Flashcards in Lecture 19 Deck (110)
What is Immunological Tolerance?
specific unresponsiveness to an Ag
All individuals are tolerant to what type of Ags?
The breakdown of self-tolerance results in what?
What type of selection of self-reactive T lymphocytes in the thymus is not perfect?
What level of physiological auto-reactivity is crucial to normal immune function?
Central tolerance is induced in what?
in immature self-reactive lymphocytes in the generative lymphoid organs
Peripheral tolerance is induced in what?
in mature self-reactive lymphocytes in peripheral sites
What does central tolerance ensure?
ensures that mature lymphocytes are NOT reactive to self Ags
What is peripheral tolerance needed for?
to prevent activation of potentially dangerous lymphocytes
T cells responding to ubiquitous Ags presented by thymic epithelial cells and hematopoietic cells are efficiently deleted when?
During intra-thymic development
In the thymus, medullary epithelial cells (mTecs) ectopically express a broad range of organ-specific genes and present or, via thymic DCs, cross-present gene products for what?
Tolerizing the T cell repertoire to (peripheral tissue Ag) PTA depends on negative selection in the thymus, but autoreactive T cells can also be eliminated where?
in the peripehry
Induction of both central and peripheral tolerance to PTA involves DCs that carry Ags acquired in nonlymphoid tissues and nonhematopoietic cells that do what?
'promiscuously' express PTA
(PTA peripheral tissue Ag)
In the periphery, lymph node stromal cells show 'promiscuous' expression and directly provide ligands that facilitate the deletion of what?
mature autoreactive T cells
TCR signaling in immature T cells triggers _______ pathway of apoptosis - negative selection
The thymus also has a special mechanism for expressing many protein Ags that are present only in what certain tissues?
Recognition of self Ags by immature T cells in the thymus leads to what 2 things?
1. the death of the cells by negative selection or
2. the development of Treg cells that enter peripheral tissues
Immature T cells in the thymus encounter what Ags?
Self Ag presented by thymic epithelial cells
Cells with T-cell receptors with no affinity for the complex of self peptide and a self MHC molecule do not receive what signal?
They DO NOT receive a surviving signal and undergo spontaneous apoptosis dying int he thymus
Cells whose T-cell receptors have a high affinity for such complexes receive what signals?
The death signal and are eliminated by means of apoptosis
The remaining T cells that have intermediate affinity for self peptide and self MHC molecule go on to do what?
mature in the thymus and migrate to the periphery, where they can become activated
Immature lymphocytes specific for self Ags may encoutner these Ags in the generative (central) lymphoid organs and are either:
change their specificity (b cells only)
develop into Treg cells
Mature self-reactive lymphocytes in peripheral tissues may be:
inactivated or deleted
suppressed by the T reg cells
Mutations in what causes Incomplete induction of tolerance in the thymus, failure of central tolerance
AIRE deficiency: autoimmune polyendocrine syndrome
Impaired production of reg T cells
FoxP3 deficiency causes IPEX syndrome
Decreased clearance and impaired tolerance induction by apoptotic cells
Complement deficiency of C1q and C4
Altered immune signaling thresholds
AIRE stands for:
What process in the thymus is necessary for the maintenance of self tolerance?
Negative selection of T cells