1.07 - Self Tolerance Flashcards
What is Immunological Tolerance?
The unresponsiveness of lymphocytes to self antigens
What are the two stages of T Cell Tolerance
Central Tolerance
Peripheral Tolerance
Describe Central T Cell Tolerance
The principal mechanisms of central tolerance for T cells are cell death and, for CD4+ cells, the generation of regulator T cells.
When an immature T lymphocyte strongly interacts with a self antigen, expressed in the thymus by APCs, the lymphocyte receives signals for apoptosis.
This is called negative selection.
What happens to some CD4+ cells that strongly recognise self antigens?
They do not die but rather develop into regulatory T cells and enter peripheral tissues.
Describe Peripheral T Cell Tolerance
Peripheral tolerance is induced when mature T cells recognise self antigens in peripheral tissues, leading to functional inactivation (anergy) or death, or when the self-reactive lymphocytes are suppressed by regulatory T cells.
May provide back up mechanisms for preventing autoimmunity in situations where central tolerance is incomplete.
Describe Anergy of T lymphocytes
It is the functional inactivation of T lymphocytes that occurs when these cells recognise antigens without adequate levels of of the costimulators (second signals) that are needed for full T cell activation.
What are the two signals needed for full T cell activation?
- Antigen
2. Co-stimulation from APCs
Describe Immune Suppression by Regulatory T Cells
Regulatory T cells develop in the thymus (majority) or peripheral tissues (some) on recognition of self antigens and block the activation of potentially harmful lymphocytes specific for these self antigens.
What are the two stages of B Cell Tolerance?
Central Tolerance
Peripheral Tolerance
Describe Central B Cell Tolerance
When immature B lymphocytes interact strongly with self antigens in the bone marrow, the B cells either change their receptor specificity (receptor editing) or are killed (negative selection) by apoptosis.
What are the two fates of an immature B lymphocyte after receptor editing during Central Tolerance?
If receptor editing is successful the cell will receive survival signals and will move to the peripheral lymphoid tissues
However if it fails to successfully change its receptor it will die via apoptosis.
Describe Peripheral B Cell Tolerance
Mature B lymphocytes that encounter high concentrations of self antigens in peripheral lymphoid tissues become anergic and cannot again respond to that self antigen.
Thought that, if B cells recognise a self antigen and do not receive T cell help (because helper T cells are absent or tolerant), the B cells become anergic.
