Ag Receptors & Ab/T-cell diversity (1/3)

Question 1

What are immunoglobulins?

What is its structure?

Answer 1

B cell receptors

They are on B cell surface & bind/recognize pathogens

Structure: Y-shaped, 2 identical heavy chains, 2 identical light chains. Amino terminal variable region + constant region. Carboxyl terminal has transmembrane domain (only difference between Ig’s and Ab’s)

It has a flexible hinge that provides flexibility & allows it to bind an antigen

Question 2

What are antibodies?

Answer 2

Soluble forms of immunoglobulins that effector B cells (plasma cells) synthesize and secrete

Question 3

What is an antigen?

Answer 3

Any molecule/cell that contains a structure that’s bound by an immunoglobulin or T cell receptor

Question 4

What does “surface receptor of lymphcyte” refer to?

Answer 4

Surface immunoglobulin and T cell receptor

Structrually & ancestrally related

Question 5

What is the structure of a T cell receptor?

Answer 5

Alpha chain, beta chain, anchored in the membrane

Has a variable/constant region

Question 6

How is genetic diversity created in B and T cell receptors?

Answer 6

Somatic recombination of V, D, (and J) segments of DNA

For Ig heavy chain and TCR beta chain: V, D, and J

For Ig light chain and TCR alpha chain: V and J only

The pieces of DNA get brought together by splicing & breaking of DNA by enzymes = gene rearrangement –> gene sequence that can be transcribed and translated

Question 7

What is clonal selection?

Answer 7

You start out progenitor cells that make a bunch of lymphcytes with unique receptors. Exposure to a matching pathogen causes proliferation of the cells that bind the pathogen

Question 8

What is a hypervariable region?

Answer 8

Part of the variable region that contributes to most of the antigen specificity of the Ag binding site. It’s flanked by “framework regions,” which are less variable.

They are found on the parts of the heavy and light chains in the variable region

Question 9

What are the 5 classes of Ig’s?

Answer 9

IgG, IgM, IgD, IgA, IgE

They are defined by differences in the heavy chains

Question 10

What 2 classes of Ig’s do newly generated naive B cells express?

What’s the process that leads to coexpression of these 2 classes?

Answer 10

IgM and IgD (think MD like doctor!); naive B cells are the only B cells that can express 2 classes of Ig’s at the same time!

RNA processing of “C miu/delta” regions gives you M and D respectively (NOT DNA splicing)

Question 11

What are the 3 mechanisms by which antibodies combat infection?

Answer 11

Neutralization of a toxin

Presenting bacteria to a macrophage

Binding to complement system

Question 12

What are monoclonal antibodies?

What are monoclonal antibodies used for?

Answer 12

They are antibodies of a single specificity that are derived from a clone of identical antibody producing cells

Uses: In flow cytometry as a diagnostic tool (i.e. cell counting in blood cancers)

Also used in treatment of disease (mouse, chimeric, humanized, or human)

Question 13

What is a V region?

Answer 13

“Variable” region. Contributes to the antigen binding site. Within the V domain, there are 3 hypervariablity regions corresponding to 3 loops clustered at one end of the domain that account for the variability.

Question 14

What is a C region?

Answer 14

“Constant region.” In the heavy chain, determines the antibody isotype & its specialized effector functions. There is also one in the light chain

Question 15

What is a D region?

Answer 15

“Diversity region.” Located only on heavy chain

Question 16

What is a J region?

Answer 16

Joining gene segment

Question 17

How is somatic recombination different for heavy and light chains?

Answer 17

For light chains: one recombination occurs between a V and J segment

For heavy chains: two recombination events occur. First, ad D and J segment join. Second, the DJ segment joins a V segment

Each time this occurs, the particular V, D, and J segments are selected at random

Question 18

What is a RSS?

Answer 18

Recombination signal sequences flank the 3’ side of the V segment, both sides of the D segment, and the 5’ side of the J segment. They are recognition sites for the enzymes that cut/join DNA and they ensure the gene segments are joined in the correct order

There are 2 types: (1) a heptamer and a nonamer separated by a 12 bp spacer. (2) a heptamer and a nonamer separated by a 23 bp spacers.

Question 19

What is RAG?

Answer 19

Recombination-activating genes. These specify the proteins that make up the V(D)J recombinase/RAG complex, which bind the 23 bp/12 bp spacers & ensure that the gene segments are joined in the correct order

Question 20

What is a coding joint? A signal joint?

Answer 20

Coding joint = the part of the DNA that’s incorporated (what you want to get after somatic recombination)

Signal joint = the DNA that gets thrown out

Question 21

How can gene diveristy that’s not encoded in the sequence of the germline DNA be created?

Answer 21

TdT (terminal deoxynucleotidyl transferase) randomly adds nucleotides (called N nucleotides for nontemplated) to the ends of the opened hairpins (after the RAG complex cleaves the RSS from D/J segments yielding DNA hairpins). Exonucleases can also remove nucleotides at the ends of the opened hairpins.

This creates “junctional diversity” which is mediated by the V(D)J recombinase (including RAG complex)

Question 22

What are the 3 processes that lead to diversity of immune receptors?

Answer 22

1. combinatorial diveristy from choosing diff V,D,J segs
2. junctional diversity
3. combinatorial diversity through heavy/light chain combos

Question 23

Why do not all rearrangements led to suitable antigen-recptors? 3 major reasons

Answer 23

Some V segments are pseudogenes (lost their protein making ability)

Junctional diversity can lead to reading frame shifts or nonsense mutations

You can get autoreactive antibody receptors

Question 24

How is this pre-immune repertoire regulated?

Answer 24

Antigen-independent B cell development: selection against autoreactivity (in marrow)

Antigen-dependent B cell development: choosing antibodies that are good & reactive (Ig class switch, somatic hypermutation, germinal center reaction)