Antibodies 2 -Diebel Flashcards
What antibody is always membrane bound?
IgD
What Ig’s cross placenta?
IgG only
What Ig’s form pentamer and dimer
- IgM forms petamer
- IgA forms dimer
What Ig’s function in complement fixation?
Mostly IgM, some IgG
Ig that functions in degranulation of Mast cell/basophil?
IgE
Ig’s that function in bacterial lysis?
Mostly IgM, some IgG and IgA
Ig’s that function in antiviral activity?
Mostly IgA, some IgM and IgG
Ig’s that function in toxin neutralization?
– IgG and IgA
Ig with highest serum half life?
Highest serum concentration?
IgG (8-23 days)
Most Ig’s in blood are IgG
Ig present in mucosal epithelia and bodily secretions?
IgA
4 ways we generate antibody diversity?
- during genetic rearrangement by mixing & matching one of each various gene segments for heavy and light chains
- Variation incorporated at joining sites for various segments of heavy and light chains
- Hypermutation in one gene segment druing proliferation of B cells
- mixing and matching heavy and light chains in combinatorial manner
Recombination:
DNA rearranges in developing B cells, to bring one of many V’s together with the correct C so they unit could be copied into mRNA
VDJ:
Gene segments V, D, and J on the variable domain region of heavy chain genes.
3 gene loci in heavy chain synthesis:
How does light chain synthesis differ?
Variable Domain
Constant Domain
VDJ
Light chain is the same but only have V and J segments, no D. and only one C domain gene.
RAG- 1 and 2 function?
Enzymes that do the recombination of antibody and T cell receptor DNA in VDJ segments
knock out these enzymes? - don’t make B or T cells –> Omenn Syndrome
TdT? (terminal deoxynucleotidyl transferase )
enzyme that ADDS a few nucleotides randomly.
-Production of V-D and D-J joints are sloppy so it does this to randomize it ==Somatic variation
Somatic Variation=
Uses exonucleases to chew away a few nucleotides
TdT enzymes adds a few nucleotides
—>BOOM, more randomization (N region)
What is the price of somatic variation/mutation?
Adding/subtracting nucleotides can cause frame-shift mutation –> nonsense or stop codon that stops transcription.
Receptor Editing
If you get a frame-shift mutation that stops transcription of heavy or light chain, you try again with other allele (from other parent)
Naive B cells express what Ig’s?
IgD and IgM
-this choice occurs at level of PROCESSING of mRNA (so cell can express both)
What happens when binds antigen and is activated?
Switch to secretory IgM
-Switch occurs at level of processing of mRNA transcripts
So the B cell keeps dividing and differentiate but a T cell comes over an is like “Don’t freak out…..but we’ve got a parasite in here.”
And B cell says…….
“Hey, I can do some class switching to handle this worm better!” –switches to IgE
Point of the story: ***last switches occur at level of REARRANGEMENTS of DNA.
Somatic Hypermutation How? What? When? Where? Why?
Only in B cells –AFTER antigenic stimulation
How: Activation-Induced Deaminase (AID) enzyme converts C –> U ==slightly different antibodies.
Might make binding better or worse. We are just trying some stuff out.
AID enzyme:
In somatic hypermutation– converts some cytosines to uracil randomly in CDR regions.
