Module 5 Flashcards
What are the six stages of B cell development?
Repertoire assembly Negative selection Positive selection Searching for infection Finding infection Attacking infection
What is the role of bone marrow strolls cells during early B cell development?
They regulate B cell development through the production of IL-7
What are the functions of the surrogate light chain?
Blocks further H-chain rearrangement
Signals proliferation
Signals light chain rearrangement
What is allelic exclusion?
A cell can only express one of its two gene copies
During B cell development what are the Ig gene recombination steps?
Pro B cell - H chain gene rearrangement
Pre B cell - L chain gene rearrangement
Immature B cell - rearrangement ceases
When is a developing B cell considered an immature B cell?
When it produces IgM surface receptors and releases from stromal cells into circulation
What Ig’s do immature B cells express?
IgD and IgM
What are anergic cells?
Nonfunctional B cells that reacted with soluble antigens in the bone marrow, but are released into circulation only to die after a few days.
What is the process of receptor editing?
The additional opportunities provided to self-reactive B cells to reorganize their light chains
What happens to developing B cells that despite reorganizing their lights chains are still self reactive?
Apoptosis
What is clonal deletion?
The death of self reactive developing B cells
What is the process of negative selection?
The elimination of self-reactive immature cells
What kinds of lymphocytes undergo negative selection?
B and T cells
What is central tolerance?
The immunological tolerance to self by B and T cells
What does peripheral tolerance do?
The peripheral tissues sometimes catch escaped self reactive B and T cells
What happens to naive B cells after the exit the bone marrow?
They head to the lymph nodes for positive selection by the FDC
What does FDC stand for?
Follicular dendritic cells, the structural stromal cells that interact with immature B cells and positively select for survival
Final two phases of B cell development depends on what?
An encounter with an antigen
What are the four steps that B cells go through in their final development phases in the lymph node?
- Mature naive B cell encounters Ag
- Activation via partnership with Th
- Migration to primary follicle
- Proliferation and differentiation in German centers
What are the four stages of B cell development that occurs in the bone marrow?
- Stem cell
- Pro B cell
- Pre B cell
- Immature B cell
What are the five stages of B cell development that occur in the secondary lymphoid organs and circulation?
- Immature B cell
- Mature naive B cell
- Antigen-activated B lymphoblast
- Antibody secreting plasma cell
- Memory cell
When the immature B cells leave the bone marrow, which Igs do they have?
They start with IgM and IgD
Once B cells are in circulation, how do they achieve higher IgM and low IgD?
Through alternative splicing to give delta and mi chains then they gain access to primary lymphoid follicle
What do nature B cells with low IgM and high IgD do next?
Enter circulation and bind antigen in lymphoid tissue draining infection
What three steps happen once B cells reach the antigen-activated B lymphoblast stage?
- Alternative splicing to secret Ig
- Isotype switching
- Somatic hypermutation
What is the purpose of B cells that have matured to the antibody secreting plasma cell level?
Fights active infections
What is the purpose of B cells that make it to the memory cell level?
Prep for a future infection
What is a thymocyte?
The T cell precursors that reach the thymus
Where is the thymus located?
Above the heart
What is the organization of the thymus?
It is sectioned into two regions, the cortex which is on top and densely packed and the medulla which is below and less densely packed.
Why do we become more dependent on our pool of mature B cells as we age?
The thymus shrinks with age
Are there more alpha-beta T cells or gamma delta T cells?
90-95% alpha beta TCR
Why are there four chances for TCR beta chain formation?
Because VDJ happens on the beta chain locus and each allele has two constant regions
What does pre-TCR signaling do to developing T cells?
Blocks further beta rearrangement and induced proliferation and expression of CD4 and CD8
What does pT alpha chain do for developing T cells?
Acts as a placeholder for TCR alpha chain much like the B cell surrogate chain
What are the two checkpoints on T cell development?
- Rearrangement first on the beta chain otherwise apoptosis
- Rearrangement second of the alpha chain otherwise apoptosis
What percentage of thymocytes do not pass the selection process?
98%
What does T cell education refer to?
The processes of positive and negative selection that thymocytes undergo
What does positive selection accomplish?
Ensures that only T cells with functional TCRs are capable of interacting with self MHC survive and determine their functional role
T cells during positive selection express what on their surface?
CD4, CD8 and TCR
How if the effector function determined during positive selection?
If T cell interacts with MHC class 1 then it keeps CD8 and if it interacts with MHC class 2 it is CD4
What does the process of negative selection accomplish?
It results in clonal deletion of self reactive T cells
How are self reactive T cells identified?
They bind to tightly to thymocytes APCs presenting self and results in apoptosis
What does AIRE stand for?
Autoimmune regulatory
What is AIRE?
A transcription factor expressed by thymic epithelial cells
What is the function of AIRE?
Induced expression of hundreds of tissue specific proteins to present on MHC to developing T cells during education
What are the three types of T cells?
CTL, Th and reg
What is the difference between tT reg cells and T reg cells?
tT are reg cells matured in the thymus and T reg cells mature in the periphery was
What do T reg cells do?
Suppress the action of autoreactive T cells and contributes to peripheral tolerance
What are the four stages of T cell development?
- Proliferation and differentiation of double-positive thymocytes
- Positive selection (T cell education)
- Negative selection (T cell education)
- Entry to circulation
