Lymphocyte Development

get a hint

hint

Clonal deletion

Clonal deletion

________: if B cells exhaust all possibilities for L- chain recombination, they are signaled to die by apoptosis in bone marrow.

DiGeorge Syndrome

________: had underdeveloped /missing thymus as well as immune deficiency.

negative thymocyte

Double- ________: express neither CD4 nor CD8; begin rearranging β, λ, δ.

Receptor Editing

________: B cells doing it to avoid self- reactivity; avoid negative selection; rearranging light chains.

FDCs

________ provide signal for B cells to finish maturation.

Β chain rearrangements

________: can possibly happen more than once if they start w. downstream.

Peripheral tolerance

________: render self- reactive T cells anergic.

Α chain

________ have a lot of V + J segments so they can rearrange many times for productive AND useful rearrangement.

Single

________- positive thymocytes: positive selection matures double- positive thymocytes into cells that express only 1 of the 2 co- receptors.

Thy

________- 1 is marker for early developing T cell.

Clonal expansion benefits

________: guarantees investment made for each functional H- chain isnt lost through failure to make L- chain.

B cells

Immature ________: rearrangement of Light chain genes stop.

Small pre B cell

________: rearranging L chain; if κ fails, λ is rearranged.

IgM associates

________ w. Igα and Igβ to form B cell receptor complex 2nd checkpoint.

T cells

________ develop in thymus- Robert Good recognized that ppl w. thymus tumors had immunologic abnormalities.

Positive Selection

________ and Negative Selection: T cell becomes either CD4 or CD8.

B cells

________ are called that because they develop in the Bursa of birds.

B cells

When immature ________ bind multivalent self- Ag, they are detained in the bone marrow to recombine the L- chain and make new B cell receptor- receptor editing.

Phase 1

B cell precursors in bone marrow rearrange Ig genes

Early pro-B cell

join DH and JH

Late pro-B cell

join VH to DJH

Else

apoptosis

Large pre-B cell

successfully rearranged Heavy chain

Clonal expansion benefits

guarantees investment made for each functional H-chain isnt lost through failure to make L-chain

Small pre-B cell

rearranging L chain; if κ fails, λ is rearranged

Immature B cells

rearrangement of Light chain genes stop

Clonal deletion

if B cells exhaust all possibilities for L-chain recombination, they are signaled to die by apoptosis in bone marrow

Phase 3

Positive selection-regulates overall of B cells

Phase 4

mature naïve B patrol lymph + blood for infections

Phase 5

activation of Ag = proliferation + clonal expansion

Phase 6

plasma cells and memory cells

Receptor Editing

B cells doing it to avoid self-reactivity; avoid negative selection; rearranging light chains

DiGeorge Syndrome

had underdeveloped/missing thymus as well as immune deficiency

Double-negative thymocyte

express neither CD4 nor CD8; begin rearranging β, λ, δ

Pre-T cells

cells that pass test of making pre-TCR

If both λ and δ productively rearrange 1st, T cell becomes λ

δ

Double-positive thymocytes

α locus starts rearranging

Entire δ is w.in α locus, so if α locus begins rearranging, T cell becomes α

β

Positive Selection and Negative Selection

T cell becomes either CD4 or CD8

Negative selection (central tolerance) occurs if TCR binds too strongly to self-peptide

MHC

Positive selection occurs if TCR binds weakly to self-peptide

MHC

Single-positive thymocytes

positive selection matures double-positive thymocytes into cells that express only 1 of the 2 co-receptors

Peripheral tolerance

render self-reactive T cells anergic

β-chain rearrangements

can possibly happen more than once if they start w. downstream

Regulatory CD4 T cells

Treg; suppress response of autoreactive CD4 T cells to their specific self-Ag