T Cell Activation After Thymus Flashcards
Naive T cells from thymus (single positive) recirculate where
Secondary lymphoid tissues LN and spleen
How do naive T cells enter lymph node
HEV
High endothelial venues
What does contact with ag cause for naive T cells
Proliferation and differentiation into effector T cells (cytotoxic CD8 or Th cells CD4)
What cells are in T cell area of LN for T cell activation and differentiation
APC with mhcs like macrophages, dendrites ,
What happens to T cells which don’t get activated by ag on apc
Leave the LN via the cortical suinuses for recirculation. They are recycled or die
What happens to activated ag T cells
They get blocked from leaving the LN until proliferated via clonal expansion and differentiation into effector cells
What helps localise T cells when they become effectors
Chemokines because they have chemokine receptors on surface
So leave the LN and go to target sites
What are CAMs
Cell adhesion molecules which help T cells attach to other cells/tissues
Give 3 things cams needed for T cell attachment
To the HEV to go to lymph node
To APC helping to stay attached for ag signal
To target cells
Give an example of a CAM which helps T cell interaction with APC
Icam 1 present on APC with MHC II on surface
Initially, for activation T cells interact with apc via low affinity ICAM1. What does this bind to on T cells
LFA 1
What does cd3 signalling when ag on MHC binds T cell do
Changes LFA shape so it has HIGH affinity for ICAM on apc. Causes T cell to stay longer
As well as the icam lfa intersction. What helps T cells attachment/interaction with MHC antigen
CD4 which attaches to the tcr in MHC II signalling
T cells need 3 signals for activation whats the first one
MHC signal via cd3 zeta phosphorylation of ITAMs which then causes change in LFA affinity for icam
What do apc have on their surface for signal 2
Co stimulatory molecules like B7 1 and 2
What do co stimulatory molecules on APC bind to on T cells for signal 2
B7 binds to cd28 on naive T cells
In signal 3, what do apc release which allows T cell activation (expansion and differentiation)
Cytokines determine type of effector cell
When T cells get activated. What do they upregulate as a negative feedback system
ICOS (binds to ICOSL on apc)
And
CTLA 4
How does CTLA4 stop T cell expansion in Negative feedback
CTLA 4 bind to B7 co stimulatory molecules on apc blocking cd28 and signal 2 of T cell activation.
Which autoimmune disease is caused by mutation in ctla4
Diabetes. T cell can’t stop the signal 2 from B7 binding to cd28 = over reactive
What does apc activation occur so that they can go on to stimulate T cell expansion
PRR like TLR
Detect pathogens by Pamps like lps
What is prr detection of pamps called
Danger signal
What do apc upregulste after danger signal to ensure signal 2 of T cell activation
B7 co stimulatory factor and MHC
What do cytokines released by apc in signal 3 do
Turn on transcription factors which cause T cells to further release them for auto proliferation
Which cytokines released by apc in signal 3 turn on a TF for th1 cells
Il 12 and ifn y
Activate th1
Th1 then produce il 2 and ifn y for own proliferation and other purposes
What cytokine is released by apc which is the released by the activated th2 cell
Il4 activated th2 differentiation then th2 further releases il4 due to a TF turn on
Which cytokine released by apc causes stimulation of tfh cells
Il 6
Do cytokines in signal 3 only determine CD4 cells eg th1,tfh and th2
Yes as CD8 don’t have others except cytotoxic T cells
What are the 3 main apc with MHC II for CD4 activation
Macrophages dendrites and B cells
How do dendritic cells uptake exogenous ag
Macropinocytosis and phagocytosis
Which type of dendritic cell is the most potent apc for T cell activation
Myeloid conventional dendritic cell (Dc 2 and 3)
6 types though
Where do immature myeloid conventional dc wait for ag uptake
Skin/epithelial tissues
When myeloid conventional dc get a danger signal what do they do
Start to express B7 co stimulatory molecules for T cell signal 2 and they move to lymph node to present ag on MHC II
Which dendritic cells are for viral infections
Plasmacytoid dendritic cells
When do myeloid conventional dc 2 and 3 stop up taking ag
When the danger signal received, they’ve uptaken a ag and moved to lymph node with a B7 on surface
Can dendrites be both mhc
Yes mhc 1 and 2
Do myeloid conventional dc produce cam like icam 1 for signal 1 of T cell activation
Yes
What directs MC dendritic cells to lymph node
Chemokines attaching to their chemokine receptors
What is cross presentation via DC 1
Where they present exogenous ag on class I instead of class 2 mhc
This allows CD8 activation which can now kill infected cells which aren’t presenting their ag on MHC II and have no co stimulatory molecules for T cell activation
How do macrophages internalise ag
Same as dc
Macropinocytosis and phagocytosis
(After a danger signal received by pamps and prr)
After internalisation of ag by macrophages what happens
They upregulste B7 and move to LN for T cell activation
They also release cytokines like Ifn y which help CD4 differentiate into th1 for example
They do this for their OWN benefit as T cell release of cytokines activates macrophages
Do B cells have good or bad phagocytosis
Bad
How are SPECIFIC ag internalised into B cells for bcr presentation
receptor mediated endocytosis
What upregulates B7 in B cells for co stimulation signal 2 of t cells
Bcr binding of specific antigens
Why do B cells activate T cells via this
Because they need T cells to in turn activate them
What has it been shown recently bcr can do
Extract ag from other cells to increase their own activation as they put it on their class II for t activation
Which cytokine is a potent T cell growth factor
Il 2 (induced T cell cell cycle)
How do IL 2 receptors on naive and activated T cells differ
Naive the receptors for il 2 are low affinity. Naive can’t proliferate fast
When T cells become activated fully via the 3 signals they gain a high affinity il 2 receptor which binds il 2 causing cells like th1 to proliferate fast
Which drugs can target il 2
Immunosuppressive drugs to stop T cell proliferation
Effector T cells enter tissues how
Leaky endothelium
Do cams change in effector T cells
Yes. They now need to stick to target tissues
What is no longer needed when effector T cells become effectors
B7 co stimulatory molecules on apc
What do CD8 kill
Infected cells presenting peptide on MHC I and that have co stimulatory molecules
Or
Infected cell once been activated by cross presenting dc1 via MHC I
(For infected cells without costimulatory molecule)
What do CD8 cells need for activation to kill
Many co stimulation molecules on apc or help from CD4 cells
What is zap
Zeta associated protein which is a tyrosine kinase causing signalling through cd3 in signal 1
