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MFMII > Lymphocyte Development > Flashcards

Lymphocyte Development Flashcards

1
Q

where does B cell development occur?

A

surface of bone marrow stromal cells

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2
Q

what is the survival signal in lymphocytes?

A

IL-7

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3
Q

what genes are part of the Heavy chain of BCR?

A

VDJ

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4
Q

what genes are part of light chain of BCR?

A

VJ

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5
Q

which chains arrange first in BCR assembly

A

heavy chain variable regions first

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6
Q

what directs recombination of the VDJ gene segments in the heavy chain?

A

recombination recognition sequences (RSS)

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7
Q

what does RAG complex do?

A

cleaves the RRS, recombines the gene segments, and ligates the new segments

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8
Q

what is somatic recombination?

A

during B cell development, areas of VDJ are cut and respliced by DNA recombination

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9
Q

what triggers the continuation of somatic recombination?

A

the successful rearrangement of D-J triggers V-DJ rearrangement

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10
Q

what is a pre-B cell?

A

VDJ of heavy chain has been rearranged, has partial BCR

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11
Q

what is allelic exclusion?

A

only 1 H chain and 1 L chain can be expressed, and the other chromosome locus undergoes epigenetic silencing FOREVER!!!!!!

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12
Q

what occurs once H chain is successfully rearranged?

A
  1. other chromosome undergoes epigenetic silencing
  2. RAG complex is degraded
  3. RAG1 and RAG2 transcription stops
  4. large pre-B cells divide to small Pre-B cells and RAG genes are reactivated to produce new RAG complexes for light chain rearrangement
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13
Q

what has to occur to result in BCR expression?

A

successful V-J rearrangement

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14
Q

what occurs if kappa L chain genes fail to rearrange?

A

lambda Light chains attempt to rearrange

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15
Q

what gives additional diversity in the Ag binding site of BCR?

A

addition of random nucleotides at coding joints by TdT ((terminal deoxynucleotidyl transferase)

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16
Q

what occurs if either the H or L chains are not produced?

A

apoptosis

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17
Q

describe circulation of B cells after BCR is made

A
  1. self reactive B cells are removed (negative selection)
  2. IgM+ immature B cells leave the bone and go to spleen (positive selection)
  3. immature B cells access lymph nodes through the high endothelial vessels to become mature B cells
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18
Q

what does travel through lymph nodes do to the B cell?

A

interaction with follicular dendritic cells and cytokines drives maturation (both IgD and IgM expression)

19
Q

how do B cells express both IgM and IgD constant regions

A

coexpression of IgD and IgM is possible by mRNA alternate splicing

20
Q

where do T cells develop

TCR

A

thymus

21
Q

what is important about the blood thymus barrier

A

keeps the environment clear of entering Ag so that T cells can be selected that don’t respond to self

22
Q

what makes up the blood thymus barrier

A

CTEC and capillary endothelial cell basal lamina, with macrophages between the layers

23
Q

what resides in the thymus cortex?

A
  1. T cells
  2. Cortical thymic epithelial cells (CTEC) assist in selecting functional T cells - have MHC I and II that interact with T cells)
  3. macrophages
  4. blood vessels
24
Q

what resides in the thymus medulla?

A
  1. T cells (not as many)
  2. medullary thymic epithelial cells (elimination of self reactive t cells) (negative selection)
  3. macrophages
  4. dendritic cells to activate Tcells
  5. hassalls corpuscles
25
Q

what T cell development step occurs in the thymic subcapsular layer?

A

double negative (CD4- CD8-_ T cells (Pro t cells) differentiate into pre-T cells expressing 1 rearranged chain of the TCR (beta chain)

26
Q

what is double negative ?

A

pro-t cell does not have CD4 or CD8 expression

27
Q

what constitutes a pro-T cell?

A

no CD4 or CD8 expression, no TCR

28
Q

what constitutes a pre-T cell

A

expresses one rearranged chain of TCR (BETA CHAIN)

29
Q

what TCR chain genes rearrange first?

A

beta chain genes

30
Q

what promotes alpha chain rearrangement?

A

successful beta chain rearrangement

31
Q

what does successful rearrangement of both beta and alpha chains trigger?

A

induces gene expression of BOTH CD4 and CD8 = double positive T cells

32
Q

where do double positive cells occur?

A

cortex of thymus

33
Q

where does positive selection occur?

A

cortex

34
Q

what cells are important for positive selection?

A

CTEC

35
Q

how are DP T cells differentiated to CD4 or CD8?

A

DP T cells engage CTEC to determine CD4 or CD8, and a significant number of DP T cells apoptose

36
Q

where do differentiated T cells undergo negative selection?

A

thymic medulla

37
Q

what occurs in the SP (specific) T cells once they travel into the medulla?

A

TCR signaling molecules are expressed, so they can form response to recognized Ag; they encounter MTEC and DC

38
Q

what does MTEC do?

A

able to produce most of the protein/peptides (SELF ANTIGENS) found throughout body system – aka presents self antigens to Tcells to ensure they arent self reactive

39
Q

what do hassal’s corpuscles do?

A

produce TSLP which matures the DC in the medulla so they can better present peptides to SP T cells

40
Q

what occurs to SP T cells that bind strongly to self Ag?

A

apoptosis (negative selection)

41
Q

what occurs to SP T cells that bind moderately to self Ag?

A

survive

42
Q

what are the surviving CD4 and CD8 T cells called in the medulla?

A

naive and mature

43
Q

what does CCR7 signal for?

A

migration to the secondary lymphoid organs

MFMII (29 decks)

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