Antibody production

Question 1

heavy chain immunoglobulin domains

Answer 1

4, 1 variable and 3 constant held together by disulfide bonds

Question 2

light chain immunoglobulin domains

Answer 2

2, 1 variable and 1 constant held together by disulfide bonds

Question 3

3 hypervariable regions

Answer 3

CDR1, 2, and 3 all involved in binding the antigen

Question 4

membrane associated antibodies

Answer 4

include the membrane and cytosol exons in the antibody transcript

Question 5

secreted antibody form

Answer 5

uses a poly a cleavage site to rid of the membrane and cytoplams exons from the antibody transcript

Question 6

T cell receptor makeup

Answer 6

has alpha and beta chain or has gamma and delta chain,

has CDR regions and also has constant and variable regions on each chain

Question 7

5 mechanisms for antibody diversity

Answer 7

many Vh and Vl genes
combinatorial association of different V, D, and J gene segments
junctional diversity by nucleotide addition
combinatorial association of Vh and Vl
somatic hypermutation…non genome encoded

Question 8

heavy chain gene regions

Answer 8

V, D, J, and C

VDJ all in Vh region

Question 9

light chain gene regions

Answer 9

V, J, and C

Question 10

CDR locations in heavy chain

Answer 10

1,2 in V region

3 in D and J regions

Question 11

CDR locations in light chain

Answer 11

1,2 in V region

3 in J region

Question 12

two light chain genes

Answer 12

kappa and lambda

both have a lot of options for V region

kappa has 5 options for J region
lambda has four options for J and C regions

Question 13

VDJ recombination process

Answer 13

chromatin opened up and allows for genes to be brought close together and a double stranded nick to be made, the variable VDJ options are now able to be transcribed and spliced to become a functional mRNA

sometimes nucleotides can be added or removed when nick is made, so leads to more variation

Question 14

heavy chain genes

Answer 14

only one gene, has many options for V, many for D and a few for J

Question 15

Recombination signal sequences

Answer 15

mediate recombination

7 nt stretch followed by 12 or 23 base pair followed by 9 nt AT rich stretch

must have 12 and 23 recombinating together, never 12 and 12 or 23 and 23

Question 16

RAG 2 and RAG 1 roles in VDJ recombination

Answer 16

RAG 2 recognizes methylation going on, it calls for RAG 1 to come in and cut/join the V/J segments

Question 17

P nucleotide addition in VDJ variability

Answer 17

at hairpin turn, artemis protein cuts strands and relocates to other strand then repair adds nucelotides for matching, when the V and J come together nuclease removes mismatches and polymerase repairs and ligase links

Question 18

N nucleotide addition in VDJ variability

Answer 18

just adds nucleotides onto the end of the strands, can be any of the four nucelotides

Question 19

CDR3 diversity

Answer 19

most diverse CDR because it is in D and J region in heavy chain and in V and J region in light chain

while 1 and 2 are only in V region in light and heavy

Question 20

allelic exclusion in antibody variation

Answer 20

if one allele leads to good antibody then other stays repressed, but if it leads to bad antibody then other allele gets expressed

Question 21

light chain isotype exclusion in antibody variation

Answer 21

kappa is first and if successful then dont do delta

but if kappa is bad then do delta

so you see kappa in about a ratio of 2:1

Question 22

class switching of antibodies

Answer 22

activated by CD40 and leads to a different C region being transcribed by recombining to different region of gene and cutting out the genetic material between sites

Question 23

affinity maturation in V regions

Answer 23

really high mutation rate (1000X normal), mutations in V region make the antibody have better affinity for antigens, lower Kd

Question 24

T cell receptor diversity

Answer 24

has different options for V,D and J regions like antibodies, have variable CDR1-3 regions, CDR3 is most variable, have VDJ joining techniques and P/N diversity like antibodies

DO NOT HAVE SOMATIC MUTATIONS

Question 25

Severe combined immunodeficiency

Answer 25

mutations in recombination enzymes like RAG 1 and 2, artemis enzymes result in loss of B and T cells

GENE THERAPY

Question 26

Hyper IgM syndrome

Answer 26

genetic defects in AID or UNG lead to inability of class switching or somatic mutation

no class switching so all IgMs and not able to fight infection

Question 27

AID

Answer 27

protein involved in class switching and somatic mutation by deaminating Cs and making Us

Question 28

UNGs

Answer 28

protein involved in class switching and somatic mutation that can remove the Uracil and leads to mutation or nicks in DNA

Question 29

Lymphoid tumors and class switching

Answer 29

oncogenes like MYC can often be close to where AID will cause switch in the antibody and can get placed within the switch and is therefor over expressed and can lead to B and T cell tumors