Immunology - Final
Thus, some immunologist picture gd T cells as being in a ___________________ state ideal for innate defense.
'resting but preactivated'
Like the granules of CTLs, the granules of NK cells contain perforin & granzymes that induce ___________ in target cells
apoptosis
Primary source of NK cells
bone marrow
The opposing functions of activatory and inhibitory receptors can be attributed to differences in their
intracellular domains
In addition to cytokines, gd T cells secrete molecules that influence
leukocyte trafficking and wound healing
NK cells are generally ______________ proteins
transmembrane
In sites of inflammation, _________ may help to activate gd T cells by supplying stimulatory cyotkines or unknown intercellular contacts
APCs
Recent studies also suggest that gd T cells may themselves serve as _________ to ab T Cells
APCs
Natural Killer Cells, GD T cells, and NKT Cells
Bridge innate and adaptive immunity in both form and function
Intensity of NK cell response is determined by a combination of two factors
How many inhibitory vs activatory receptors are engaged and the affinity of those receptors for their ligands
In both humans and mice, the majority of T cells in the body are
CD4+ or CD8+ ab T cells
NK Cells are distinguished from NKT, B & T Cells how
Lack of TCRs or BCRs expression and have TCR or BCR genes in germline configuration
NK Cells
Large, non-phagocytic lymphoid cells that possess cytoplasmic granules containing perforin and granzymes
NK Cell tolerance
Mature NK cells are usually described as 'self-tolerant' because they do not attack normal self cells
Natural cytotoxicity is the _______________ model of NK-mediated natural cytotoxicity
Missing self
Some non-classical MHC molecules can act as activating ligands for
NK activating receptors
Cytokines produced by gd Th effectors activate ___________________________; support the ______________________ and influence ____________________________.
NK cells and macrophages; differentiation of activated ab Th0 cells into conventional ab Th1, Th2 or Th17 effectors; isotype switching in B cells
The activation of some gd T cells may be regulated more like that of NK cells than ab T cells as some gd T cells express
NK inhibitory receptors that recognize MHC class I.
Common lymphoid progenitors (CLPs) that remain in the bone marrow can generate
NK/T precursors
secondary source of NK cells
NK/T precursors that have migrated from the bone marrow to the thymus and can generate a subset of thymic NK cells
During infection and inflammation, NK cells can be rapidly recruited to
almost any tissue in the body
FcgRIIIA (CD16) expressed on NK cells can trigger ADCC by
binding to IgG molecules that have engaged epitopes on tumer cells or virus infected cells
Natural killer group 2 & Killer Ig-like receptor classes include
both activating & inhibitory members
TCRgd ligands may be soluble or
bound to a cell surface
gd T cells can respond to Ags that are derived from a
broad range of pathogens or abnormal/stressed host cells
In general, gd TCRs lack the fine antigenic specificity of ab TCRs and are often
broadly cross reactive
Abnormal host cell is "missing self" relative to the level of MHC class I present on heatlhy cells and so
cannot stop the activation of the NK cells, which then kill the target
Double negative peripheral T cells
carry either homodimeric CD8aa coreceptors or no coreceptor at all
NK activating receptors are triggered by ligands either
constitutively expressed on healthy cells or may be induced or upregulated in response to viral infection, malignant transformation (tumor) or other cellular stresses
gd T cells proliferate and differentiate more rapidly, in smaller numbers, and often in the absence of conventional ________________ un like ab T cells
costimulation
The anatomical distribution of gd T cells is strikingly ______________ from that of ab T cells
different
The balance between activating and inhibitory signals enable NK cells to
distinguish healthy cells from infected, cancerous, or abnormal cells (opposing-signals model of NK cells)
Infected & cancerous cells frequently __________________ their MHC class I expression
downregulate
Once activated by Ag, gd T cells generate __________ in a manner similar to ab T cells, although the signaling pathways linking TCR stimulation to new transcriptions are slightly different
effectors
Under the influence of ______________________________, distinct waves of gd T cells come out to populate specific organs.
fetal thymic stromal cells
gd T cells are the __________ defenders to confront invading pathogens or injurious substances
first
The first waves of T cells produced in human or mice embryo are
gd T cells
Vg9Vd2 TCRs occur on
gd T cells in the skin and peripheral blood.
Once activated, gd T cells respond by proliferating and differentiating into
gd Th and gd CTL effectors like ab T cells.
NK/T precursors
give rise to NK cells
In the skin, activated gd T cells secrete keratinocyte growth factor (KGF) that stimulates the
growth and differentiation of skin epithelial cells necessary to close wounds.
Killing by natural cytotoxicity also results
if the host cell expresses normal level of self MHC class I but abnormally high levels of activating ligands
NK receptor on placenta
induces maternal uterine NK cells to secrete cytokines that promote the formation of new blood vessels, helping to ensure a successful pregnancy
IFN-g produced cytokines from NK cells enhance TH1 cell development via
inhibitory effects on TH2 & induction of IL-12 by macrophages & dendritic cells.
in humans, Vg1Vd2 TCRs are prevalent on
intestinal gd T cells
The release of cytokines by gd T cells can ___________ the activation of ab T cells by several days
precede
Unlike CTLs, NK cells have _______________________ and they need not to be synthesized in response to activation of NK cells
preformed granules
Subsequent activation of primed NK cells by overwhelming activatory receptor engagement or FcgRIIIA stimulation leads to
production of a number of chemokines, growth factors, and cytokines such as IFN-g, TNF, IL-1, IL-3 & IL-6
Unlike activated T & B cells, activated NK cells do not
proliferate & differentiate into seperate effector cells in order to function. Thus, peak NK response can be detected within hours of infection
Experienced NK cells increase their longevity and upon second time infection, these cells can
proliferate and exhibit enhanced cytolytic and cytokine secretion capabilities
Some stress molecules are small ______________________. while others are ___________________________________ released by necrotic cells
pyrophosphate-like molecules; peptides or whole proteins
Some gd T cell subsets are _________ to stress molecules that are expressed only by host cells suffering from injury, infection or cancerous transformation.
specific
Unlike ab T cells, gd T cells resident in a particular tissue express a dominant or 'canonical' TCR containing
specific V gene segments.
The engagement of FcgRIIIA (CD16) activates
the NK cells and causes it to release the contents of its cytotoxic granules.
No effector differentiation is required, resting NK cells do not usually acquire significant cytolytic competence until
they are primed through exposure to cytokines such as IFN-alpha, IFN-beta, IL-12, IL-15
gd T cells arise in _________ from the same NK/T precursor which generates ab T cell & NK cell but it is not known which specific precursor is destined to become gd T cell
thymus
Unlike ab TCR, the TCRs of many gd T cells can bind directly
to low molecular weight non-peptide antigens, without the need for presentation by another molecule or cells.
Priming cytokines induce
upregulation of many activating & inhibitory receptors on NK cells as well as adhesion molecules that stabilize their binding to target cells
NK Cells control _________ replication during the time required for activation, proliferation, & differentiation of CTL-P cells into effector CTLs
viral
NK cells are involved in the early response to infection with certain
viruses and intracellular bacteria
NK cells make up ______% of human peripheral blood cells
10-15%
NK cells are first line of defense against virus infection and they peak almost ____ days after viral infection
3
Life span of mature NK cells
7-10 days
Rearrangement of TCRgd genes is detected in thymocytes by ____________________ in human fetus & by day _______ of gestation in mice
8 weeks; 12.5
These gd T cells provide immune defense in fetus and neonates before ____________ immunity mediated by the more powerful ab T cells is fully established
adaptive
NK inhibitory receptors
Bind only to classical MHC class I molecules expressed by the host
Some gd T cells can be activated with phosphorylated metabolites without
CD28 or CD40-mediated costimulation.
The gd T cells in peripheral tissues tend to undergo conventional
CD28-mediated costimulation
NK cells may interact with DCs and promote
DC maturation & efficient induction of Th & CTL responses
NK activity is stimultaed by innate immune cytokines _________ whcih are produced early during course of viral infection
IFN-alpha, IFN-beta, IL-12
In response to infection, phagocytes & innate leukocytes produce __________________ & other cytokines that first _________________ & then induce them to synthesize ________________ which mediates many biological functions.
IFNa/b, IL-12, IL-15, TNF; prime NK cells; IFN-g
activatory receptors signal through associated signaling units having
ITAMS
inhibitory receptors or their associated signaling chain have
ITIMS
What can serve as TCRgd ligands
Intact proteins or peptides from pathogens or stressed host cells, & non-protein Ags such as lipids & phosphorylated nucleotides
Almost all normal host cells express
MHC class I
gd T cells do not require involvement of
MHC or processing & presentation of peptide Ags by APCs.
Immunological memory is ______ a feautyre of gd T cells
Not
gd T cells are interspersed among the ________ and __________.
Salt and Malt
Resting NK cells are found in high frequency in
Spleen, liver, uterus, and peripheral blood with moderate numbers in bone marrow, LNs, and peritoneum
NK cells cytokines directly regulate
T & B cells functions and differentiation
NK cell originate from the same bone marrow-derived hematopoietic precursors that give rise to
T cells
gd T cells express TCRs composed of
TCRg and TCRd chains plus the CD3 complex.
NK Cells, GD T Cells, and NKT Cells
These cells are considered to be part of adaptive immunity as these cells are related to T cell lineage
GD T Cells and NKT Cells
These cells express TCRs
NKT Cells, GD T Cells and NKT Cells are part of the innate immune response because
They are rapid and involved broad recognition of Ag independent of classical pMHC complexes
Expression of single stress Ag in response to a variety of infections/injuries allows
a gd T cell population with limited Ag receptor repertoire to monitor a variety of assaults.
Some gd T cell subsets (defined by V segment usage) are specific to certain type of determinants and thus may counter
a whole group of pathogens
Natural cytotoxicity recetor class contains only
activating receptors
gd TCRs interact with ligands in a way similar to
ligand recognition by pattern recognition receptors
only very ______ numbers of gd T cells are found in secondary lymphoid tissues and thymus of mice and humans
low
NK cell that survive infection may show characteristics of
memory lymphocytes
gd-T cells are minor population of T cells in ___________ but a major population in
mice & humans; ruminants & pigs
Cytolysis may be induced by
natural cytotoxicity, ADCC or cytotoxic cytokines
NK Cells have surface expression of
neural cell adhesion molecule (NCAM;CD56) &/or low affinity IgG receptor FcgammaRIIIA (CD16)
Some stress molecules that can be recognized by gd T cells are not recognized by myeloid cells such as
neutrophils & macrophages, so gd T cells fill critical gaps in host defense.
Activated gd T cells can induce neighboring epithelial cells to produce the antimicrobial compound
nitric oxide
Primary functions of NK cells
non-specifically kill tumor or virally infected cells and to secrete cytokines
some non-peptide Ags are also presented by
nonclassical Class Ib molecules or by non-polymorphic CD1 family of MHC like molecules (CD1c) to gd T cells.
Recognition of target cells by NK cells is
not MHC restricted, show similar NK-cell activity with syngeneic and allogeneic tumors
epidermal & intestinal gd T cells are costimulated when
other surface receptors are engaged by stress ligands.