Immune polyphony : dissecting coordinated multicellular networks of antiviral immunity
Abstract/Contents
- Abstract
- Viral diseases remain a major cause of morbidity and mortality worldwide and emerging viral pathogens represent a perennial threat to human health. The rapidity, quality, and duration of the immune response to a viral pathogen is a major determinant of disease outcome in viral disease. This immune response to a viral pathogen involves the activity of multiple cell types with distinct and multifaceted functional roles to mount a response that is appropriate in both time and space. An insufficient response may result in unrestrained viral replication while an overly robust response can result in direct tissue damage. Thus, an effectively regulated antiviral immune response requires complex coordination, communication, and regulation between individual immune cells. We coin the term "immune polyphony" to describe these coordinated multicellular networks -- a reference to musical polyphony where multiple individual voices come together to create harmony. Here we present a framework to study and engineer immune polyphony and apply this framework to dissect the features of well-balanced immune responses in multiple viral diseases. First, we examine immune responses in patients with COVID-19 across the full range of the disease severity spectrum to reveal widespread dysregulation of innate immunity in severe COVID-19. Next, we introduce a novel computational framework for the analysis of cell-cell communication pathways at the resolution of the single-cell. We then apply this methodology to analyze inflammatory networks that distinguish immune responses to pathogenic vs. non-pathogenic lentiviruses. Finally, we describe a technique for bio-orthogonal manipulation of primary immune cells, thus providing a pathway for future efforts to engineer polyphonic immune responses to promote effective antiviral immunity.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Wilk, Aaron James |
|---|---|
| Degree supervisor | Blish, Catherine |
| Thesis advisor | Blish, Catherine |
| Thesis advisor | Bintu, Lacramioara |
| Thesis advisor | Greenleaf, William James |
| Thesis advisor | Kim, Peter, 1958- |
| Thesis advisor | Krams, Sheri Michele |
| Degree committee member | Bintu, Lacramioara |
| Degree committee member | Greenleaf, William James |
| Degree committee member | Kim, Peter, 1958- |
| Degree committee member | Krams, Sheri Michele |
| Associated with | Stanford University, Program in Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Aaron James Wilk. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/fx947zj9187 |
Access conditions
- Copyright
- © 2022 by Aaron James Wilk
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...