Tolerance and Autoimmunity Flashcards
How did we find out about tolerance?
During WW2 they took skin graphs from people and tried to replace the burned skin of pilots but this always failed
What experiments where done to find out tolerance?
They took a skin graft from one mouse (mouse A) and placed it on another (mouse B) - this was rejected.
They then took the mouse B and put another skin graft on it. This was also rejected but faster due to memory cells.
They then took a skin graft from mouse A and put it on a brand new mouse (mouse C) and transferred mouse B’s lymphocytes into mouse C - this was rejected.
What was the experiment done to show the theory self and non self are defined during embryogenesis?
Take a skin graft from strain A and put it on strain B = rejection
Take white blood cells from strain A into strain B embryos and then do the above graft you wont get rejection
Why do we need tolerance?
Because of the recombination of T and B cells this leads to some T and B cells being specific for self antigens which could lead to autoimmunity. These therefore need to be eliminated.
What is autoimmunity?
Reaction of the immune system against self components
What is central tolerance?
Occurs in generative lymphoid organs during development of the immune system in the thymus for T cells and bone marrow for B cells.
What causes central tolerance?
Negative selection - immature lymophocytes specific for sel-antigens undergo deletion (apoptosis) in both T and B cells, receptor editing (B cells) and differentiation into Treg cells (CD4 T cells).
What is peripheral tolerance?
Occurs in peripheral tissue
What happens to any mature self-reactive lymphocytes that escape central tolerance?
They are rendered nonresponsive, deleted or supressed by Tregs.
When does T cell tolerance occur?
During T cell development
What is negative selection in central tolerance?
Deletion or modification of autoreactive CD8 and CD4 T cells in the thymus.
Why do you need negative selection in central tolerance?
Recognition of self would lead to autoimmunity and therefore you need to get rid of autoreactive T cells
How does negative selection in central tolerance happen?
SP T cells interact with DC and mTECs (which present self antigens from tissues around the body). If there is high affinity binding apoptosis occurs
CD4 Tcells can bind with intermediate affinity for Treg differentiation.
What do naive Tregs do?
Go to the peripheral tissue and suppress other immune cells preventing autoimmunity
What is APECED?
A rare disorder that is autosomal recessive diagnosed by having 2 of the three symptoms (Candidiasis, hypoparathyroidism and addisons disease).