Immunology exam 1 Flashcards
(103 cards)
Pro B cells
The earliest identifiable cells of the B-cell lineage. The main event in the pro-B stage in the rearrangement of the heavy chain genes
Early Pro B cell
Joining of D (H) and J (H) segments occurs at this stage.
Late Pro B cell
Joining of a V (H) segment to the rearranged DJ (H)
Large Pre-B cell
successfully rearranged a heavy chain gene and make a mu heavy chain, they have stopped have stopped heavy chain rearrangement. Light chain not yet rearranged
Small Pre- B cell
Rearrangement of light chain genes
Immature B cell
VDJ rerranged, VJ rearranged, mu heavy and lambda or kappa light chain IgM on surfance
Stromal Cell in B cell Dev- functions
1) Make specific contact with the developing B cells through the interaction of adhesion molecules and their molecules. 2) Produce growth facts that act on the attached B cells ex: membrane-bound stem cell factor (SCF), which is recognized by Kit on maturing B cells, growth factor IL-7 that is a cytokine that acts on late pro-B and pre-B cells
Nonproductive rearrangements
Gene rearrangements that do not translate into a useful protein
RAG1 and RAG2 - recombination-activating genes
Proteins that is needed for DNA rearrangement
E2A and EBF
Transcription factors responsible for changing gene expressions of RAG1 and RAG2. Also cause the expression of Pax-5
Pax-5
Transcription factor that is responsible for switching on the genes for many proteins that are expressed only in B cells, including Ig alpha and a cell surface protein called CD19, which in mature B cells forms part of the B cell co-receptor that helps the cell respond to antigen
B cell dev: 1st checkpoint criteria
1) Make a mu heavy chain, mu chain must demonstrate ability to combine with a light chain
VpreB and Lambda5
Two proteins synthesized by pro B cells which bind to mu heavy chains in a manner that mimics the light chain. Vpre B = variable region , Lambda5 - constant region , together they form the surrogate light chain. Transcription of their gene is controlled by E2A and EBF
pre B cell receptor
Receptor made from heavy chain, surrogate light chain, IgBeta, IgAlpha . When receptor is formed it allows a pro B cell to become a pre B cell. Also prevents B cells from making more than one functional mu chain by signaling for transcription of the RAGE genes to stop and signals for RAG proteins to be degraded and the for the structure of the chromatin of the heavy chain locus to be rearranged into a state that resists gene rearrangement (leads to allelic exclusion)
Allelic exclusion
when one of two copies of a gene is expressed
B cell dev: 2nd checkpoint
Light chains that bind the existing mu heavy chain and assemble a functional B cell receptor will live
B cell dev: self tolerance - negative selection
Immature B cells in bone marrow are exposed to self antigen expressed by stromal cells, hematopoietic cells and macromolecules circulating the blood plasma. During this process, immature B cells are only expressing IgM on their surfaces.
B cell dev: receptor editing for autoreactive B cells
When the immature B cell binds to self antigen in the bone marrow, the B cell will reduce the amount of IgM on its surface and maintain expression of the RAG proteins, which permits the B cell to continue rearranging its light chain loci and will remove the original light chain. If all light chin possibilities end, then cells will die.
Clonal Deletion
The selective death of developing lymphocytes and the consequent removal of their self- reactive receptor specificities from the B cell repertoire
B cell dev: anergy
If immature B cell binds to soluble monovalent self antigens, they will become inactivated and unresponsive to their specific antigen and be development arrest called anergy. Anergic cells make both IgD and IgM, but unlike in mature B cells, the IgM is prevent from assembling a functional B cell receptor and is retained in the cell. IgD is on the cell surface but it does not activate B cell on antigen binding.
Central Tolerance
Immunological tolerance developed in a primary lymphoid organ- the bone marrow in the case of B cells
Peripheral Tolerance
Immunological tolerance induced to antigens outside the bone marrow
CCL21 and CCL19
Chemokines that attract immature B cells to enter the secondary lymphoid tissue through the walls of HEVs. CCL21 is secreted by stromal cells in the lymph node cortex AND dendritic cells within lymph node. CCL21 binds CCR7 receptor on B cells. CCL19 is expressed by dendritric cells.
CXCL3
Chemokine secreted by follicular dendritic cells located in primary lymphoid follicles. They that attracts B cells into primary follicle where they interact with proteins on FDCs that signal their final maturation into mature B cells. Surface proteins on B cells called lymphotoxin binds to receptor on FDC to preserve the integrity of its network.