tolerance and autoimmunity -Thrush Flashcards
What is central tolerance?
destruction of self-reactive cells (via apoptosis) in the primary lymphoid organs:
B cells-bone marrow
T cells - thymus (negative selection)
–> not all self reactive cells are destroyed.
What is peripheral tolerance? What can cause peripheral tolerance?
in the periphery, self-reactive cells are suppressed
peripheral tolerance can be through a lack of proper second signals (co-stimulation of T cells) and/or an interaction of CTLA-4 (instead of CD28) with B7 (CDLA-4 is the inhibitory T cell signal)
What can induce tolerance (5)?
tolerance inducers:
- high doses of antigen
- persistence of antigen in host
- i.v. or oral introduction
- absence of adjuvants
- low levels (or lack) of co-stimulator molecules
Is tolerance antigen-specific or a general suppression of the immune response?
Tolerance is antigen-specific!
What happens if tolerance is broken?
if tolerance is broken, autoimmune diseases can result
What is the function of Tregs? What do Tregs express?
suppression of self-reactive tissues.
these cells have an intermediate affinity for self-antigens –> so they can become activated and suppress other immune cells.
Tregs have CD4 and CD25 constitutively expressed
What is Foxp3? What can a mutation in Foxp3 lead to?
Foxp3 is a signaling molecule in Tregs
A mutation in Foxp3 will lead to autoimmunity due to a decrease in Treg functioning
What are the potential causes of autoimmunity? (5)
- release of sequestered antigens
- loss of suppression (due to loss of Tregs)
- cross-reactive antigens–> infectious antigens cross-react with self-antigens
- altered self-antigens due to viral or chemical infections
- “break” of tolerance due to a combination of factors
Why might women more susceptible to autoimmune disease (AID) than men? (3)
- females produce more Abs than males
- females have higher CD4 cell counts
- in mice, females favor a Th1 response
What is Hashimoto’s thyroiditis?
autoantibodies AND Th1 cells (see DTH; ADCC) can damage the thyroid–>lack of iodine uptake causes hypothyroidism
What causes pernicious anemia?
autoantibodies to intrinsic factor. Intrinsic factor is needed for the uptake of vitamin B12–> without vitamin B12, will get autoimmune anemia
How is insulin-dependent diabetes mellitus an autoimmune disorder?
Organ specific autoimmunity! CTLs attack the pancreatic isles beta cells, destroying them leading to an underproduction of insulin
What is Myasthenia gravis due to?
Auto-antibodies that block acetylcholine receptors on muscles, preventing acetylcholine from binding, leading to muscle weakness.
In some cases, complement can be activated, leading to a destruction of the muscle cells
What is systemic lupus erythematosis?
Production of autoantibodies to DNA, histones, RBCs, platelets, clotting factors.
What are anti-nuclear antibodies (ANA)? How can they cause autoimmune diseases?
ANA should be cleared by macrophages as normal cells die. If they are not removed quickly, they can form immune complexes with antigens after they are released from a dead cell.
ANAs cannot get into cells but the accumulation of immune complexes can activate an inflammatory reaction that can kill bystander cells (often damages blood vessels near the kidneys)
