Lymphocyte differentiation in central lymphoid organs Flashcards
where do lymphocytes originate from
pluripotent hematopoietic stem cells of bone marrow
what happens to the lympocytes that differentiate in bone marrow, and those that go to thymus
B cells
T cells
what kind of lymphoid organs are Bone marrow nd thymus
central/primary
what is antigen independant differentiation
immature lymphocytes build their receptors for antigen (become immunocompetent)
what kind of genes do germline DNA NOT contain
- doesn’t contain ready made genes for variable parts of Igs + TCR chains
- has numerous tandemly arranged gene fragments. the random combos produces the genes for variable parts
What is VDJ recombination
cutting and joining together DNA fragments
WHat is the light Ig chain and TCR chain made from
what is the heavy chain and TCR β chain made from
- 2 fragments: V + J (respectively)
- 3 fragments: V, D + J (respectively)
How is additional diversity created
enxyme: terminal deoxynucleotidyl transferase (Tdt)
inserts single random nucleotides btw fragments
Red bone marrow + location
main hematopoietic organ (except in embryo + foetus)
Located in spongy bones, filling spaces btw bone trabeculae
what is the stroma of the bone marrow
(connective tissue from mesynchymal cells)
- provides microenvironment for blood cell differentiation
- formed by stromal/ reticular cells cos the fibres prod by them form 3D network
what do hematopoietic stem cells give rise to
lymphoid stem cell / common lymphoid progenitor
some lymphoid stem cells become pro B cells which poliferate and differnetiate. what the most imp elemt of B cell differentiation
become immunocompetent (building antigen receptor)
Pro B cells will rearrange heavy chain genes - D J then VDJ. What is allelic exclusion
if first rearrangement successful,
the cell will use only the rearranged chromosome and will not touch its homologue.
why does first rearrangement become unsuccessful. what happens after
- if frameshift / early stop codon obtained
- cell then tries to rearrange 2nd chromosome, if fail again then it will commit apoptosis
what happens to successful pro B cells
They synthesize class mu heavy chain. It remains in the
cytoplasm
What do Pre B cells rearrange
what happens with failure
VJ of light chain gens starting with Kappa. success leads to allelic exclusion.
- failure: homologous chromosome rearranged.
- if both kappa attempts fail, lambda genes tried
what happens when cells acquires light chain
it expresses IgM receptor on its surface and becomes
an immature B cell. It is immunocompetent.
Immature B cells are checked for eventual
reaction of their IgM receptor with a normal
tissue component called what
autoantigen
B lymphocytes that react with autoantigens are called what
self reactive / autoreactive