Lecture 4 - Antibodies and Antibody Diversity Flashcards
What is a complementarity-determining region (CDR)?
very genetically variable regions on both light and heavy chains that constitute the antigen-binding site of Ig
Instructive Theory of antibody creation.
similar to making crowns. Cells respond to antigen by IMPRINTING the shapes of the antigen and make antibodies accordingly.
Not likely.
Selective Theory of antibody creation.
antibodies are pre-made for everything we could possibly encounter. We don’t have enough genes for this theory to be possible!
How many genes are needed to create all the antibodies in your body?
3
Which Ig genes are in mature B cells?
mIgM and MIgD
Describe a Pro-B gene (parent gene to a specific antibody)
Made up of V and C domains.
Has way too many stop codons. No gene product is made.
Describe a B gene (that makes a specific antibody).
The stop codons from the Pro-B cell get deleted, and a specific antibody is made from the B gene that results.
What is germ line DNA
DNA that is passed down through the gametes before it is modified by somatic recomination of maturation.
Where is germ line DNA found?
Pro-B cells (bone marrow stem cells) contain germ line DNA
What are the 4 mechanisms of antibody diversity?
- No Ig production in Pro-B cells, only in B cells
- Production of (kappa) chain protein
- Production of (lambda) chain protein
- Production of heavy chain protein
- Recombinational Inaccuracy
- N-nucleotide addition
- Somatic mutation
- Class Switching
How does the production of the Kappa chain protein create antibody diversity?
During synthesis, only 1/30 V, 1/5 J, and 1C segment is randomly selected to be in the kappa chain out of many of these segments. Variability = 150
How does the production of the LAMBDA chain protein create antibody diversity?
1/30 V, 1/7 J, 1/7 C
Variability = 210
1/51 V, 1/30 D, 1/6 J
Variability = 9180
Diversity created by production of heavy chain protein.
Which 3 genes do 2 x 10^6 antibodies come from?
kappa chain, lambda chain, heavy chain
What is recombinational inaccuracy?
When V and J boxes are joined, they are recombined by enzymes in a different way for each B cell
What is N-nucleotide addition?
Sometimes extra nucleotides are inserted between boxes when they are joined.
What is somatic mutation?
VDJ genes in B cells can make single base changes (at CDR region) after antigen stimulation to create more affinity.
What chains to T-cells have?
alpha and beta chains
What is positive selection in the thymus?
If a T-cell has a moderate affinity to MHC, it is rescued from programmed cell death.
What is LACK of positive selection in the thymus?
If a T-cell has no affinity for MHC, it undergoes apoptosis.
What is negative selection in the thymus?
If a T-cell has a HIGH affinity for MHC, it undergoes apoptosis.
