midterm 2 Flashcards
what causes APCs to secrete cytokines
binding to PAMPs on PRR
p
polarizing cytokines for TH1
il12
IFN Y
IL18
master gene regulator to th1
T bet
signature cytokines for TH1
IFN Y and TNF
what does TH1 protect against
intracellular pathogens and viruses
what does IFNY do
activates macrophages which inc their microbicidal actiivty and secrete IL-12 to further skew the enciroemnt to TH1
induces B cells to class switch to igG (phagocytosis and complement)
polarizing cytokines for TH2
il4
TGF B
master gene regulator for TH2
GATA 3
signature cytokines for TH2
IL4, 5, 13
what does TH2 do
clear extracellullar parasites including worms
what does IL4 do
favours TH2 and activates eosinophils and induces B cells to class switch to igE
how do we cross regulate between T helper cells
cytokines from APCs activate signalling pathways to activate the master regulator for the target cell to be activated and inhibit the other master gene regulator
positive feedback
polarizing cytokines for TH17
IL6
IL 23
TGF B
master gene regulator for TH17
RORYT
signature cytokine for TH17
IL7
function of TH17
dulal role in protective and pathogenic functions
protection against bacteria and fungi
implicated in inflamatory bowel disease, artritis, multiple sclerosis, and other autoimune disease
TH17 in disease
implicated in autoimmune diseases, mutated in hyper igE syndrome HIES due to mutation in STAT 3
polarizing cytokines for peripheral T reg
IL2
TGF B
master regualtor for peripheral T reg
fox p3
what induces t reg peripheral polarization
retinoic acid (vit a metabolite)
what do IL10 and TGF B in T reg peripheral do
inhibit APC function by directly targeting other T cells
T reg and autoimmunity
decrease it, needed for healthy pregnancy, reduce risk for preclampsia
cross regulation of T reg and TH17
TGF B induces both RORYT and FOXP3 but IL6 skews it to TH17
importance for TH17 and Treg
both important at barrier tissues to balance immune response
what are the polarizing cytokines for Tfh cells
IL 6
IL 21
mster gene regulator for Tfh CELLS
Bcl 6
SIGNATURE CYTOKINE FOR Tfh cells
IL4
IL21
what do Tfh cells do
required for the formation of germinal centres
drive affinity maturation
high levels of CD 40L
express CXCR5 chemokine receptor which attracts these T cells to the GC bc it has high levels of CXCL 13 (its ligand)
costimulatory receoptor ICOS needed for CXCR5 receptorwh
what does Bcl2 do
inhibits T bet, gata 3, and ROTYT
what T helper cells help B cells
T fh
What helper T cells help B cells
Th1
what do inhibitory receptors do to T cells
induce anergy
b7 Inhibitory receptor
CTLA 4
PD L1/2 inhibitory receptor
PD-1
what receptors turn T cell activtion off
negative costimulatory receptors
when do negative costimulatory receptors act
induced within 24 hours of activation and peak 2-3 days post stimulation
it is also stronger binding to CD28 than B7
what does ipilimumab do
blocks CTLA4 blocking inhibition of costimulation and allowing T cells to be activated to improce cancer therapy
what do nivolumab and pembrolizumab do
anti PD1 mAB therapy
what does fas do
its activation (when activated T cells increase its expression along with its ligand) initiates apoptosis of the actiavtaed T cell and other activated T cells
steps of FASL acting
it interacts with its receptor to induce trimerization
- adapter protein FADD is recruited
-pro apoptotic caspase protein activated
-apoptosis
what happens if we only get signal two on T cells
nothing
what allows DC to use the cross presentation pathway
interaction with Th cells
how do cytotoxic T cells get generated
DC use the cross presentation pathway when they are licsenced by an interaction with Th cels
they present endogenous antigen on Class I MHC and actiavte naive Tc cells
this can be sequential or simultaneous as the DC gets licensed it is activating the Tc cell
what are the steps to CTLs lethal hit delivery and recycling
form a CONJUGATE
CTL cytoplasmic rearrangement
CTL granule exocytosis
dissociation
CTL recycling
what are the important things that are used by NK cells and CTL to induce apoptosis
2 pathways
FASL holds granzyme B and perforin
what do NK cells share and differ with Tc cells
same cytotoxic machinery and different forms of target recognition and regulation
how to NK cells recognize and regulate target
they have a mix of inhibitory and activating signals
tolerance NK cells
inhibitory receptors bound by healthy cell MHC I
few activtaing ligands from healhty cell bound to activating receptor on NK cell
NK cell is inhibited
missing self NK cell
only activating ligand is bound to activating receptor by altered self cell- loss of MHC I and therefore NK cell is activated and promotes killing of the altered self ecll
balanced signals NK cell
up regulation of stress induced ligands promotes killing of altered self cell even though MHC I is bound to the NK cell
NK cell is activated and it promotes killing of altered self cell
NK experiment
showed that NK cell memory exists and will lead to more effective killing of infected cells or protects immunodeficient mice from infection
this occurs becasue the NK cell was exposed to a infected cell and led to its epansion and contraction of long lived experienced nK cell
what is ADCC
Ab dependent cell mediated cytotoxicity
antibodies recruit other cytotoxic cells to target cells
uses Fc receptor- lytic enzymes, perforins, TNF, and granzymes
how can memory CTLs be activated
without T cell help
they synthesize their own iL2
how are memory B cells actiavted
still need Th cell help
