L9, immunoglobin genes

Question 1

define adaptation:

Answer 1

the adjustment of organisms to their environment in order to improve their chances at survival in that environment

Question 2

with adaptation, there is a greater need for..

Answer 2

greater specificity and diversity = adaptive immunity

Question 3

what is specificity in the adaptive immune system?

Answer 3

highly specific; discriminates between even minor differences in molecular structure of microbial or nonmicrobial molecules

Question 4

what is diversity in the adaptive immune system?

Answer 4

a very large number of receptors arising from genetic recombination of receptor genes in each individual

Question 5

how is an immune response against very diverse and evolving pathogens generated?

Answer 5

need to be able to generate diverse and flexible repertoire of receptors and antibodies and minimize the expression of self-antigen receptors/antibodies

Question 6

what is the general structure of B cell receptors?

Answer 6

1. light chain - includes antigen-binding site
2. heavy chain, base of the B cell that is attached to the transmembrane region

Question 7

what is the general structure of T cell receptors?

Answer 7

variable regions, constant regions, transmembrane region

2 chains - alpha and beta chain

Question 8

what is the general structure of an antibody?

Answer 8

1. composed of 4 polypeptide chains:
   2 light (L) identical chains
   2 Heavy (H) identical chains
   - held by disulfide bonds (S-S) bonds
2. variable region and constant region:
   variable region mediates antigen (Ag) binding and has immense diversity. the constant region mediates effector functions and is conserved between Ig of a given isotype

Question 9

what is pepsin digestion?

Answer 9

proteolysis - heavy chain is degrades and the light chains are cleaved

Question 10

what is papain digestion?

Answer 10

proteolysis - light chain and heavy chain are cleaved

Question 11

what is the “conundrum”?

Answer 11

how a finite amount of genetic information can encode a vast number of different antigen-binding sites

Question 12

what was the significance of Hozumi and Tonegawa experiment?

Answer 12

observed a single smaller fragment in antibody producing cells due to cuts and recombination events of the genetic DNA during differentiation

Question 13

what are the different possible combinatorial recombination events of different gene segments?

Answer 13

Variable, diversity (onle in BCR/antibody heavy chains and beta chain of TCR), joining, constant (downstream of all other gene segments)

Question 14

what are the genes and chromosomes that encode the different antigen-binding sites?

Answer 14

1. Kappa genes on human chromosome 2, mouse chromosome 6
2. lambda genes on human chromosome 22, mouse chromosome 16
3. heavy chain genes on human chromosome 14, mouse chromosome 12

Question 15

what are the regulated steps in V(D)J genetic recombination?

Answer 15

1. recognition of the RSS by RAG1/2 enzyme complex
2. one-stranded cleavage at the junction of the coding and signal sequences
3. formation of V and J region hairpins and blunt signal ends
4. ligation of the signal ends
5. hairpin cleavage
6. overhang extension can lead to addition of palindromic (P) nucleotides
7. ligation of light-chain V and J segments
8. exonuclease trimming
9. N-nucleotide addition
10. ligation and repair of the heavy-chain gene

Question 16

what are the 5 mechanisms that generate antibody diversity?

Answer 16

1. multiple gene segments - which gene segments are put together
2. heavy chain/ light chain combinatorial diversity
3. P nucleotide addition
4. exonuclease trimming
5. non-templated N nucleotide addition