Tolerance and Autoimmune Flashcards
(86 cards)
As B cells and T cells randomly recombine their V,D, J gene segments to create antigen receptors, it is inevitable that some receptors will be——–
Specific for self antigens
These self reactive lymphocytes must be deleted or rendered anergic to prevent——
autoimmune reactions from occuring
——is induced when self-reactive B cells and T cells are DELETED in the central lymphoid tissues
Central Tolerance
——-is induced when the few self-reactive lymphocytes that escape deletion in the central lymphoid organs are rendered ANERGIC in the peripheral lymphoid organs
Peripheral tolerance
——result when the occasional anergic lymphocyte becomes re-activated and starts attacking self tissues
Autoimmune diseases
——-occurs when thymocytes are rescued from apoptosis by moderate affinity interactions with sefl-MHC molecules
Positive selection
Positive selection occurs by epithelial cells where—–
in the cortex of the thymus
—–occurs when autoreactive T cells are deleted when the T cells interact with dentritic cells or epithelial cells that display non-MHC self antigens along with self-MHC molecules
negative selection
Negative selection occurs where?
at the cortico-medullary junction and in the medulla of the thymus
When the T cell progenitors produced in the bone marrow enter the thymic cortex, these pro-T cells express neither—–nor—-(double negative thermocytes)
CD4 nor CD8
Pro-T cells develop into pre- T cells, which express the—–chain of the—-
beta chain of the TCR
Pre- T cells develop into double positive immature T cells, which express both —-and—–, along with——levels of complete TCR molecules
CD4 and CD8/low
The double positive thymocytes interact with thymic—–that express high levels of both—–and——MHC molecules
cortical epithelial cells/class I/class II
Thymocytes with——-for these self-MHC molecules are allowed to develop further, while thymocytes with affinities—-or——for self MHC are induced to die by——–
moderate affinities/too high/too low/apoptosis
The positively selected thymocytes begin to express—-of TCR molecules, some of which recognize normal body components other than self-MHC
high levels of TCR molecules
—– —- —-present self antigens that are always present within the thymus at the————
Intergigitating dendritic cells (IDCs)/at the cortico-medullary junction
in the—–the thymocytes interact with “non-thymic” self antigens processed and presented by—- —— ——
in the medulla/medullary epithelial cells
—– —- —–produce a transcription factor regulator called——- that allows these cells to synthesize non-thymic antigens typically found in the peripheral tissues
medullary epithelial cells/AIRE
People with an AIRE gene defect suffer from—– —– —-due to autoreactive T cells that are not deleted (pt present with hypothyroidism/adrenal insufficiency/thyroiditis/type 1 diabeties/ovarian failure
autoimmune polyendocrine syndrome
Only thymocytes that—-to recognize self antigens are allowed to survive and proceed along the maturation process, with the remainder undergoing apoptosis
fail
T cells that survive the negative selection process lose either CD4 or CD8, becoming —- —-T cells
single positive
Some immature CD4+ T cells that recognize self antigens in the thymus do not die by instead develop into—–regulatory T (Treg) that enter the peripheral tissures
CD25+
Development of Treg cells is controlled by the transcription factor —-under the influence of —–
Foxp3/TGFbeta
T reg cells protect the host from the harmful effects of other self-reactive lymphocytes, namely— —- —- by secreting —- and —–
TH1, TH2, TH17 by secreting TGFbeta and IL10
