T cell activation Flashcards
activation is not initiated until the second signal is received by a co-stimulator ___________________________ between the APC and naïve T cell
receptor-ligand binding pair
what is the purpose of plasmacytoid dendritic cell?
involved in the early stages of innate immune response secreting anti-viral cytokines IFNa and IFNb. They are key players against viral infections
what is the purpose of myeloid dendritic cells?
involved in T cell activation. These dendritic cells are found throughout the tissues
of the body in sites of antigen exposure (i.e. skin)
what is the dendritic cell in the skin?
langerhans cell
what are immature dendritic cells?
dendritic cells that have not been activated tend to express high levels of antigen receptors for pathogens (i.e. Toll-like receptors and phagocytic receptors), but low levels of MHC on their cell surface
what happens if a mature dendritic cell already resides in secondary lymphoid tissue?
it would initiate Ag presentation to T cells and B cells accompanied by the secretion of cytokines (i.e. IL-12
what would happen if the mature dendritic cell resided in peripheral tissues like Langerhans cell?
in addition to the upregulation in MHC class I and MHC class II molecules, the dendritic cell would upregulate adhesion molecules and chemokine receptors to aid in its migration into the lymphatics and ultimately to the draining lymph nodes to present processed Ag to the circulating naïve T cells or memory T cells, if the host had encountered the antigen previously
how does the dendritic cell become mature?
Upon recognition and internalization of foreign antigens (i.e. pathogens), the dendritic cell is
activated and changes it cell surface protein expression molecules toward an increase in MHC molecules bound with linear peptide Ag
what do activated APCs express?
a multitude of MHC molecules with different linear Ag peptides with the potential to activate many different T cells
why does MHC and TCR have such a low affinity binding event?
association between the MHC and TCR is based on such a small peptide and only components (i.e. amino acid sequences) of that peptide.
what stabilizes the MHC-TCR binding and also lowers the threshold of T cell activation?
additional binding of the co-receptor (i.e. CD4) to the invariant portion of the MHC
what is B7-CD28 binding required for?
second signal and T cell activation
what is upregulated upon activation of T cells?
CD152
what deactivates the T cell with expression of CD152?
if bound by CD80 or 86
what is upregulated when the T cell becomes activated and upregulating the expression of the CD80 or CD86 molecules and also has important role when T cells interact with B cells in antibody synthesis?
CD154
list 3 adhesion molecules
CD54 (ICAM-1)-CD11a/CD18 (LFA-1), CD58 (LFA-3)- CD2, and LFA-1-CD50 (ICAM3)
define immunologic synapse?
collective association of the MHC-TCR, co-receptors and adhesion molecules between the
APC and T cell
how do we creen these cell surface
molecules to evaluate the different stages of cell activation as well as help determine if there is a defect cell surface molecule when we suspect some abnormal immune response?
flow cytometry
what does linker for activation of T cells (LAT) serve as?
an adapter protein to bind more proteins such as SLP76. This protein when bound promotes the reorganization of cellular actin as well as binding to phospholipase Cγ1 (PLCγ1)
what does linker for activation of T cells (LAT) serve as?
an adapter protein to bind more proteins such as SLP76. This protein when bound promotes the reorganization of cellular actin as well as binding to phospholipase Cγ1 (PLCγ1)
Upon binding of the MHC-peptide TCR, _________ kinases Fyn and Lck (members of Src family) are activated via dephosphorylation by membrane-bound protein CD45 and are drawn to the ITAMS on the cytoplasmic domains of the CD3 and ζ chains.
tyrosine
______ is a key mediator of 3 distinct cell signaling pathways all of which result in the activation of transcription factors
PLCγ1
The impact of the second signal B7-CD28 at the intracellular level promotes lipid rafts to
transport additional kinases and other molecules to the TCR site to enhance signaling. In addition, binding of B7-CD28 attracts the enzyme phosphatidylinositol-3 (PI3). It is believed that these combined events serve to promote ____ synthesis by increasing the rate of ____ gene transcription
IL-2
how has the calcineurin pathway been used as a therapeutic target?
to downregulate T cell activation following tissue/organ transplantation
Upon activation of the T cell (naïve or mature), what is the goal of the adaptive immune system?
proliferate
This first and second signal response activates a number of intracellular signaling pathways that results in the activation of what 3 transcription factors?
NFAT, NFκ-B and AP-1
transcription factors activated transcribe select gene segments in activated T cell to yield a host of proteins to promote what?
cell proliferation
In resting T cells, IL-2R exists as a ____ affinity 2-chain surface protein and upon activation of the T cell it changes to the ____ affinity 3-chain surface protein
low
high
what kind of signal is classified as a molecule produced by a cell that stimulates or activates the same cell?
autocrine
describe paracrine signal?
A molecule produced by a cell that locally affects other cells
describe endocrine signal
A molecule that is produce by a cell and affects cells elsewhere in the body
what two kind of signals does IL-2 function as?
autocrine and paracrine
what does the cluster of homing molecules
that are upregulates would appear to determine ?
which tissue a particular T cell will migrate
activated T cells upregulate the expression of
the ______ as a “shutdown” control switch
CD152 (CTLA-4)
what is the program cell death CD279 (PD-1) protein role?
inducing “exhausted T cells” to die, suppressing activated T cells (i.e autoreactive T cells) and rescuing regulatory T cells.
______ is expressed on many normal cells as well as most cancer cells
PD-L1
______ is more restricted to dendritic cells and some tumor cells
PD-L2
when PD-1 is activated, what does it inhibit?
ZAP-70
Therapeutic protocols have been designed around blocking the _____ binding site
to treat certain cancers and have included commercial antibodies anti-PD1 and anti-CTLA4.
PD-1
what are some plant based products that can non-specifically stimulate T cells?
Concanavalin A (Con A) and phytohemagglutinin (PHA)
what does Pokeweed mitogen (PWM) stimulate?
T cells, B cells and monocytes/macrophages.
what does PMA target and activate?
protein kinase C (PKC) and ionomycin is a calcium ionophore
Con A, PHA and PWM are quite mitogenic at concentrations in the g/mL
range, whereas PMA and ionomycin are highly mitogenic at ng/mL and pg/ml,
