T-cell development (complete)

Question 1

where does very early thymocyte development occur

Answer 1

in the bone marrow

Question 2

where does final thymocyte development occur

Answer 2

in the thymus

Question 3

what are the steps of thymocyte development in the thymus

Answer 3

1. Double negative
2. Double positive
3. Positive/Negative selection to become single positive
4. final screening to remove autoreactive cells
5. release into blood stream

Question 4

When cells arrive at the thymus they aren’t technically T-cells until what

Answer 4

a receptor on the cells known as Notch commits them to the T cell lineage

Question 5

What is the transcription factor that become active when a T-cell is activated by Notch

Answer 5

GATA-3

Question 6

What are the T-cell analogs for the B-cell heavy chain and light chain

Answer 6

Alpha chain = light chain

Beta chain = heavy chain

Question 7

Most T-cells have alpha-Beta TCR’s, what is the other type of TCR that some T-cells have

Answer 7

gamma-delta

Question 8

does allelic exclusion occur in TCR expression, like it does in the Ig expression of B-cells

Answer 8

yes, only one of each allele is used in the TCR

Question 9

The first step of T-cell development is the Double Negative stage, what happens in the development of the TCR in that stage?

Answer 9

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)

Question 10

what defines a double negative Thymocyte

Answer 10

it has no CD4 or CD8

Question 11

what defines a double positive thymocyte

Answer 11

it has both CD4 and CD8

Question 12

once a thymocyte has gone through Beta selection and has a pre-T alpha chain, what happens next

Answer 12

they are at the Double positive stage of development, and a functional TCR alpha chain replaces the pre-TCR alpha

Question 13

most thymocytes are in the double positive stage of development. They undergo positive and negative selection. what is positive selection

Answer 13

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)

Question 14

what is negative selection (central tolerance) of T-cells

Answer 14

testing to see how tightly you bind self MHC. to ensure self tolerance.
they fail if they bind too tightly (they are killed)

Question 15

what happens to T-cells that don’t bind self MHC, and what happens to T-cells that bind self MHC too tightly

Answer 15

the cells that don’t bind at all die of neglect (anergy?)

the cells that bind too tightly are killed (apoptosis?)

Question 16

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

Answer 16

when it binds to the MHC class 2 it also binds with the CD4 molecule, making it a CD4+ T-cell (Helper)

Question 17

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

Answer 17

when it binds to the MHC class 1 it also binds to the CD8 molecule, making it a CD8+ cell (cytotoxic)

Question 18

what do you call a thymocyte that have just exited the thymus

Answer 18

Recent thymic emigrants (RTEs)

Question 19

what are the main differences between the two types of cell death, Necrosis and apoptosis

Answer 19

apoptosis is planned cell death, and doesn’t induce inflammation
Necrosis isn’t planned, and does induce inflammation

Question 20

what do you always find with apoptosis, regardless of the stimuli that causes it

Answer 20

caspases

Question 21

what are the two types of caspases

Answer 21

initiator caspases and effector caspases

Question 22

what do initiator caspases do

Answer 22

they are activated by the death stimulus and activate the effector caspases

Question 23

what do effector caspases do

Answer 23

1. cleave critical targets necessary for cell survival

2. activate other enzymes that dismantle the cell

Question 24

what is required for T-cells to become activated

Answer 24

1. antigen presentation
2. a costimulatory ligands
   They need two signals, and the antigen is the first signal

Question 25

what happens once a T-cell becomes active

Answer 25

they differentiate into their effector forms (CD8+ = cytotoxic cell, CD4+ = other cells)

Question 26

what makes a cSMAC (central supramolecular activating complex)

Answer 26

TCR/MHC-peptide complexes and coreceptors

Question 27

what makes a pSMAC (peripheral supramolecular activating complex)

Answer 27

adhesion molecules/bound ligands

Question 28

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?

Answer 28

Yes They are cytokines (IL-2, IL-12) they direct T-cells to differentiate into distinct effector cell types

Question 29

are all costimulatory signals activating (for T-cells)

Answer 29

no, there are some that are activating (positive), there are some that are negative

Question 30

what are examples of positive costimulatory signals

Answer 30

CD28, and ICOS

Question 31

what are examples of negative costimulatory signals

Answer 31

CTLA-4, PD-1, and BTLA

Question 32

where is CD28 found, and what does it bind to

Answer 32

it is found on the majority of T-cells, and it binds to B7-1 and B7-2 on APCs

Question 33

Where is ICOS found, and what does it bind to

Answer 33

it is found on memory and effector T-cells, and it binds the ICOS-ligand on APCs

Question 34

Where is CTLA-4 found, and what does it bind to

Answer 34

it is found on the T-cells and binds B7-1 and B7-2

Question 35

which has a higher affinity for the B7-1 and B7-2 on APCs, CD28 and CTLA-4

Answer 35

CTLA-4 (this shuts down the activation)

Question 36

what does PD-1 (the negative costimulator) stand for

Answer 36

program death

Question 37

what does BTLA ( the negative costimulator) stand for

Answer 37

B and T lymphocytes attenuator

Question 38

what happens to T-cells if they don't receive their second activating signal (the costimulator)

Answer 38

it undergoes clonal anergy

Question 39

what is the benefit of T-cells becoming anergic if they don't revceive a costimulator

Answer 39

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

Question 40

what is the third signal that helps in T-cell activation

Answer 40

cytokines

Question 41

what is the autocrine type of cytokine that helps in T-cell activation

Answer 41

IL-2 (autocrine means that it produces the cytokine and produces the receptor for it)

Question 42

does the binding of IL-2 to activating T-cells cause a strong response

Answer 42

yes, it causes a strong proliferation signal

Question 43

do Dendritic cells, macrophages, and B-cells have costimulatory characteristics

Answer 43

yes

Question 44

What are superantigens

Answer 44

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

Question 45

what affect do superantigens have on T-cell activation

Answer 45

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)

Question 46

what are the two types of Superantigens

Answer 46

exogenous (secreted by bacteria) | endogenous (viral gene produced cell membrane proteins)

Question 47

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 ___

Answer 47

memory and effector clonal cell populations

Question 48

What are the different types of helper T-cells

Answer 48

``` TH1 TH2 Th17 TH REG TFH ```

Question 49

What cytokine causes the proliferation of TH1 helper cells, and how does that happen?

Answer 49

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

Question 50

What cytokine causes the proliferation of TH2 helper cells, and how does that happen?

Answer 50

IL-4 | just like IL-12 (PRRs bind PAMPS and (On APCs and secrete IL-4) which causes the prouction of TH2 helper cells

Question 51

what microbe causes the production of TH1 helper cells via IL-12

Answer 51

viruses

Question 52

what microbe causes the production of TH2 helper cells via IL-4

Answer 52

worms

Question 53

what kind of Helper cells do worms cause to be proliferated

Answer 53

TH2 helper cells (Via IL-4)

Question 54

what kind of helper cells do viruses cause to be proliferated

Answer 54

TH1 helper cells (Via IL-12)

Question 55

What do TREG cells do

Answer 55

Regulate and suppress immune and inflammatory responses

Question 56

what do TH17 cells do

Answer 56

cause inflammation

Question 57

what doTH2 cells do

Answer 57

Allergic and anti-helminth responses

Question 58

what do TFH cells do

Answer 58

B cell help in germinal centers

Question 59

what do TH1 cells do

Answer 59

Cell mediated immunity, macrophage activation, inflammation

Question 60

Leprosy can affect the differentiation of T-cells. Which type of leprosy stimulates which type of T cell

Answer 60

Tuberculoid leprosy stimulates a TH1 response | Lepromatous leprosy stimulates a TH2 response