Lecture 5

Question 1

Which are the central/primary lymphoid organs?

Answer 1

-bone marrow (leukocytes except T cells) and thymus (T cells)

Question 2

Which immunoglobulins distinguish progenitor stages of developing B cells in bone marrow?

Answer 2

-IgH and IgL antibody genes

Question 3

What are the stages of B cell maturation?

Answer 3

-pro-B cells to pre-B cells to immature B cells to B mature cells

Question 4

Failure to signal through which stage results in apoptosis of pre-B cells in bone marrow?

Answer 4

pre-BCR

Question 5

A defect in Bruton’s tyrosine kinase (BTK) results in which B cell immunodeficiency disease?

Answer 5

X-linked agammaglobulinemia (XLA)

Question 6

What are thymocytes called at the earliest stage of T cell maturation?

Answer 6

double negative due to lack of expression of CD4 and CD8

Question 7

Double negative TCRs are called what?

Answer 7

pre-TCR

Question 8

Define somatic gene recombination.

Answer 8

occurs during B cell maturation in the bone marrow and during T maturation in the thymus

Question 9

What are the inherited (germline) conformation for BCR and TCR?

Answer 9

• BCR: IgH and IgL

- TCR: TCR-alpha and TCR-beta

Question 10

Which gene segments are associated with IgH and TCR-beta loci?

Answer 10

-variable, diversity, and joining gene segments

Question 11

Which gene segments are associated with IgL and TCR-alpha loci?

Answer 11

-contain only V and J gene segments

Question 12

Which enzymes help bring together gene segments for gene recombination?

Answer 12

RAG enzymes (recombinase activating genes)

Question 13

How many tandem C gene segments are found for IgH locus?

Answer 13

-nine tandem C gene segments

Question 14

What are the steps involved in somatic gene recombination?

Answer 14

• D and J segments are brought together
• V segment juxtaposed making VDJ
• the intervening DNA is lost
• rearrangements of IgH and TCRbeta loci allow RNA splicing of VDJ gene to C segment to generate mRNA
• produce u or beta chain protein

Question 15

What is the mechanism for IgL and TCR alpha loci rearrangement?

Answer 15

• V gene segment to J gene segment
• intervening DNA lost
• transcription of rearranged loci and splicing of VJ gene to C gene segment generates mRNA

Question 16

(T/F) Once IgL and TCRalpha chain locus rearranged the BCR or TCR can be expressed at cell surface

Answer 16

True

Question 17

What are the two ways to generate diversity of antigen receptors?

Answer 17

• combinatorial diversity and mediated by RAG enzymes

- junctional diversity (related to variability in CDR3 regions of antigen receptor chains)

Question 18

What is junctional diversity?

Answer 18

• Addition or deletion of nucleotides at the junctions of the recombining V, D, and J gene segments
• addition of P nucleotides, DNA polymerase, and N nucleotides by terminal deoxynucleotide transferase (TdT)

Question 19

Which mechanism is the greatest contributor to antigen receptor diversity?

Answer 19

junctional diversity

Question 20

define central tolerance

Answer 20

immature autoreactive B and T cells are eliminated (apoptosis) in generative lymphoid organs

Question 21

positive selection

Answer 21

CD4/CD8 double positive thymocytes interacting with self-peptide/self-MHC expressed on thymic EC progressed to next stage of development

Question 22

negative selection

Answer 22

CD4/CD8 double positive thymocytes expressing TCR interacting with self-peptide/self-MHC expressed on surface of APC with high affinity induced to die by apoptosis