Diebel-Antibodies II Flashcards
What are Abs?
Cell surface and soluble proteins that are involved in the recognition, binding and adhesion processes of cells.
Which Ab has the highest number of monomers, highest molecular weight and is the best at fixing complement?
IgM
Why does IgD, the monomer expressed on every B cell, have a low serum conc?
It is always membrane bound or associated w/ a B cell.
Which is the only Ab that can cross the placenta?
IgG
Which Ab isotype has the lowest serum conc and is responsible for mast cell and basophil degranulation?
IgE
It is not expressed at high levels and when it is expressed it gets picked up by mast cells and basophils through an Fc receptor.
Which Ab isotype is
IgE
Elevated levels of IgM reflect…
Recent infection/exposure to antigen.
Fights viruses and bacteria and serves as a BCR but is not useful in protecting immunocomp pts. Can be present in bodily secretions.
Which isotype can be used to protect immmunocomp individuals, block Ab to TNF production (RA) and block antibody to block allergens?
IgG
Good for virus, toxins, bacteria.
Present in interstitial fluids.
Which Ab mediates hemolytic disease of the newborn?
IgG
Daily production of what Ab is greater than any other and why?
IgA
B cells that produce IgA migrate to the subepithelial tissue so that the IgA secreted lines the mucosal epithelium.
Good for virus, toxin, bacteria
Which Ab is present in bodily secretions (breast milk and clostrum)?
IgA
What are the two major roles of IgE and how does it work?
- Combat parasite infections
- Combat pulmonary fungal infections
Crosslinking of IgE on a mast cell or basophil causes the release of histamine and syntehsis of inflammatory mediators.
What causes allergies?
The overproduction of IgE to allergy inducing antigens.
What is the clonal selection theory?
T cells make only ONE antibody. The choice of which antibody to make is not random. The entire population of T cells exists in an individual before it has had contact w/ an antigen. The best fitting T cells are selected by the antigen.
What is the difference between an isotype and an allotype?
Isotype: IgA, IgE, IgD
Allotypes: genetic variations between people, specifically between h and l chains of Ab. We have two copies of H and L (from mom and dad) only one H chain and one L chains is synthesized in a B cell (allotypic exclusion)
What is recombination?
Changing the relative positions of 2 pieces of DNA
How do you make a heavy chain?
The developing B cell brings one random D segment close to one J. Cutting and joining occurs. It then brings a V segment up to DJ. More cutting and joining occurs. Then the entire region from the assembled VDJ unit to the end of IgD constant region gene is transcribed to RNA. Primary RNA transcripts are then processed using alternative polyA sites and splicing first to make IgM and then to make IgM and IgD.
How do you make light chains?
Pretty much the same way as you’d make a heavy chain, but w/ only V and J segments, no D and only 1 C domain gene (for kappa or lambda).
What do RAG1/2 do and how do they work?
These are the recombinases responsible for the recombination of antibodies.
- Recombinases bind splice signals (12/23 bp sequences) to the right of a D segment and left of a J segment. Pulls them together, cuts and splice.
- Then they look for a splice seq to the right of a V seg and do it again.
What is Omenn Syndrome?
A very rare disease that occurs if recombinases are knocked out. If RAGs are knocked out you can’t make B and T cells.
What is somatic variation?
RAG cells are kinda messy so the VD and DJ joints are sloppy. Exonucleases can chew away nucleotides before joining or Tdt can ADD nucleotides but you can’t predict the sequence of the joining area. (N region)
Somatic variation comes from when you pull VDJ segments together and their are MISTAKES.
What are the pros and cons of the N region?
It produces A LOT of random diversity.
BUT 2/3 times the N region creates a frame shift mut that leads to a nonsense codon that terminates trxn.
What is receptor editing?
If sloppy recombination leads to termination you can try again w/ another allele if RAG is still active.
Why do mature B cells initially express IgD and IgM?
These are b cell receptors that are selected for when mRNA is processed.
