adaptive immunity - T cells Flashcards
what T cells activate B cells in the lymph node?
T follicular helper cells
what T cells activate macrophages?
Th1 cells (CD4+)
through what vessels to T cells leave lymph node towards site of infection?
efferent lymphatic vessels -> thoracic duct -> blood stream
which Th1 cytokines promote what at the site of infection?
- granzyme and porforin trigger cytotoxic T cell killing
- IFN-y trigger macrophage ROS killing
what ligand on CTL binds to what on infected cells? this triggers what?
FasL on CTL binds to Fas on infected cell, triggering lysis/apoptosis
what directs T cell differentiation into effector cell types?
cytokines from APCs
what cytokines promotes T cell proliferation?
IL-2
what 3 categories can t cells differentiate into?
CD4+ T helper cells
CD8+ T cells
Regulatory T cells
what is cool about an activated effector T cell?
it does not require co-stimulation to act
big picture about effector t cells role?
they have the ability to impact the functionality of other immune cells
give examples of how different PAMPs trigger different cytokines production and TH differentiation
- Viruses stimulate IL-12 to induce TH1 subset
- Worms stimulate IL-4 to induce TH2 subset
what signal regulates T helper cell differentiation?
signal 3 cytokines (polarizing cytokines) released from APCs
describe TH1
- polarizing cytokines (signal 3): IFN-Y, IL-12
- produce IFN-y, CD40L
- target bacteria
- STAT1 and 4 -> T-bet
describe TH2
- polarizing cytokine: IL-4
- produce IL-4, IL-5, IL-13, CD40L
- against Helminth
- STAT6 -> GATA-3
describe TH17
- polarizing cytokines: TGF-B, IL-6, IL-23
- produce IL-17, IL-22, CD40L
- STAT3 -> RORyT
describe TFH
- polarizing cytokine: IL-6
- produce IL-21
- STAT3 -> Bcl-6
describe Treg
- polarizing cytokines: TGF-B, IL-2
- produce TGF-B, IL-10
- inhibit DCs
- STAT5 -> FoxP3
what are stat proteins?
act as TFs to help differentiate T cells by transcribing genes that also act as TFs
what are called the “2nd” TFs involved in T cell differentiations?
master transcriptional regulators
type 1 vs type 2 response (relating to T cell differentiation)
type 1 = intracellular pathogens induce cell-mediated immunity
type 2 = pathogens inducing humoral immunity ex Helminth
how is the Th cell differentiation system made flexible?
each naive CD4 T cell expresses all of the STAT proteins (stay unphosphorylated until polarizing cytokine activates it)
when are Fas ligand and CD40 ligand expressed?
on effector T cells surface following signals 1, 2, 3
describe Fas and CD40 ligands
transmenbrane ligands, part of TNF family, cell-to-cell interaction
on what cells are Fas ligand expressed? what do they bind?
expressed on effector CD8+ cells for cytotoxic effect and on TH1 cells;
Fas ligand binds Fas on infected cells at the site of infection
on what cells are CD40 ligand expressed? what do they bind?
expressed by Th1, Th2, Th17, Tfh cells;
bind CD40 on B cells and innate immune cells to activate them
name one function of CD40 ligand
bind CD40 and allows for DC licensing and expression of more co-stimulatory molecules
what cytokine is required for CD8+ T cells differentiation?
only require IL-2!
what does CD8+ T cells required in higher quantity than CD4+ T cells?
CD8+ cells require more co-stimulation (signal 2)
where can CD8+ T cells get IL-2 signal from?
autocrine (like usual), but also from Th1 or Th17 cell!
what help do CD8+ T cells require for activation?
help of effector CD4+ T cells
how do CTLs (effector CD8+ T cells) act?
CTLs recognize and kill infected/tumor cells via recognition with their TCR
how do CD8+ T cells usually get activated?
via cross presentation (CD4 effector T cells licenses an APC)
how do CD8+ T cells sometimes get activated? (rare)
via activated dendritic cells that have high costimulatory activity
what are the 2 methods of cross presentation?
- sequential: APC gets licensed by CD4+ cell and then interacts with CD8+ cell independently
- simultaneous: APC interacts with both CD4+ and CD8+ T cells at the same time
in cross presentation, what does CD40 signaling lead to?
leads to DC licensing and expression of more costimulatory molecules
difference between sequential and simultaneous cross presentation cell proliferation signal?
in sequential, CD8+ T cell only recieve its own IL-2 signal (autocrine).
in simultaneous, CD8+ recieves IL-2 from both CD4+ and from itself
remember: What needs to happen to CD4+ T cells in order for CD8+ T cells activation to occur?
- find its p:MHC Class II match
- receive all 3 ligands (signals)
- CD40 ligand gets expressed and binds to CD40 on APC
remember: What needs to happen to DCs to allow them to present antigen to both CD4+ and CD8+ T cells?
- encouter a PAMP
- travel to lymph node
- present MHC Class II to CD4+ T cell
- Gets licensed through CD40 binding
- Present exogenous antigen on MHC class I to CD8+ T cell
what is 4-1BBL?
molecule that provides CD8+ T cell additional costimulatory signal with B7
CTLs can kill infected cells in the periphery via what interaction?
TCR and CD8 co-receptor with pMHC Class I
in what 2 ways can CTLs kill infected cells?
- Fas-FasL interaction
- granules
how does CTL find its match?
binds to nonspecific adhesion molecules on cells until it finds its pMHC match on an infected cell
how does killing via Fas-FasL work?
FasL on CTL binds Fas on infected cells -> triggers cleavage of procaspases into caspases -> apoptosis
how does CTL granule-mediated killing work?
TCR:pMHC recognition -> Reorganization of cytoskeleton and cytoplasmic contents to bring granules close to target cell -> granules released
what contains the CTL granules?
perforin (forms pores) and granzymes B (serine proteases; activate apoptosis)
how do granzymes B cause apoptosis?
enters the cytoplasm and cleaves pro-caspase into caspase (like Fas-FasL) causing DNA fragmentation
what do cells infected with granzymes display after 40 minutes?
membrane blebbing
what do both (Fas and granules) CTL killing method converge onto?
caspase 3 activation
what kind of cytokines are FasL and CD40L?
TNF: they are transmembrane ligands (only do cell-to-cell mechanism)
remember: how do NK cells recognize infected cells?
lack of MHC class I