Human immune system: Exploring diversity across individuals and populations

Abstract

The immune response is an intricate system that involves the complex connection of cellular and molecular components, each with distinct functional specialisations. It has a distinct capacity to adjust and mould the immune response in accordance with specific stimuli, influenced by both genetic and environmental factors. The presence of genetic diversity, particularly across different ethnic and racial groups, significantly contributes to the impact of incidence of diseases, disease susceptibility, autoimmune disorders, and cancer risks in specific regions and certain populations. Environmental factors, including geography and socioeconomic status, further modulate the variety of the immune system responses. These, in turn, affect the susceptibility to infectious diseases and development of autoimmune disorders. Despite the complexity of the relationship, there remains a gap in understanding the specificity of immune indices across races, immune reference ranges among populations, highlighting the need for deeper understanding of immune diversity for personalized approaches in diagnostics and therapeutics. This review systematically organizes these findings, with the goal of emphasizing the potential of targeted interventions to address health disparities and advance translational research, enabling a more comprehensive strategy. This approach promises significant advancements in identifying specific immunological conditions, focusing on personalized interventions, through both genetic and environmental factors.

Keywords: Autoimmunity; Cancer; Diversity; Immune system; Infection; Population.

Fig. 1

The flowchart describes the workflow with two distinct stages: the ideation stage and the writing stage.

Fig. 2

The Involvement of Genetic Factors in Racial and Ethnic Differences in Diseases. A. Prostate Cancer: FOXA1 influences androgen receptor signaling critical for prostate cancer cell survival. Mongoloids have poor outcomes with FOXA1 overexpression, Negroids show high incidence due to FOXA1 mutations, and Caucasians have increased risk linked to TMPRSS2 and ERG mutations [241,275]. B. Type I Diabetes: T1DM involves B cell destruction and varies by race, with unique genetic risk markers: C1858T, ZFHX3, and HLA in Mongoloids; HLA-DQA103:01-HLA-DQB102:01 in Negroids; and rs1990760 and IFIH1 in Caucasians [246,276,277]. C. Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE): Caucasians face severe RA linked to SLC22A4/5 SNPs, while African individuals often experience earlier onset and more severe SLE due to elevated TLR expression [254,278]. D. Infections: Mongoloids have doubled risks of severe COVID-19 due to rs17713054 and LZTFL1. Negroids are more protected against severe malaria linked to rs1050501, while Caucasians show weak malaria resistance associated with the Fc-GammaR pathway [260,261,279,280].

Fig. 3

Epigenetic influence through a lifetime of exposure, DNA interactions and cancer development.

Fig. 4

Exploring the Complexity of Immune System Diversity: Drivers, Responses, and Medical Applications. A. The human immune system can be conceptualized as a complex network with three primary drivers: genetic variations; geographic factors, including infectious agents, diet, nutrition, climate, and environmental toxins; and socioeconomic factors such as access to healthcare, sanitation, hygiene, and lifestyle. These primary drivers interact with one another and significantly influence the body's microbiome, which acts as a protective interface for the immune system. B. This strong foundation allows the immune system to develop robustly, resulting in individual diversity. Such diversity manifests in varied expressions of infectious diseases, autoimmune disorders, and allergies. C. Understanding this conceptual framework suggests that medical researchers should adopt multi-omics approaches to diseases, develop novel diagnostic tools, and consider the polymorphism of biomarkers based on racial and regional factors. D. Investigating the interplay between the drivers and responses of the immune system forms the basis for the development of targeted therapeutics, personalized interventions, immunotherapies, and vaccines. E. Furthermore, examining the interplay between diseases and socioeconomic factors through the lens of immune interactions highlights the future of preventive healthcare. This approach focuses on reducing environmental pollutants, improving living conditions, promoting healthy lifestyles, and addressing socioeconomic disparities.