Antibodies Part II- Diebel Flashcards
(33 cards)
What is the Ig supergene family?
It is a large group of cell surface proteins that are involved in recognition, binding, adhesion, etc…..
Antibody are part of this…
Also, ICAM, VCAM, TCR, MHC molecules
All members have one or more immunoglobin domains, beta pleated sheets arranged in opposite directions so it kinda forms a barrel like structure.
What isotype has the highest serum concentration?
IgG
What isotype has the longest half life in the serum?
IgG
Does IgG cross the placenta? Do any other isotypes cross?
IgG does cross!
No other isotypes cross….
Which isotype is best at complement fixation?
IgM
Which isotype is best at bacterial lysis?
IgM
Which isotypes are best at toxin neutralization?
IgG and IgA
Which isotype facillitates Mast Cell/basophil degranulation?
IgE
Isotype IgA is pretty good at two things, what are they?
Antiviral activity
Toxin Neutralization
Biological functions of IgM????
- Virus neutralization
- bacterialcidal
- agglutination of antigens
- complement fixation
- first aby in response to antigen exposure
Does NOT bind to macrophage Fc receptors
Biological functions of IgG?
- Virus neutralization
- Toxin neutralization
- Bactericidal
- Agglutination/precipitation of antigens
- Complement fixation
- Binds to macrophage Fc receptors
- Crosses the placenta
- Present in interstitial fluids
Some therapeutic uses of IgG?
- protecting immunocompromised individuals (gamma globins)
- blocking aby for TNF production (rheumatoid arthritis)
- blocking aby to block allergens (desensitization to hypersensitivity)
Biologic functions of IgA?
- Viral neutralization
- toxin neutralization
- agglutination/precipitation of antigens
- Highest daily production of all isotypes
- secreted by b cells in subepithelial tissues of most mucosal epithelial and glandular epithelia
- Present in breastmilk, protects newborn against respiratory and intestinal infections
Does NOT bind to macrophage Fc receptors
Biological functions of IgE?
- Cross-linking of IgE on surface of mast/basophil cells causes release of histamine; synthesis of prostaglandins, leukotrienes, and other chemokines and cytokines
- Parasitic infections
- pulmonary fungal infections
- Type I hypersensitivity
- Role in asthma
Keys to antibody diversity?
- Genetic rearrangement by mixing and matching gene segments for light and heavy chains
- Variation at the joining sites
- Hypermutation in the variable region of the light and heavy chains during proliferation of B cells
- Mixing and matching light and heavy chains
What is clonal selection theory?
Basically that a B cell makes only one specific antibody, this preexists randomly before exposure to antigen (so we’re not making them to adjust to environment we just have ‘em already!) When an antigen comes around the best fitting one is selected by the antigen….these then proliferate….
Explain allotypic exclusion?
We have two copies of kappa and lambda and also heavy chain genes since we’re diploid (one from mom and one from dad)…..we only express one H chain, and one L chain….all other genes are silenced….this allows us to have a lot more diversity
How to make heavy chains?
- B cell brings random D segment close to J segment
- DNA is cut, intervening DNA is discarded
- V segment is brought next to recombined DJ segment (junk is spliced out)
- VDJ segment is transcribed with the constant region into RNA
- These primary RNA transcripts are processed to make IgM right away….later then can CSR to make IgG
What determines whether or not IgM is secretory or membrane bound?
There is a secretion signal and membrane bound signal in the DNA…whichever one is expressed will result in either secretion or membrane boundness…
How to make light chains?
-Same as heavy chains but there is no D region….random V and J segments are selected and spliced together (junk is removed)……you either use kappa or lambda, but not both
What do RAG recombinases do? What happens if they get knocked out?
RAG-1 and RAG-2 are enzymes that do the recombination of antibody and TCR DNA. They bind to splice signals on the right of D segments and the left of J segmnet, pull them together and then cut and splice. THey then go to the right of V segment and do it again.
If knocked out you don’t get B or T cells….Omenn Syndrome (really rare in humans)
What do exonucleases do?
Chews away nucleotides inbetween VDJ regions after DNA is cut and before they are put together…..leads to more diversity.
What does terminal deoxynucleotidyl transferase (TdT) do?
Adds nucleotides in between VDJ regions….more variability
What is the N region?
This is the joining regions between VDJ, they’re really sloppy which leads to a lot of diversity……about 2/3 of these receptors are no good because of this and are trashed as a result.
