Autoimmune Diseases - Hunter Flashcards
Are TypeI hypersensitivity responses involved in autoimmune diseases?
No, they mainly involve allergies.
Can Types II-IV hypersensitivity responses cause autoimmune diseases?
Yes, if the antigen involved is self antigen and not an extrinsic antigen.
How does central T-cell tolerance work?
- Tcells are made in the bone marrow and they migrate to the thymus to mature.
- The randomly generated T-cell receptor is tested to see how it binds to MHC. If it cannot bind then it is destroyed and if it binds too tightly then it is destroyed.
- T-cell receptors are tested to see if they recognize self peptides, if they do then they are destroyed. Non-self reacting Tcells are released into the body and are mediators of adaptive immunity.
- There are so many Tcell receptors generated and not all self peptides are present in the thymus that some self - reactive T-cells are let out into the peripheral system where they undergo peripheral tolerance.
What are the fates of self-reactive Tcells?
- They recognize a self-peptide that is present in the thymus and they are programmed to undergo apoptosis.
- They recognize a self-peptide that is not present in the thymus so they escape the thymus without being tested.
- In the periphery, they recognize a self peptide that is bound to MHC on a tissue cell or an APC that lacks co-stimulatory molecules. They do not get signal 2 so they become anergic and then die.
Do B cells undergo tolerance?
No, they undergo receptor editing in the bone marrow. If they are found to be self-reactive then they have a chance to change their receptor.
Do most B-cell responses require T cell help?
yes
What percentage of T cells leave the thymus?
3%
Name a co-stimulatory molecule on APC’s.
B7, which is also known as CD80 and CD86.
What are macrophages in the CNS called?
Microglia
The occurrence of autoimmune disease requires what?
- T cell receptors that see self peptides.
- Genes for MHC that produce MHC molecules that can display self-peptides.
- A trigger that upregulates co-stimulatory molecules on APC’s.
What are the 2 mechanisms through which an autoimmune reaction can occur?
- Induction of co-stimulators on APC’s that are displaying self antigen.
- molecular mimicry.
Describe the induction mechanism of autoimmunity.
- If there is an APC that has an MHC molecule that is capable of displaying a self- peptide and there is also a T-cell that has a receptor that can recognize that same self-peptide.
- That APC that is displaying a self-peptide is also dealing with a foreign peptide. This causes that APC to up regulate expression of its co-stimulatory molecules.
- The APC interacts with the antigen specific T cell and both signals are present so the T cell initiates an immune response.
Describe molecular mimicry.
This is a way for autoimmunity to occur. Basically an APC presents a microbial peptide that resembles a self-antigen and the Tcell specific for it proliferates and is activated. This Tcell then comes into contact with the self-antigen that is so similar that it can bind and cause an immune response.
What is the most important risk factor for developing an autoimmune disease?
Having a gene for an MHC molecule that can display self-antigens.
Give an example of susceptibility to autoimmune disease based on HLA type.
HLA is the gene for MHC molecules. The B27 allele for HLA gives a relative risk of 87.4 for developing ankylosing spondylitis. This means that you are 87 times more likely to develop this disease if you express the B27 allele.
