B-VI T-cell function

Question 1

Which organ does T-cells go to mature?

Answer 1

Thymus

Question 2

What immune cells can be found in the thymus?

Answer 2

T-cells, dendritic cells, macrophages

Question 3

Describe the stages of T-cell development

Answer 3

Pro T-cell
* No TCR
* Recombination of the beta-chain
Pre-T-cell
* Has pre-TCR
* Beta chain + T-alpha chain
* Recombination of alpha-chain
* Expression of CD4 and CD8
Double positive T-cell
* Has TCR
* Expression of CD4 and CD8
Single positive immature T-cell
* Expresses either CD4 or CD8
* Has TCR

Question 4

Describe positive selection of T-cells

Answer 4

Only T-cells interacting with self-MHC molecules get survival signal.

Question 5

Describe negative selection of T-cells

Answer 5

T-cells that binds too strongly to self-MHC + self-peptide gets apoptosis signals

Question 6

At which stage of maturation does T-cells face selection?

Answer 6

Double positive

Question 7

Describe the TCR

Answer 7

Two chains (alpha and beta), with a constant and a variable region, a transmembrane region and a cytoplasmic tail.

Question 8

Can the TCR cause intracellular signaling?

Answer 8

No, not without a helping chain

Question 9

Describe the formation of the TCR

Answer 9

Gene rearrangement starts on the beta-chain, which has VDJ gene segments. D-J rearrangement and then V-DJ. The beta-chain is then tested together with a pre-T alpha chain. If it works, alpha gene rearrangement starts, has V-J segments.

Question 10

What are four receptors found on the naive T-cell?

Answer 10

L-selectin, CCR7, LFA-1, IL-2R (w/o alpha chain; intermediate affinity for IL-2)

Question 11

L-selectin

Answer 11

Recognizes and binds to carbohydrates such as GlyCAM-1 and CD34 displayed on HEV, which causes a rolling interaction between the naive T-cell and the endothelial cells

Question 12

CCR7

Answer 12

Responds to CC-ligand on endothelial surface by activating LFA-1

Question 13

LFA-1

Answer 13

Binds tightly to ICAM-1, which causes cell arrest on the vessel wall, so that it can cross the endothelium

Question 14

How does the T-cells leave the lymph nodes?

Answer 14

Via cortical sinus

Question 15

Describe important receptors on effector T-cells

Answer 15

VLA-4, E & P-selecting ligand (PSGL-1), IL-2R (with alpha chain)

Question 16

What is the main difference between the pathways of MHC Class I and II?

Answer 16

The antigen uptake is different; Class II is by endocytosis of extacellular proteins, while Class I breaks down a cytosolic proteins

Question 17

Describe important molecules on the surface of a helper-T-cell

Answer 17

CD4; stabilize the interactions with MHC Class II
LFA-1; adhesion to another cell
CD3 and zeta; have ITAM and can send intracellular signals when TCR binds
CD28 - binds to B7-1 and -2. Important for co-stimulatory signal.
IL-2R - affinity for IL-2 depending on presence of alpha chain

Question 18

What is the second signal?

Answer 18

When a B7 molecule on the APC binds to CD28. Its important for activation of T-cells, and regulation of the immune response; no second signal causes apoptosis.

Question 19

Describe important molecules on the surface of a cytotoxic-T-cell

Answer 19

CD8; stabilize the interactions with MHC Class I
LFA-1; adhesion to another cell
CD3 and zeta; have ITAM and can send intracellular signals when TCR binds
CD28 - binds to B7-1 and -2. Important for co-stimulatory signal.
IL-2R - affinity for IL-2 depending on presence of alpha chain

Question 20

CTLA-4

Answer 20

Competes with CD28 to bind to B7 - acts a dampen on the immune response as fewer cells can get the second signal

Question 21

CD40 & CD40L

Answer 21

Activated CD4+ T-cells express the CD40L, which interacts with CD40 in antigen-presenting cells. Interaction between CD40L and CD40 activates the antigen presenting cells.

Question 22

Macrophages and IFN-γ

Answer 22

Macrophages have an IFN-gamma receptor, and binding cause them to fully kill the microbe they have eaten

Question 23

Th1

Answer 23

Caused by: IFN-γ, IL-12
Effect: Macrophage activation, IgG production, CD8+ T-cell activation,
Against: Intracellular bacteria
Effector cytokines: IFN-γ, IL-2

Question 24

Th2

Answer 24

Caused by: IL-4, IL-2
Effect: Mast cell degranulation, eosinophil activation, IgE and IgG4 production
Against: Helmith parasites
Effector cytokines: IL-4, IL-5, IL-13

Question 25

Th17

Answer 25

Caused by: IL-6, IL-23 Effect: Inflammation, Neutrophilic cell stimulation. Mostly found in intestinal tract Against: Extracellular bacteria, fungi Effector cytokines: IL-17, IL-22

Question 26

Tfh

Answer 26

Caused by: IL-6 possibly Effect: B-cell activation, affinity maturation, isotype switching Effector cytokines: IL-21

Question 27

Treg

Answer 27

Caused by: IL-2 Effect: Dampen the immune response by competition with CD28 for B7, reduce amount of circulating IL-2 Effector cytokines: TGF-beta, IL-10

Question 28

IFN-γ in T-cell function

Answer 28

Differentiates T-cells into Th1 cells. Also expressed by Th1 cells, where they are a signal to macrophages to kill intracellular bacteria

Question 29

IL-12 in T-cell function

Answer 29

Differentiates T-cells into Th1 cells by amplifying IFN-γ production.

Question 30

IL-4 in T-cell function

Answer 30

Differentiates T-cells into Th2 cells. Also expressed by Th2 cells, where they signal the bone marrow to produce more eosinophils, basophils and mast cells. Inhibits Th1. Causes isotype switching to IgE or IgG1/IgG4 (mouse/human)

Question 31

IL-6 in T-cell function

Answer 31

Differentiates T-cells into Th17 cells and possibly Tfh cells.

Question 32

IL-23 in T-cell function

Answer 32

Differentiates T-cells into Th17 cells

Question 33

How is the helper T-cells differenced into the different subsets?

Answer 33

Antigen presenting cells release cytokines

Question 34

IL-5 in T-cell function

Answer 34

Expressed by Th2 cells, where they signal the bone marrow to produce more eosinophils, basophils and mast cells.

Question 35

IL-13 in T-cell function

Answer 35

Expressed by Th2 cells, where they signal goblet cells to produce mucus

Question 36

IL-17 in T-cell function

Answer 36

Expressed by Th17 cells, where they signal other cells to release chemokines

Question 37

IL-22 in T-cell function

Answer 37

Expressed by Th17 cells, where they signal epithelial cells to release antimicrobial peptides such as defensins

Question 38

IL-21 in T-cell function

Answer 38

Expressed by Tfh cells, works as a signal to B-cells for isotype switching, affinity maturation

Question 39

TGF-β in T-cell function

Answer 39

Expressed by Treg cells, inhibits B-cell activation and T-cell activation

Question 40

IL-10 in T-cell function

Answer 40

Expressed by Treg cells, inhibits T-cell activation

Question 41

What does the granules in CD8+ T-cells contain?

Answer 41

Perforin, granzyme, serglycin

Question 42

CTL-mediated cell lysis

Answer 42

Perforin delivers granzymes into the infected cell, where granzyme cleaves Bid activates pro-caspase-3

Question 43

How could a CTL cell get activated?

Answer 43

1) APC has MHC Class I with antigen + B7 2) If a CTL is bound to an APC, a Th could also bind to the APC and produce cytokines which activates the CTL 3) Th cells activate APCs to express B7, which gives them the ability to stimulate CTL

Question 44

NK T-cells

Answer 44

Have neither CD8 or CD4. CD1 instead.

Question 45

γ:δ T-cells

Answer 45

Less common; can be double positive, single positive or single negative. Can be both helper and cytotoxic. Is at the epithelial barrier as an early defense.