Linking Innate and Adaptive Immunity 6 Flashcards
what occurs inside the cells when APC activates T cells?
intracellular signaling
what occurs during the 3 signals of T cell activation?
- Activation - pMHC:TCR (w coreceptor CD4/CD8)
- Survival - B7:CD28 (costimulatory molecules)
- Differentiation - release of cytokines
what are 2 types of receptors involved in T cell activation?
- receptors w intrinsic kinase activity
- receptors w extrinsic kinase activity
describe receptors with intrinsic kinase activity
signaling is initiated by dimerization and transphosphorylation by a kinase domain that is part of the receptor
describe receptors with extrinsic kinase activity
signaling is initiated by recruitment of a kinase, dimerization, and transphosphorylation
what is SH2?
recognizes phosphorylated tyrosine on the receptor to allow for other proteins to join
what are the 3 proteins responsible for regulation of signaling? and their roles?
- kinases –> phosphorylation
- phosphatases –> dephosphorylation
- ubiquitinated –> target proteins for degradation
what are the 4 components of the TCR complex?
- TCR
- CD3
- ITAMs
- zeta chains
how is signaling initiated by TCR binding? (2)
pMHC:TCR bind
coreceptor (CD4, CD8) binds MHC
what happens when signaling is initiated by TCR binding?
Lck is recruited to cause more signaling
what type of protein is Lck?
coreceptor-associated kinase
how does Lck cause more signaling?
phosphorylates ITAMs
what happens once ITAMs are phosphorylated?
Zap-70 kinase is phosphorylated, causing many downstream signaling molecules to be activated
ultimately, what does Signal 1 cause?
- initiation of many signaling cascades in parallel, leading to transcription of many genes
where are costimulatory ligands located? what are 2 examples?
on APC
CD80/B7.1 and CD86/B7.2
where are costimulatory receptors located? what is an example?
on T cell
CD28
is CD28 a positive or negative costimulatory receptor? what does this mean?
positive –> allows activation of T cell
what are 2 examples of negative costimulatory receptors? what does this cause?
CTLA-4 and PD-1
turn off activation of T cell –> ANERGIC T cel
what is an anergic T cell?
nonresponsive/non-activated T cell
what type of molecule is CD28? (3 qualities)
- transmembrane
- glycoprotein
- homodimer
where and when is CD28 found?
found on all naive T cells at baseline
what does CD28 bind? when?
binds B7.1/CD80 and B7.2/CD86 which are expressed when APCs are activated (not baseline)
is the kinase activity for CD28 extrinsic or intrinsic?
extrinsic
what are the 4 steps for CD28 signaling?
- binding to B7.1/B7.2
- phosphorylation of CD28 receptor by extrinsic kinase
- recruitment of another kinase via SH2
- additional signaling
when do T cells become anergic? (2)
- negative costimulatory receptors
- APC can’t present B7.1/B7.2 due to mutation for ex.
when do T cells stop being anergic?
they don’t –> they are anergic forever, even if they receive a functional APC, then die
WHAT OCCURS WHEN pMHC BINDS TCR?
- pMHC binds TCR
- co-receptor (CD4/CD8) binds MHC
- Lck (co-receptor associated kinase) recruits to CD
- Lck phosphorylates ITAMs
- Zap-70 phosphorylated
- downstream effects
