Immunological Tolerance Flashcards
What is tolerance?
Lack of immune response when immune cells are exposed to antigen.
What is central tolerance?
Elimination of self reactive T and B cells during development in the thymus or bone marrow.
What is peripheral tolerance?
Mechanisms after the lymphocyte has left bone marrow or thymus and encounters self antigen.
What are the two options for a T cell that has a high affinity for self-antigen in the thymus?
- Deletion by apoptosis.
2. Become regulatory T cells.
The transcription factor responsible for the regulation of expression of peripheral proteins in the thymus is encoded by what gene?
Autoimmune Regulatory Gene (AIRE)
What syndrome occurs when AIRE is defective?
Autoimmune Polyendocrine Syndrome (APS).
How can autoimmune polyendocrine syndrome (APS) present?
- Mucocutaneous candidiasis.
- Hypoparathyroidism.
- Adrenal insufficiency.
What do regulatory T cells express?
CD25 and transcription factor Foxp3.
What arises from a mutation in Foxp3?
IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome).
What cytokines do regulatory T cells produce?
IL-10 (inhibits activation of lymphocytes)
TGF-Beta
What three things can occur when a self reactive T cell i the periphery encounters its self antigen?
- Anergy
- Apoptosis
- Suppression by T reg cells.
What are 2 ways a T cell can be put in a state of anergy?
- Lack of costimulation.
2. Inhibitory receptors.
What two signals to CD4 helper T cells need to be activated?
- MHC/antigen
2. B7 binding CD28
What inhibitory receptor do T cells use when the recognize self antigens?
CTLA-4 binds and blocks B7 on the APC and delivers inhibitory signals to the T cell.
When is CTLA-4 expressed?
Always on reg T cells, on cytotoxic T cells AFTER activation, serving as an “off switch”.
What has a higher affinity for B7, CD28 or CTLA-4?
CTLA-4
What two pathways of apoptosis can be triggered by peripheral engagement of a T cell with a self antigen?
- Poor costimulation causing the leak of mitochondrial proteins which will activate caspases (enzymes that induce apoptosis).
- Poor costimulation leading to stimulation of Fas-FasL apoptosis pathway.
What do reg T cells express that blocks B7 on APCs?
CTLA-4
What two processes can occur when B cells encounter self antigen in the bone marrow?
- Edit their receptors
2. Deletion through apoptosis
What genes are reactivated during B cell receptor editing?
RAG genes
Which Ig chain is edited during B cell receptor editing?
Light chain.
What type of dendritic cells promote reg T cells?
CD103+ dendritic cells.
