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thymocytes
daughter cells in the thymus and they develop into T cells
thymus
site of T cell maturation; only lymphoid organ that does not have lymphoid follicles
cortico-medullary junction
where thymocytes start
thymic nurse cells
hold thymic lymphoblasts and induce them to become thymocytes; without these cells there is no development of thymocytes
thymic stroma
also known as thymic nurse cells
DN2 thymocytes
found in the capsular region of the cortex; these are not yet committed cells if taken out of the thymus
CD44+/CD25+ double negative thymocytes
DN2
DN3
CD44-/CD25+ pre-TCR+ double negative thymocytes
pre-T cell receptor
expresses the TCR beta and pre-T cell receptor alpha which allows for assembly and testing of the functional rearrangement of TCR beta
B cells
have two attempts at VDJ
T cells
have four attempts since there are two constant gene segments each with their own D and J segments
DN4
CD44 double negative thymocytes
TCR alpha
rearranges both genes at the same time; allows for very rapid screening of the genes; continues until both alleles are no longer able to be recombined until positive selection occurs
nonfunctional TCR
many of the TCRs that are generated will no longer recognize MHC at all
positive selection
screens for TCRs that can interact with MHC class I or MHC class II; if the cell cannot interact properly with the cortical epithelial cells then they will undergo apoptosis
autoreactive TCR
TCR is generated and reacts to host antigens
negative selection
screens TCRs that interact with host antigen displayed by antigen presenting cells in the thymus
cortical epithelial cells
function as antigen presenting cells expressing both MHC class I and MHC class II with a variety of host peptides; important for positive selection
single positive thymocytes
screened for interaction with MHC class I or class II; results in either a CD4 or CD8 T cell
dendritic cells
screen thymocytes as they enter to medulla from the cortex
medullary epithelial cells, macrophages, and dendritic cells
all express MHC class I and MHC class II; express B7 to interact with CD28; phagocytic and internalize antigen
AIRE
gene known as an autoimmune regulator; important for the expression of non-thymic genes in the thymus
hassall’s corpuscle
contain degenerating epithelial cels rich in high molecular weight cytokeratins; important for generating self antigens presented by neighboring dendritic cells
regulatory T cells
very small population of autoreactive T cells that inhibit T cell responses in the periphery; leave as memory cells
invariant NKT cells
bind to CD1 recognize lipid antigens and leave thymus as memory cells
peripheral tolerance
interacts too strongly with dendritic cells and become anerguc or undergo apoptosis
gamma delta T cells
do not express CD4 or CD8; not MHC class restricted; subgroups of both innate and adaptive; important for detecting epithelial stress and promoting inflammation
15
peak size of thymus is at this age; after this very few mature T cells are produced
tolerance
lack of immune response to self antigens
auto-antigens
self-antigens are also known as this
autoimmunity
immunity to self anitgens is known as this
autoimmune polyglandular syndrome
lack of central tolerance in the thymus; autoimmune disease affecting multiple glands of the bod; reduced thyroid function, stunted growth, abnormal puberty, etc.
rheumatoid factor
antibodies to self IgG
rheumatoid arthritis
chronic inflammation but is normally short lived as the immune complexes are rapidly cleared and stimulation of B cells ceases
immunologically privileged sites
some areas of the body that do not allow for entry of immune cells; unless damage or severe infections these areas see little immune cells
sympathetic opthalmia
one eye is damaged/ruptured and an immune response develops that leads to an autoimmune response to the second eye; can lead to total blindness
CD4+/CD25+ regulatory T cells
recognize self-anitgen; function by supressing the immune response mediated by thymocytes and anitgen presenting cells
TH3 and TR1 cells
found in mucosal immune system; important for oral tolerance to the food we ear and to a very limited extent of our normal flora
clonal exhaustion
chronic infections, persistent antigen can lead to reduced T cell function; prevents a never ending immune response