repertoire to be selected against other self proteins.
A mutation in AIRE leads to a autoimmune phenotype.
- You need AIRE to make sure that most of the self reactive T cells are purged in the thymus. The circles with the white dots are the ones that are self-reactive but stick around when AIRE isnt around.If you have AIRE then the thymocytes will be introduced to more self-antigens .WIthout AIRE they won’t introduce the thymoctes to the antigens so you will have a lot of self-reactive T cells later on.
What proteins are found. On Tregs?
CD25 - IL-2 receptor
Cd127 - IL-7 receptor
FoxP3 - transcriptional activator
Molecular mimicry
— Exposure to an antigen very similar to a self antigen. Infectious agents resemble epitopes that resemble self-antigen that leads to activation of self-reactive T-cells
Organ Specific autoimmune disease
Autoimmune disease specific to certain organs.
- ex - Type I diabetes, Hashimotos, graves, addisons
Systemic autoimmune diseases
Many organs/tissues are involved in this autoimmune disease
Ex - RA, lupus
What type of protein is commonly seen in patients with rheumatoid arthritis?
Citrulinated proteins. There is an enzyme called peptidyl-arginine-deaminase (PAD) that converts arginine to citruline. This makes the protein look like non-self because it binds to MHC differently.
PAD
Peptidyl-arginine-deaminase - Enzyme that converts arginine to citruline and causes autoimmunity/RA
What are some things that could cause you to get. An autoimmune disease?
Genes
Environment
Infection
Drugs
How might an infection cause you to get an autoimmune disease?
The infection provides the perfect environment that promotes lymphocyte activation.
- for instance, an infection might cause tissue/cell damage and thus the release of self-antigens that look like virally infected cells
Why might drugs cause autoimmunity?
The drugs got binds to the MHC pocket where peptides are supposed to bind. The normal peptide can’t fit properly into the pocket so it sticks out and bit and looks like no-self. Or, a different peptide is presented that can fit better than looks like non-self.
Why is autoimmunity often chronic?
- the initiating trigger can’t be eliminated, like you just can’t get rid of your beta cells in your pancreas
- epitope spreading - the immune response starts with one antigen but as cells die and release other antigens the autoimmunity could get worse.
Molecular mimicry
— Exposure to an antigen very similar to a self antigen. Infectious agents resemble epitopes that resemble self-antigen that leads to activation of self-reactive T-cells
