T cellls: Intro/overview/signal 3 Flashcards
Describe big picture image
Signal 3 happens in lymph node
T and B cell activation
Cell mediate immunity = back to site of infection
Regulation = downreg and memory
Activation of cd4 and cd8 T cells
Signal 1 - pmhc:tcr
Signal 2 - b7:cd28
Signal 3 - cytokines
What do effector functions depend on
Subset T cells - cd8 or cd4
Describe cd4 effector functions
Activation of macrophages, B cells and other cels
Describe cd8 effector functions
Killing of infected target cells, macrophage activation
Describe activation of B cells
Via Tfh - follicular helper cells
Signal 1 - p:bcr
Signal 2- th2 cytokines
Linked recognition
Name some diff roles of diff effector T cells
Some help activate B cells
Some help activate macrophages - especially ones with infection persisting in macrophage
Some kill infected cells directly
What do effector T cells do
Leave lymph node
Efferent lymphatic vessels —>thoracic duct —> blood stream
Describe cell mediated immunity
Th1 cytokines promote tc killing and macrophage ros killing
What is signal 3
Differentiation
Cytokines directing T cell differentiation into distinct effector cell types
What do the 3 signals result in
Intracellular signalling Leading to change
Activation, proliferation, survival, differentiation
What is lymphocyte activation
= proliferation + differentiation
Describe what activated T cells do
Proliferate in response to il2
Differentiate
What can T cells differentiate into
Cd4+ t helper cells - th0 to th1, th2, tfh or th17 or others
Cd8+ T cells = cytotoxic t lymphocyte - ctl
Regulatory T cells
Describe regulatory T cells
Some th0 cells can differentiate to t reg but also some naive T cells are already t reg
What is naive T cell
Th0
What do effector T cells result from
Must have gotten all 3 signals
Effector T cells are resulting from differentiated T cells from activated T cells
How can effector T cells be classified
Tf they express
Profile of cytokines they make
Main function in adaptive immunity
What do naive cd8+ T cells differentiate into
Cytotoxic t lymphocytes
Only one option
Describe effector T cells once activated
Does not require co stimulation to act - only interacts with tcr bc need to be specific.
Recognition —> proliferation/differentiation —> effector function
HAS TO ONLY RECOGNIZE p:Mhc1 to see if specific to this cell
What determines the fate of T cells
Cytokines
Name 5 subsets of cd4 T cells
Th1
Th2
Th17
Tfh
Treg
Describe what effector T cells secrete
Diff cytokines secreted by effector cytokines have diff functions
Effector T cells = impact functionality of other immune cells
Clear diff microorganisms
Cd4 T cells help clear infections in many ways
What does pathogen do
Depends on pathogen
Pathogen —> polarizing cytokine —> diff effector functions
What regulates differentiation of t helper cells
Regulated by signal 3 cytokines
= called polarizing cytokines - responsible for guiding T cell towards one of several diff effector fates
Describe apcs binding to pampas
Apcs bind pamps via prrs = induce cytokine secretion
Diff prrs engaged via diff pamps = diff cytokines produced
What induced th 2 subset
Worms/helminth stimulate il-4 polarizing cytokines to induce th2 subset
What induces th1 subset
Viruses stimulate il-12 polarizing cytokine to induce th1 subset
Name steps to make effector T cell
Pamps from pathogens bind prrs —> polarizing cytokines —> stats —> master gene regulators —> effector cytokines
Describe polarizing cytokines
Fate specifying cytokines
Impact differentiation of T cells - signal 3
What are produced by differentiate T cells
Effector cytokines
How does signal 3 exert its effect - cytokines
Cytokines bind their receptor and induce intraclelualr signalling
Occurs through stat proteins —> once phosphorylated = act as Tfs - go inside nucleus and bind promoters
How does signal 3 exert its effect - genes
Key gene transcribed is another tf = master transcription regulator
= go into nucleus and bind promoter regions fo genes that encode specific effector cytokines that subset T cells will produce
How does signal 3 exert its effect - new tf
New tf can then bind response element on promoter regions of genes coding for specific effector cytokines—> determine activity of activated differentiated T cell subset
Signal 3 summary
Signal 3= polarizing cytokines
Tf = phosphorylation of stats, diff stat proteins activated,
Then master transcriptional regulator = depends on type of stat phosphorylated
Dictates effector cytokines
Describe type 1 response gen
Virus
Il12 = polarizing cytokine
Stat4 and stat1 = phosphorylated
T bet = master transcriptional regulator - after express = then considered effector cell —> th1 —>secreted ifn-gamma effector cytokine
Describe type 2 response gen
worm
Il4= polarizing cytokine (from dc and neighbouring cells)
Stat6 = phosphorylated
Gata3 = master transcriptional regulator - after express = then considered effector cell —> th2 —>secretes il4,5,13 effector cytokines
What happens after clearance of infection
Downreg T cell activity and immunological memory
Name the 3 main steps of T cell differentiation
Tcr signalling
Costimulattory interaction
Cytokines signalling = autocrine il2 and paracrine il12
Polarizing cytokine secreted by what
Apc - dendritic cell
By neighbouring innate and adaptive immune cells
