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Establishing a Comprehensive and Dynamic Map of the Alloimmune Response in Solid Organ Transplantation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Establishing a Comprehensive and Dynamic Map of the Alloimmune Response in Solid Organ Transplantation./
Author:	Harden, James Terrell.
Description:	1 online resource (163 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-04, Section: B.
Contained By:	Dissertations Abstracts International84-04B.
Subject:	Spleen. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29342278click for full text (PQDT)
ISBN:	9798351496115

Establishing a Comprehensive and Dynamic Map of the Alloimmune Response in Solid Organ Transplantation.
Harden, James Terrell.

Establishing a Comprehensive and Dynamic Map of the Alloimmune Response in Solid Organ Transplantation. - 1 online resource (163 pages)

Source: Dissertations Abstracts International, Volume: 84-04, Section: B.

Thesis (Ph.D.)--Stanford University, 2022.

Includes bibliographical references

There's a multitude of functions that our immune system has to carry out in order to sustain the human body. It actively protects us from cancers, diseasecausing microbes, and toxins, all while maintaining tolerance to non-dangerous foreign substances such as pollen and gut bacteria. It also has additional regulatory functions that impact pregnancy, tissue recovery, and wound healing. The dynamic and multi-dimensional properties of our immune system that makes it so remarkable are the same properties that cause us problems in solid-organ transplantation and causes acute rejection. Our immune system views genetically different tissue of the transplanted organ as a dangerous foreign substance similar to a pathogen and attacks it. The ongoing challenge is to determine how we can circumvent the natural defense mechanisms of the immune system without sacrificing its numerous regulatory functions.The datasets described in this thesis address this challenge by applying high-dimensional cytometry analysis to deep profile the peripheral immune cells involved in acute rejection using a murine model of transplantation. More than 40 different markers are used to obtain a highly granular and multi-parametric proteomic overview of the immune signature that defines acute rejection. This analysis is performed in spleen and lymph node over multiple days post-transplant from day 1 to day 7. T cells, NK cells, monocytes, macrophages, and dendritic cells are expansively profiled to ascertain the differences in protein composition that associate with acute rejection. This high resolution characterization of the immune response reveals a unique phenotypic signature of rejection that is evident by day 5 post-transplantation, and clearly distinguishes rejecting from non-rejecting grafts. This alloimmune phenotype is furthermore conserved across two distinct models of acute rejection. Lastly, strategies to prolong allograft survival are investigated with the use of plasmacytoid dendritic cells (pDC). The results reported here reveal tolerogenic properties that are unique to pDC when compared to conventional dendritic cells. The molecular profile of these pDC points to a potential mechanism of harnessing the immune system's natural immune suppressive capabilities to prolong graft survival. Taken together, these data provide a comprehensive and dynamic map of the alloimmune response in solid organ transplant and provides a foundation for unveiling new therapeutic strategies that can effectively delay graft rejection.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798351496115Subjects--Topical Terms:

3561759
Spleen.
Index Terms--Genre/Form:

542853
Electronic books.

Establishing a Comprehensive and Dynamic Map of the Alloimmune Response in Solid Organ Transplantation.
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245 1 0 $a Establishing a Comprehensive and Dynamic Map of the Alloimmune Response in Solid Organ Transplantation.
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502 $a Thesis (Ph.D.)--Stanford University, 2022.
504 $a Includes bibliographical references
520 $a There's a multitude of functions that our immune system has to carry out in order to sustain the human body. It actively protects us from cancers, diseasecausing microbes, and toxins, all while maintaining tolerance to non-dangerous foreign substances such as pollen and gut bacteria. It also has additional regulatory functions that impact pregnancy, tissue recovery, and wound healing. The dynamic and multi-dimensional properties of our immune system that makes it so remarkable are the same properties that cause us problems in solid-organ transplantation and causes acute rejection. Our immune system views genetically different tissue of the transplanted organ as a dangerous foreign substance similar to a pathogen and attacks it. The ongoing challenge is to determine how we can circumvent the natural defense mechanisms of the immune system without sacrificing its numerous regulatory functions.The datasets described in this thesis address this challenge by applying high-dimensional cytometry analysis to deep profile the peripheral immune cells involved in acute rejection using a murine model of transplantation. More than 40 different markers are used to obtain a highly granular and multi-parametric proteomic overview of the immune signature that defines acute rejection. This analysis is performed in spleen and lymph node over multiple days post-transplant from day 1 to day 7. T cells, NK cells, monocytes, macrophages, and dendritic cells are expansively profiled to ascertain the differences in protein composition that associate with acute rejection. This high resolution characterization of the immune response reveals a unique phenotypic signature of rejection that is evident by day 5 post-transplantation, and clearly distinguishes rejecting from non-rejecting grafts. This alloimmune phenotype is furthermore conserved across two distinct models of acute rejection. Lastly, strategies to prolong allograft survival are investigated with the use of plasmacytoid dendritic cells (pDC). The results reported here reveal tolerogenic properties that are unique to pDC when compared to conventional dendritic cells. The molecular profile of these pDC points to a potential mechanism of harnessing the immune system's natural immune suppressive capabilities to prolong graft survival. Taken together, these data provide a comprehensive and dynamic map of the alloimmune response in solid organ transplant and provides a foundation for unveiling new therapeutic strategies that can effectively delay graft rejection.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
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650 4 $a Transplants & implants. $3 3562683
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