what are randomly generated by gene rearrangement
epitope-specific TCRs and BCRs
self-reactive lymphocytes undergo what
apoptosis
what is included in the B cell lineage
B 1 and B 2 cells
what is included in the T cell lineage
alpha-beta TCRs
gamma-delta TCRs
NKT cells
what cells are transitional
gamma-delta TCRs and B 1 cells
what cells are adaptive
alpha-beta TCRs and B2 cells
precursors of the T cell lineage
prothymocytes
migrate from bone marrow to the thymus
prothymocytes
enter at cortical region and lacks TCRs, CD3, CD4, CD8 molecules
thymocytes
how much percent of thymocytes become T cells
5%
remainder of thymocytes leaves what
thymus before selection or die by apoptosis
When cells arrive at the thymus, they can become what
NK cells, dendritic cells, B cells and even myeloid cells
a receptor on cells commits them to the T lineage
notch
can commit cells to T lineage even without the thymus being present
notch binding
dense outer region
cortex
looser inner region
medulla
connective tissue capsule with
trabeculae
arrive from the bone marrow as double negative cells that do not express CD4, CD8, CD3, or TCR
precursor cells
proliferate and differentiate into double positive thymocytes that express both CD4 and CD8 in addition to CD3 and TCR
double negative cells
die within 3-4 days unless they recognize pMHC I or pMHC II on cortical epithelial cells in the cortical region
double positive cells
this is also known as positive selection
surviving positive selection express only CD4 or only CD8 in addition to CD3 or TCRs
thymocytes
interact strongly with self peptides on MHC I or pMHC II of antigen presenting cells undergo apoptotic death
medullary thymocytes
this is also known as negative seletion
cross the endothelium of a venule and exit they thymus as T cells
mature single positive thymocytes
very early thymocyte development occurs in the bone marrow
alpha-beta T cell
Different stages of alpha-beta T cell (five)
double negative
double positive
positive/negative selection to become a single positive
final screening to remove autoreactive cells
release into the peripheral bloodstream
recombination of TCR gene segments occurs in the double negative stages, yielding what
either an alpha-beta or a gamma-delta T cell
selection must bind to MHC
positive
selection removal of cells that interact with antigen-presenting cells
negative
if a cell passes both negative and positive selection is will what
leave the thymus and become T cells
what percent of cells fail positive selection and fail to receive needed survival signals
95
selects thymocytes bearing receptors capable of binding self-MHC molecules, resulting in MHC restriction
positive selection
selects against thymocytes bearing high-affinity receptors for self-MHC/peptide complexes, resulting in self-tolerance
negative selection
what cells make up 80% of thymic cells
double positive thymocytes
migrate preferentially to respiratory organs, skin, peritoneal cavity
gamma-delta T cells
leave the thymus shortly after receiving TCRs and CD3
gamma-delta T cells
have limited variability, respond quickly, and no memory
gamma-delta T cells
Very early thymocyte development occurs in the bone marrow
Cells migrate to the thymus for further development
Alpha beta T cell
Recombination of TCR gene segments also occurs in the double negative stages yielding what
Alpha beta T cell
Gamma delta T cell
What are the different stages that cells migrate for further development
Double negative
Double positive
Positive or negative selection become a single positive
Final screening to remove auto reactive cells
Release into the peripheral bloodstream
Must bind to MHC
Positive selection
Removal of cells that interact with antigen presenting cells and it is potentially auto reactive
Negative selection
If this passes both negative and positive selection what happens
Becomes a T cell and leaves the thymus
Double positive thymocyte a make up what percent of thymocyte cells
80
Selects thymocyte said bearing receptors capable of binding self-MHC molecules, resulting in MHC restriction
Positive selection
Selects against thymocyte a bearing high-affinity receptors for self-MHC/peptide complexes, resulting in self-tolerance
Negative selection
What percent of cells fail positive selection and fail to receive needed survival signals
95
What cortical thymocyte a express alpha beta TCR and only later express CD4 and CD8 to become what type of thymocyte
Double negative
Double positive
What type of cells attempt to bind with pMHC I or pMHC II on cortical epithelial cells
Double positive
Double positive thymocytes that bind pMHC II cease what
CD8 expression
Double positive thymocytes that fail to bind to either pMHC I or pMHC II will do what
Die
Double positive thymocytes that bind pMHC I cease to do what
CD4 expression
What type of thymocytes migrate to the thymus medulla
Single positive
Do not undergo same selection process Leave thymus shortly after receiving TCRs and CD3 Limited variability Respond quickly No memory
Gamma delta T cell
What type of T cell migrates preferentially to respiratory organs, skin, peritoneal cavity
Gamma delta T cell
Express several markers and receptors Undergo some development in thymus Express TCRs Limited in repertoire to lipids, glycolipids, and some specialized peptides Either CD4 or CD4CD8 Recognize nonclassical MHC I molecules
NK T cell
Cell death without triggering inflammation
Programmed cell death
Apoptosis
Results from injury and it is the release of cell contents meaning inflammation
Necrosis
The site of what generation changes during gestation
B cell
Blood cell development changes locations until bone marrow is formed and can take over
B cell
What doesn’t exist at fertilization
Bone marrow
Contains connective tissue, blood vessels, fat, and cells and has vascular importance
Bone marrow
Give rise to myeloid, granuloid, erythroid, and lymphoid cells
Hematopoietic stem cells
Stem cells within this differentiate into many cell types
Stromal cells provide support and growth factors to developing cells
Structure is dynamic and complex
Bone marrow
Conventional and widely distributed Require interaction with T cells for activation and proliferation Continually replace from bone marrow Vast repertoire Repeated antigen exposure meaning stronger, faster response Often accompanied by class switching Immunologic memory More IgD expressed gotten IgM
B2 cells
Arise from fetal liver
Importance in innate and autoimmunity
Limited repertoire
Often directed against conserved microbial antigens
Most natural antibodies
Predominantly in areas of microbial entry
Self renewing
B1 cells
What is different in the fetal liver from that in the adult bone marrow
Hematopoietic
What are the major sites of B1 cells vs the B2 cells
B1 peritoneal and pleural cavities
B2 secondary lymphoid organs
How does b1 cells get new cells vs b2
B1 self renewing
B2 precursors in the bone marrow
How diverse is b1 vs b2
B1 restricted diversity
B2 highly diverse
Which B cell 1 or 2 has somatic hyper mutation
B2
Which types of Ig is produced in b1 and b2
B1 IgM
B2 IgG
Which B cell responds to carbohydrate antigens
B1
Which B cell responds to protein antigens
B2
Which B cell has memory
B2
Hematopoiesis stages are defined by what three things
Cell-surface markers
Transcription factor expression
Ig gene rearrangements
What does both b and T cell developmental pathways share
Four things
Rearrangement of gene segments
Screening processes to avoid self-reactivity
Production of small subsets with discrete functions
Production of larger general purpose subsets
What screening processes are used in B cells and T cells
T cells positive and negative selection
B cells negative selection
B cells require what to hell and secrete antibodies
T cells
T cells require what for helper and killer subsets
Presentation and differentiate