Tolerance Flashcards
What is autoimmunity?
Failure of self tolerance
What are the mechanisms that contribute to self tolerance?
- negative selection in the bone marrow and thymus
- expression of tissue-specific proteins in the thymus
- immune privilege to certain tissues (AKA no lymphocyte access)
- Treg suppression of autoimmune responses
- anergy induction in autoreactive B & T cells
What is central tolerance
mechanisms established during B & T cell development in bone marrow and thymus. ie. negative selection to eliminate autoreactive cells
What is peripheral tolerance?
mechanisms that act outside of the bone marrow and thymus to eliminate or silence autoreactive B & T cells that escaped negative selection
What are the subcategories of peripheral tolerance?
- immune privilege - CNS, eyes, testes & uterus during pregnancy. Protection from random immune attacks since regeneration more difficult
- suppression - mediated by cytokines IL-10, TGF-beta & Treg
- anergy - induction of frozen state upon autoreactive B or T cells
Explain negative selection in the thymus
Thymic APCs present self antigens to thymocytes. If they bind too tightly, they are selected for elimination.
What is AIRE?
A protein. A transcription factor expressed in thymic APCs in medulla. Autoimmune regulator. It induces expression of a variety of self tissue specific proteins that are processed and presented on MHC molecules to developing T cells as part of negative selection.
What is APECED?
A multi-organ autoimmune syndrome in the absence of AIRE allowing the immune system to attack endocrine glands. Autoimmune polyendocrinopathy candidiasis ecto- dermal dystrophy
Explain negative selection in the bone marrow
If an immature B cell binds too strongly to an antigen in the marrow, it is retained and induced to edit its Ag specificity with more light chain rearrangements. If self-reactivity continues, B cell death is induced.
Do autoreactive B cells exit bone marrow?
Yes, there are many self proteins in the periphery so autoreactive B cells do exit the marrow.
How are self reactive B cells kept from being activated against the self?
Most B cells require T cells for activation, so the self reactive B cell activation is prevented by T cell tolerance that deprives the B cells of their help. Without the T cell co-stim, the autoreactive B cell that meets a self antigen in the secondary lymphoid tissue will die by apoptosis
Explain anergy in peripheral tolerance
When an APC presents an antigen in the absence of co-stim, the T cell will enter an anergic, non-responsive state
What type of cells play an important role in peripheral tolerance?
Tregs
What is tolerance?
Unresponsiveness of the immune system toward certain substances or tissues that are normally capable of stimulating an immune response
