#2 - Life of a T Cell: Mobilizing the Troops Flashcards
what self-peptide target of a T cell is the cause of MS?
myelin basic protein (MBP)
what does the ‘i’ in iNK stand for?
invariant
what CD4 count is associated with HIV (for the 12-18 age group)
<400
approximately what percentage of the total lymphocytes are T cells, in the spleen
20%
what are the three signals for T Cell activation?
Signal 1 is through the TCR
Signal 2 is via costimulation (from APC) via CD28 or ICOS
Signal 3 is a cytokine
where does T cell activation occur?
in a secondary lymphoid organ
name four of the adhesion molecules that bring APC’s and T cells together
VCAM, LFA-1, VLA-4, CD2, ICAM-1
B cell question: what happens in the germinal centers?
b cell activation, somatic hyperstimulation and class switch recombination
about how many HLA molecules are likely to express foreign peptides?
3-5 (out of 50,000-100,000)
how do these few HLA’s produce a response big enough to activate the T cell?
First, the TCRs rearrange the membrane of both the T cell and the APC to bring all the activated TCR’s together; this produces a site called the immunological synapse
Second, the TCRs internalize, replace themselves and recycle to continuously use the HLA
what is the first step of the TCR activation pathway?
tyrosine kinase activation that phosphorylates ITAM (ITAM - immunoreceptor tyrosine activation motif)
what’s the second step of the TCR activation pathway?
phosphorylation of ZAP-70/Syk (this is via Src PTK, but that’s not on the test)
what’s the third step of the TCR activation pathway?
activation of calcineurin, which increases intracellular Ca levels
what’s the fourth and final step of the TCR activation pathway?
activation of NFAT, NFkB and MAPK transcription factors (increase mRNA stability)
what is the mechanism of action for the transplant enabling drug, cyclosporin?
inhibition of calcineurin, which inhibits the T cell activation pathway
what other types of cells use this pathway?
B cells, NK cells, Ig receptors, Fc receptors, neuronal receptors
what does CD28 bind to?
B7-1 and B7-2 (CD80, CD86)
what does CD28 do inside a T cell?
activation of PI3K
what happens when signal 1 and signal 2 are both activated?
release of the IL-2
what happens if a T cell receives signal 1 but NOT signal 2?
the cell becomes functionally impaired
what changes occur in activated T cells?
increased expression of chemokine receptors, upregulation of CD40 ligand, increased expression of SIP1 and expression of CD25 (a IL-2 receptor)
what does IL-2 do?
it is a growth factor that encourages rapid T cell proliferation
what does CD40L do?
aids in interactions with B cells and macrophages; this is important to isotype switching
what do mutations in CD40L cause?
Hyper-IgM which means that B cells are unable to switch from their default IgM setting and therefore the immune system is unable to respond adequately to many threats
where does the signal 3 cytokine come from? what determines which cytokine the T cell is exposed to?
APC; the PRR on the APC
what does IL-12 produce? transcription factor?
Th1 cells that secrete gamma-IFN; T-bet
what do IL-4 and IL-25 produce? TF?
Th2 cells (B helper cells) that produce IL-4, IL-5, IL-13; GATA3
what do IL-1, IL-6 and TGF-beta produce? TF?
Th17 cells that produce IL-17; ROR
what does the TF Foxp3 produce?
iTreg cells that produce IL-6 and IL-10 (anti-inflammatories)
what do IL-6 and IL-21 produce? TF?
Tfh cells that produce IL-21; bcl6
