T-cell priming in COVID-19 era Flashcards
What are the 3 signals required for T-cell activation?
MHC/TCR binding, Co-stimulation by CD80/86 and cytokines which determine effector cell subset.
Which low affinity naive T-cell receptor will become high affinity on activation?
the IL-2 receptor.
What is the difference between central memory and effector memory T cells?
Central memory cells express CCR7 and remain in the lymphoid tissue, effector memory cells lack CCR7 and migrate to tissues.
Which subset of memory T-cells remain in the tissues and provide local protection?
Tissue resident memory T-cells. (But during a secondary infection some resident memory T-cells migrate into the lymph nodes to provide systemic protection.)
What is the effect of chronic presence of antigen in viral infections and cancer?
It leads to exhaustion of T-cells and so loose effector functions and express inhibitory molecules such as PD1.
Which MHC class is on which T-cell and what do they bind?
MHC class I on CD8 T-cells binds endogenous peptides and MHC class II on CD4 T-cells binds exogenous peptides.
How does cross-presentation work and when is it important?
Exogenous peptides can be presented on MHC class I (which normally presents endogenous peptides) due to cross-presentation by DCs. It is important for viral and tumor immune responses.
What is MHC polymorphism and is it good or bad?
There are multiple variants of each MHC gene present within the population.
This polymorphism is centered at the peptide groove, so they can harbour different peptides.
The more different MHC alleles in a population/individual, the better.
What are techniques to measure antigen specific T-cell responses?
- Measuring T-cell proliferation by CFSE or CTV dilution with flow cytometer.
- Measuring cytokine production with an ELIspot assay.
- Measuring cytokine production with an intracellular cytokine assay, which determines the number of cytokine producing cells by flow cytometry.
- Measuring upregulation of activation markers with AIM (activation induced marker) assay. This is flowcytometry of markers which are upregulated by activation.
- MHC-peptide tetramer staining determines the number of Ag specific T-cells. Instead of antibodies you use a tetramer with MHC ligands which binds to MHCI on T-cells-cells. These can than be measured with flow cytometry.
Which proteins of SARS-CoV-2 are able to lead T-cell priming?
The spike proteins, envelope proteins, membrane proteins and neucleocapsid proteins.
What is the mechanism of action of SARS-CoV-2?
The virus binds with it’s spike proteins to the ACE2 receptor on respiratory cells. The virus replicates in the cells and it’s antigens are presented. This will result in neutralizing antibodies.
What effects could the neutralizing antibodies produced against SARS-CoV-2 have?
- The neutralizing antibodies mostly bind the spike protein and so preventing the virus from interacting with the ACE2 receptor or blocking confromational changes of the spike protein to fuse with the host membrane.
- The antibodies could also enhance viral entry into immune cells by binding the spike protein and the Fc receptors onf the cell. This is not what you want to happen.
Why do we also need T-cells to fight off SARS-CoV-2?
CD4+ T-cell help is essential for B-cell responses as well as for DC licensing and CD8+ T-cell responses. CD40L/CD40 interaction is important in both.
