Antibodies

Question 1

how many isotypes of antibodies are there and what are they?

Answer 1

IgG, IgA, IgM, IgD, IgE

Question 2

describe the polypeptide structure of Abs

Answer 2

they are comprised of 2 H and 2 L chains. One L chain is bound via disulfide bonds to one H chain, and the H chains are likewise bound via disulfide bonds. The H and L chains are identical on a given Ab. A given B cell only produces 1 type of Ab.

Question 3

what determines the isotype of an Ab?

Answer 3

the type of heavy chain. there are 5 that correspond to the 5 isotypes (IgG, A, M, D, E)

Question 4

what is allelic exclusion in B cells

Answer 4

B cells encode a large amount of DNA regarding of L and H chains, but a B cell only produces one type of Ab. During development, allelic exclusion occurs when a recombined H and L chain are made correctly and expressed.

once 1 chromosome has properly recombined, the other chromosome is repressed. furthermore, further recombination on the active chromosome is also repressed

Question 5

how many types of L chains are there?

Answer 5

there are two types

Question 6

describe variable and constant regions on the heavy and light chains

Answer 6

both the H and L chains have intrapolypeptide (within the same chain) disulfide bonds that form loops with distinct properties.

on the heavy chain, the 3 loops on the C-terminal end of the Ab are Constant regions. All Abs of the same subtype have identical C regions. This region is called the Fc region, and they determine the effector function of the Ab. The CH2-CH2 region forms the hinge of the Ab and is a binding site for complement. The final loop on the N-terminal side is the Variable region, which works with the VL region to form the Ag binding site

the light chain also has a V and C site. the N terminal sides of both chains with the V regions are together called the Fab. the C-terminus of the light chain also has a constant region

Question 7

how does TCR and Ab binding differ?

Answer 7

Abs bond to native structures and can bind more than peptides

TCRs must bind MHCs that have processed peptide fragments on them

Question 8

epitope

Answer 8

the smallest unit of an Ag that an Ab can bind

Question 9

multi-determinant Ag

Answer 9

most Ags have multiple epitopes, and thus can be recognized by different Abs

Question 10

Ab valence

Answer 10

the maximum number of Ags it can bind

Question 11

Ab affinity

Answer 11

the tightness with which an Ab binds

Question 12

Ab avidity

Answer 12

the combination of valence and affinity. having multiple sites (valence) is beneficial to keeping an Ag bound

Question 13

IgG

Answer 13

IgG is dimeric and the most abundant Ig in the blood. It provides the bulk of immnunity to blood-borne Ags and is the only Ig to provide passive immunity to the fetus.

there are 4 subtypes: 1-4

Question 14

IgM

Answer 14

found in 2 locations: in the blood and on the membrane

when expressed on the surface, it is a dimer and acts as the B-cell receptor

in the blood, it is expressed as a 5 4-chain units. additionally the J chain is necessary for the combination of 5 subunits. It is the first Ab produced in the immune response, and it binds with low affinity but has a combined 10 binding sites (high avidity)

Question 15

IgA

Answer 15

present in serum and secretions

in the serum, it exists as a monomer

in secretions, it exists as a dimer, along with the J-chain, and secretory component. the SC helps with transepithelium journey. it is found in musous, milk, and other secretions

Question 16

IgD

Answer 16

only present in low amounts in the circulation. Mostly found in mature naive B cells (along with IgM- both specific for the same Ag). Differences in IgD can be used to differentiate effector types and developmental stages

Question 17

IgE

Answer 17

found in low levels in the sera- mostly associated with amplifying inflammation, allergic reactions, and protection from worms. Bind to Fc receptors on mast cells which cause the release of inflammatory compounds

Question 18

allotypes

Answer 18

differences in the AA sequence of Abs that are inhereted. these are minor polymorphic differences

Question 19

idiotype

Answer 19

the set of epitopes on the V region of an Ab

Question 20

how many gene loci are there for antibodies?

Answer 20

there are 3- one for K light chain, on for lambda light chain, and one for H chain

Question 21

describe VDJ recombination

Answer 21

It begins at the loci for the H chain, which contains ~100 V regions, ~27 D regions, and ~6 J regions. The first step is that a D and a J region will move together to form a DJ region. Then, a V region will join them, forming a VDJ region. These recombinations are random, and are the source for Ab diversity. Downstream are the C regions, usually u for IgM. the DNA is transcribed and the introns (nonVDJ material) is excised.

This combination is uninterrupted in mature B cells

A similar process occurs for the L chain, except they do not have D regions. It can occur either at K or lambda C loci, but not both. It tries at the K region first.

Question 22

how does an Ab become membrane bound or released?

Answer 22

it depends where the poly A tail is added. There is a hydrophobic AA sequence that would become the transmembrane sequence, but if it is poly Aed before that sequence, it will be released. These exons are separate from the C regions

Question 23

What are the CDR1-3.

Answer 23

these are found on the heavy and light chains in the V regions. they are hypervariable and go a long way in determing specificity, especially CDR3. 1 and 2 are in the V region, while 3 is determined partly by V, and also by D and J.

Question 24

what is imprecise joining

Answer 24

when the V, D, and J regions move, they may cause the deletion or addition of a nucleotide, changing the structure

Question 25

P and N diversity

Answer 25

N- when recombinatoin is occuring, and enzyme called terminal deoxynucleotidyl transferase can add N nucleotides to change the sequence. P nucleotides are added when DNA is cleaved for recombination leaving overhangs.

Question 26

somatic mutations

Answer 26

occur in the germinal center and cause a change to the DNA that may cause greater or decreased affinity. this process is affinity maturation

Question 27

how do B cells start producing IgD?

Answer 27

they are originally producing IgM, which begins to be differentially spliced so that the C regions now produce IgD

Question 28

isotype (class) switching

Answer 28

cells that originally only expressed IgM can change the isotype while keeping the specificity during an immune response

Question 29

describe the maturation process of the B cell

Answer 29

occurs in the bone marrow
first the heavy chain is rearranged and expressed, where a surrogate light chain temporarily binds it. then the light chain is rearranged and expressed, forming an immature B cell. the final stage is expression of IgD.

Question 30

what are the roles of Iga and Igb

Answer 30

in membrane bound Igs, these subunits are what transmits the signal into the cells.

Question 31

describe some coreceptors on b-cells

Answer 31

CD21- complement receptor
CD32- Fc receptor for IgG
CD19 and CD81- signaling molecules

these especially increase the signal of the BCR if they are both activated on the same antigen

Question 32

CD19 deficiency

Answer 32

loss of this coreceptor results in a weakened immune system but can be treated with IGIV

Question 33

describe B cell tolerance

Answer 33

2 rounds- negative selection in bone marrow for autoreactive receptors, then again in the periphery if T cells will not cooperate with them