A4: Antigen Recognition in Adaptive Immunity

Question 1

How many polypeptide chains does an antibody have, and what are the chains called?

Answer 1

4 polypeptide chains; 2 identical light chains and 2 identical heavy chains

Question 2

What are the two domains or regions that all antigen receptor molecules have? What do each function in?

Answer 2

A variable and a constant region. The variable region recognizes the antigen (via the hypervariable or complementarity determining regions) and the constant region is involved in signal transduction and structural integrity

Question 3

What are the 5 isotypes of antibodies, and what structure is each of the secreted forms?

Answer 3

IgA: mainly as a dimer
IgD: monomer
IgE: monomer
IgG: monomer
IgM: pentamer

Question 4

What is negative selection?

Answer 4

Elimination of strongly self-reactive B and T lymphocytes. Eg: does this cell recognize self?

Question 5

What is positive selection?

Answer 5

Survival of only T cells that recognize MHC molecules in the thymus (and applies for B cells, but is mainly based on expression of complete antigen receptors)

Question 6

What are the versions of the light chain constant regions that are possible? What are the versions of the heavy chain constant regions?

Answer 6

Light chain: kappa or lambda

Heavy chain: IgM, IgD, IgG, IgA, or IgE

Question 7

What are the two versions of the two chains that make up TCRs?

Answer 7

Alpha and beta (majority)

Gamma and delta (minority)

Question 8

What is the segment of the variable region that contributes most to antigen binding?

Answer 8

CDR3

Question 9

What is the difference between the Fab and the Fc region?

Answer 9

The Fab region has the entire light chain and is involved in antigen recognition. The Fc region has the heavy chain C domain.

Question 10

What is required for B isotype switching?

Answer 10

Helper T cell activation

Question 11

What is a cross reaction, and what is an example?

Answer 11

When antibodies that are produced against a certain antigen actually bind to a structurally similar antigen. Classic example is rheumatic fever

Question 12

What is the difference in subunits between the antibody from a B cell and a TCR?

Answer 12

B cell antibody has heavy and light chains, TCR has beta and alpha chains

Question 13

What components make up the TCR complex?

Answer 13

The TCR, CD3 and zeta chains that transmit the signal when the TCR receives the antigen

Question 14

Which T cells have the gamma and delta chains rather than the alpha and beta chains for their TCR?

Answer 14

TCRs that are innate and abundant in epithelia

Question 15

What are the 4 steps to lymphocyte development?

Answer 15

1. Commitment of hematopoietic progenitors to B or T cell lineage
2. Proliferation of the progenitors
3. Rearrangement and expression of antigen receptor genes
4. Selection to preserve and expand cells that have useful receptors

Question 16

Which cytokine is key in the proliferation and survival of immature lymphocytes?

Answer 16

IL-7

Question 17

Which segments of genes do the light chains contain? What about the heavy chains?

Answer 17

Light chains have V and J segments, but the heavy chains have V D and J segments (also the TCR beta chain contains the D segment)

Question 18

What enzymes make up the VDJ recombinase? What does this enzyme do?

Answer 18

RAG1 and RAG2 genes make up the VDJ recombinase. Cleaves Ig or TCR loci at recombination signal sequence motifs. VDJ recombinase is only expressed in immature B and T lymphocytes

Question 19

What are the 5 mechanisms of creating Ig and TCR repertoire diversity?

Answer 19

1. Many V, D, and J germline gene segments that are inherited
2. Combinatorial diversity
3. Junctional diversity
4. Associational diversity (diff pairing of heavy and light chains)
5. Somatic hypermutation

Question 20

In VDJ recombination, which chain of Ig rearranges first? Within the heavy chain, which segments rearrange first?

Answer 20

The heavy chain rearranges before the light chain, and the D-J rearrangement occurs before the V-DJ rearrangement

Question 21

What is the first heavy chain isotype produced in recombination?

Answer 21

Mu is the first chain made

Question 22

In light chain rearrangement, what segments rearrange?

Answer 22

ONLY V and J segments rearrange. Light chain has no D segment

Question 23

What makes up the CDR3 loop?

Answer 23

The junctional sequences of the D and J segments encode the amino acids of the CDR3 loop which is the most variable and most contributes to antigen binding

Question 24

What are pro B cells? What are pre B cells? What is a pre-B cell receptor complex?

Answer 24

Pro B cells are those that are committed to B cell line
Pre B cells are those that can make the mu heavy chain successfully
Pre BCR complex is the complex of the mu chain and surrogate light chains

Question 25

How does the pre-BCR complex contribute to maturation of B cells?

Answer 25

Signals from pre-BCR complex promote B cell proliferation and survival if the B cell has made productive rearrangement at the IgH chain. If not, the cell will die if it hasn’t made a mu chain

Question 26

What are the 3 key roles of the pre-BCR complex?

Answer 26

1. transmit signals for maturation and survival of B cells that have successfully made a mu chain
2. cause allelic exclusion
3. triggers recombination at the kappa light chain (lambda is formed if the kappa fails)

Question 27

What is the final step in B cell maturation?

Answer 27

Expression of IgM and IgD, and is able to respond to antigen. VDJ heavy chain is spliced onto C mu or C delta in the primary transcript, leading to expression of IgM and IgD

Question 28

What are 3 subsets of mature B cells based on where they are found?

Answer 28

1. Most are in follicles in lymph node and spleen and are called follicular B cells
2. Marginal zone B cells are in the margins of splenic follicles
3. B-1 lymphocytes are found in lymphoid organs and peritoneal cavity

Question 29

What are the steps in maturation and selection of T cells?

Answer 29

1. Double negative cells are immature progenitors, and expand under IL-7 influence
2. TCR Beta chain recombination occurs via VDJ recombinase
3. pre-TCR complex forms to promote survival
4. Double positive T cells form (CD4 and CD8 both expressed with alpha and beta chains)