B Cells 9 Flashcards
(48 cards)
what is the purpose of tolerance?
prevents immune system from destroying host tissue
why do we need tolerance?
many random rearrangements used to create B and T cell receptors could be SELF-REACTIVE, so tolerance prevents them from circulating in bloodstream
where does T cell development occur?
initially develop in the bone marrow, then mature in thymus
what are developing T cells called?
thymocytes
how do T cells mature?
by a rigorous selection process
what are the 2 regions of the thymus?
- cortex
- medulla
what are the 4 cell types in the thymus?
- cortical epithelial cells
- medullary epithelial cells
- thymocytes
- macrophages
which regions of the thymus are thymocytes and macrophages in?
both cortex and medulla
what type of cells are T cell precursors when they enter the thymus?
Double Negative cells –> don’t express CD4 or CD8
describe how CD4 and CD8 receptor expression changes during development in the thymus and which regions of the thymus each step occurs in
- double negative –> cortex
- double positive (both CD4 and CD8) –> cortex
- single positive (1 of CD4 or CD8) –> medulla
- then leaves for circulation
which part of the thymus do T cell precursors enter?
cortex
what do T cells develop during development?
develop MHC restriction and undergo a process for self-tolerance
what is positive selection?
selects FOR thymocytes with receptors that can bind self-MHC molecules, resulting in MHC restriction
what is negative selection?
selects AGAINST thymocytes with high-affinity receptors for self-MHC/self-peptide complexes, resulting in self-tolerance
describe the process of positive selection and 3 possibilities
- cortical epithelial cells express high levels of MHC I and II
- double positive T cells browse peptide MHC on the surface of these cells
(1) if TCRs can’t bind –> die by neglect
(2) if TCRs bind too strongly –> cells die bc too reactive to a self-peptide
(3) if TCRs bind low-just right –> positive selection to single positive stage
what happens to the T cells that die due to improper binding?
macrophages in cortex clean up debris
what percent of T cells will die bc they can’t bind?
90-96%
what allows a double positive T cell to become a single positive T cell?
if TCR binds low to just right
what type of single positive T cell occurs when a T cell binds MHC II with its CD4?
Becomes single positive CD4+ T cell
what type of single positive T cell occurs when a T cell binds MHC I with its CD8?
Becomes single positive CD8+ T cell
why is negative selection necessary?
ensures self-tolerance
how does negative tolerance occur?
medullary epithelial cells express TF called AUTOIMMUNE REGULATOR (AIRE) which induces expression of many tissue-specific proteins in thymic epithelial cells which can be processed and presented on MHC I or II
then single positive T cells will browse self p:MHC on the surface of thymic epithelial cells
where does positive tolerance occur?
in cortex
where does negative tolerance occur?
in medulla
