T-cell development (complete) Flashcards
where does very early thymocyte development occur
in the bone marrow
where does final thymocyte development occur
in the thymus
what are the steps of thymocyte development in the thymus
- Double negative
- Double positive
- Positive/Negative selection to become single positive
- final screening to remove autoreactive cells
- release into blood stream
When cells arrive at the thymus they aren’t technically T-cells until what
a receptor on the cells known as Notch commits them to the T cell lineage
What is the transcription factor that become active when a T-cell is activated by Notch
GATA-3
What are the T-cell analogs for the B-cell heavy chain and light chain
Alpha chain = light chain
Beta chain = heavy chain
Most T-cells have alpha-Beta TCR’s, what is the other type of TCR that some T-cells have
gamma-delta
does allelic exclusion occur in TCR expression, like it does in the Ig expression of B-cells
yes, only one of each allele is used in the TCR
The first step of T-cell development is the Double Negative stage, what happens in the development of the TCR in that stage?
they undergo Beta selection (creating the Beta chain). then it binds to pre-Talpha chain (just holds the place for the future alpha chain (now it is a double positive thymocyte)
what defines a double negative Thymocyte
it has no CD4 or CD8
what defines a double positive thymocyte
it has both CD4 and CD8
once a thymocyte has gone through Beta selection and has a pre-T alpha chain, what happens next
they are at the Double positive stage of development, and a functional TCR alpha chain replaces the pre-TCR alpha
most thymocytes are in the double positive stage of development. They undergo positive and negative selection. what is positive selection
positive selection is testing to see how tightly a T-cell binds self MHC molecules.
they fail if they don’t bind at all (they are supposed to loosely bind)
what is negative selection (central tolerance) of T-cells
testing to see how tightly you bind self MHC. to ensure self tolerance.
they fail if they bind too tightly (they are killed)
what happens to T-cells that don’t bind self MHC, and what happens to T-cells that bind self MHC too tightly
the cells that don’t bind at all die of neglect (anergy?)
the cells that bind too tightly are killed (apoptosis?)
what does the TCR also bind to when it binds to an MHC class 2 in the transition from a double positive cell to a single positive cell
when it binds to the MHC class 2 it also binds with the CD4 molecule, making it a CD4+ T-cell (Helper)
what does the TCR bind to when it binds to an MHC class 1 in the transition from a double positive cell to a single positive cell
when it binds to the MHC class 1 it also binds to the CD8 molecule, making it a CD8+ cell (cytotoxic)
what do you call a thymocyte that have just exited the thymus
Recent thymic emigrants (RTEs)
what are the main differences between the two types of cell death, Necrosis and apoptosis
apoptosis is planned cell death, and doesn’t induce inflammation
Necrosis isn’t planned, and does induce inflammation
what do you always find with apoptosis, regardless of the stimuli that causes it
caspases
what are the two types of caspases
initiator caspases and effector caspases
what do initiator caspases do
they are activated by the death stimulus and activate the effector caspases
what do effector caspases do
- cleave critical targets necessary for cell survival
2. activate other enzymes that dismantle the cell
what is required for T-cells to become activated
- antigen presentation
- a costimulatory ligands
They need two signals, and the antigen is the first signal
what happens once a T-cell becomes active
they differentiate into their effector forms (CD8+ = cytotoxic cell, CD4+ = other cells)
what makes a cSMAC (central supramolecular activating complex)
TCR/MHC-peptide complexes and coreceptors
what makes a pSMAC (peripheral supramolecular activating complex)
adhesion molecules/bound ligands
after the T-cell has had its first signal (antigen) and its second signal (costimulatory ligand) does it receive more signals? If yes, what? and what does it cause?
Yes
They are cytokines (IL-2, IL-12)
they direct T-cells to differentiate into distinct effector cell types
are all costimulatory signals activating (for T-cells)
no, there are some that are activating (positive), there are some that are negative
what are examples of positive costimulatory signals
CD28, and ICOS
what are examples of negative costimulatory signals
CTLA-4, PD-1, and BTLA
where is CD28 found, and what does it bind to
it is found on the majority of T-cells, and it binds to B7-1 and B7-2 on APCs
Where is ICOS found, and what does it bind to
it is found on memory and effector T-cells, and it binds the ICOS-ligand on APCs
Where is CTLA-4 found, and what does it bind to
it is found on the T-cells and binds B7-1 and B7-2
which has a higher affinity for the B7-1 and B7-2 on APCs, CD28 and CTLA-4
CTLA-4 (this shuts down the activation)
what does PD-1 (the negative costimulator) stand for
program death
what does BTLA ( the negative costimulator) stand for
B and T lymphocytes attenuator
what happens to T-cells if they don’t receive their second activating signal (the costimulator)
it undergoes clonal anergy
what is the benefit of T-cells becoming anergic if they don’t revceive a costimulator
this can be good if the T-cell wasn’t correctly screened against a self antigen in the periphery during development. so even if it binds the antigen, it wont work without a costimulator
what is the third signal that helps in T-cell activation
cytokines
what is the autocrine type of cytokine that helps in T-cell activation
IL-2 (autocrine means that it produces the cytokine and produces the receptor for it)
does the binding of IL-2 to activating T-cells cause a strong response
yes, it causes a strong proliferation signal
do Dendritic cells, macrophages, and B-cells have costimulatory characteristics
yes
What are superantigens
a special class of T-cell activators. they are viral/bacterial proteins that bind to VB regions of TCRs and the alpha chain of class 2 MHC molecules
what affect do superantigens have on T-cell activation
they essentially cause the T-cells to not need costimulation, and cause dramatic cytokine production by a lot of inappropriately activated T-cells
(cause T-cells to become overactive)
what are the two types of Superantigens
exogenous (secreted by bacteria)
endogenous (viral gene produced cell membrane proteins)
after a t-cell has received type 1 and 2 signals and become active it produces cytokines and their receptors, which causes activation and a robust proliferation of ___
memory and effector clonal cell populations
What are the different types of helper T-cells
TH1 TH2 Th17 TH REG TFH
What cytokine causes the proliferation of TH1 helper cells, and how does that happen?
IL-12
PAMPS are bound by PRRs on APCs. this causes them to secrete IL-12. and IL-12 causes proliferation of TH1 Helper cells
What cytokine causes the proliferation of TH2 helper cells, and how does that happen?
IL-4
just like IL-12 (PRRs bind PAMPS and (On APCs and secrete IL-4) which causes the prouction of TH2 helper cells
what microbe causes the production of TH1 helper cells via IL-12
viruses
what microbe causes the production of TH2 helper cells via IL-4
worms
what kind of Helper cells do worms cause to be proliferated
TH2 helper cells (Via IL-4)
what kind of helper cells do viruses cause to be proliferated
TH1 helper cells (Via IL-12)
What do TREG cells do
Regulate and suppress immune and inflammatory responses
what do TH17 cells do
cause inflammation
what doTH2 cells do
Allergic and anti-helminth responses
what do TFH cells do
B cell help in germinal centers
what do TH1 cells do
Cell mediated immunity, macrophage activation, inflammation
Leprosy can affect the differentiation of T-cells. Which type of leprosy stimulates which type of T cell
Tuberculoid leprosy stimulates a TH1 response
Lepromatous leprosy stimulates a TH2 response
