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Thesis
Adenosine deaminase-1 (ADA-1) induces DC maturation and improves adaptive immunity
Master of Science (M.S.), Drexel University
Dec 2020
DOI:
https://doi.org/10.17918/00000317
Abstract
Due to their role as professional antigen-presenting cells (APCs), dendritic cells (DCs) bridge innate and adaptive immunity. They are strong initiators of adaptive immunity due to their unique capacity to present antigen from invading pathogens to naïve and quiescent cytotoxic and helper CD4+ and CD8+ T cells. The heterogeneity in the resulting immune responses makes DCs a potent tool in the repertoire of vaccine immunology. One of the effector functions of CD4+ T cells is their ability to interact with cognate B cells to stimulate T-cell dependent antibody responses within germinal centers (GC). These specialized T cells are known as follicular helper T cells (Tfh) and they are critical for humoral immunity following infection or immunization. Given the importance of Tfh cells, identifying the underlying mechanisms and specific molecules that enhance this phenotype via DCs is a promising field of study. To this end, the enzyme adenosine deaminase-1 (ADA-1) has been identified as a regulator of the Tfh program, and despite a growing interest in the pathway, there is still a great deal unknown about ADA-1 and its effects in immune cells. We hypothesize that upon stimulation by ADA-1, DCs will promote a pro-Tfh microenvironment, leading to enhanced immunogenicity, and superior capacity for antigen presentation. We found that ADA-1 does induce DCs to differentially secrete cytokines that may skew naïve CD4+ T cells towards a Tfh pathway and that these DCs have increased immunogenicity that enhance their ability to activate T cells. We also found that memory T cells differentially secrete cytokines and chemokines in response to antigen presentation by ADA-1 DCs. Altogether, these results add to our knowledge of how ADA-1 affects human innate immunity and how it may be utilized in a vaccine-adjuvant platform
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Details
- Title
- Adenosine deaminase-1 (ADA-1) induces DC maturation and improves adaptive immunity
- Creators
- Bhavani Taramangalam
- Contributors
- Elias El Haddad (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vi, 59 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991014833049204721