Feb. 21st (Exam 2) Flashcards
What are the checkpoints that the immune system utilizes in their conservative fashion of B cell production?
- At the Late Pro-B cell stage, the presence of a Pre-B cell receptor gives the cell survival signals to survive and continue onto more differentiation - this ensures a competent heavy chain can be made.
- At the Small Pre-B cell stage, the ability of a rearranged light chain to join a heavy chain and Ig (alpha) and Ig (beta) give it more survival signals to stay alive to become immature B cells.
Why is cancer relevant to lymphocyte development?
If there are improper expression of certain genes (proto-oncogenes) or translocations that happen as a result of heavy chain rearrangement, this can lead to tumor suppressors becoming faulty or proto to oncogene transition.
Think of the proto oncogene BCL-2 that usually prevents apoptosis but then gets expressed widely - not alone enough to cause cancer, but certainly could with other mutations.
What is the difference between B1 and B2 cells?
B1 cells are the early embryonic cells that express a cell surface marker called CD5 - they come from a stem cell that is most active during the prenatal period.
Because the TdT enzyme is not expressed that early, there is little N nucleotides (responsible for junctional diversity in part). By consequence, the antibodies are of lower affinity and they bind to many different antigens (they are less diverse).
B2 cells are the majority subset of B cells in humans.
What does the term Polyspecific mean?
Polyspecific is the idea that some antibody or antigen binding region, instead of binding to one specific antigen instead binds to many types of antigens present on the surface of a pathogen or otherwise.
What is the second phase of B cell Development called?
Negative Selection.
What are self antigens?
These are parts of our body (self) that an immature B-cell has the capacity to bind to and cause a disastrous immune response.
What does the term self-reactive or auto-reactive mean?
This is a characteristic of immature B cells and their receptors (or B cells and their antibodies in general if they are not filtered out) that bind to a person’s own tissues.
What happens to immature B cells that are self reactive?
What about immature B cells that are not self-reactive?
What percent of them make it out?
If they are, they are retained in the bone marrow.
If they are not, they get to leave.
Only like 25 percent make it out.
What will a B cell that makes it out of the bone marrow begin to express on its surface (Ig)?
Ig-D
Why is phase 2 of deciding which immature B cells can leave the bone marrow called negative selection?
Because immature B cells have receptors that are wired to generate negative intracellular signals if it binds to antigen.
AKA, once the immature B cell binds to something within the bone marrow, it receives negative signals to, back up, try again.
What is the first part of maturation of an immature B cell that is self tolerant?
What comes next?
The first step is that we see alternative splicing of the heavy chain mRNA sot hat the cell makes IgD as well as IgM
As the alternative splicing begins, there is presently more IgM than there is IgD, so the next step is that there is a shift to there being more IgD than IgM on the surface of the mature B cell.
What is a multivalent antigen?
This is an antigen that contains more than one epitope or more than one copy of the same epitope.
What happens to immature B cells if they are self-reactive?
After the first rearrangement after interaction with self antigen, what happens?
- Binding to a multivalent (stronger signal) self antigen in the bone marrow causes the immature B cell to reduce the amount of IgM on its surface and to maintain the expression of RAG.
Because RAG is still expressed, the cell can continue to rearrange its light-chain loci.
Further rearrangement takes out the old rearrangement, and it has the ability to make another functional light chain.
- If the rearrangement was successful and the immature B cell does not run into any more self antigens, it may be able to leave the bone marrow. If not it can undergo the same mechanism as in the first question - this is called receptor editing.
What is clonal deletion?
After many attempts at receptor editing, if the B cell can still not avoid running into self antigen, the B cell dies via apoptosis and is eaten by macrophages.
What happens to B cells that bind to monovalent self antigens?
What is this called?
They become inactivated and unresponsive to their specific antigen.
This is called anergy.
What is characteristic of anergic cells?
They may make both IgM and IgD, but unlike mature B cells, the IgM is unable to make a functioning B-cell receptor, so it stays in the cytoplasm.
If there is still plenty of IgD on the surface of these anergic B cells, why can’t they activate the B cell when they encounter antigen?
They just are unable to activate the B cell for some reason.
What happens to Anergic B cells that are deemed anergic within the bone marrow?
They are allowed to enter the peripheral circulation, but they have a much smaller life-span.
What is central tolerance?
These is the B cells that are tolerant to the cell antigens that are present in the bone marrow - it is called central because it is induced within the primary lymphoid organ.
Why can B-cells who encounter a monovalent self antigen, in say, the blood after being deemed centrally tolerant, not undergo receptor editing once more?
Because the machinery for doing all of that has been shut down.
What is peripheral tolerance?
This is the tolerance induced to antigens outside the bone marrow - it removes B cells reactive against the self antigens of all the tissues that are not bone marrow.
Fate of B cells that are deemed NOT peripherally tolerant?
They either die by apoptosis or they are rendered anergic.
Beyond central tolerance and peripheral tolerance, what have we missed?
There are places that are still going to be inaccessible to B cells - like the inside of other cells.
What can happen in times of stress disease, or trauma?
Self antigens that are new to the B cell population can provoke an autoimmune response.
DNA
autoimmune lupus erythematosus
