2. Self Recognition and Tolerance Flashcards
(34 cards)
immune tolerance
specific induced UNresponsiveness towards a particular antigen; tolerance is induced by exposure to the antigen, it is not a lack of response
tolerance can be induced to foreign __ and also prevents the immune system from attacking __
antigens, itself (self-tolerance has to be learned)
when is self-tolerance learned
pre-/neo-natal period
the immune system randomly generates a great diversity of ___ __, some of which are self reactive. __ and __ cells bearing these self reactive receptors must be eliminated.
antigen-specific receptors, T and B
prevention of self-reactivity is not __ determined. self-reactivity is prevented by processes that occur during __ and __ cell development
genetically, T and B
self vs nonself discrimination is __ during immune development
“learned”
immunological “self” means
all epitopes encoded by an individual’s DNA, but the structure of a molecule itself does not define “self”
central tolerance occurs during
development of T and B cells in primary lymphoid organs
- T cells in thymus
- B cells in bone marrow
what does central tolerance result in
elimination of self-reactive cells
in central tolerance, self-reactive cells that escape into the periphery can still be __ or __
“tolerized”, suppressed
what is key to the development of self-tolerance
T cell-tolerance; T cells “learn” to recognize self
when does T cell tolerance occur
during development of T cells from precursors in the thymus
two rounds of thymic selection
- positive selection
- negative selection
where does positive selection occur
thymic cortex
in positive selection, __ (CD4+/CD8+) T cells that bind (via TCR) to self ___ molecules (on thymic epithelial cells) are selected for __. this binding “rescues” T cells from death by __.
immature, MHC, survival, apoptosis
in positive selection, surviving T cells are those that recognize __ __ molecules (give two examples) and then migrate into __ __ for negative selection.
self MHC, thymic medulla
- CD4+ cells recognize MHC-II
- CD8+ cells recognize MHC-I
where does negative selection occur
thymic medulla
in negative selection, specialized __ in thymic medulla express all self __ and present __ in MHC. T cells that bind strongly to ____ on MHC are selected for death by __. Surviving cells escape into periphery as __ T cells.
APC, proteins, peptides, self-peptides, apoptosis, mature
stages in development of T cells
- random expression of alphabeta TCR repertoire (low alphabeta)
- positive selection: exposure to MHC molecules (low alphabeta)
- negative selection: exposure to self antigen (high alphabeta)
- mature T cell pool (high alphabeta)
which cells in positive selection continue onto negative selection
cells that engage with MHC class I or II; otherwise there is programmed cell death
which cells in negative selection continue onto mature T cell pool
cells that have no interaction with MHC class I/II + self peptide; otherwise there is TCR-induced cell death
a few mature T cells that recognize self antigens may escape into the periphery. these can be suppressed by other post-thymic mechanisms like
peripheral tolerance mechanisms
in peripheral tolerance mechanisms, if self-reactive T cells interact with __ presenting self-peptides but without ___ molecules, it leads to __
APC, costimulatory, apoptosis
in peripheral tolerance mechanisms, regulatory T cells (nTregs) are also generated in the __ to regulate (suppress) self-reactive T cells in the __
thymus, periphery
