B-VI T-cell function Flashcards
Which organ does T-cells go to mature?
Thymus
What immune cells can be found in the thymus?
T-cells, dendritic cells, macrophages
Describe the stages of T-cell development
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
Describe positive selection of T-cells
Only T-cells interacting with self-MHC molecules get survival signal.
Describe negative selection of T-cells
T-cells that binds too strongly to self-MHC + self-peptide gets apoptosis signals
At which stage of maturation does T-cells face selection?
Double positive
Describe the TCR
Two chains (alpha and beta), with a constant and a variable region, a transmembrane region and a cytoplasmic tail.
Can the TCR cause intracellular signaling?
No, not without a helping chain
Describe the formation of the TCR
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.
What are four receptors found on the naive T-cell?
L-selectin, CCR7, LFA-1, IL-2R (w/o alpha chain; intermediate affinity for IL-2)
L-selectin
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
CCR7
Responds to CC-ligand on endothelial surface by activating LFA-1
LFA-1
Binds tightly to ICAM-1, which causes cell arrest on the vessel wall, so that it can cross the endothelium
How does the T-cells leave the lymph nodes?
Via cortical sinus
Describe important receptors on effector T-cells
VLA-4, E & P-selecting ligand (PSGL-1), IL-2R (with alpha chain)
What is the main difference between the pathways of MHC Class I and II?
The antigen uptake is different; Class II is by endocytosis of extacellular proteins, while Class I breaks down a cytosolic proteins
Describe important molecules on the surface of a helper-T-cell
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
What is the second signal?
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.
Describe important molecules on the surface of a cytotoxic-T-cell
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
CTLA-4
Competes with CD28 to bind to B7 - acts a dampen on the immune response as fewer cells can get the second signal
CD40 & CD40L
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.
Macrophages and IFN-γ
Macrophages have an IFN-gamma receptor, and binding cause them to fully kill the microbe they have eaten
Th1
Caused by: IFN-γ, IL-12
Effect: Macrophage activation, IgG production, CD8+ T-cell activation,
Against: Intracellular bacteria
Effector cytokines: IFN-γ, IL-2
Th2
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
Th17
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
Tfh
Caused by: IL-6 possibly
Effect: B-cell activation, affinity maturation, isotype switching
Effector cytokines: IL-21
Treg
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
IFN-γ in T-cell function
Differentiates T-cells into Th1 cells. Also expressed by Th1 cells, where they are a signal to macrophages to kill intracellular bacteria
IL-12 in T-cell function
Differentiates T-cells into Th1 cells by amplifying IFN-γ production.
IL-4 in T-cell function
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)
IL-6 in T-cell function
Differentiates T-cells into Th17 cells and possibly Tfh cells.
IL-23 in T-cell function
Differentiates T-cells into Th17 cells
How is the helper T-cells differenced into the different subsets?
Antigen presenting cells release cytokines
IL-5 in T-cell function
Expressed by Th2 cells, where they signal the bone marrow to produce more eosinophils, basophils and mast cells.
IL-13 in T-cell function
Expressed by Th2 cells, where they signal goblet cells to produce mucus
IL-17 in T-cell function
Expressed by Th17 cells, where they signal other cells to release chemokines
IL-22 in T-cell function
Expressed by Th17 cells, where they signal epithelial cells to release antimicrobial peptides such as defensins
IL-21 in T-cell function
Expressed by Tfh cells, works as a signal to B-cells for isotype switching, affinity maturation
TGF-β in T-cell function
Expressed by Treg cells, inhibits B-cell activation and T-cell activation
IL-10 in T-cell function
Expressed by Treg cells, inhibits T-cell activation
What does the granules in CD8+ T-cells contain?
Perforin, granzyme, serglycin
CTL-mediated cell lysis
Perforin delivers granzymes into the infected cell, where granzyme cleaves Bid activates pro-caspase-3
How could a CTL cell get activated?
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
NK T-cells
Have neither CD8 or CD4. CD1 instead.
γ:δ T-cells
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.
