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.
Name some autoimmune type II hypersensitivity diseases that result in autoantibodies against surface antigens on blood cells.
Autoimmune hemolytic anemia and autoimmune thrombocytopenic purpura.
Name some autoimmune type II hypersensitivity diseases that result in autoantibodies against surface antigens on fixed tissues.
Pemphigus vulgaris, Goodpasture’s syndrome, acute rheumatic fever.
Name some autoimmune type II hypersensitivity diseases that result in autoantibodies against cellular receptors.
Myasthenia gravis and Grave’s disease.
Can IgG antibodies cross the placenta?
Yes
What happens if the mom has an autoimmune disease and passes her autoantibodies to the baby?
The baby can get mom’s IgG autoantibodies and will exhibit the same symptoms as mom but these symptoms are transient - about 3-6 weeks or about as long as the half-life of the IgG antibody. Can also do plasmapheresis to remove the antibodies and permanently cure the disease.
