Chapter 7 Flashcards
signaling receptors typically located on the cell surface generally do what?
initiate signaling in the cytosol,
followed by a nuclear phase.
what is the most prominent category of immune receptors contributing to innate and adaptive immunity?
immune receptors that
belong to a receptor family in which non-receptor
tyrosine kinases phosphorylate tyrosine-containing
ITAM motifs on the cytoplasmic tails of proteins in
the receptor complex
Antigen receptors use coreceptors to do what?
s to enhance signaling. Coreceptors bind to the same antigen
complex that is being recognized by the antigen
receptor
how can signaling from antigen receptors be attenuated?
by inhibitory receptors
The TCR complex is made up of what?
the TCR α and β
chains that contribute to antigen recognition and
the ITAM-containing signaling chains CD3 γ, δ,
and ε as well as the ζ homodimer. The CD3 chains
each contain one ITAM, whereas each ζ chain
contains three ITAM
TCR ligation results in what?
n tyrosine phosphorylation of
CD3 and ζ ITAMs by Src family kinases and the
recruitment of ZAP-70 to the phospho-ITAMs,
each SH2 domain of ZAP-70 binding to one phosphorylated tyrosine of the ITAM
activated ZAP-70 phosphorylates what?
tyrosine residues on adaptors, and downstream enzymes are
recruited to the signalosome
Enzymes that mediate the exchange of GTP for
GDP on small G proteins such as Ras and Rac help
initiate what?
MAP kinase pathways. These pathways
lead to the induction or activation of transcription
factors such as Jun and Fos, components of the
AP-1 transcription factor
Activation of PLCγ1 leads to the release of what?
IP3 from
PIP2, and IP3 induces release of calcium from
intracellular stores. Depletion of calcium from
intracellular stores facilitates the opening of CRAC
what is CRAC?
a store-operated channel on the cell surface that
maintains the raised intracellular calcium levels.
Calcium binds to calmodulin and activates downstream proteins including calcineurin, a phosphatase that facilitates the entry of the NFAT
transcription factor into the nucleus
when is Diacylglycerol generated?
in the membrane when
PLCγ1 releases IP3 from PIP2. DAG can activate
PKC-θ, which among other things can contribute
to NF-κB activation
A lipid kinase called PI3-kinase converts PIP2 to
PIP3. PIP3 can do what?
recruit and activate PH domain–
containing proteins to the plasma membrane. PIP3
activates Itk in T cells and Btk in B cells. It activates
PDK1, a kinase that can phosphorylate a downstream kinase called Akt that mediates cell
survival
Costimulatory receptors initiate signaling separately from antigen receptors, but signaling outputs
from antigen receptors and costimulatory receptors synergize where?
in the nucleus. The major costimulatory receptor in T cells is CD28
T cell signaling can be inhibited by what?
phosphatases
that may be recruited by inhibitory receptors such
as CTLA-4 and PD-1
T cell signaling is also attenuated by what?
ubiquitin E3
ligases that can contribute to the monoubiquitination and lysosomal degradation of activated signaling proteins
The B cell receptor is made up of what?
membranebound immunoglobulin and an associated
disulfide-linked Igα and Igβ heterodimer. Both Igα
and Igβ contain ITAM motifs in their cytoplasmic
tails. Signaling pathways linked to the BCR are
broadly similar to signaling pathways downstream
of the TCR.
The coreceptor for the BCR is what?
CD21, also known as CR2 (complement receptor type 2)
Attenuation of immune receptor signaling in B
cells, T cells, and NK cells, among others, is mediated by what?
inhibitory receptors that frequently contain
inhibitory tyrosine–containing motifs or ITIMs in
their cytoplasmic tails
Another important mechanism of signal attenuation involves what?
the ubiquitination of signaling proteins by E3 ubiquitin ligases
Cytokine receptors can be divided into a few broad
categories based on what?
structural considerations and
mechanisms of signaling
Many cytokine receptors use non-receptor tyrosine kinases called what?
JAKs to phosphorylate transcription factors called STAT
Some cytokine receptors such as those of the TNF
receptor family activate what?
either canonical or noncanonical NF-κB signaling.
Canonical NF-κB signaling is activated downstream of many receptors, including what?
TNF receptor
family cytokine receptors, TLRs and IL-1R family
members, and antigen receptors. The pathway
involves activation of IKKβ in the IKK complex,
phosphorylation of the IκBα inhibitor by activated
IKKβ, ubiquitination and proteasomal degradation of IκBα, and transport of NF-κB to the
nucleus.
