Adaptive Antigen Recognition Flashcards
BCRs are composed of a surface immunoglobulin and two invariant chains, ______ and ______. These ensure surface expression of immunoglobulin and also function in signal transduction.
Ig-alpha
Ig-beta
The TCR complex consists of an alpha/beta heterodimer associated with ______ complex proteins. These proteins ensure the cell surface expression of the TCR and is involved in signal transduction.
CD3
This is the term for gene rearrangement events that occur in the absence of antigen.
Clonal selection
What are the major mechanisms for generation of lymphocyte receptor diversity?
- Combinatorial diversification
- Junctional diversity
- Somatic hypermutation
T/F. The mechanisms accounting for immune diversity for BCR/Antibodies and T-cell/Receptors are IDENTICAL.
True
***Production of heavy chain B cell = Production of Beta chain T cell
Production of light chain B cell = Production of alpha chain T cell
T/F. Somatic hypermutation occurs only in T-cells.
False. Somatic hypermutation does not occur in TCRs.
Recombination of VDJ segments is directed by what signal?
RSS
These are responsible for recombining VDJ segments.
RAG-1
RAG-2
***VDJ recombinase
At the junction between D and J segments there is often an insertion of a series of nucleotides which is catalyzed by the enzyme…
TdT
**Junctional diversity
TdT catalyzes the random polymerization of nucleotides into DNA without the need for a template. ________ are added to asymmetrically cleaved hairpins in a templated manner. ________ are added in a non-templated manner.
P-nucleotide
N-nucleotide
At what stage of B-cell development do surrogate light chains appear then get shut off?
Pre-B cell
At what stage do lymphocytes become dependent to self-antigen?
Immature lymphocyte
Recombination between VJ and VDJ is not always perfect, it can lead to _________. This can triple the diversity.
Frameshifts
In the light chain formation (for B-cells and the Alpha chain of T-cells) explain the formation.
- DNA between V and J deleted
- VJ joins
- mRNA transcribed
- VJ and C separating mRNA is spliced
- VJC joins
- VJC mRNA translated to protein
In the heavy chain formation (for B-cells and the Beta chain of T-cells) explain the formation.
- DNA between D and J deleted
- DJ joins
- DNA between V and DJ is deleted
- VDJ join
- mRNA transcribed
- VDJ and C separating mRNA is spliced
- VDJC joins
- VDJC mRNA is translated to protein
At the junction between D and J segments there is often an insertion of a series of nucleotides which is catalyzed by TdT. What is this process called?
Junctional diversity
At what stage of B-cell development are RAG and TdT expressed?
Pro-B to Pre-B
What are the surface markers of a pro-B cell?
CD43+
CD19+
CD10+
Signals from the ________ are responsible for the largest proliferative expansion of B lineage cells during B cell development.
pre-BCR
***pre-TCR does the same for T cells
Signals from the pre-BCR (pre-TCR) signals to irreversibly inhibit rearrangements of the Ig heavy chain (Beta chain) locus on the other chromosome. This is called…
Allelic exclusion
This is the term for when an individual B cell can express one heavy chain encoded by only one of the two inherited alleles. It ensures that every B cell will express a single receptor, thus maintaining clonal specificity.
Allelic exclusion
B cells and stem cells initially interact through _______ and _______. This promotes another interaction between the stem cell factor (SCF) and ______ leading to proliferation.
VCAM-1
VLA-4
Kit
At what stage of B-cell development do they undergo negative selection?
Immature B cells
The pre-mRNA can be processed in two ways, one to bring the VDJ next to the _____ gene and the other to bring the VDJ next to the _____ gene. The resulting mRNAs have the LVDJ and ______ or ______ exons.
Cu
Cd
***Will code for a mu or a delta heavy chain
T/F. Selection deletes or functionally inactivates cells that display antigen receptors that are self-reactive. Tolerance is acquired by immature B cells that do NOT become activated when challenged with self antigen.
True
This occurs in developmentally arrested immature B-cells. RAG protein synthesis remains on for additional rearrangement of light chain genes. If the new light chain is not reactive with self-antigen, then tolerance is established and the B cell will mature.
Receptor editing
***Does NOT occur in T cells, if they are negatively selected then they will undergo apoptosis right away
What does the thymus consist of?
Thymic cortex (outer cortical region) Medulla (inner cortical region)
In humans, _______ activity peaks during puberty and declines thereafter.
Thymic
The immature T cells contained within the thymus are called _________, and are embedded in epithelial cells called thymic stroma. Express both classes of MHC/HLA.
Thymocytes
The thymus is a primary lymphoid organ involved in the production of primary lymphocytes, not antigen presentation. As such, the only route by which progenitor cells enter the thymus and mature T lymphocytes leave is via the ________.
Blood
(PRE/IMMATURE) B/T cells express one chain of antigen receptor.
Pre
(PRE/IMMATURE) B/T cells express the complete antigen receptor.
Immature
Double positive thymocytes undergo selection. This selection occurs with the establishment of self-restriction; recognition of self MHC/HLA.
Positive selection
Double positive thymocytes undergo selection. This selection occurs with the establishment of central self tolerance; T lymphocytes do not become activated by self antigen.
Negative selection
If there is a strong recognition of either class I or class II MHC + peptide, then the cells will undergo ________ selection.
Negative
If there is a weak recognition of either class I or class II + peptide, then the cells will undergo ________ selection.
Positive
Small population of self-reactive CD4+ T lymphocytes undergo differentiation to become _______. These function to inhibit self-reactive Th1 cells in the periphery.
Tregs
Tregs express both ______ and ______ on their surface, have a unique transcription factor ______.
CD4
CD25
FoxP3
