THE ROLE OF IMMUNOGENICS IN ORAL HEALTH: INSIGHTS INTO MECHANISMS AND INTERVENTIONS



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Abstract

The oral cavity represents a dynamic environment in which the host immune system and resident microbiota continuously interact to maintain tissue integrity and prevent disease. This review explores the complex interplay between immunogenic and oral health, emphasizing the pivotal role of mucosal immunity in sustaining microbial balance and providing defense against pathogenic challenges. The innate and adaptive immune responses including the actions of secretory immunoglobulin A (SIgA), dendritic cells, macrophages and T and B lymphocytes work synergistically to regulate microbial colonization, neutralize invading pathogens, and modulate inflammatory reactions. Dysregulation of these immune pathways, combined with ecological shifts in the oral microbiome, contributes to the pathogenesis of major oral diseases. Periodontal disease is now understood as a dysbiosis driven condition characterized by synergistic polymicrobial communities and an exaggerated inflammatory response that disrupts tissue homeostasis. Similarly, dental caries results from an imbalance in microbial ecology, driven by acidogenic and aciduric species that coordinate biofilm formation through quorum sensing systems such as CSP and AI-2. In the context of oral cancer, impaired immune surveillance and tumor-induced immune evasion further highlight the importance of coordinated innate and adaptive responses in maintaining oral health. The expanding knowledge of immunological mechanisms in the oral cavity has supported the development of innovative diagnostic and therapeutic strategies. Saliva-based diagnostics now enable the detection of immunoglobulins, cytokines, and microbial markers using non-invasive and highly sensitive platforms, including nanobiosensors and spectroscopic technologies. Furthermore, advances in mucosal immunotherapy and vaccine design offer promising avenues for enhancing local immunity and preventing infection driven oral diseases. By integrating current evidence from immunology, microbiology, and clinical practice, this study underscores the central role of immune-microbiome interactions in oral health and disease. A deeper understanding of these pathways may guide the development of targeted diagnostic tools and personalized preventive and therapeutic interventions, ultimately improving oral and systemic health outcomes.

About the authors

Shahad Fayiz Abd

Uruk University, Baghdad, Iraq

Email: shahad.f.abed@uruk.edu.iq
ORCID iD: 0009-0005-1691-3247

M.Sc. MSc., Oral Microbiology and Clinical immunology

Academic Title: Assistant Lecturer

Academic Degree: MSc in Oral Microbiology and Clinical Immunology

Tenure/Position: Department of Medical Science, College of Dentistry, Uruk University

Iraq

Ahmed Qasim Talib

Ashur University, Baghdad, Iraq

Author for correspondence.
Email: ahmed.qasim@au.edu.iq
ORCID iD: 0000-0002-5437-2956

Academic Title: Assistant Lecturer

Academic Degree: MSc in Conservative Dentistry

Tenure/Position: Department of Restorative Dentistry, College of Dentistry, Ashur University

Iraq

References

  1. Wilhelm G, Mertowska P, Mertowski S, Przysucha A, Strużyna J, Grywalska E, Torres K. The Crossroads of the Coagulation System and the Immune System: Interactions and Connections. Int J Mol Sci 2023;24:12563. https://doi.org/10.3390/ijms241612563.
  2. Santos-Neto JF, Oliveira FO, Hodel KVS, Fonseca LMS, Badaró R, Machado BAS. Technological Advancements in Monoclonal Antibodies. The Scientific World Journal 2021;2021:1–19. https://doi.org/10.1155/2021/6663708.
  3. Varadé J, Magadán S, González-Fernández Á. Human immunology and immunotherapy: main achievements and challenges. Cell Mol Immunol 2021;18:805–28. https://doi.org/10.1038/s41423-020-00530-6.
  4. Zhou X, Wu Y, Zhu Z, Lu C, Zhang C, Zeng L, Xie F, Zhang L, Zhou F. Mucosal immune response in biology, disease prevention and treatment. Signal Transduct Target Ther 2025;10:7. https://doi.org/10.1038/s41392-024-02043-4.
  5. Kogut MH, Lee A, Santin E. Microbiome and pathogen interaction with the immune system. Poult Sci 2020;99:1906–13. https://doi.org/10.1016/j.psj.2019.12.011.
  6. Radaic A, Kapila YL. The oralome and its dysbiosis: New insights into oral microbiome-host interactions. Comput Struct Biotechnol J 2021;19:1335–60. https://doi.org/10.1016/j.csbj.2021.02.010.
  7. Medappa BKA, Fareed N, Battur H, Praveena J. Impact of Oral Health Programmes on the Oral Health-Related Quality of Life among Children: A Systematic Review. Journal of Indian Association of Public Health Dentistry 2023;21:217–21. https://doi.org/10.4103/jiaphd.jiaphd_130_22.
  8. Tsakos G, Allen F. Oral Health-Related Quality of Life, 2021, p. 319–32. https://doi.org/10.1007/978-3-030-50123-5_20.
  9. Chimbinha ÍGM, Ferreira BNC, Miranda GP, Guedes RS. Oral-health-related quality of life in adolescents: umbrella review. BMC Public Health 2023;23:1603. https://doi.org/10.1186/s12889-023-16241-2.
  10. Nutbeam D, Muscat DM. Health Promotion Glossary 2021. Health Promot Int 2021;36:1811–1811. https://doi.org/10.1093/heapro/daab067.
  11. de Abreu MHNG, Cruz AJS, Borges-Oliveira AC, Martins R de C, Mattos F de F. Perspectives on Social and Environmental Determinants of Oral Health. Int J Environ Res Public Health 2021;18:13429. https://doi.org/10.3390/ijerph182413429.
  12. Janakiram C, Dye BA. A public health approach for prevention of periodontal disease. Periodontol 2000 2020;84:202–14. https://doi.org/10.1111/prd.12337.
  13. Kalevski K, Vojinovic J, Gajic M, Aleksic E, Tambur Z, Milutinovic J, Borotic N, Mladenovic R. The Outcomes of an Interventional Oral Health Program on Dental Students’ Oral Hygiene. Int J Environ Res Public Health 2021;18:13242. https://doi.org/10.3390/ijerph182413242.
  14. Li X, Liu Y, Yang X, Li C, Song Z. The Oral Microbiota: Community Composition, Influencing Factors, Pathogenesis, and Interventions. Front Microbiol 2022;13. https://doi.org/10.3389/fmicb.2022.895537.
  15. Ptasiewicz M, Bębnowska D, Małkowska P, Sierawska O, Poniewierska-Baran A, Hrynkiewicz R, Niedźwiedzka-Rystwej P, Grywalska E, Chałas R. Immunoglobulin Disorders and the Oral Cavity: A Narrative Review. J Clin Med 2022;11:4873. https://doi.org/10.3390/jcm11164873.
  16. Deslauriers N, Seguin J, Trudel L. Differential Recognition of Oral Indigenous Bacteria by Salivary Immunoglobulins A and G. Microbiol Immunol 1987;31:199–209. https://doi.org/10.1111/j.1348-0421.1987.tb03084.x.
  17. Li Y, Jin L, Chen T. The Effects of Secretory IgA in the Mucosal Immune System. Biomed Res Int 2020;2020. https://doi.org/10.1155/2020/2032057.
  18. Mira Al Shoufy, Naseeb Danaf, Kholoud Al Jebawi, Sandra Said Aboudaher, Adel Ayash, Ahmad Al Kadi, Batoul Shokor, Fatima Zeidan, Nourhan Kanso, Razan Salha, Shubh Prashant Mehta, Mohammad Shamseddine, Jamil Nasrallah. Cascading defenses: A multifaceted narrative of immune responses in head and neck physiology. Magna Scientia Advanced Research and Reviews 2024;10:194–222. https://doi.org/10.30574/msarr.2024.10.1.0018.
  19. Fábián TK, Hermann P, Beck A, Fejérdy P, Fábián G. Salivary Defense Proteins: Their Network and Role in Innate and Acquired Oral Immunity. Int J Mol Sci 2012;13:4295–320. https://doi.org/10.3390/ijms13044295.
  20. Pelaez-Prestel HF, Sanchez-Trincado JL, Lafuente EM, Reche PA. Immune Tolerance in the Oral Mucosa. Int J Mol Sci 2021;22:12149. https://doi.org/10.3390/ijms222212149.
  21. Caputo V, Libera M, Sisti S, Giuliani B, Diotti RA, Criscuolo E. The initial interplay between HIV and mucosal innate immunity. Front Immunol 2023;14. https://doi.org/10.3389/fimmu.2023.1104423.
  22. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245–52. https://doi.org/10.1038/32588.
  23. Farber DL, Netea MG, Radbruch A, Rajewsky K, Zinkernagel RM. Immunological memory: lessons from the past and a look to the future. Nat Rev Immunol 2016;16:124–8. https://doi.org/10.1038/nri.2016.13.
  24. Lam N, Lee Y, Farber DL. A guide to adaptive immune memory. Nat Rev Immunol 2024;24:810–29. https://doi.org/10.1038/s41577-024-01040-6.
  25. Shepherd FR, McLaren JE. T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion. Int J Mol Sci 2020;21:6144. https://doi.org/10.3390/ijms21176144.
  26. Brandtzaeg P, Johansen F. Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev 2005;206:32–63. https://doi.org/10.1111/j.0105-2896.2005.00283.x.
  27. Wei H, Wang J-Y. Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis. Int J Mol Sci 2021;22:2284. https://doi.org/10.3390/ijms22052284.
  28. Zhou T, Xu W, Wang Q, Jiang C, Li H, Chao Y, Sun Y, A L. The effect of the “Oral-Gut” axis on periodontitis in inflammatory bowel disease: A review of microbe and immune mechanism associations. Front Cell Infect Microbiol 2023;13. https://doi.org/10.3389/fcimb.2023.1132420.
  29. Suárez LJ, Garzón H, Arboleda S, Rodríguez A. Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review. Front Immunol 2020;11. https://doi.org/10.3389/fimmu.2020.591255.
  30. Abdulkareem AA, Al-Taweel FB, Al-Sharqi AJB, Gul SS, Sha A, Chapple ILC. Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis. J Oral Microbiol 2023;15. https://doi.org/10.1080/20002297.2023.2197779.
  31. Toor D, Wsson MK, Kumar P, Karthikeyan G, Kaushik NK, Goel C, Singh S, Kumar A, Prakash H. Dysbiosis Disrupts Gut Immune Homeostasis and Promotes Gastric Diseases. Int J Mol Sci 2019;20:2432. https://doi.org/10.3390/ijms20102432.
  32. Nyvad B, Takahashi N. Integrated hypothesis of dental caries and periodontal diseases. J Oral Microbiol 2020;12:1710953. https://doi.org/10.1080/20002297.2019.1710953.
  33. Hajishengallis E, Parsaei Y, Klein MI, Koo H. Advances in the microbial etiology and pathogenesis of early childhood caries. Mol Oral Microbiol 2017;32:24–34. https://doi.org/10.1111/omi.12152.
  34. Philip N, Suneja B, Walsh L. Beyond Streptococcus mutans: clinical implications of the evolving dental caries aetiological paradigms and its associated microbiome. Br Dent J 2018;224:219–25. https://doi.org/10.1038/sj.bdj.2018.81.
  35. Markowska K, Szymanek-Majchrzak K, Pituch H, Majewska A. Understanding Quorum-Sensing and Biofilm Forming in Anaerobic Bacterial Communities. Int J Mol Sci 2024;25:12808. https://doi.org/10.3390/ijms252312808.
  36. Zhu Y, Wang Y, Zhang S, Li J, Li X, Ying Y, Yuan J, Chen K, Deng S, Wang Q. Association of polymicrobial interactions with dental caries development and prevention. Front Microbiol 2023;14. https://doi.org/10.3389/fmicb.2023.1162380.
  37. Jayaraman A, Wood TK. Bacterial Quorum Sensing: Signals, Circuits, and Implications for Biofilms and Disease. Annu Rev Biomed Eng 2008;10:145–67. https://doi.org/10.1146/annurev.bioeng.10.061807.160536.
  38. Mukherjee S, Bassler BL. Bacterial quorum sensing in complex and dynamically changing environments. Nat Rev Microbiol 2019;17:371–82. https://doi.org/10.1038/s41579-019-0186-5.
  39. Yang Y, Lin J, Harrington A, Cornilescu G, Lau GW, Tal-Gan Y. Designing cyclic competence-stimulating peptide (CSP) analogs with pan-group quorum-sensing inhibition activity in Streptococcus pneumoniae. Proceedings of the National Academy of Sciences 2020;117:1689–99. https://doi.org/10.1073/pnas.1915812117.
  40. Chen J-Y, Shih L-J, Liao M-T, Tsai K-W, Lu K-C, Hu W-C. Understanding the Immune System’s Intricate Balance: Activation, Tolerance, and Self-Protection. Int J Mol Sci 2025;26:5503. https://doi.org/10.3390/ijms26125503.
  41. Chen Y, Yu D, Qian H, Shi Y, Tao Z. CD8+ T cell-based cancer immunotherapy. J Transl Med 2024;22:394. https://doi.org/10.1186/s12967-024-05134-6.
  42. Kim SK, Cho SW. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment. Front Pharmacol 2022;13. https://doi.org/10.3389/fphar.2022.868695.
  43. Knight SC, Burke F, Bedford PA. Dendritic cells, antigen distribution and the initiation of primary immune responses to self and non-self antigens. Semin Cancer Biol 2002;12:301–8. https://doi.org/10.1016/S1044-579X(02)00016-0.
  44. Yamashita Y, Takeshita T. The oral microbiome and human health. J Oral Sci 2017;59:201–6. https://doi.org/10.2334/josnusd.16-0856.
  45. Willis JR, Gabaldón T. The Human Oral Microbiome in Health and Disease: From Sequences to Ecosystems. Microorganisms 2020;8:308. https://doi.org/10.3390/microorganisms8020308.
  46. Ptasiewicz M, Grywalska E, Mertowska P, Korona-Głowniak I, Poniewierska-Baran A, Niedźwiedzka-Rystwej P, Chałas R. Armed to the Teeth—The Oral Mucosa Immunity System and Microbiota. Int J Mol Sci 2022;23:882. https://doi.org/10.3390/ijms23020882.
  47. Matsuoka M, Soria SA, Pires JR, Sant’Ana ACP, Freire M. Natural and induced immune responses in oral cavity and saliva. BMC Immunol 2025;26:34. https://doi.org/10.1186/s12865-025-00713-8.
  48. Pittman TW, Decsi DB, Punyadeera C, Henry CS. Saliva-based microfluidic point-of-care diagnostic. Theranostics 2023;13:1091–108. https://doi.org/10.7150/thno.78872.
  49. Warnakulasuriya S, Patil S. Salivary and Serum Liquid Biopsy Biomarkers for HPV-Associated Oral and Oropharyngeal Cancer: A Narrative Review. J Clin Med 2025;14:7598. https://doi.org/10.3390/jcm14217598.
  50. Taha GI, Talib EQ, Abed FB, Hasan IA. A review of microbial pathogens and diagnostic techniques in children’s oral health. Sri Lanka Journal of Child Health 2024;53:355–9. https://doi.org/10.4038/sljch.v53i4.11043.
  51. Kumari S, Samara M, Ampadi Ramachandran R, Gosh S, George H, Wang R, Pesavento RP, Mathew MT. A Review on Saliva-Based Health Diagnostics: Biomarker Selection and Future Directions. Biomedical Materials & Devices 2024;2:121–38. https://doi.org/10.1007/s44174-023-00090-z.
  52. Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C. Diagnostic Potential of Saliva: Current State and Future Applications. Clin Chem 2011;57:675–87. https://doi.org/10.1373/clinchem.2010.153767.
  53. Iwasaki A. Mucosal Dendritic Cells. Annu Rev Immunol 2007;25:381–418. https://doi.org/10.1146/annurev.immunol.25.022106.141634.
  54. Corthésy B, Bioley G. Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection. Front Immunol 2018;9. https://doi.org/10.3389/fimmu.2018.00431.

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