immunoregulation Flashcards
what is the function of Tregs
prevent excessive immune responses to foreign antigens and immune responses to self-antigens missed by tolerization
cell surface markers expressed by Tregs
CD4+
FoxP3+
CD25+
autoimmune disease caused by inability to produce Treg cells
IPEX syndrome
CTLA-4
expressed by Tregs
inhibit activation of T cells
binding of CTLA-4 to B7 molecules on APCs reduces ability of APCs to activate T cells
IL-10
suppresses immunity by shutting down IL-12 production by dendritic cells and macrophages downregulates expression of costimulatory molecules and class II MHC
TGF beta
suppresses activation of macrophages and TH1 cells
promotes development of more Tregs
how do Tregs suppress immune responses
production of suppressive cytokines IL-10 and TGF beta
binding of CTLA-4 to B7 molecules on APCs
consumption of IL-2, depriving other cells of this growth factor
cytokines that downregulate immunity
IL-10 and TGF beta
induced state of unresponsiveness to an antigen
tolerance
characteristics of tolerance
antigen-specific
self-acquired/not inborn
all individuals have capacity to respond to self antigens, and therefore to develop autoimmunity
antibody feedback
a
idiotypic regulation
a
central tolerance
occurs in bone marrow or thymus
clonal deletion
deletion of self-reactive lymphocytes in bone marrow or thymus
AKA central tolerance
clonal anergy
functional inactivation of lymphocytes in periphery
viability is maintained
mechanisms of clonal anergy
functional inactivation of T cells in periphery
expression of self-antigens in absence of co-stimulatory molecules normally produces clonal anergy
receptor editing
rearrangement of antibody genes to try to produce a non-self-reactive antibody
if still self-reactive after editing, undergoes clonal deletion
thymocytes, on arrival to the cortex of the thymus, express
neither CD4 nor CD8
double negative
as thymocytes course through the cortex, they express
CD4 AND CD8
become double positive
what destroys thymocytes
corticosteroids
duration of T and B lymphocyte tolerance
T = long lasting B = short lived
positive thymic selection
eliminates thymocytes that recognize foreign MHC proteins
leaves behind self-reactive T lymphocytes
mediated by thymic cortical epithelial cells (thymic nurse cells)
negative thymic selection
eliminates self-reactive T lymphocytes
carried out by DCs at cortico-medullary junction
AIRE gene
allows thymus to express tissue specific self antigens that can be used in the negative selection process
