자료유형  

 학위논문

Control Number  

0016932047

International Standard Book Number  

9798379750954

Dewey Decimal Classification Number  

576

Main Entry-Personal Name  

Sukhina, Alisa.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pennsylvania., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(129 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

General Note  

Advisor: Bailis, Will.

Dissertation Note  

Thesis (Ph.D.)--University of Pennsylvania, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Undernutrition is a persistent global health crisis that heavily impacts both adults and children. The main underlying cause of morbidity and mortality from undernutrition is infectious disease. Although for over a century the link between poor infection outcomes and undernutrition has been reported, the cellular and molecular mechanisms of how chronic undernutrition causes immunodeficiency remains unknown. To investigate these mechanisms, we adapted a murine restrictive diet model to mimic physical characteristics of human undernutrition. We then performed comprehensive characterization of the immune system in these experimental mice before and after infection using flow cytometry. We found that both innate and adaptive immune responses were impaired in undernourished mice. Most myeloid cells, B cells, and T cells were all decreased in number before and after infection. Additionally, T cells exhibited delayed effector responses and diminished inflammatory cytokine production. But neutrophil numbers and their production levels during immune response to infection were decreased the most among all immune populations. After performing this characterization, we examined whether refeeding interventions, a standard of treatment for undernourished patients, can rescue immune cell numbers and function. We developed a safe refeeding protocol and performed the same analysis on refed mice. We found that most immune cell numbers and function have recovered, but neutrophils and their production levels stayed significantly lower in mice that used to be undernourished. These findings gave us insights into which arms of immune responses are most affected by undernutrition and the therapeutic potential of refeeding interventions on nutritionally acquired immunodeficiency. The findings of this study suggest that neutrophils are the population most negatively affected by undernutrition and that refeeding interventions have limitations in how effectively they can rescue immune responses. We hope that our work can both provide a solid foundation for future research into undernutrition-induced immunodeficiency and inform future standards of care and global policy focused on eradicating undernutrition.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Nutrition.

Index Term-Uncontrolled  

Immunodeficiency

Index Term-Uncontrolled  

Infection

Index Term-Uncontrolled  

Malnutrition

Index Term-Uncontrolled  

Refeeding

Index Term-Uncontrolled  

Undernutrition

Added Entry-Corporate Name  

University of Pennsylvania Cell and Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 84-12B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:640880