Exam 2 Flashcards
What is the solution that explains antibody diversity?
genes for both chains come from multiple discontinuous genetic segments
How many constant regions does a kappa chain gene have?
1
Describe the differences of the J and C region between kappa and lambda chain genes
- kappa: one C region with J regions grouped separately
- lambda: J and C are grouped together; before every C region there is a J region
What cells express these chain genes and can they express both kappa and lambda at the same time?
- B cells
- express one or the other; once one is expressed, the other will be permanently silenced
- this gives 300 possible variable regions and 5 different isotypes (4 from lambda, 1 from kappa)
Which chromosome are kappa chain genes located?
chromosome 2
Which chromosome are lambda chain genes located?
chromosome 22
Which chromosome are heavy chain genes located?
chromosome 14
How many constant region does a lambda chain gene have?
4-5
How many constant region does a heavy chain gene have?
9
Where can VDJ recombinase be found?
only in B cell and T cell
What does VDJ recombinase do in B cells?
rearrangement of Ig genes
What does VDJ recombinase do in T cells?
rearrangement of T cell receptor
How does VDJ recombinase change the genome?
2 RAG subunits on the linear chain come together to form a loop which gets budded off; I remember RAG as Re Arrange Genome (not sure what it really stands for)
IgM producing cells
produce both IgM and IgD; this happens via how they process RNA transcript viav alternate splicing
Stages of B cell development
- Stem cell
- Early pro-B cell
- Late pro-B cell
- Large pre-B cell
- Small pre-B cell
- Immature B cell
- Mature B cell
What happens in the bone marrow after B cell generation before those B cells are activated?
the B cells that are self-reactive are eliminated
What happens during pro-B cell phase?
heavy chain starts to assemble; light chain is still in the germline
What happens during pre-B cell phase?
heavy chain is rearranged; light chain starts to rearrange but not expressed yet; surrogate light chain serves as quality control to make sure that the heavy chain that has been expressed is not useless
What happens during immature B cell phase?
both heavy and light chain are rearranged; will express lambda or kappa but not both; have mature antibody appear on the surface
What happens during mature B cell phase?
IgD and IgM antibody both appear on the surface
Define antibody
protein produced in response to an immunogen; specifically binds to immunogen that stimulated its formation
composition of immunoglobulin
- two identical heavy chains (H)
- two identical light chains (L)
What are examples of secondary activities of Ig?
- activation of complement
- opsonization
- transport across placental barrier into fetal circulation
- secreted in external secretions of the body
Where are the N-termini and C-termini region on the antibody?
- N-termini are located on the antigen binding region
- C-termini are at the C region of the heavy chain where Fc receptors are
What does gamma globulin refer to?
total collection of immunoglobulin or antibody molecules present
Where is the hypervariable region and what is its purpose?
- near the variable region end
- give each CDR its properties
How is cleft formed and what is its purpose?
- formed by folded Vh and Vl regions
- plays a role in antigen binding
What is the purpose of the intermolecular disulfide bonds that link the heavy and light chains?
stabilize the structure
What is the purpose of the intramolecular disulfide bonds? (in antibody)
stabilize constant and variable region
What are advantages of using pepsin instead of papain?
- crosslinking tumor antigens can trigger apoptosis
- penetrate tissue better
T/F: If you undergo class switch, classes will change but CDR remains the same.
True
How many different heavy chain isotypes are there in humans?
9: four IgG, two IgA, IgM, IgD, IgE
Why is IgE so low in concentration in the serum?
they are not free floating; they are tied up to mast cells; their half life is 2 days
What are the two forms of IgM and how do you get them?
there are two polyadenylation site encoded in the gene and the primary transcript looks the same; depending on the processing steps and which polyadenylation site gets recognized, you can get transmembrane or secreted IgM
Properties of IgM
- 10% of serum
- decavalent pentamer [macroglobulin]
- efficient complement activator
- major receptor on B cells
- natural antibody to A and B blood group antigens
- diffuses poorly
Properties of IgG
- 75% of serum Ig
- longest half life
- complement activator (G3 best, no G4)
- cross placenta (G2 poor)
- opsonizing antibody
Properties of IgG4
- can swap half of its molecule with another IgG4 antibody molecule
- compete with IgE to bind to allergens
- help dampen allergic immune response
- tie up antigen because cannot crosslink
Properties of IgA
- 15% of serum
- high concentration in external secretions
- dimeric IgA via J chain
- tetravlent dimer
- serum IgA is monomer
What is the secretory piece?
- synthesized by epithelial cells
- protein that reacts with IgA
- when IgA binds, it triggers receptor mediated endocytosis
Properties of IgD
- interacts with basophils
- surface receptor with IgM
Properties of IgE
- cytophilic for mast cells and basophils via Fc receptors
- may be involved in immunity against some parasites
Why does allergic response happen so fast?
once IgE on mast cells is attached to its antigen, it triggers degranulation of mast cells and gets dumped out into surrounding tissues; IgE already primed on mast cells
Define allotypes
Genetically-determined differences in the proteins (antigens) between individuals in the same species; usually differ by 1 aa
Effect on immunogenicity in allotype variation.
Variant C regions can be immunogenic in some circumstances
What are the different types of Fc receptors and their function?
- FcγRI – Binds IgG
- FcεRI – Binds IgE
- FcRn – Transports IgG across epithelia
- FcγRIIB1 – Negative feedback mechanism to limit antibody synthesis
What are Fc receptors on NK cells good for?
to detect virally infected cells
Immunity in prenatal stage: 8 weeks
B cells in fetal liver
Immunity in prenatal stage: 10 weeks
Small amounts of immunoglobulin may be detected in this order
IgM > IgD > IgG > IgA