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Printable Handouts
Navigable Slide Index
- Introduction
- The example project in this lecture
- The complexity of the immune system
- A systems immunological approach to dissect ongoing immune responses
- How to use single cell technologies and systems immunology
- Impaired type I IFN activity and inflammatory responses
- Autoantibodies against type I IFNs
- What other factors may account for severe cases?
- The adaptive immune system reacting to SARS-CoV-2 over time
- Chronic presence of plasmablasts in peripheral blood during severe COVID-19
- 10x genomics technology
- Transcriptomic clusters of activated B cells in COVID-19 patients
- Activated B cells of severe COVID patients show no IFN-instruction later on
- Cytokines are targeting immunoglobulin switch recombination to distinct classes
- Antibody-isotypes report the cytokines driving the immune reaction
- Is it an immune reaction against SARS-CoV-2?
- IgA2 of COVID-19 patients is not specific for SARS-CoV-2 spike protein
- If not SARS-CoV-2, what are the antibodies targeting?
- None of the cloned BCRs recognize the SARS-CoV-2 spike or nucleoprotein
- Severe COVID-19: TGF-β chronic immune reaction
- Could TGF-β be to blame for delayed IFN response seen in severe COVID-19?
- Early peak of serum TGF-β during severe COVID-19
- A TGF-β response gene signature of NK cells is characteristic for severe COVID-19
- TGF-β response is specific to severe COVID-19 and limits antiviral function of NK cells (1)
- TGF-β response is specific to severe COVID-19 and limits antiviral function of NK cells (2)
- Antiviral function of NK cells can be restored by anti-TGF-β
- Which cells are expressing and responsible for the early peak of TGF-β
- Lung cells from deceased COVID-19 patients express increased levels of TGF-β1 (1)
- Lung cells from deceased COVID-19 patients express increased levels of TGF-β1 (2)
- How does SARS-CoV-2 induce or mimic TGF-β responses in infected cells?
- SARS-CoV-2 nucleoprotein (N) interacts with activated SMAD3
- SARS-CoV-2 factors which promote TGF-β
- Studying immune responses in severe COVID-19 at single cell level
- Induction of a TGF-β response and the delayed IFN response in patients with severe COVID-19
- Acknowledgements
Topics Covered
- Severe COVID-19
- Impaired type 1 interferon activity
- The adaptive immune system and COVID-19
- Chronic presence of plasmablasts
- 10x genomics technology
- Transcriptomic clusters
- IgA2
- IgG1
- IgM
- IgA1
- Spike protein and nucleoprotein
- TGF-β
Links
Series:
- The Immune System - Key Concepts and Questions
- Periodic Reports: Advances in Clinical Interventions and Research Platforms
Categories:
Therapeutic Areas:
Talk Citation
Mashreghi, M. (2023, January 31). Studying immune responses “one cell at a time” [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved February 5, 2025, from https://doi.org/10.69645/NWQQ7832.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Mir-Farzin Mashreghi has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Immunology & Inflammation
Transcript
Please wait while the transcript is being prepared...
0:00
First of all, I would like
to thank the organizers
for choosing me
and inviting me to participate
in the HSTalks lecture series.
This is a great honor for me.
My name is Farzin
Mashreghi and I lead
the therapeutic gene
regulation group
at the German Rheumatism
Research Centre in Berlin.
In this role, I
am applying state
of the art single-cell
technologies to decipher
potentially disregulated
adaptive immune responses
in usually chronic inflammatory
rheumatic diseases.
0:34
I have chosen an example
project for this lecture today
in which we unveiled the role
of the cytokine host
factor TGF-Beta
in the pathogenesis
of severe COVID-19.
Here, we use the very
sophisticated sorting
and single cell sequencing
approach in which we
studied immune responses
longitudinally
after SARS COVID-2 infection.
We studied that in a way
that we analyze one
cell at a time.
1:04
Understanding how our
immune system functions
is difficult because of the
many different cell types
and biomolecules involved
and because of its
extremely dynamic nature.
It is in constant
co-evolution with pathogens
and must respond rapidly
and specifically
in each individual
to a vast variety of
potential threats.
We have more than 100
immune cell subsets
expressing more than 100
cytokines and chemokines,
more than 350 surface proteins,
and more than 1,000 genes in
different constellations.
To make it even
more complicated,
T and B cells of the
adaptive immune system
express more than 10 million
different antigen receptors.
These immune cells also interact
in different constellations.
Conventional analysis,
for example flow
cytometry based analysis,
is very biased and limited
to the availability
of specific antibodies
and reagents.