Antibody Structure/ Generation of B cell diversity

Question 1

What are the highly variable recognition molecules of the adaptive immune response?

Answer 1

Immunoglobulin (BCR) and T cell receptors

Question 2

What is active immunity? Passive immunity?

Answer 2

Active is generated in the host (infection, vaccine); Passive is generated elsewhere and transferred to host

Question 3

True or False: Antigen receptors are unique to the adaptive immune response

Answer 3

True

Question 4

What is the basic structure of the TCR?

Answer 4

A heterodimer composed of two transmembrane glycoproteins

Question 5

What is the name of the regions of antigen molecule recognized by the BCR/TCR?

Answer 5

Epitopes

Question 6

What kind of antigens can B cells recognize? T cells?

Answer 6

B cells can recognize free, surface bound, or degraded antigen; TCRs only recognize processed antigen peptides presented on an MHC

Question 7

What is an immunogen?

Answer 7

Epitopes that induce an immune response and are recognized by antigen receptors

Question 8

What are haptens?

Answer 8

Small, non-immunogenic, but antigenic molecules

Question 9

What are the characteristic of an antigen that favor induction of an immune response?

Answer 9

Size (>10 kDa), Complexity, conformation (accessible), and chemically cleavable

Question 10

What confers the different functions in different antibody isotypes?

Answer 10

Differences in the Fc region

Question 11

By what cells are antibodies secreted?

Answer 11

Plasma cells

Question 12

What polypeptides make an antibody?

Answer 12

2 identical heavy chains and 2 identical light chains

Question 13

What domains are contained within the immunoglobulin light chain? Heavy chain?

Answer 13

One variable domain and one constant domain; One variable and 3 or 4 constant domains

Question 14

What makes up the antigen-binding site of immunoglobulins?

Answer 14

The combination of the variable domains from one L chain and one H chain

Question 15

What are the different H chains? L chains?

Answer 15

Gamma, mu, delta, alpha, and episilon; kappa and lambda

Question 16

What is the hinge region of an antibody and what is its importance?

Answer 16

The flexible, unstructured portion in the middle of the Ab; allows antigen binding arms to adopt different orientations

Question 17

What are the two fragments an antibody can be cleaved into by proteases?

Answer 17

Fab (fragment antigen binding=arms) and Fc

Question 18

Where on the antibody are the hypervariable regions? How many are there per variable domain?

Answer 18

There are 3 HV per variable domains and they are located on loops at the end of the arm

Question 19

What are complementarity-determining regions?

Answer 19

Hypervariable regions on antibodies

Question 20

What forms the Ag binding site at the tip of each Fab on an antibody?

Answer 20

Pairing of HV regions from the H and L chains

Question 21

How many total hypervariable regions are their per antibody? How many different HV regions/ antibody?

Answer 21

12– 2 identical pairs of 6

Question 22

What dictates the specificity of an antibody?

Answer 22

The different sequences of variable regions which create different antigen binding sites

Question 23

True or False: An antibody that recognizes one pathogen is also designed to recognize other pathogens

Answer 23

False

Question 24

What is a multivalent antigen?

Answer 24

An antigen with more than one epitope

Question 25

What are the different types of epitopes? What is each

Answer 25

Linear epitopes (sequential amino acids) and discontinuous epitopes (amino acids brought together via protein folding

Question 26

True or False: Not all 6 complementary determining regions may make contact with an antigen

Answer 26

True

Question 27

What is avidity?

Answer 27

Combined strength between more than one antigen binding site and more than one epitope

Question 28

What is avidity?

Answer 28

Combined strength between more than one antigen binding site and more than one epitope

Question 29

What antibody generally has low affinity but high avidity?

Answer 29

IgM

Question 30

What are abzymes?

Answer 30

A catalytic antibody; a monoclonal antibody that binds and changes the antigen

Question 31

What are polyclonal antibodies?

Answer 31

Antibodies generated from a mixture of different B cells and recognizes multiple epitopes

Question 32

True or False: Humoral immunity response to infection is polyclonal?

Answer 32

True

Question 33

How are monoclonal antibodies generated?

Answer 33

B-cell hybridomas- b cells fused with tumor cells

Question 34

What is agammaglobulinemia?

Answer 34

The absence of antibodies

Question 35

What are chimeric and humanized monoclonal antibodies?

Answer 35

Chimeric- mouse variable region + human constant regions; Humanized- mouse CDR replaces human CDR

Question 36

How is diversity of antigen receptors generated?

Answer 36

Somatic recombination - Gene rearrangement

Question 37

What segments are in the variable domain?

Answer 37

Heavy chains- V(ariable), D(iversity), and J(oining); Light chains- V and J

Question 38

What cells in the body undergo somatic recombination?

Answer 38

Only B and T cells

Question 39

True or False: Somatic recombination must occur before the gene can be transcribed?

Answer 39

True

Question 40

What is clonal selection and expansion?

Answer 40

Clonal selection is the process by which only B and T cell receptors that recognize a given pathogen are activated to proliferate and form clones of cells with identical receptors (clonal expansion)

Question 41

What is the order of rearrangements to make the V region in the Ig heavy chain?

Answer 41

D and J and then DJ and V

Question 42

What is V(D)J recombinase?

Answer 42

A set of enzyme required for V-D-J?

Question 43

What is the RAG complex?

Answer 43

RAG-1 and RAG-2 form a RAG complex which binds to recombination signal sequences and initiates recombination events

Question 44

What is junctional diversity?

Answer 44

The RAG compex cleaves RSSs from the D and J (or DJ and V) gene segments to yield DNA hairpins, and then it opens the hairpins generating palindromic P-nucleotides. Terminal deoxynucleotidyltransferase randomly fills in the gaps with non-templated nucleotides (N nucleotides)

Question 45

True or False: Each B cell will produce hundreds of Heavy and Light chain combinations

Answer 45

False: only one

Question 46

What kind of Ig is expressed on naive B cells?

Answer 46

IgM and IgD

Question 47

What is the mechanism by which both IgM and IgD are expressed on naive B cells?

Answer 47

mRNA splicing

Question 48

What confers the difference between surface-Ig and secreted antibodies? What is the mechanism by which Ig changes from surface to secreted?

Answer 48

Membrane Ig have hydrophobic tails and secreted have hydrophilic tails; Alternative RNA splicing

Question 49

What is somatic hypermutation?

Answer 49

When a B cell undergoes clonal expansion the clones will accumulate small point mutations in the CDR loops and some mutations will increase the affinity

Question 50

What is affinity maturation? What enzyme is required?

Answer 50

The process by which the interaction between antibody and epitope improves; Activation-induced cytidine deaminase (AID)

Question 51

True or False: T cells do not undergo somatic hypermutation?

Answer 51

True

Question 52

What is the first antibody produced?

Answer 52

IgM

Question 53

What is the structure or IgM antibodies?

Answer 53

Pentameric-- 10 arms total

Question 54

What is the reason for isotype/class switching? What enzyme is required?

Answer 54

Production of antibodies with different effector functions but same antigen specificity; AID

Question 55

What is the mechanism of Isotype switching?

Answer 55

Rearrangement of VDJ and C genes

Question 56

What factors dictate which isotype is needed?

Answer 56

Location and type of infection

Question 57

What stimulates isotype switching?

Answer 57

T-cell signals

Question 58

What generates TCR diversity?

Answer 58

Somatic recombination through RAG1 and RAG2- V segment joins to J segment in the alpha chain, and D with J and DJ with V in beta chain

Question 59

True or False: RAG is required for generation of diversity of both T and B cells?

Answer 59

True