Chapter 3: Lymphocyte Development and Selection

Question 1

The mature naive B lymphocyte expresses what 2 isotypes within its surface membrane?

Answer 1

IgM and IgD

Question 2

What receptor on the B cell does EBV bind to?

Answer 2

CD 21

Question 3

mRNA molecules are created which join variable domains to what type of constant domains in B cell heavy chains?

Answer 3

mu or delta

Question 4

Order with which VDJ combination takes place in heavy chains?

Answer 4

1. D-J joining
2. V-DJ joining

Question 5

What does VDJ stand for?

Answer 5

variable, diversity, joining

Question 6

Order VDJ recombination takes place in light chains?

Answer 6

V-J joining thats it really

Question 7

Which chain on T cell receptor is synonymous with the B cell heavy chain?

Answer 7

beta

Question 8

Which on TCR is synonymous with the B cell light chain?

Answer 8

alpha

Question 9

What type of constant chain domains do the light chain bind to?

Answer 9

kappa or lamda

Question 10

Purpose of Tdt?

Answer 10

While heavy chain gene segments undergo recombination, this enzyme, terminal deoxyribonucleotidyl transferase, randomly inserts bases (without a template on the complementary strand) > junctional diversity

Question 11

Allelic exclusion?

Answer 11

When recombination has generated a functional product then allele on homologous chromosome is turned off.

Question 12

Difference between N-nucleotide addition in B and T cells?

Answer 12

B cells (only heavy chains)
T cells (all chains)

Question 13

RAG 1 and RAG 2

Answer 13

2 proteins found within recombinase, a protein complex

Resoposbile for B and T cell rearrangment to create functioning receptors on the surface

Question 14

What is the inheritance pattern of Omenn Syndrome?

Answer 14

AR

Question 15

Inheritance pattern of SCID?

Answer 15

severe comibined immunodeficiency is an AR condition can also be X-linked

Question 16

Omenn Syndrome molecular defect?

Answer 16

• missense mutation in RAG genes
• the RAG enzymes have only partial activity

Question 17

Symptoms of Omenn Syndrome?

Answer 17

• Lack of B cells (below limits of detection)
• marked decrease in predominantly Th2
  *characterized by early onset, failure to thrive, red rash (generalized), diarrhea, and severe immune deficiency

Question 18

What is the molecular defect in SCID?

Answer 18

• null mutations in RAG1 or RAG 2 genes
• no RAG enzyme activity

Question 19

What are the symptoms of SCID?

Answer 19

• total lack of B and T cells
• total defects in humoral and cell-mediated immunity

Question 20

Is bone marrow considered a primary or secondary lymphoid organ?

Answer 20

primary lymphoid organ

Question 21

B lymphocytes whose idiotypes have too great an affinity for normal cellular molecules go through what processes?

Answer 21

• They are either deleted in the bone marrow (clonal deletion)
• They are inactivated in the periphery (clonal anergy)

Question 22

How does clonal anergy take place?

Answer 22

anergic B cells express high levels of IgD on their surface rendering them inactive

Question 23

Which B cells are released to the periphery?

Answer 23

only those cells which are selectively unresponsive (tolerant) to self antigen

Question 24

Label Cell differentiation picture. (B Cells)

Answer 24

Question 25

Is the thymus a primary of secondary lymphoid organ?

Answer 25

primary

Question 26

Pre-thymic T cells are referred to as double negative or double positive T lymphocytes? Why?

Answer 26

double negative ; since they do not express CD4 or CD8 on their surface

Question 27

Cortex of the thymus contains immature or more mature T cells?

Answer 27

Packed with immature T cells

Question 28

Thymic T cells undergoing rearrangement of beta and alpha chains and coexpressing CD3 complex as well as CD4 and CD 8 co-receptors are collectively referred to as what?

Answer 28

double positive

Question 29

MHC stands for?

Answer 29

major histocompatibility complex

Question 30

Overall describe MHC genes and location?

Answer 30

collection of highly polymorphic genes on the short arm of chromosome 6 in the human

Question 31

Another name for MHC gene products?

Answer 31

HLA (human leukocyte antigen)

Question 32

What are class I MHC gene products?

Answer 32

HLA-A, HLA-B, HLA-C

Question 33

What are the class II MHC gene products?

Answer 33

HLA-DP, HLA-DQ, HLA-DR, HLA-DM

Question 34

Why is HLA-DM different from the other MHC II gene products?

Answer 34

HLA DM is not a cell surface molecule but functions as a molecular chaperone to promote proper peptide loading

Question 35

Where are Class I molecules expressed?

Answer 35

all nucleated cells in the body, as well as platelets

Question 36

How are class I MHC molecules expressed on the nucleated cells of the body?

Answer 36

in a codominant fashion, meaning that each cell expresses 2 A, 2 B, and 2 C products (one from each parent)

Question 37

What is the purpose of the second light chain, B2- microglobulin in the MHC function?

Answer 37

is not encoded within the MHC and functions in peptide-loading and transport of the class I antigen to the cell surface)

Question 38

Where is Class II MHC presentation usually found?

Answer 38

codominantly on the professional APCs of the body (primarily macrophages, B lymphocytes, and dendritic cells)

Question 39

Describe positive selection of T cells.

Answer 39

1. In thymus, each of these MHC products are loaded with normal self peptides are presented to developing double positive thymocytes 2. Those that have TCRs capable of binding with low affinity will receive a positive selection signal to divide and establish clones that will eventually mature in the medulla

Question 40

Describe failure of positive selection of T cells?

Answer 40

those that fail to recognize self MHC at all will not be encouraged to mature (failure of positive selection)

Question 41

Describe negative selection of T cells?

Answer 41

those that bind too srongly to self MHC molecules and self-peptide will be induced to undergo apoptosis (negative selection) because the cells will have potential to cause autoimmune disease

Question 42

CD4 cells recognize which class of MHCs to become "helper T cells?

Answer 42

MHC II

Question 43

CD8 cells recognize which class of MHCs to become cytotoxic T lymphocytes?

Answer 43

MHC I

Question 44

What is the function of T regs?

Answer 44

inhibit self reactive Th1 cells in the periphery

Question 45

How are T regs selected?

Answer 45

While most self- reactive T cells will be deleted in the thymus a small population will differentiate into T regs

Question 46

How are Tregs identified? What markers?

Answer 46

by their constitutive expression of CD25 on the surface and by the expression of the transcription factor FoxP3

Question 47

What do T regs secrete to inhibit inflammation?

Answer 47

IL-10 and TGF-B

Question 48

What is a major function of T regs?

Answer 48

shown to be critical in prevention of autoimmunity

Question 49

Stages/location of T cells?

Answer 49

Pre-thymic > thymic cortex > thymic medulla > circulating T cells

Question 50

What are the stages Tdt is found in Human T cell differentiation?

Answer 50

pre-thymic > early thymic medulla

Question 51

What stages is rag expression of T cells?

Answer 51

thymic cortex

Question 52

What stages is CD2 expressed in development of T cells?

Answer 52

thymic cortex stage to when it becomes a circulating T cells

Question 53

What stage is CD3 expressed in development of the T cells?

Answer 53

thymic cortex to when it becomes a circulating T cell

Question 54

What stage is the TCR found in the development of the T cell?

Answer 54

thymic cortex to when it becomes a circulatory T cell

Question 55

When does double expression of CD4 and CD8 on T cells become expression of one or the other?

Answer 55

late thymic cortex stage