T cells: cytokine patterns, cross regulation, receptors, homing Flashcards
Describe polarizing cytokines
Polarizing cytokines are secreted by dcs and neighbouring innate and adaptive immune cells
Tells T cell which to become
What do polarizing cytokines do
Activates diff stat proteins within each cell
When Th1 response
When infections by viruses and intracellualr pathogens
When Th2 response
When parasites and other extra cellular pathogens - also allergy
When Th17 response
Infections by extracellular bacteria and fungi - also in autoimmunity
When Tfh response
Activating B cells in lymph node
Are all cd4+ T cell subsets always active
Noooo
Cell mediated response is dominated by one of the T cell subsets - will have others but one dominates
What is activated when viruses and intracellular pathogens
Ctl
Th1
What is activated when helminths and extra cellular pathogens
Th2
What is activated when extra cellular bacteria and fungi
Th17
What types of cells does th1 target
Macrophages
What types of cells does th2 target
Eosinophil, mast cell, basophil
What types of cells does th17 target
Neutrophils
Cytotoxic T cells - effector molecules and cytokines
Perforin
Granzyme b
Fas ligand
Infy - type 2 ifn
Th1 cells - effector molecules and cytokines
Ifny
Cd40 ligand
Fas ligand
Th17 cells - effector molecules and cytokines
Il-17
Il-22
Cd40 ligand
Treg cells - effector molecules and cytokines
Il-10
Tgf-beta
Describe cross regulation - gen
Combo of diff T cells but one more dominant
Effector cytokines help reinforce the predominant subtype they are part of
Name specifically what happens when cross regulation
2 patterns cross regulate
Th2 secretes I’ll-4 = inhibits th1 differentiation
Th1 secrets ifn-y = Inhibits th2 proliferation
Il-4 or ifn-y inhibits th17
MAKES SURE ONE DOMINATES
Describe th1/th2 cross regulation
MASTER TRAscnriptional regulators commit T cells to one subset or the other
How does th1 regulated th2
Il-12—> stat4 —> t bet
Suppresses gata3
Increases ifn-y (effector cytokine)
But suppress il-4, Il-5=th2 effector cytokines
= promotes th1
(Tbet suppresses th2 pathway gene expression)
How does th2 regulate th1
Il-4 —> stat6 —>gata3
Inhibit t bet, and ifn-y
But promote il-4, Il-5 = promotes th2
(Gata3 suppresses th1 pathway gene expression)
Describe decision between th17/treg - gen
Tgf-b is a key cytokine for differentiation of both subsets
Describe decision between th17/treg - what helps decide
Il-6 = switch = induces th17 subset differentiation instead
Depends on environment
Balance between 2 is ideal, depends on what is needed - beneficial outcomes of each
What favours Treg instead of th17
Normal state favours development of itreg population to keep inflammation down
What favours th17 over treg
Infection = lead to Il-6 production = would stimulate more antibacterial th17 differentiation
Where do these cells exert their effector function
Polarizing cytokines impact differentiation of T cells - signal 3, effector cytokines are produced by differentiated T cells —>
th1, th2, th17 = Leave lymph node and migrate to site infection, To repsond to infection
Tfh = stay in lymph node and activate B cells
What are cell surface molecules
Different cell surface molecules are expressed by naive vs effector T cells since they travel to different locations in body
What do effect T cells express
Effector T cells express molecules that target them to specific tissues - like skin vs gut = depends on site of infection
Diff adhesion molecules
What determines where effector T cells travel
Partly determined by which lymph node they get activated - if activated in lymph node that drain skin = effector T cells will upreg homing molecules that send them to the skin
Depends on which lymph node
Effector cytokines patterns—>
Tied to function
Describe decision point
Addition of diff cytokines can switch induction of one T cell subset over another like treg and th17
Summarize homing
Tissue specific molecules target effector T cells to diff tissues
Naive vs effector T cells have some Differenet adhesion molecules
Th1 signal 3 polarizing cytokine
Ifn-y and Il-12
Th1 effector cytokine
Ifn-y
Th1 master transcriptional regulator
T bet
What does th1 do
Macrophages activation - that has persistent infection
Activation and differentiation of naive cytotoxic T lymphocyte precursors into effector ctl - through cd40L binding - licence dcs
What does th1 respond to
Intracellular pathogens - like intracellular bacteria - m tuberculosis and salmonella
Intracellular parasites - leishmania and toxoplasma and viruses
Th1 tfs activated
Stat 1 and stat 4 proteins get activated
= phosphorylated
What does th1 secrete
Infy at point of interaction
Th1 functions - gen = secrets, targets, aids
Targets macrophages - th1 cell tcr recognizes pmhc-2 on macrophage surface
To aid in killing of microorganisms that persist in macrophages vesicles
Th2 cells - effector molecules and cytokines
Il-4
Il-5
Il-13
Cd40 ligand
