Conducting research on the connections between iron deficiency anemia (IDA) and NK cell activity is aimed to broaden understanding of how IDA affects the innate immune system and disease pathogenesis in order to help identify potential therapeutic interventions, improve diagnostic capabilities, and enhance treatments for vulnerable populations. Moreover, this is an underrepresented and understudied area, and addressing it will fill critical gaps in the literature on both immune function and iron metabolism.

 

This research project will be a type of literature review called a scoping review and will utilise secondary data analysis in order to answer a guiding research question. 

 

Literature review

A literature review is any research study or paper that synthesizes and is a critical analysis of existing research on a specific topic, it is usually used to demonstrate current knowledge and identify gaps for future research. A literature review normally has a guiding question and uses previously published works to answer that guiding question. The term can refer to a full scholarly paper or scholarly work such as books or articles. The purpose of a literature review is to make aware of the state of scholarship about a given topic or research question, while also organizing and evaluating the major points of each source. According to charles sturt university, there are 5 main types of literature reviews. Narrative/traditional literature reviews, Critically appraised topic (CAT) reviews, Scoping reviews, Systematic literature reviews, meta analysis and annotated bibliographies. This research project will be making use of a scoping review technique due to the scoping reviews effectiveness in identifying gaps and key concepts in areas of literature that are understudied. 

 

Academic writing: What is a literature review? | SFU Library. (n.d.). https://www.lib.sfu.ca/about/branches-depts/slc/writing/assignments/lit-review

Library Guides: Literature Review: Types of literature reviews. (n.d.). https://libguides.csu.edu.au/review/Types

 

Data collection method

 

Secondary data analysis

 

Due to the nature of a literature review, any type of literature review will use secondary data analysis in order to answer a research question. Secondary data analysis is a term for any analysis of already existing data,the data used in a secondary data analysis may be quantitative, qualitative or a mixed methods approach in which both are used. This research project will be an analysis of both quantitative and qualitative pre-existing data, making it a secondary data analysis that is mixed methods in nature.  

 

Scoping review

A scoping review is a type of evidence synthesis that maps the breadth of evidence available on a topic, field, or issue, often used to clarify concepts, identify gaps, and inform future research or systematic reviews. Scoping reviews are meant to be exploratory in nature and aim to map existing literature instead of providing definitive answers to the research question. Usually, scoping reviews cover a wider variety of sources, and focus on the quantity of sources used. Often the sources used don't directly link to the research topic, however through analysis can be used to answer a research question. Compared to systemic reviews that focus on specifics and usually cover less sources, a scoping review usually provides an overview and covers many sources. 

 

According to the PRISMA guidelines, the steps of gathering data for a scoping review is identification, screening, eligibility, and inclusion.

 

Identification- This refers to the process of finding articles and sources to use for the literature review.

Screening- This refers to the process of excluding articles that cannot be used to prove or answer the guiding research question

Eligibility- This refers to the exclusion of articles that do not fit the exclusion criteria, Ex dates the articles must be written between, or topics covered in the articles.

Inclusion- This refers to the inclusion of all articles that fit the required criteria and can be used in the project. 

 

For this project the exclusionary criteria will be as follows. 

1, Must be written in between 1970 and 2025

2, Must include or cover the topics, iron deficiency anemia and NK cells.

3, If an article does not specifically mention IDA or NK cells, but the comparison between iron levels and immunity is made and a reasonable conclusion of the effects of iron levels and NK cell activity can be made ( ex. cytotoxicity), then the article may be included. This decision was made purely due to the lack of existing research on this topic.

4, Must be written in english due to the language capacities of the researcher. 

5, Must be published in an accredited and valid scientific journal

 

Munn, Z., Peters, M. D. J., Stern, C., Tufanaru, C., McArthur, A., & Aromataris, E. (2018). Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Medical Research Methodology, 18(1). https://doi.org/10.1186/s12874-018-0611-x

Mak, S., & Thomas, A. (2022). Steps for conducting a scoping review. Journal of Graduate Medical Education, 14(5), 565–567. https://doi.org/10.4300/jgme-d-22-00621.1

 

Why were these methods chosen?

 

A scoping review is beneficial for a research project that focuses on a gap in research, or emerging evidence. They are exploratory in nature and allow for greater freedom in choosing between mixed methods, quantitative and qualitative data. Due to the ambiguous nature of studies comparing IDA and immunology, a scoping review is a much better choice then a systematic review or meta analysis. 

 

How will the research project be carried out? 

 

Google scholar will be used to collect a variety of past studies, sources, articles, and other means of research that relate to the question of this study. Exclusion criteria will be used to sort out articles found through google scholar and the articles found will be used to create data in order to write a report and create a conclusion on this topic. All data collected will be sorted into the main areas of research, NK cell Activity, Growth, Production, Cytotoxicity, and Neuroimmune Interactions. Separate conclusions will be made for all 5 of the areas of research, and a broad conclusion will be made for the entire research question ( is their correlation between IDA and NK cells). Definitions of each of the main areas of research will be made in the report ( research section in CYSF platform). All citations submitted will follow APA 7.

 

 

 

Full research paper will be provided during CYSF 2025 fair, as of march 21 this is incomplete due to personal health issues and hospitalization.

This link should lead to a doc that will have a complete paper/article done by cysf 2025 fair https://docs.google.com/document/d/1zPsqOmfNpE7dbGCFDcCgtlG6O98GAFbsqOkoz0SeP0w/edit?usp=sharing

NK cell factor definitions and key terms to search for in research

1. NK Cell Activity:

• General Activity: This refers to how NK cells recognize, respond, and eliminate abnormal or infected cells. Look for:
  • Cytokine production (e.g., IFN-γ, TNF-α)
  • Receptor expression (e.g., activating and inhibitory receptors like NKG2D, KIRs)
  • NK cell activation and degranulation.
  • Changes in NK cell metabolism (e.g., glycolysis vs. oxidative phosphorylation) in response to different stimuli (like iron levels).
• Key idea to look for when choosing articles: How does iron deficiency influence the overall activation and function of NK cells?
• Reactivity to MHC-1. This is a cell marker that binds to the nk cells inhibitory receptors and turns the NK cell killing function off, This mechanism is how the nk cell recognizes host cells. Look for Nk cell reaction and response regarding MHC-1
• Release of perforin and granzymes to kill a target cell. Abnormal use and release of perforin and granzymes may indicate Nk cell issues

2. Cytotoxicity:

• NK Cell Cytotoxicity refers to the ability of NK cells to kill target cells, like virus-infected or tumor cells. Focus on:
  • Lytic granules (e.g., perforin, granzymes) released by NK cells to induce target cell apoptosis.
  • Target cell recognition: Whether iron deficiency affects the ability of NK cells to identify and kill abnormal cells.
  • Mechanisms of killing (e.g., death receptor signaling, granule exocytosis).
• Key thing to investigate: Does iron deficiency reduce NK cell cytotoxicity by affecting granule release or target cell recognition?
• Interleukins (IL)-2, IL-12, IL-15, IL-18, IL-21 and type I interferons positively regulate NK cell function. Studies connecting these cytotoxins and IDA should be highlighted.  

3. NK Cell Production:

• Production refers to the increase in NK cell numbers, which is important in responding to infections or tumors. Production will always refer to the creation of new cells and not development of old ones. 
  • Look for changes in NK cell count over time in response to stimulation.
  • Investigate how iron levels (or deficiency) affect NK cell division (e.g., markers like Ki-67 or BrdU incorporation).
  • Examine any differentiation of NK cells (e.g., whether they become more or less mature).
• Key thing to investigate: Does iron deficiency reduce the ability of NK cells to produce in response to infection or stress?

4. NK Cell Growth:

• Growth refers to the increase in NK cell size, metabolism, and overall functional capacity. Basically it is the maintenance and chain in NK cells after they have already been created.
  • Look for changes in metabolic activity: Does iron deficiency affect the metabolic pathways that support NK cell growth (glycolysis, oxidative phosphorylation)?
  • Investigate whether iron deficiency alters the survival or expansion of NK cells in the context of inflammatory conditions or infections.
  • Abnormal growth patterns should be studied
• Key thing to investigate: Does iron deficiency impair NK cell growth and metabolic adaptation?

5. Neuroimmune Interactions:

• Neuroimmune Interactions describe the communication between the immune system and the nervous system. In particular, look for:
  • How iron deficiency impacts the interaction between NK cells and the central nervous system (CNS), especially in the context of neuroinflammation or neuroimmune responses.
  • The role of neurotransmitters, cytokines, and other immune molecules involved in this interaction (e.g., dopamine, norepinephrine).
  • Investigate if iron deficiency can impact the brain’s immune response by modulating NK cell activity.
• Key thing to investigate: Does iron deficiency affect how NK cells interact with the brain or nervous system in terms of inflammatory responses or neuroimmune balance?

Due to personal health issues the research paper and some of the data extraction remain unfinished. The following table is the completed initial data extraction. Multiple data tables will be created from this and synthesized for judging. All required compnonents including the research paper will be available during cysf 2025 fair and judging. As of march 21, 72 articles have been included in the data collection, half of the articles have had data extraction.

https://docs.google.com/spreadsheets/d/1pH3J255SGhnfhTuHBK2jyLbSRfNM8447-WAKNhURo80/edit?usp=sharing

Due to Technical difficulties uploading the pictures of my data graphs, i have instead provided the links.

Will be provided during CYSF 2025 fair and judging, Incomplete as of march 21 due to unforseen personal health issues and hospitalization.

Hallquist, N. A., & Sherman, A. R. (1989). Effect of iron deficiency on the stimulation of natural killer cells by macrophage-produced interferon. Nutrition Research, 9(3), 283–292. https://doi.org/10.1016/s0271-5317(89)80071-5

Beisel, W. (1982). Single nutrients and immunity. American Journal of Clinical Nutrition, 35(2), 417–468. https://doi.org/10.1093/ajcn/35.2.417

Rosch, L. M., Sherman, A. R., & LaSingle nutrients and immunity - ScienceDirectyman, D. K. (1987). Iron deficiency impairs protein synthesis in immune tissues of rat pups. Journal of Nutrition, 117(8), 1475–1481. https://doi.org/10.1093/jn/117.8.147

Sherman, A. R., & Lockwood, J. F. (1987). Impaired natural killer cell activity in Iron-Deficient rat pups. Journal of Nutrition, 117(3), 567–571. https://doi.org/10.1093/jn/117.3.567

Chegni, H., & Taheri, M. S. (2024). The Relationship between Iron-Deficiency Anemia (IDA) and the Function of the Immune System Archives of Advances in Biosciences, Vol. 15 No. 1. journals.sbmu.ac.ir. https://doi.org/10.22037/aab.v15i1.44987

Rahmani, S., & Demmouche, A. (2015). Iron deficiency anemia in children and alteration of the immune system. J Nutr Food Sci, 5(1), 333–333. https://doi.org/10.4172/2155-9600.1000333

Sottile, R., Federico, G., Garofalo, C., Tallerico, R., Faniello, M. C., Quaresima, B., Cristiani, C. M., Di Sanzo, M., Cuda, G., Ventura, V., Wagner, A. K., Contrò, G., Perrotti, N., Gulletta, E., Ferrone, S., Kärre, K., Costanzo, F. S., Carlomagno, F., & Carbone, E. (2019). Iron and Ferritin modulate MHC Class I expression and NK cell recognition. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.00224

 

Badran, O., Cohen, I., & Bar-Sela, G. (2024). The impact of iron on Cancer-Related immune Functions in Oncology: Molecular mechanisms and clinical evidence. Cancers, 16(24), 4156. https://doi.org/10.3390/cancers16244156

Schimmer, S., Sridhar, V., Satan, Z., Grebe, A., Saad, M., Wagner, B., Kahlert, N., Werner, T., Richter, D., Dittmer, U., Sutter, K., & Littwitz-Salomon, E. (2025). Iron improves the antiviral activity of NK cells. Frontiers in Immunology, 15. https://doi.org/10.3389/fimmu.2024.1526197

Xu, X., Li, Z., Liu, H., Huang, Z., Xiong, T., & Tang, Y. (2025). Gene prediction of the relationship between iron deficiency anemia and immune cells. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2462857

Spear, A. T., & Sherman, A. R. (1992). Iron deficiency alters DMBA-Induced tumor burden and natural killer cell cytotoxicity in rats. Journal of Nutrition, 122(1), 46–55. https://doi.org/10.1093/jn/122.1.46

Bönnemann, V., Claus, M., Butzeck, B., Collette, D., Bröde, P., Golka, K., & Watzl, C. (2020). Analysis of Natural Killer cell functions in patients with hereditary hemochromatosis. PubMed, 19, 430–441. https://doi.org/10.17179/excli2020-1116

DeBarra, C., Ryan, E., Sugrue, M., Ryan, O., Lynn, E., Heneghan, H. M., McCarthy, C., Moynagh, P. N., Sinclair, L. V., Jones, N., Hogan, A., & Shea, D. O. (2024). Iron deficiency in people with obesity drives defective natural killer cell mitochondrial fitness and function. bioRxiv (Cold Spring Harbor Laboratory). https://doi.org/10.1101/2024.01.10.575005

Liu, H., Zhang, T., Chen, Y., Liu, C., Qi, W., Shao, Y., Yu, H., Chen, T., Ding, S., Li, Y., Wang, T., Shao, Z., & Fu, R. (2020). Proteomics analysis reveals alterations of NK cells in patients with severe aplastic anemia. International Journal of Laboratory Hematology, 42(3), 308–315. https://doi.org/10.1111/ijlh.13175

Jiang, X., & Elliott, R. L. (2017, May 1). Decreased iron in cancer cells and their microenvironment improves cytolysis of breast cancer cells by natural killer cells. Anticancer Research. https://ar.iiarjournals.org/content/37/5/2297.short

Chapman, D. E., Good, M. F., & Powell, L. W. (1988). The effect of iron, iron‐binding proteins and iron‐overload on human natural killer cell activity. Journal of Gastroenterology and Hepatology, 3(1), 9–17. https://doi.org/10.1111/j.1440-1746.1988.tb00212.x

Ni, S., Yuan, Y., Kuang, Y., & Li, X. (2022). Iron metabolism and immune regulation. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.816282

Hua, Y., Wang, C., Jiang, H., Wang, Y., Liu, C., Li, L., Liu, H., Shao, Z., & Fu, R. (2017). Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes. International Journal of Hematology, 106(2), 248–257. https://doi.org/10.1007/s12185-017-2237-x

Littwitz-Salomon, E., Moreira, D., Frost, J. N., Choi, C., Liou, K. T., Ahern, D. K., O’Shaughnessy, S., Wagner, B., Biron, C. A., Drakesmith, H., Dittmer, U., & Finlay, D. K. (2021). Metabolic requirements of NK cells during the acute response against retroviral infection. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-25715-z

Zohora, F., Bidad, K., Pourpak, Z., & Moin, M. (2018). Biological and Immunological aspects of iron deficiency Anemia in Cancer Development: A Narrative review. Nutrition and Cancer, 70(4), 546–556. https://doi.org/10.1080/01635581.2018.1460685

Flynn, M. G., Mackinnon, L., Gedge, V., Fahlman, M., & Brickman, T. (2003). Influence of iron status and iron supplements on natural killer cell activity in trained women runners. International Journal of Sports Medicine, 24(3), 217–222. https://doi.org/10.1055/s-2003-39095

Hallquist, N., McNeil, L., Lockwood, J., & Sherman, A. (1992). Maternal-iron-deficiency effects on peritoneal macrophage and peritoneal natural-killer-cell cytotoxicity in rat pups. American Journal of Clinical Nutrition, 55(3), 741–746. https://doi.org/10.1093/ajcn/55.3.741

Cnops, J., De Trez, C., Stijlemans, B., Keirsse, J., Kauffmann, F., Barkhuizen, M., Keeton, R., Boon, L., Brombacher, F., & Magez, S. (2015). NK-, NKT- and CD8-Derived IFNΓ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-Associated acute anemia. PLoS Pathogens, 11(6), e1004964. https://doi.org/10.1371/journal.ppat.1004964

Cahyadi, A. I., Ghozali, M., Ghrahani, R., Reniarti, L., & Panigoro, R. (2021). Hyperferritinemia Correlated with Activated Population of Natural Killer Cells in Pediatric Major β-Thalassemia Patients. Global Medical & Health Communication (GMHC), 9(1). https://doi.org/10.29313/gmhc.v9i1.6346

 

Taylor & Francis. (n.d.). Effects of iron deficiency and its indicators on lymphocyte subsets: a study at King Fahd Hospital of the University, Saudi Arabia. https://www.tandfonline.com/doi/full/10.2147/JBM.S342321

Kurtoğlu, A. U., Uğur, S., Göçer, M., & Kurtoğlu, E. (2024). Effects of splenectomy on natural killer cell levels in Β‐Thalassemia major patients. Journal of Clinical Laboratory Analysis, 38(9). https://doi.org/10.1002/jcla.25046

Lockwood, J. F., & Sherman, A. R. (1988). Spleen Natural Killer Cells from Iron-Deficient Rat Pups Manifest an Altered Ability to be Stimulated by Interferon. Journal of Nutrition, 118(12), 1558–1563. https://doi.org/10.1093/jn/118.12.1558

Hess, C., Stern, M., & Held, W. (n.d.). Iron metabolism dictates NK cell function  - edoc. https://edoc.unibas.ch/78403/

Bonaccorsi-Riani, E., Danger, R., Lozano, J. J., Martinez-Picola, M., Kodela, E., Mas-Malavila, R., Bruguera, M., Collins, H. L., Hider, R. C., Martinez-Llordella, M., & Sanchez-Fueyo, A. (2015). Iron deficiency impairs Intra-Hepatic lymphocyte mediated immune response. PLoS ONE, 10(8), e0136106. https://doi.org/10.1371/journal.pone.0136106

ElAlfy, M. S., Adly, A. a. M., Ebeid, F. S. E., Eissa, D. S., Ismail, E. a. R., Mohammed, Y. H., Ahmed, M. E., & Saad, A. S. (2018). Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy. Immunologic Research, 66(4), 480–490. https://doi.org/10.1007/s12026-018-9010-y

Santos, P., & Falcão, R. (1990). Decreased lymphocyte subsets and K-Cell activity in iron deficiency anemia. Acta Haematologica, 84(3), 118–121. https://doi.org/10.1159/000205047

Farthing, M. J. G. (1989). Iron and immunity. Acta Paediatrica, 78(S361), 44–52. https://doi.org/10.1111/apa.1989.78.s361.44

Guo, R., Kong, J., Tang, P., Wang, S., Sang, L., Liu, L., Guo, R., Yan, K., Qi, M., Bian, Z., Song, Y., Jiang, Z., & Li, Y. (2023). Unbiased Single‐Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation. Advanced Science, 11(10). https://doi.org/10.1002/advs.202304539

Zhang, T., Yuan, X., Liu, C., Li, Y., Liu, H., Li, L., Ding, K., Wang, T., Wang, H., Shao, Z., & Fu, R. (2017). Decreased TIM-3 expression of peripheral blood natural killer cells in patients with severe aplastic anemia. Cellular Immunology, 318, 17–22. https://doi.org/10.1016/j.cellimm.2017.03.003

Hrabinski, D., Hertz, J. L., Tantillo, C., Berger, V., & Sherman, A. R. (1995). Iron repletion attenuates the protective effects of iron deficiency in DMBA‐induced mammary tumors in rats. Nutrition and Cancer, 24(2), 133–142. https://doi.org/10.1080/01635589509514401

Akbar, A. N., Fitzgerald-Bocarsly, P. A., De Sousa, M., Giardina, P. J., Hilgartner, M. W., & Grady, R. W. (1986). Decreased natural killer activity in thalassemia major: a possible consequence of iron overload. The Journal of Immunology, 136(5), 1635–1640. https://doi.org/10.4049/jimmunol.136.5.1635

Brock, J. H. (2018). Iron and the immune system. In CRC Press eBooks (pp. 161–178). https://doi.org/10.1201/9781351073899-6

Sherman, A. R. (1992). Zinc, copper, and iron nutriture and  immunity ,. Journal of Nutrition, 122, 604–609. https://doi.org/10.1093/jn/122.suppl_3.604

Coe, C. L., Lubach, G. R., & Shirtcliff, E. A. (2007). Maternal stress during pregnancy predisposes for iron deficiency in infant monkeys impacting innate immunity. Pediatric Research, 61(5, Part 1), 520–524. https://doi.org/10.1203/pdr.0b013e318045be53

Braun, W. A., Flynn, M. G., Carl, D. L., Carroll, K. K., Brickman, T., & Lambert, C. P. (2000). Iron status and resting immune function in female collegiate swimmers. International Journal of Sport Nutrition and Exercise Metabolism, 10(4), 425–433. https://doi.org/10.1123/ijsnem.10.4.425

Bergman, M., Bessler, H., Salman, H., Siomin, D., Straussberg, R., & Djaldetti, M. (2004). In vitro cytokine production in patients with iron deficiency anemia. Clinical Immunology, 113(3), 340–344. https://doi.org/10.1016/j.clim.2004.08.011

Tsouchnikas, I., Tsilipakou, M., Daniilidis, M., Kyriazis, G., Pasadakis, P., Parapanissiou, E., Vargemezis, V., & Tsakiris, D. (2007). Effect of iron loading on peripheral blood lymphocyte subsets and on circulating cytokine levels in Iron-Depleted hemodialysis patients receiving erythropoietin. Nephron Clinical Practice, 107(3), c97–c102. https://doi.org/10.1159/000108650

 

Good, M., Powell, L., & Halliday, J. (1988). Iron status and cellular immune competence. Blood Reviews, 2(1), 43–49. https://doi.org/10.1016/0268-960x(88)90007-0

Kuvibidila, S. R., Gardner, R., Velez, M., & Yu, L. (2010). Iron deficiency, but not underfeeding reduces the secretion of interferon-gamma by mitogen-activated murine spleen cells. Cytokine, 52(3), 230–237. https://doi.org/10.1016/j.cyto.2010.08.004

Weiss, G., Wachter, H., & Fuchs, D. (1995). Linkage of cell-mediated immunity to iron metabolism. Immunology Today, 16(10), 495–500. https://doi.org/10.1016/0167-5699(95)80034-4

Marques, O., Weiss, G., & Muckenthaler, M. U. (2022). The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation. Blood, 140(19), 2011–2023. https://doi.org/10.1182/blood.2021013472

Kleinbeck, S. N., & McGlone, J. J. (1999). Intensive indoor versus outdoor swine production systems: genotype and supplemental iron effects on blood hemoglobin and selected immune measures in young pigs. Journal of Animal Science, 77(9), 2384. https://doi.org/10.2527/1999.7792384x

Aksan, A., Farrag, K., Aksan, S., Schroeder, O., & Stein, J. (2021). Flipside of the coin: iron deficiency and colorectal cancer. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.635899

Weiss, G. (2005). Modification of iron regulation by the inflammatory response. Best Practice & Research Clinical Haematology, 18(2), 183–201. https://doi.org/10.1016/j.beha.2004.09.001

Aly, S. S., Fayed, H. M., Ismail, A. M., & Hakeem, G. L. A. (2018). Assessment of peripheral blood lymphocyte subsets in children with iron deficiency anemia. BMC Pediatrics, 18(1). https://doi.org/10.1186/s12887-018-0990-5

Yadav, D., & Chandra, J. (2010). Iron deficiency: beyond anemia. The Indian Journal of Pediatrics, 78(1), 65–72. https://doi.org/10.1007/s12098-010-0129-7

Abo, T., Cooper, M. D., & Balch, C. M. (1981). 893 MORPHOLOGY, DEVELOPMENT AND DISTRIBUTION OF HUMAN NK CELLS IDENTIFIED BY a MONOCLONAL ANTIBODY (HNK-1). Pediatric Research, 15, 591. https://doi.org/10.1203/00006450-198104001-00918

Kuvibidila, S., & Warrier, R. P. (2004). Differential effects of iron deficiency and underfeeding on serum levels of interleukin-10, interleukin-12p40, and interferon-gamma in mice. Cytokine, 26(2), 73–81. https://doi.org/10.1016/j.cyto.2003.12.010

Dondero, A., Casu, B., Bellora, F., Vacca, A., De Luisi, A., Frassanito, M. A., Cantoni, C., Gaggero, S., Olive, D., Moretta, A., Bottino, C., & Castriconi, R. (2017). NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27. Oncotarget, 8(21), 35088–35102. https://doi.org/10.18632/oncotarget.17070

Iriarte-Gahete, M., Tarancon-Diez, L., Garrido-Rodríguez, V., Leal, M., & Pacheco, Y. M. (2024). Absolute and functional iron deficiency: Biomarkers, impact on immune system, and therapy. Blood Reviews, 68, 101227. https://doi.org/10.1016/j.blre.2024.101227

Huntington, N. D. (2023). Ironman training for NK cells. Nature Immunology, 24(10), 1599–1601. https://doi.org/10.1038/s41590-023-01626-7

Resch, T., Ashraf, M. I., Ritschl, P. V., Ebner, S., Fabritius, C., Brunner, A., Schäfer, G., Regele, H., Günther, J., Weiss, G., & Kotsch, K. (2017). Disturbances in iron homeostasis result in accelerated rejection after experimental heart transplantation. The Journal of Heart and Lung Transplantation, 36(7), 732–743. https://doi.org/10.1016/j.healun.2017.03.004

Latunde‐dada, G. O., & Young, S. P. (1992). Iron deficiency and immune responses. Scandinavian Journal of Immunology, 36(s1), 207–209. https://doi.org/10.1111/j.1365-3083.1992.tb01654.x

Role of iron in immunity and infection. | Nutrition and immune function. (2002). Frontiers in Nutritional Science. https://www.cabidigitallibrary.org/doi/abs/10.1079/9780851995830.0209

Spear, A. T. (1992.). Cytokine activities and natural killer cell cytotoxicity in response to food restriction and iron deficiency in rodents - ProQuest. https://www.proquest.com/openview/0e2c9ae8544e8252489c62a6e1b8c8c5/1?cbl=18750&diss=y&pq-origsite=gscholar

 

Haddad, E. H., Berk, L. S., Kettering, J. D., Hubbard, R. W., & Peters, W. R. (1999). Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. American Journal of Clinical Nutrition, 70(3), 586S-593S. https://doi.org/10.1093/ajcn/70.3.586s

Prasad, A. S. (2020). Lessons Learned from Experimental Human Model of Zinc Deficiency. Journal of Immunology Research, 2020, 1–12. https://doi.org/10.1155/2020/9207279

Greil, J., Verga-Falzacappa, M. V., Echner, N. E., Behnisch, W., Bandapalli, O. R., Pechanska, P., Immenschuh, S., Vijayan, V., Balla, J., Tsukahara, H., Schneider, M., Janka, G., Claus, M., Longerich, T., Muckenthaler, M. U., & Kulozik, A. E. (2016). Mutating heme oxygenase-1 into a peroxidase causes a defect in bilirubin synthesis associated with microcytic anemia and severe hyperinflammation. Haematologica, 101(11), e436–e439. https://doi.org/10.3324/haematol.2016.147090

Bell, H. N., & Zou, W. (2024). Ironing Out the Kinks: Arming Natural Killer Cells against Ovarian Cancer. Cancer Discovery, 14(10), 1771–1773. https://doi.org/10.1158/2159-8290.cd-24-1012

Terpiłowska, S., & Siwicki, A. K. (2011). Review paper
The role of selected microelements: selenium, zinc, chromium and iron in immune system. Termedia.pl. https://www.termedia.pl/-Review-paper-The-role-of-selected-microelements-selenium-zinc-chromium-and-iron-in-immune-system,10,17949,0,1.html

Erickson, K. L., Medina, E. A., & Hubbard, N. E. (2000). Micronutrients and innate immunity. The Journal of Infectious Diseases, 182(s1), S5–S10. https://doi.org/10.1086/315922

Chardalias, L., Papaconstantinou, I., Gklavas, A., Politou, M., & Theodosopoulos, T. (2023). Iron deficiency anemia in colorectal cancer patients: Is preoperative intravenous iron infusion indicated? A narrative review of the literature. Cancer Diagnosis & Prognosis, 3(2), 163–168. https://doi.org/10.21873/cdp.10196

Maria, N. S. S., Barnes, S. R., Weist, M. R., Colcher, D., Raubitschek, A. A., & Jacobs, R. E. (2015). Low dose focused ultrasound induces enhanced tumor accumulation of natural killer cells. PLoS ONE, 10(11), e0142767. https://doi.org/10.1371/journal.pone.0142767

Barua, S., Ciannella, S., Tijani, L., & Gomez‐Pastora, J. (2023). Iron in blood cells: Function, relation to disease, and potential for magnetic separation. Biotechnology and Bioengineering, 120(7), 1707–1724. https://doi.org/10.1002/bit.28388

Kim, S., Kim, S., Chai, H., Cho, J., & Paek, Y. (2024). Increasing natural killer cell activity of mineral nanomaterial ALP1018 in healthy adults: a randomized, Double-Blind, placebo comparative clinical trial. Nutrients, 16(6), 850. https://doi.org/10.3390/nu16060850

 

 

This research project was a very formidable task and quite daunting in nature due to completing this project in my first year of high school. I have participated in CYSF for a few years, however every year I participated I not only had a partner, I had less demanding coursework in school. Balancing my project with school, while not having a partner to support me was incredibly difficult. Scoping reviews normally take a team, last year I submitted a scoping review with a partner - this year I completed a scoping review myself.

 

Which is why I would really like to thank my parents, Naznin Yousuf and Md Moshfiq Khan for always supporting me and allowing me to try my best. I would also like to thank all three of my sisters for always putting a smile on my face.

A special thank you goes to Rayna Rija Choudhury. She has been my partner for CYSF all throughout middle school, CYSF was our thing and we struggled and persevered together through all the projects we did. It was with her that I learned the lessons that allowed me to submit my project this year to the best of my ability. And it is in her honour that I participate and enter another project into CYSF this year. Even though she has moved to America her impact on me still remains and her participation in previous years not only provides me knowledge to compete this year, yet also makes this process incredibly difficult. I don't believe I will ever participate in CYSF with another partner as this was something special we shared, And even though she cannot compete this year or again, I plan to continue competing in her honor and for the memories we made together working on the projects we did. Last year, after years of hard work, we achieved a gold award together. This year I cannot hope to do as well, yet I will continue to do my best and keep pushing forward, inspired by the journey we shared.