The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behaviors. Observing the immune system can guide how to respond to various daily situations, including when to react, tolerate, or ignore. Recognizing this analogy between our lives and the immune system should motivate us to adopt a wisdom-based approach when investigating the mechanisms and future discoveries related to this system and to deepen our understanding of this complex system with newfound respect. In this context, the present review examines several integral biological processes of the immune system by drawing parallels between them and human life, activities, and behaviors to learn how we must behave based on the insights offered by this complex organization. The literature search was conducted in international databases such as PubMed/MEDLINE and Google Scholar search engine using English equivalent keywords from 1998 up to April 2023. The search strategy used the following subject heading terms: Immune system, analogy, human life, cellular dynamics, memory, tolerance, and ignorance. In conclusion, the immune system is a complex organization comprising various cells interacting within specific sites and networks, communicating, drawing experiences, and learning how to tolerate certain conditions that make it share certain similarities with human life.
References
[1]
Bollerot, K., Pouget, C. and Jaffredo, T. (2005) The Embryonic Origins of Hematopoietic Stem Cells: A Tale of Hemangioblast and Hemogenic Endothelium. Journal of Pathology, Microbiology and Immunology, 113, 790-803. https://doi.org/10.1111/j.1600-0463.2005.apm_317.x
[2]
Lim, W.F., Inoue-Yokoo, T., Tan, K.S., Lai, M.I. and Sugiyama, D. (2013) Hematopoietic Cell Differentiation from Embryonic and Induced Pluripotent Stem Cells. Stem Cell Research & Therapy, 4, Article No. 71. https://doi.org/10.1186/scrt222
[3]
Ng, A.P. and Alexander, W.S. (2017) Haematopoietic Stem Cells: Past, Present and Future. Cell Death Discovery, 3, Article No. 17002. https://doi.org/10.1038/cddiscovery.2017.2
[4]
Anaya, J.M., Shoenfeld, Y., Rojas-Villarraga, A., Levy, R.A. and Cervera, R. (2013) Autoimmunity: From Bench to Bedside. El Rosario University Press. https://www.ncbi.nlm.nih.gov/books/NBK459447/
[5]
Marshall, J.S., Warrington, R., Watson, W. and Kim, H.L. (2018) An Introduction to Immunology and Immunopathology. Allergy, Asthma & Clinical Immunology, 14, Article No. 49. https://doi.org/10.1186/s13223-018-0278-1
[6]
Hato, T. and Dagher, P.C. (2015) How the Innate Immune System Senses Trouble and Causes Trouble. Clinical Journal of the American Society of Nephrology, 10, 1459-1469. https://doi.org/10.2215/cjn.04680514
[7]
Zhang, P., Zhang, C., Li, J., Han, J., Liu, X. and Yang, H. (2019) The Physical Microenvironment of Hematopoietic Stem Cells and Its Emerging Roles in Engineering Applications. Stem Cell Research & Therapy, 10, Article No. 327. https://doi.org/10.1186/s13287-019-1422-7
[8]
Farber, D.L. (2021) Tissues, Not Blood, Are Where Immune Cells Function. Nature, 593, 506-509. https://doi.org/10.1038/d41586-021-01396-y
[9]
Hampton, H.R. and Chtanova, T. (2019) Lymphatic Migration of Immune Cells. Frontiers in Immunology, 10, Article 1168. https://doi.org/10.3389/fimmu.2019.01168
[10]
Martin-Almedina, S., Mortimer, P.S. and Ostergaard, P. (2021) Development and Physiological Functions of the Lymphatic System: Insights from Human Genetic Studies of Primary Lymphedema. Physiological Reviews, 101, 1809-1871. https://doi.org/10.1152/physrev.00006.2020
[11]
Xie, J., Tato, C.M. and Davis, M.M. (2012) How the Immune System Talks to Itself: The Varied Role of Synapses. Immunological Reviews, 251, 65-79. https://doi.org/10.1111/imr.12017
[12]
Zlotnik, A. (2020) Perspective: Insights on the Nomenclature of Cytokines and Chemokines. Frontiers in Immunology, 11, Article 908. https://doi.org/10.3389/fimmu.2020.00908
[13]
Lee, S. and Margolin, K. (2011) Cytokines in Cancer Immunotherapy. Cancers, 3, 3856-3893. https://doi.org/10.3390/cancers3043856
[14]
Boylston, A. (2012) The Origins of Inoculation. Journal of the Royal Society of Medicine, 105, 309-313. https://doi.org/10.1258/jrsm.2012.12k044
[15]
Belongia, E.A. and Naleway, A.L. (2003) Smallpox Vaccine: The Good, the Bad, and the Ugly. Clinical Medicine & Research, 1, 87-92. https://doi.org/10.3121/cmr.1.2.87
[16]
Ratajczak, W., Niedźwiedzka-Rystwej, P., Tokarz-Deptuła, B. and Deptuła, W. (2018) Immunological Memory Cells. Central European Journal of Immunology, 43, 194-203. https://doi.org/10.5114/ceji.2018.77390
[17]
CDC (2021) History of Smallpox. https://www.cdc.gov/smallpox/history/history.html
[18]
Gray, D. (2002) A Role for Antigen in the Maintenance of Immunological Memory. Nature Reviews Immunology, 2, 60-65. https://doi.org/10.1038/nri706
[19]
Miller, J. (2019) The Early Work on the Discovery of the Function of the Thymus, an Interview with Jacques Miller. Cell Death & Differentiation, 27, 396-401. https://doi.org/10.1038/s41418-019-0462-y
[20]
Gardner, J.M., Fletcher, A.L., Anderson, M.S. and Turley, S.J. (2009) AIRE in the Thymus and Beyond. Current Opinion in Immunology, 21, 582-589. https://doi.org/10.1016/j.coi.2009.08.007
[21]
Crotty, S. (2015) A Brief History of T Cell Help to B Cells. Nature Reviews Immunology, 15, 185-189. https://doi.org/10.1038/nri3803
[22]
Eiz-Vesper, B. and Schmetzer, H.M. (2020) Antigen-Presenting Cells: Potential of Proven Und New Players in Immune Therapies. Transfusion Medicine and Hemotherapy, 47, 429-431. https://doi.org/10.1159/000512729
[23]
Chen, L. and Flies, D.B. (2013) Molecular Mechanisms of T Cell Co-Stimulation and Co-Inhibition. Nature Reviews Immunology, 13, 227-242. https://doi.org/10.1038/nri3405
[24]
Marsman, C., Verhoeven, D., Koers, J., Rispens, T., ten Brinke, A., van Ham, S.M., et al. (2022) Optimized Protocols for In-Vitro T-Cell-Dependent and T-Cell-Independent Activation for B-Cell Differentiation Studies Using Limited Cells. Frontiers in Immunology, 13, Article 815449. https://doi.org/10.3389/fimmu.2022.815449
[25]
Jones, K., Savulescu, A.F., Brombacher, F. and Hadebe, S. (2020) Immunoglobulin M in Health and Diseases: How Far Have We Come and What Next? Frontiers in Immunology, 11, Article 595535. https://doi.org/10.3389/fimmu.2020.595535
[26]
Overton, A. and Lowry, A. (2013) Conflict Management: Difficult Conversations with Difficult People. Clinics in Colon and Rectal Surgery, 26, 259-264. https://doi.org/10.1055/s-0033-1356728
[27]
Maison, D.P. (2022) Tuberculosis Pathophysiology and Anti-VEGF Intervention. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 27, Article 100300. https://doi.org/10.1016/j.jctube.2022.100300
[28]
Ehlers, S. and Schaible, U.E. (2013) The Granuloma in Tuberculosis: Dynamics of a Host-Pathogen Collusion. Frontiers in Immunology, 3, Article 411. https://doi.org/10.3389/fimmu.2012.00411
[29]
Mackay, I.R. (2001) Tolerance and Autoimmunity. Western Journal of Medicine, 174, 118-123. https://doi.org/10.1136/ewjm.174.2.118
[30]
Pan, P., Ozao, J., Zhou, Z. and Chen, S. (2008) Advancements in Immune Tolerance. Advanced Drug Delivery Reviews, 60, 91-105. https://doi.org/10.1016/j.addr.2007.08.025
[31]
Radi, Z.A. and Wynn, T.A. (2020) Opinion on Immune Tolerance Therapeutic Development. Toxicologic Pathology, 48, 712-717. https://doi.org/10.1177/0192623320948805
[32]
Griesemer, A.D., Sorenson, E.C. and Hardy, M.A. (2010) The Role of the Thymus in Tolerance. Transplantation, 90, 465-474. https://doi.org/10.1097/tp.0b013e3181e7e54f
[33]
Carl, J.W., Liu, J., Joshi, P.S., El-Omrani, H.Y., Yin, L., Zheng, X., et al. (2008) Autoreactive T Cells Escape Clonal Deletion in the Thymus by a Cd24-Dependent Pathway. The Journal of Immunology, 181, 320-328. https://doi.org/10.4049/jimmunol.181.1.320
[34]
Pugliese, A. (2017) Autoreactive T Cells in Type 1 Diabetes. Journal of Clinical Investigation, 127, 2881-2891. https://doi.org/10.1172/jci94549
[35]
Ahmad, H.I., Jabbar, A., Mushtaq, N., Javed, Z., Hayyat, M.U., Bashir, J., et al. (2022) Immune Tolerance vs. Immune Resistance: The Interaction between Host and Pathogens in Infectious Diseases. Frontiers in Veterinary Science, 9, Article 827407. https://doi.org/10.3389/fvets.2022.827407
[36]
Murphy, K. and Weaver, C. (2017) Janeway’s Immunobiology. 9th Edition, Garland Science, Taylor & Francis Group and Limited Liability Company.
[37]
Elson, C.J., Barker, R.N., Thompson, S.J. and Williams, N.A. (1995) Immunologically Ignorant Autoreactive T Cells, Epitope Spreading and Repertoire Limitation. Immunology Today, 16, 71-76. https://doi.org/10.1016/0167-5699(95)80091-3
[38]
Zecher, D. and Lakkis, F.G. (2008) Ignorance Is Bliss. Blood, 111, 4426-4427. https://doi.org/10.1182/blood-2008-02-135996
Essery, G., Feldmann, M. and Lamb, J.R. (1988) Interleukin-2 Can Prevent and Reverse Antigen-Induced Unresponsiveness in Cloned Human T Lymphocytes. Immunology, 64, 413-417.
[41]
Artal-Sanz, M. and Tavernarakis, N. (2005) Proteolytic Mechanisms in Necrotic Cell Death and Neurodegeneration. FEBS Letters, 579, 3287-3296. https://doi.org/10.1016/j.febslet.2005.03.052
[42]
Jan, R. and Chaudhry, G. (2019) Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics. Advanced Pharmaceutical Bulletin, 9, 205-218. https://doi.org/10.15171/apb.2019.024
[43]
Sakaguchi, S., Wing, K. and Miyara, M. (2007) Regulatory T Cells—A Brief History and Perspective. European Journal of Immunology, 37, S116-S123. https://doi.org/10.1002/eji.200737593
[44]
Kim, J., Lahl, K., Hori, S., Loddenkemper, C., Chaudhry, A., deRoos, P., et al. (2009) Cutting Edge: Depletion of Foxp3+ Cells Leads to Induction of Autoimmunity by Specific Ablation of Regulatory T Cells in Genetically Targeted Mice. The Journal of Immunology, 183, 7631-7634. https://doi.org/10.4049/jimmunol.0804308
[45]
Grover, P., Goel, P.N. and Greene, M.I. (2021) Regulatory T Cells: Regulation of Identity and Function. Frontiers in Immunology, 12, Article 750542. https://doi.org/10.3389/fimmu.2021.750542
[46]
Komai, T., Inoue, M., Okamura, T., Morita, K., Iwasaki, Y., Sumitomo, S., et al. (2018) Transforming Growth Factor-Β and Interleukin-10 Synergistically Regulate Humoral Immunity via Modulating Metabolic Signals. Frontiers in Immunology, 9, Article 1364. https://doi.org/10.3389/fimmu.2018.01364
