T-cell priming Flashcards
What could be a reason for individuals showing immune reactivity to SARS-CoV-2 before being infected by the virus itself?
Individuals who have been infected with other sorts of common cold coronaviruses (CCC) are more reactive to the coronavirus.
What is the concept of immune cross-reactivity based on?
It is based on the concept that there are pre-existing memory T-cells that can react to a new pathogen.
These pre-existing memory cells may have been made when an individual was infected with a different, homologous, pathogen.
Where are naive T-cells activated and by what?
CD4+ and CD8+ are activated in the secondary lymphoid organs by dendritic cells.
What is another name for CD80 and 86?
B7.1 and B7.2 respectively.
How many cells respond, when a dendritic cell presents an antigen?
Roughly 1 in 100 000
What receptors and molecules are involved in which of the 3 steps of T-cell activation?
Signal 1: MHC loaded with antigen binds to TCR.
Signal 2: Co-stimulation between CD80/86 (B7.1/B7.2) on the dendritic cell and CD28 on the T-cell
Signal 3: Cytokines released by the dendritic cell determine effector cell subset
Name five examples of T-helper subsets and the cytokines which lead to their induction.
- Th1 : IL-12 and INF-y
- Th2 : IL-4
- Th17 : IL-6, TGF-b and IL-23
- Tfh : IL-6. IL-21
5 Treg : TGF-b
What is the function of CD40L and CD40?
CD4+ T-helper cells activate CD8+ and B-cells. They do so through CD40L (on the Th cell) and CD40 (on B-cells and CD8+) mediated activation.
What are CD62L and CCR7 characteristics of?
Naive T-cells and some memory T-cells
Which molecules are both important for entering the lymph nodes?
CCL19 and CCL21
What are the characteristics of Central Memory T-cells?
- L-selectin (CD62L) positive
- CCR7-positive
- Circulate the lymphoid organs
- Stem-cells-like, can be activated by antigen and cytokines
What are the characteristics of Effector memory T-cells?
- L-selectin (CD62L) negatice
- CCR7-negative
- Circulate lymphoid and non-lymphoid tissues
- Already differentiated and have high levels of effector molecules
What is the role of Resident Memory T-cells?
They are found only in tissues and are responsible for the response to local infections.
What are the CD8 and CD4 receptors on T-cells doing?
CD8 and CD4 are both co-receptors of TCR. CD8 is on cytotoxic T-cells and CD4 is on T-helpers.
What cells can present extracellular antigen on their MHC-I?
Dendritic cells.
What is cross-presentation important for?
It is important for inducting a viral and tumor immune response.
How many MHC-I/II variants are out there?
3 MHC-I and 3 MHC-II
What part of the MHC molecule is the most affected in terms of polymorphism?
The peptide groove
What is the main difference between different MHC forms?
Each MHC can then bind different peptide sets.
What techniques can be used to study the proliferation of T-cells?
- CFSE / CTV dilution
What techniques can be used to study the proliferation of T-cells?
- CFSE / CTV dilution
- 3H-thymidine incorporation
- Ki67 staining (not used much anymore)
What is the concept of CFSE/CTV (cell trace violet) dilution?
Cells stained with the dye inherit 50% of the staining intensity. By measuring the stain color intensity, one could measure how many divisions/generations of cells have happened.
How can one measure cytokine production in T-cells?
- ELISA
- Elispot
- Intracellular cytokine staining
Briefly explain how Elispot works.
Elispot is a measuring method in which a well is coated with cytokine-specific antibodies. T-cells are then thrown into the well and they release cytokines. The cytokines then form precipitates which are visible as dots.
Quantification of T-cells that produce a specific cytokine is based on the number of dots produced after stimulation.
