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38 Cards in this Set

  • Front
  • Back
How many chains does an ab have/
2 - heavy and light
Which chain binds the antigen?
both do at the ends
T/F both chains have constant AND variable regions
true.
Name the constant and variable regions of both chains
Heavy: Ch1, Ch2, Ch3 and Vh
Light: Cl, Vl
How can there be so much variability among all of the ab in the body?
all ab have the similar structure, but becuase of the many diff. regions on both chains (constant and variable) this can make many diff. combos
When discussing only the constant regions of both ab = biological variability (determines which ab it is)
when discussing only the variable region = antigen variability
In 3-D what does the antibody look like?
like a lobster
How has nature made it ideal for antigen binding?
- tight contact
- perfect matching of surface contour (key and lock)
- **binding mediated by weak forces
- no covalent binding
Why many weak bonds instead of covalent bond?
strong force with multiple weak forces, this kind of design solves the problem of specificity and needs to discriminate between self and non-self
if it was covalently: binds to anything, doesn't care (like superglue) doesn't care if it is the specific antigen it wants to bind.
THus with all of the characteristics the antibody is highly selective, discriminating self vs. non-self, discriminating different pathogens = a price to pay, which is?
each antibody can only be used against very limited types of pathogens.
SO, if our enemy comes in all shapes and sizes, and ab plays a role in combating ALL of these, how?
So, millions of different ab are required
so....the only way to accomplish this is through antibody diversity: difference in the structure of ab. (many diff. kinds)
What is CDR: complementarity -determining region
the regions where the variability is VERY HIGH. - so the Vh or Vl
The combination of CDRs on both light and heavy chains constitutes?
the antigen-binding site of Ig
How do we generate diverse antibody molecules from apparent rigid DNA molecule?
ab still produced from central dogma...via the instructive vs. selective theory for generating antibody diversity
What theory is similar to making crowns?
instructive;
antigen = teeth
- Cells respond to antigen by imprinting the shapes of the antigen and make antibodies accordingly
What is the problem with the instructive theory?
- antigens do not come in contact with DNA
- The flow of cellular information is from DNA to protein, not from protein to DNA
Which theory is where "antibodies are pre-made!"
Selective theory
How does the body make antibodies without prior knowledge of antigen?
Antiobody specificity is generated randomly if over 10^7 types of antibodies can be premade, a sufficient antibody army is constituted.
What are the problems with the selective theory?
1 - a single B cell produce only one specificity
2 - We do not have enough!
But, he is ALMOST right...
How many gene loci are need to go from Genome to Ig?
3!!!!!!
2 genes for light chain (lambda and kappa)
1 for heavy chain
Does an immature B cell produce antibody?
mIgM is expressed
An immature and mature B cell reside in the Bone marrow, what does the mature B cell express here?
m(membrane) IgM+mIgD
Once in the periphery B cells have antigen stimulation - now what does it express?
PLasma cells secrete Ig
Memory B cells express mIg after stimulation is gone
The unique structure of Ig gene is determined by segmentation - what does this mean?
The presence of all segments -> (Pro-B cell, just like muscle cell, no modification) -> No gene product

Deletion and recombination of different segments -> (mature B cell) -> Generation of specific antibody
What is the mechanism of segmentation?
Has to do with open reading frame: can start and stop at different places.

In pro-B cells there are so many stop codons interrupting

In mature B cells the deletions delete certain stop codons

Start codon is always AUG
Stop codon is UAA, UAG, UGA
What is germ line DNA?
DNA which is passed down through the gametes before it is modified by somatic recombination or maturation.
What cells contain germ line DNA?
Pro-B cells (bone marrow stem cells) contain germ line DNA.
T/F the gene loci for Ig production in Pro-B cells are non-functional due to the lack of open reading frame
true
How does the kappa chain come to be?
Your body "throws the dice" selecting a V, J, and C from the germline DNA = B cell DNA => mRNA => kappa chain
How many V J and C are there in the germline DNA?
about 30 V
5 J
1 C (so all have C)
What makes up the constant vs. variable regions form the germline DNA?
Constant region encoded by the C gene
Variable region encoded by the VJ genes
How is the lambda chain created?
similar to kappa chain
now there are many C
Always joins it's own constant segments J1 joins with C1
- B Cell DNA contains rearranged germ line DNA with selected V, J segments.
How is the heavy chain protein created?
Use V, D (diversity region) and J - combined with the lambda and kappa chain = GREAT diversity!!!!
What is recombinational accuracy?
instead of end to end joining, a few nucleotides can be cut during recombination. This process is not precise = more variability and diversity
(takes advantage of inaccuracy)
What is N-nucleotide addition?
A few nucleotides may be inserted between D and JH and between VH and D to create further diversity. This is called N-nucleotide addition.
What is somatic mutation?
"good at conserving energy"
After antigen stimulation, the V, D, J genes in B cells can make single base cahnages (often at the region of CDR). this is called somatic mutation which occurs to INCREASE THE AFFINITY OF ANTIBODY (affinity maturation)
- fine tuning
What is class switching?
on 3' end of gene that encodes constant region has different areas of the gene that code for specific kinds of IgM, vs. IgA
How does it know to make IgM vs IgA etc..
uses several mechanisms:
1. alternative splicing - changes in the RNA = both IgD and IgM, or others.
2. Deletion of GENE (DNA recombination - which is reversible!)= cuts out other DNA sequence for other Ig's = expression of IgG1 (or others)
- loop and cut process is similar to VDJ joining
T/F once the DNA is decided it is stuck, now you can alternate what is expressed via RNA
true;
but deletion in GENE is IRREVERSIBLE