What is an Epitope?
The part of an antigen that is recognized by lymphocyte antigen receptors (also known as antigenic determinant)
What are the domains of TCR and BCR receptors? (2)
Constant Region and Variable Region
What causes the proliferation of T cells from the lymphoid progenitor? Where does this occur?
IL-7 in the bone marrow
Where does T-Cell induction take place?
In lymphatic tissues (lymph nodes or the spleen)
Does the constant region of TCR or BCR change?
BCR constant region: can change TCR constant region: fixed
What does the TCR need to do to get passed the FIRST checkpoint during maturation?
Express the variable and constant region of the beta chain
What does the TCR need to do to get passed the SECOND checkpoint during maturation?
Express the variable and constant region of the alpha chain
What are the recombination events that lead to the beta chain of TCR?
1st recombination event: D and J recombination
2nd recombination event: V with DJ
3rd recombination event: VDJ with the Constant region Note: many different types of V, D and J
What are the recombination events that lead to the alpha chain of TCR?
1st recombination event: V with J
2nd recombination event: VJ with the Constant region Note: many different types of V and J
Where is most of the variability found in the TCR alpha and beta chains?
3 regions of hyper-variability in both chains CDR1, CDR2, CDR3
What are the mechanisms of antigenic diversity for the TCR and BCR? (2)
Combinatorial Variability Junctional Variability
What is Combinational Variability?
TCR and BCR variability caused by variation among possible V-D-J (beta chain) and V-J (alpha chain) exon combinations
What is Junctional Variability? (3 mechanisms)
TCR and BCR variability caused by modifications to the genes during the recombination process. 3 mechanisms: 1) Removal of nucleotides 2) Addition of nucleotides by TdT enzyme 3) Strand repair
What is the TdT enzyme? What would a mutation to the TdT enzyme cause?
adds nucleotides to TCR or BCR receptor gene - contributes to TCR or BCR variability Mutation: immune-compramise
What is the FIRST SIGNAL in T Cell activation?
TCR and CD4/CD8 co-receptor recognize MHC/antigen complexes presented by APC's
What is LFA1? What does it bind to?
LFA1 is a T cell intagrin that increases its affinity when the TCR recognizes an antigen/MHC complex. Binds to ICAM-1 on the APC cell surface
What is CD4?
CD4 is a TCR co-receptor that INDEPENDENTLY recognizes MHC Class II
What is CD8?
CD8 is a TCR co-receptor that INDEPENDENTLY recognizes MHC Class I
What do CD4+ T-Cells differentiate into?
Helper T Cells
What do CD8+ T-Cells differentiate into?
Cytolytic T Lymphocytes (CTLs)
How many TCR/co-receptors need to be engaged in order to activate naive T cells? (for the first signal)
2 or more
What is the SECOND SIGNAL in T Cell activation?
T cell CD28 needs to interact with B7, a co-stimulatory molecule on the APC cell surface.
What is CD3?
CD3 is a signaling receptor expressed on ALL T cells. Used as a marker.
What is ITAM?
Activating signal on T cells, part of CD28
What is CD28?
T cell co-stimulatory molecule that interacts with B7 on the APC cell surface. Is the second signal in T Cell activation. Occurs EARLY in the process.
What is CTLA4?
T cell co-stimulatory molecule that interacts with B7 on the APC cell surface. However, it INHIBITS the T-Cell activation and occurs LATE in the process
What is ITIM?
Inhibiting signal on T cells, part of CTLA4
What is ICAM-1?
On the APC cell surface, binds to LFA-1 on T Cell
What is PAMP? Where does it bind? What does it Cause? (3)
What: Pathogen associated molecular patterns
Where does it bind: receptors (toll-like) on dendridic cells or macrophages
What does it cause:
Upon digestion of pathogen:
1) Upregulate co-stimulatory molecule B7
2) Increase levels of MHC
3) Secret cytokines
Once a T-Cell is activated, how does proliferation occur? Genes expressed? (3) When it begins and how long it takes? CD4 expansion? CD8 expansion?
Genes produced: IL-2 cytokine (secreted) and IL2R(alpha) chain - this establishes the high-affinity receptor so that only activated cells will proliferate When it begins/how long it takes: starts 1-2 days after activation (3-4 days to proliferate before it detaches from complex) CD4 expansion: 100 - 1000 fold during infection CD8 expansion: 10,000 fold (10-20% of leukocytes during infection)