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High Throughput Co-culture Assays for the Investigation of Microbial Interactions
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Beginnings of coinhibition
1Department of Microbiology & Immunology, Western University (The University of Western Ontario), London, Ontario, Canada.
Scandinavian Journal of Immunology
|December 23, 2021
Summary
Immune responses use coinhibitory mechanisms, like Fc receptor signaling, to maintain self-tolerance. Dysfunctional Fc signaling in COVID-19 may drive autoimmune issues, highlighting therapeutic potential.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmunity
Background:
- Immune responses are regulated by costimulatory and coinhibitory signals, ensuring specificity and appropriate levels.
- Theoretical models of immune regulation, including Fc receptor-mediated inhibition, are crucial for understanding immune control.
- Antibody Fc portions play a role in suppressing immune responses, a mechanism observed decades ago.
Purpose of the Study:
- To explore the role of Fc receptor-mediated coinhibition in immune regulation.
- To investigate potential Fc-mediated mechanisms underlying autoimmune complications in COVID-19.
- To connect historical models of immune coinhibition with current clinical challenges.
Main Methods:
- Review of theoretical models of immune coinhibition, focusing on Fc receptor crosslinking.
- Analysis of recent observations regarding anti-SARS-CoV-2 antibodies in COVID-19 patients.
- Examination of antigen localization and Fc binding in germinal centers of COVID-19 patients.
Main Results:
- Monoclonal anti-SARS-CoV-2 antibodies may inhibit autoimmune antibody induction by providing negative Fc signals.
- COVID-19 patients might exhibit blocked Fc signaling, potentially leading to autoimmune issues.
- Impaired localization of SARS-CoV-2 antigen suggests a block in Fc binding to follicular dendritic cells.
Conclusions:
- Fc receptor-mediated coinhibition is a critical mechanism for immune regulation and self-tolerance.
- Dysregulation of Fc signaling in COVID-19 could contribute to the development of autoimmune diseases.
- Understanding these complex immunological models offers pathways for addressing clinical problems like COVID-19.
Keywords:
B cellsCOVID‐19Fc gamma RIIbFc receptorsFc‐portionInfectionsSARS‐CoV‐2antibodies/immunoglobulinsautoantibodiesautoimmunitybone marrowcancergene rearrangementimmune theoriesimmunoreceptor tyrosine‐base activation motif (ITAM)immunoreceptor tyrosine‐based inhibitory motif (ITIM)tripartite inactivation model (TIM)
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