Week 1: Antibodies Flashcards
What is the function of a J-chain on IgM?
holds all 5 subunits of the pentamer together
Which is better at activating complement: IgG or IgM? Why?
IgM; better because all the units of the antibody are right next to one another
Does IgM have an Fc portion to bind to lymphocytes?
No- it mainly functions to start complement activation
Which antibodies have a J chain?
IgM and IgA
Where is IgD found?
Nearly entirely bound to B cell membranes
What are the five kinds of heavy chains?
gamma, alpha, mu, epsilon, delta
What are the 2 kinds of light chains?
Kappa and Lambda
What changes during a class switch: the heavy or light chain?
The heavy chain changes; the light chain stays the same
What does valence refer to?
the number of antigenic determinants (epitopes) an antibody molecule can theoretically bind.
How many constant domains are there in a light chain?
1
How many constant domains are there in epsilon and mu heavy chains?
4
What is an allotype?
Minor changes in the constant region contribute to a person’s allotype being different from anothers
What is an isotype
The different possible heavy chains (10 different isotypes)
What is an idiotype?
The changes to the variable regions
What is the function of IgG?
neutralizes toxins and blood-borne viruses, binds bacteria and facilitates their destruction by activating complement and opsonizing them
What is the function of IgA?
the dimer form of secretion is able to bind and prevent infection at mucosal membranes
What is the function of IgM?
very efficient at activating complement; doesn’t help with opsonization
What is the function of IgD?
mainly a receptor of a naive B cell
What is the function of IgE?
antibody which causes type 1 hypersensitivy, helps in resistance to worms and other parasites
What occurs when an antibody initially binds an antigen? What is the function of this?
The “hinge” region turns the shape of the antibody into more of a “T” shape; helps to show phagocytic cells that it’s bound to something
What two steps occur when an Ab has bound an antigen?
(1) Ab binds onto phagocytic FcRs; (2) C1q is the first component of complement system that binds to two adjacent Fcs and is activated
What is the only Ab that can cross the placenta?
IgG
What do elevated levels of IgM indicate?
a recent infection or other exposure to antigen
Does IgM neutralize toxins well?
Nope
What antibody mediates hemolytic diseases of the newborn?
IgG
What are therapeutic options of IgG?
protect immunocompromised individuals, block TNF production (rheumatoid arthritis), blocks allergens (desensitize hypersensitivity)
Where do B cells that produce IgA migrate to?
subepithelial tissue of most mucosal epithelia and glandular epithelia
What antibody is found in very high levels of colostrum?
IgA
What are three processes that generate antibody diversity
Variation at joining sites for various segments of heavy and light chains, mutation in one of the gene segments (variable regions) of heavy and light chains, mixing and matching of heavy and light chains
At what level does the variation of light and heavy chains occur? DNA, mRNA, or protein?
DNA
What are the steps to recombination of the variable region of heavy chains in general?
(1) Random D segment close to random J segment, (2) cut DNA, (3) Brings V segment up to recombined DJ (4) cuts DNA and joins. (5) transcription of VDJ DNA, (6) addition of constant regions
What is different in making light chain variable regions?
Light chains do not contain a D segment, only V and J are combined with a constant region
Name the enzymatic processes of recombination.
(1) RAG-1/2 Bind to the right of a D segment and the left of a J segment and pull them together and cut
(2) RAG-1/2 and HMG binds to the right of a V segment, RAG performs a single stranded nick at 5’ border of both V and J segments.
(3) Hydroxyl group attacks phosphate group of non-coding strand to make a hairpin coding end
(4) Artemis cuts open hairpin loop at random
(5) IN LIGHT CHAIN, DNA repair enzymes repair and DNA ligase IV rejoins them
(6) IN HEAVY CHAIN: at both VD and DJ joints, exonuclease cleavage results in coding nucleotides at joint at complete random
(7) non-coding nucleotides are added at coding joint by TDT completely randomly
(8) DNA ligase IV and NHEJ proteins join ends together.
What’s the difference between light and heavy chain recombination?
Heavy chain recombination has the additional steps of exonuclease cleavage and TdT addition of nucleotides before joining joints together; Light chain skips these after the cleavage of the hairpin loops.
What is the issue with completely random recombination?
Two times out of three, the N region will create a frame-shift mutation which can terminate transcription
What occurs when a cell has a nonsense frame mutation in a gene for a heavy or light chain?
The cell tries again with the other allele inherited from the other parent.
T/F: a B cell can class switch from IgM to IgG without changing its DNA?
True; only changes the splicing of the mRNA transcripts
T/F: a B cell can class switch from IgG to IgA without changing its DNA?
False; cell must rearrange its DNA after the secretory ORFs of the IgG genes
Can mutation of the variable regions occur in B cell daughter cells? What does it do?
Yes, it is able to slowly accumulate a higher affinity of antibody as cells divide- called affinity maturation
How does somatic hypermutation occur?
Activation-induced cytidine deaminase (AID) randomly converts cytosines in the variable region of the heavy chain into uracil. Cell recognizes it as DNA damage, cuts it out, error-prone DNA polymerases fill in the gap, and the daughter cells will be slightly different
What is the main protein implicated in class switching of B cells? What instructs it?
AID changing DNA; cytokines (IL-5 makes class switch to IgE molecules)
