4- Antibody Structure and B cell Diversity Flashcards
How many different kinds of Ag’s can an Ab bind to?
Just 1
What is are the constant and variable regions called of the light chain Fab part of the Ab?
CL (Constant Light) and VL (Variable Light)
What is the constant part of the heavy chain called in the Fc region?
CH (Constant Heavy)
What are the hypervariable regions of the Ab?
They are the different amino acid composition of the variable regions of the variable domains.
What are hypervariable regions also called? Why?
Complementarity-determining Regions (CDR’s) because they bind complementary Ag’s.
What are the antigenic determinants/epitopes?
They are the part of the Ag that the Ab bins to.
What is formed between the VH and VL chains to bind the Ag?
Deep pocket
What is the linear epitope?
Ab’s bind to several adjacent sugars and use shallower clefts
What is a discontinuous epitope?
When a protein folds, it binds well to an Ab
What type of chemical bond is formed between the Ag and Ab?
Noncovalent forces
How are monoclonal Ab’s used clinically?
They’re used to block T cell responses and prevent rejection of transplants.
What condition is monoclonal Ab’s used to treat?
Non-Hodgkin B cell lymphomas
What does cytometry analyze?
Cell populations and the size of cell populations (like the amt of B or T cells)
What is added to the 1 dimensional cytometry plot?
monoclonal Ab
When an anti-TCR monoclonal Ab is added to a blood solution for a 1 dimensional cytometry analysis, what peaks occur?
1 peak for the lymphocytes that do not bind the Ab (everything except T cells) and the 2nd peak for the T cells that bind the Ab
What is used for the 2 dimensional cytometry plot?
2 monoclonal Ab’s
What happens when you add a anti-TCR and anti-IgM monoclonal Ab to a blood solution for a 2 dimensional cytometry analysis?
It splits up into 4 quadrants, sepatating the B cells (binding to anti-IgM) from the T cells (bind the anti-TCR) from cells that dont bind either (like NK) and from cells that bind both TCR and IgM (which are no cells)
How is the V (variable) region of the light chain made?
It’s made by the combination of one V and one J (joining) segment.
How is the V chain of the heavy chain made?
It’s encoded by 1 V, 1 D (diversity), and 1 J segment.
How is the C (constant) of the light and heavy chains made?
By 1 C gene. That’s it.
How do the variable regions of the light chain form by somatic recombination?
V and J are cut and spliced together on rearranged DNA
How do the variable regions of the heavy chains form by somatic recombination?
The D first forms the J (DJ) and then the DJ joins the V region to form the rearranged DNA.
What is the recombination signal sequence (RSS)?
They are genetic sequences that cut and rejoin DNA during somatic recombination to make sure that the gene segments are joined in the correct order.
What are the set of enzymes that are needed to recombine V, D and J segments?
V(D)J recombinase
Where is V(D)J recombinase found?
Lymphocytes
What are the complement proteins for V(D)J recombinase?
Recombination Activating Gene-1 and 2 (RAG-1 and RAG-2)
What would happen if there was a defect in V(D)J recombinase?
The B cells couldn’t create Ab’s –> severe immune system defects.
What does the enzyme Terminal deoxynucleotidyl transferase (TdT) do?
It adds random nucleosides to the DNA to diversify the Ab variable region.
What is the process of junctional diversity?
It contributes P and N nucleotides which adds to the diversity in the 3rd hypervariable region between the D and J segment.
How is the IgM and IgD produced in the naive B cell?
By differential splicing of the same primary RNA transcript
What is allelic exclusion?
It means that Ig gene rearrangement is tightly controlled so that only 1 heavy chain and 1 light chain are produced.
What is the function of the B-cell receptor (BCR)?
It binds a specific antigen and passes it signal inside to cause the B cell to divide and differentiate
What is the function of Ig α and Ig β?
They tell the intracellular proteins to have the B cell divide and differentiate.
How does a B cell begin to produce secreted Ab’s rather than BCR’s?
When an Ag binds to the BCR it signals the B cell to secrete Ab’s that bind to the same sequence of the Ag.
What is somatic hypermutation?
It’s the point mutations throughout the rearranged V regions of the heavy and light chain genes.
What is affinity maturation?
It’s the increasing affinity of Ab’s for the infecting pathogen as somatic hypermutation occurs.
What shape is the IgM on the B cell?
Monomeric- Y shaped
What shape is the secreted IgM?
Pentamer
What occurs during isotype switching?
In proliferating B cells, there can be recombination of the C genes that enables the rearranged V region to be used with other heavy C chains.
What 2 Ab’s have subtypes?
IgG (1-4) and IgA (1&2)
Which Ab is high in the mucosa?
IgA
Which Ab is highest in the serum?
IgG1
Which Ab is produced in the primary immune response?
IgM
Which Ab is produced in the secondary immune response?
IgG
Which Ab forms a dimer?
IgA
How is the IgA dimer formed?
It’s formed by 2 monomers being joined by a J chain
Where is the dimeric IgA found?
Mainly in the lymphoid tissue under mucosal surfaces and in secretions like milk, saliva, sweat and tears.
