17 - T cells I : Module intro/overview & signal 3: T cell differentiation Flashcards
where is signal 3
in lymph node
t cell exert their function is also called … immunity
cell-mediated immunity
once infection cleared, there are…
regulation& memory
3 signals to activate T cells
- Signal 1: pMHC:TCR
- Signal 2: B7:CD28
- Signal 3: Cytokines
-Lead to differentiation of T cell
main job of CD8+ T cell once becomes effector T cells
directly kill infected/targeted cells
TFH (Follicular Helper T cell), what do they do?
- TFH – helps B cells get activated
Different roles of different effector T cells (examples)
- Some help activate B cells
- Some help activate macrophages
- Some kill infected cell directly
for T cells to carry out its function, it has to…, what is the road they take?
leave the lymph node
Efferent lymphatic vessels -> thoracic duct -> blood stream -> site of infection
once T cell is at the site of infection…it exerts…
Cell-Mediated immunity
example: Th1 cytokines promote Tc Killing & macrophage ROS killing
once T cell have exerted their function, and infection has been hopefully cleared… there is…
Downregulation of T cell activity & immunological Memory
- Some are downregulated
- Some become memory T cells
why is Signal 3 important
for T cell differentiation
waht is signal 3?
cytokines directing T-cell differentiation into distinct effector cell types
all 3 signals ( TCR signaling, costimulatory interaction & cytokine signaling) lead to
intracellular signal, leading to change in T cell:
o Activation
o Proliferation
o Survival
o Differentiation
Activated T cells will ….
o Proliferate
o Differentiate - CD4+, CD8+ T cells & Regulatory T cells
differentiation of CD4+ T helper cells
- From TH0 to (Depending on cytokine)
TH1, TH2, TFH, TH17, Others
differentiation of CD8+ T cells
cytotoxic T lymphocyte (CTL)
what is Effector T cells
resulting differentiated T cells from activated T cells
-have an effect on immune response
effector Cells classified depending on
o Transcription factors they express
o Profile of cytokines the make
o Main function in adaptive immunity
Once activated - an effector T cell doesn’t require … to act
co-stimulation (signal 2)
Different effector cells have…
different functions
5 subtypes of CD4+ T cells
o TH1
o TH2
o TH17
o TFH
o Treg
Effector T cells can impact
functionality of other immune cells
Different cytokines secreted by effector T cells
have different function
Differentiation of T helper cell subsets – regulated by
signal 3 cytokines (polarizing cytokines)
different pathogens –>
polarizing cytokine –> different functions
role of polarizing cytokines
guiding a T cell toward one of several different effector fates
APCs bind … via …, induce….
PAMPS via PRRs
Induce cytokine secretion
Different PRRs engaged - via…
different PAMPs = different cytokines produced
examples:
o Viruses stimulate IL-12 to induce TH1 subset
o Worms/helminths stimulate IL-4 to induce TH2 subset
Fate-specifying cytokines (polarizing cytokines) –> ….
diffeent T cell subset (Effector T cells)–> effector cytokines
How does signal 3 exert its effect?
- Cytokines bind their receptor & induce intracellular signaling–> STAT proteins phosphorylated (Act as TF) —-> Go inside nucleus –> bind to specific promoters on specific genes & lead to their trancription & translation
- Key gene being transcribed = alsoTF (Master Transcriptional Regulator)–> can bind response elements on promoter regions on genes coding for specific effector cytokines –>determines activity of activated, differentiated T cell subtype
example for type (1&2)
Type of responses
Master transcription regulators
Effector cytokines
o Type 1: intracellular pathogens
o Type 2: extracellular parasites
o Type 1 response: T-Bet
o Type 2 response: GATA-3
o From TH1
-IFN-y
o From TH2
IL-4, IL-5, IL-13
each naive CD4+ T cell must…
express of STAT proteins
which one gets phosphorytlated makes the difference
pathogen type/PAMP determine
Type of cytokine produced by APC leading to polarizing cytokines
Cytokine signals via
STAT proteins, depeding on waht gets phosphorylated,
Induce expression of new TF – master transcriptional regulators
Promote expression of genes encoding for specific cytokines – effector cytokines – help exert function
signal 3 result:
Result = differentiated effector T cell with distinct function
