antibody structure and generation of B cell diversity

Question 1

the 2 components of an antibody

Answer 1

fragment antigen binding (Fab)
fragment crystallization (Fc)

Question 2

Antibody classes (heavy chain, light chain)

Answer 2

heavy: G, M, D, A, E
light: kappa and lambda (kappa is first choice during selection)

Question 3

Are immunoglobulin chains folded into compact and stable protein domains?

Answer 3

Yes

Question 4

what makes up the V domain (antigen binding domain)

Answer 4

heavy and light chain together

Question 5

Do C domains have sequence variation?

Answer 5

No

Question 6

what is the 3D structure of the Ig C and V domains

Answer 6

sammich

Question 7

what are hypervariable regions?

Answer 7

loops

Question 8

what are framework regions made of?

Answer 8

beta strands

Question 9

what do VL and VH make

Answer 9

a composite site
which is a antigen binding site
complementarity determining regions (CDR)
and hypervariable regions (HV)

Question 10

what is the epitope/antigenic determinant made up of?

Answer 10

protein or carbohydrate:
- glycoproteins
- polysaccharides
- glycolipids
- peptidoglycans

Question 11

what are the destructive antigen binding sites?

Answer 11

autoimmune (lupus/DNA)
allergy (antibiotics)

Question 12

what are multivalent antigens

Answer 12

antigen containing more than one epitope or multiple copies of the same epitope

Question 13

which multivalent antigen would have stronger binding strength?
same or different epitopes

Answer 13

same epitopes because it would be more sticky and have stronger binding strength

Question 14

what can epitopes bind to on an antibody antigen binding site

Answer 14

pockets, grooves, extended surfaces, or knobs

Question 15

types of forces behind antigen-antibody interactions

Answer 15

non-covalent:
electrostatic
van der waals
hydrogen bonds
hydrophobic interactions

Question 16

what is the affinity of antigen-antibodies interactions based on?

Answer 16

the strength of the interactions

Question 17

where are monoclonal antibodies produced from

Answer 17

a clone of antibody-producing cells

Question 18

what 2 things are antibodies useful tools for

Answer 18

specificity and affinity strength

Question 19

4 types of therapeutic monoclonal antibodies

Answer 19

1. mouse
2. chimeric
3. humanized
4. human

Question 20

specific example of chimeric and humanized Monoclonal antibody names and what it treats

Answer 20

chimeric: rituximab, b-cell non-hodkins lymphoma
humanized: trastuzumab, metastatic breast cancer

Question 21

how is nearly limitless antibody variety achieved

Answer 21

a unique genetic organization from gene segments: that are families of alternative versions arrayed sequentially in DNA AND germline form/config.: which is inherited form of immunoglobulin genes

Question 22

the variable region is comprised of what in both light and heavy chains

Answer 22

light chain: 1 variable and 1 joining segment
heavy chain: 1 variable, diversity and joining segments

Question 23

does random recombination of gene segments produce diversity in antigen binding sites?

Answer 23

yes

Question 24

what is the order of regions being joined together during recombination

Answer 24

diversity and joining regions first and then variable region after

Question 25

which segment has the most variation

Answer 25

variable region in heavy chain, then kappa light chain and then gamma light chain

Question 26

do light chains have any diversity region?

Answer 26

no

Question 27

which segment has the highest amount of constant regions

Answer 27

heavy chain

Question 28

are the amount of joining regions pretty similar between both chains?

Answer 28

yes

Question 29

where are RAG genes made

Answer 29

in lymphocytes

Question 30

are RAG genes active in any other cell type than lymphocytes?

Answer 30

no

Question 31

are RAG genes important for functional adaptive immunity?

Answer 31

yes they are critical

Question 32

is P nucleotide insertion palindromic?

Answer 32

yes

Question 33

how is N nucleotides inserted

Answer 33

it is non templated and inserted by terminal deoxynucleotidyl transferase (TdT)

Question 34

how is the antibody isotype determined

Answer 34

by the heavy chain

Question 35

which immunoglobulin chains do all naive B cells start with

Answer 35

with mew and delta which are able to be expressed simultaneously

Question 36

what determines expression of either IgM or IgD and at what level

Answer 36

differential splicing, RNA level

Question 37

how many allele/copy is expressed in each B cell, and what is the result

Answer 37

only 1 and each B cell has a single antigen specificity

Question 38

what makes the specificity of antibody response a central principal of adaptive immunity

Answer 38

the fact that each antibody has a single antigen specificity

Question 39

what location is immunoglobulin first made on

Answer 39

membrane bound form that is present on B cell surface

Question 40

which Ig is produced in large numbers: IgM or IgD

Answer 40

IgM is produce in large numbers

Question 41

how are secreted antibodies produced and is rearrangement required

Answer 41

an alternative pattern of heavy chain RNA processing, no rearrangement necessary

Question 42

how are rearranged V region sequences further diversified

Answer 42

somatic hypermutations by AID

Question 43

what is affinity maturation

Answer 43

selection of mutated immunoglobulins with improved antigen-binding

Question 44

what does affinity maturation do

Answer 44

allows the human immune system to keep up with the pathogen evolution

Question 45

do the initially made IgM have limitations

Answer 45

yes, binds well to repetitive sequences, but has limited ability to clear

Question 46

when does isotype switching occur

Answer 46

during an active immune response

Question 47

what is isotype switching dependent on

Answer 47

during an active immune response done by cytokines. (antigen-activated T-cell cytokine secretion)

Question 48

what mechanism initiates antibody secretion?

Answer 48

RNA processing/splicing

Question 49

what are the 2 ways antibodies aid in pathogen clearance

Answer 49

1. neutralization 2. opsonizing

Question 50

does somatic hypermutation enhance affinity or avidity

Answer 50

affinity (single site)

Question 51

when would IgG replace IgM

Answer 51

when there are 2 sites being of sufficient avidity

Question 52

what Ig is responsible for the synthetization of mast cells

Answer 52

IgE

Question 53

what Ig is responsible for transport across the epithelium

Answer 53

IgA

Question 54

what Ig i most responsible for transport across the placenta

Answer 54

IgG1 (and IgG3,4)

Question 55

where is dimeric IgA made

Answer 55

in the lymphoid tissues underlying the mucosal surfaces and is then secreted across them

Question 56

is flexibility crucial for Ig molecules

Answer 56

yes, because it binds simultaneously to pathogens and to effector molecules and receptors of the immune system

Question 57

types of movement on Fab arms

Answer 57

wave, rotate, wag, bend

Question 58

which IgG subclass has high susceptibility of hinge to proteolytic cleavage

Answer 58

IgG3

Question 59

which is the subclass of IgG that has different half life in serum

Answer 59

IgG3 (7 days) the rest have 21 days