12 - Lymphocyte Activation and Differentiation Flashcards
What are the 2 effector forms T-cells differentiate to?
CD8+ CTLs | CD4+ Th cells
What is the T-cell activation stage?
naive T-cells recognize cognate antigen in secondary lymphoid tissues resulting in effector and memory T-cells
What are memory T-cells? Where do they reside?
ready to undergo clonal expansion when it comes into contact with cognate antigen again | basis of vaccination | at site of primary infection
What are the 3 signals needed to fully activate T-cell army which will undergo expansion? What are these signals needed for?
TCR engagement (for activation) | co-stimulation (for activation) | cytokine signaling (for expansion, IL2)
What is an immunological synapse? What do the proteins involve ensure?
when APC and T-cell come together along with all of the proteins necessary for activation = ensures interaction remains constant for enough time to fully activate the T-cell (lipid rafts bring proteins togther)
Which co-receptor mediates the first signal: TCR engagement?
CD3
What does CD3 have that TCRs do not have?
cytosolic signaling molecules such as ITAM and ITIM
What role does CD4/CD8 have on TCR engagement?
activates Lck
What is Lck?
tyrosine kinase | activates ITAM regions on CD3
In TCR engagement, what does the activation of ITAM regions lead to?
turns on transcription factor of a certain gene needed to be expressed
What is CD28? What is it needed for?
homodimer co-stimulatory receptor expressed on naive T-cells | enhances TCR-induced proliferation and survival, activates naive T-cells
What are the 2 ligands of CD28? Where are these expressed?
CD80 (on T-cells and APCs) and CD86 (only on APCs)
If you wanted to activate T-cell in vitro, what could you do?
1st signal = use anti-CD3 antibody to make T-cell think it is interacting with MHC molecule | 2nd signal = use anti-CD8 antibody
What is the function of negative costimulatory receptors in T-cell activation?
helps turn activation off
What are the 2 ways in which negative co-stimulation occurs?
CTLA-4 and clonal anergy
What is CTLA-4?
shuts down T-cell activation pathways and binds to CD28
How can clonal anergy cause negative costimulation in T-cell activation?
when second signal (costimulatory) is absent
What is the role of APCs?
express the co-stimulatory molecule to activate T-cells (no other cells can do this, just APCs)
What is the cytokine IL2?
autocrine cytokine | induces lymphocytes to expand | upregulates IL-2R so that it can undergo proliferation/expansion itself
What do the cytokines that the APCs secrete dictate?
outcome of T-cell activation = what type of T-cell we get
What is telling the APC what polarizingcytokines to produce? What turned on those cytokines or genes encoding for it in the APC?
PRR signaling - what PRR is activated = affect which polarizing cytokines APC will produce = affects the type of Th subset we get
What are polarizing cytokines?
produced by APCs, dictates which Th cell a naive T-cell will be
In which stage during T-cell activation does the naive T-cell differentiate into a specific subset?
differentiation stage
What are the 3 things that initial activation signals 1 and 2 induce?
upregulation of pro-survival genes (ie: Bcl-2) | transcription of IL2 and IL2R (CD25) | activation/proliferation of memory and effector T-cells
What is the role of polarizing cytokines?
cause the mature naive T-cell to undergo differentiation
Where are polarizing cytokines secreted from?
APCs
What do polarizing cytokines induce?
induces expression of master gene regulator
What is a master gene regulator?
regulates expression of certain effector cytokines
What pathway is involved in T-cell differentiation?
JAK/STAT pathway
What are the 4 effector functions of T-reg cells?
suppress immune response | causes anergy | turns off cytokine production | turns off effector cell function in other T-cells
What is the role in disease of T-reg cells?
helps induce tumor responses (bad) | inhibits autoimmunity
