Genetic basis of antibodies + t cell receptors

Question 1

what are the 2 theories of immunity

Answer 1

Instructive
selective

Question 2

what does instructive theory entail

Answer 2

antigen instructs the immune system how to produce antibodies specific for it

Question 3

what does selective theory entail

Answer 3

antigen selects pre made antibody specific for it

Question 4

is the side chain theory selective or instructiv? and who found it

Answer 4

selective
Paul Ehrlich
* figureed out antibodies must be produced by cells

Question 5

what’s the gist of the side chain theory

Answer 5

When an antigen comes, it binds to
a matching side chain. Then the cell stops synthesis of other side chains + makes only the one that has reacted. It accumulates and is secreted as a soluble antibody.

Question 6

why was the side chain theory abandoned

Answer 6

. New data emerged showing unlimited ability of the immune system to produce diverse antibodies. (so 1 cell doesnt secrete side chains)
This ability was demonstrated e.g., by Landsteiner’s experiments

Question 7

What was the suggested template theory

Answer 7

suggetsed that all antibodies had the same primary structure + When an antigen
comes, the precursor polypeptide chain bends around it and becomes a functional antibody.
- thought antigen was the template for structure of antibody. (not mRNA)

Question 8

What is the clonal selection theory

Answer 8

David Talmage
. antibody diversity is generated before any
antigen is met;
. antibodies are exposed on the surface of
cells producing them;
. after that, antigens select matching
antibodies

** every cell produces only 1 type of antibody

Question 9

*****Immunoglobin genes are rearranged in B cells. what are the parts on the AB light chain

Answer 9

V and C parts
. Germline DNA contains dozens of gene frafments for the V region. In every differentiating B lymphocyte, one
of them is (randomly) selected.

Question 10

• What is VJ recombination of light chain

Answer 10

. one of the V fragments and one of several
smaller fragments called J (from “joining”). This of
course increases the diversity of the variable region.

Question 11

what is VDJ recombination for heavy chain

Answer 11

heavy chain has additional diversity

between the V and the J segments, there is a group of short D (“diversity”) segments.
So, the “gene” for the variable region is obtained by VDJ
recombination at two stages.

Question 12

what are V D J segements flanked by

Answer 12

Recombinaiton signal seq (RSS)

Question 13

what does RSS consist of

Answer 13

heptamer and nonomer separated by 12/23 base pairs

Question 14

what are RSS recognized by

Answer 14

VDJ recombinases

Important = RAG ( recombination activating gene)

Question 15

what does VDJ recombination create

Answer 15

Combinatorial diversity

Question 16

what do differnetiating lymphocytes contain.

Answer 16

Enzyme: terminal deoxynucleotidyl transferase Tdt

Question 17

what do Tdt do?

Answer 17

Adds random nucleotides to an exposed 3’ end of DNA.

Question 18

how is junctional diversity introduced

Answer 18

During V(D)J recombination, before coding ends are joined together, Tdt may insert one or several
nucleotides between V and J for light chain + between V and D / D and J for the heavy chain.

Question 19

what is somatic hypermutation (additional diversity)

Answer 19

When a mature B cell binds Ag and is activated to produce a clone,

Question 20

genes for variable domains tend to have point
mutations, especially in the hypervariable regions (CDR). what does these increase

Answer 20

increases the variability and gives
chances to create new B cell clones that synthesize
antibodies with improved affinity for antigen.

Question 21

summarize: combinatorial diversity, Junctional diversity, somatic hypermutation

Answer 21

C- produced by random
combination of germline V, D and J segments

J - produced by random addition of
nucleotides at the joints between these segments

S - involves entire variable region during T - dependant humoral immune responses

Question 22

How does TCR diversity arise

Answer 22

.From genetic recombination of the
gene segments in individual somatic T cells
by V(D)J recombination and by junctional
diversity created by TdT

Question 23

which diversity is not used by t cells

Answer 23

Somatic hypermutation - could genertae autoreactive TCRs

Question 24

what happens if therre is a mutation in VDJ recombinases.

Answer 24

• severe combined immunodeficiency (SCID)
• theres no immunocompetant lymphocytes (B + T cells)

Question 25

Treatment for SCID

Answer 25

bone marrow transplant

• until then they hv to be kept in sterile enviroment (bubble)