Ch. 11 Flashcards
Summarize a day in the life of a naive T cell
• After T cells leave the thymus, they enter circulation on an epic journey to find their cognate antigen
o Highly motile, but otherwise boring cells (G0 of the cell cycle, chromatin is condensed, little cytoplasm and little transcriptional activity)
Travel between SLO sites using blood circulation every 12-24 hours
• If t cells scan through and SLO and cannot find their cognate antigen, they simply leave and move on to the next SLO
• However, if they do happen to find an APC presenting their antigen, then IT. IS. ON!
What is Signal 1 of T cell activation?
o The first requirement for T cell activation is antigen recognition via TCR/MHC (& coreceptor) interactions
The low-affinity interactions of MHC/TCR at the contact point between the cells in a region called the central supramolecular activating complex (cSMAC) are stabilized by coreceptors CD4/8 & CD3
• This increases the avidity of the synapse
o Avidity=you can make a strong binding of weak bonds if there are several of them (like h-bonds in water)
What is signal 2 of T cell activation?
o However, even further contact must be made between an APC and a T cell for full activation
Activating coreceptors
• CD28 binding CD80/86
Adhesion molecules in the peripheral supramolecular activating complex (pSMAC)
What is signal 3 of T cell activation?
o However, even further contact must be made between an APC and a T cell for full activation
Activating coreceptors
• CD28 binding CD80/86
Adhesion molecules in the peripheral supramolecular activating complex (pSMAC)
All three signals are necessary, with 1&2 triggering “activation,” and 3 indicated what the cell should differentiate into. What is the response?
In response, IL-2 is produced to trigger cell proliferation
Under what circumstances does clonal anergy result for a T cell?
- result if a costimulatory signal is absent
- this helps provide tolerance (especially in periphery)
- if only signal one is received, the cell is rendered nonresponsive (might happen if a T cell isn’t screened against a peripheral self-antigen during development)
Autocrine signaling of IL-2 has what outcome for an activating T cell?
- IL-2 is an example of an autocrine type of cytokine response system
- T cells produce the cytokine and the receptor for it
- Binding of this ligand induces a very strong proliferation signal during activation stages
What are polarizing cytokines?
cytokines that can send the T cell down different subset developmental pathways
What are superantigens
special class of T-cell activators - viral/bacterial proteins that bind to specific VB regions of TCRs and a chain of class II MHC molecules
Why are superantigens detrimental to our health?
- Specific for the VB
- Any T cell expressing the particular VB chain will be activated
- effectively short-circuits activation by antigen
- activates large numbers
- produces dramatic cytokine secretion by large proportion of inappropriately activated T cells (cytokine storm)
Cytokine storm
DIC, shock, lung injury, cardiac damage, immune paralysis, renal failure
What are the three outcomes of the signaling between a dendritic cell APC and a naive T cell?
- cell survival
- cell cycle entry
- cell differentiation
How many cells can be derived from a single activated naive T cell that has developed into a blast cell? How many days does it take for this population of cells to be formed in an SLO?
1-2 days following activation via interaction with an APC in a T-cell zone of an SLO, T cells will enlarge into a blast cell which starts undergoing repeated rounds of cell divisions
-divide 2-3 times a day for 4-5 days
-2 divisions for 4 days=256 cells
-3 divisions for 5 days=32,768
production of memory and effector clonal cell populations
What is the purpose of an effector CD4+ cell?
CD4+ effectors secrete cytokines to regulate the activity of the other immune cells
- some subtypes stay in SLO to help B cells and generate memory
- others return to sites of infection and enhance activity of phagocytic and cytotoxic cells
What is the purpose of an effector CD8+ T cell?
CD8+ effectors leave lymphoid tissues and circulate to sites of infection, binding and killing infected cells