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During the last century, changes in hygiene, sanitation, and the advent of childhood vaccination have resulted in profound reductions in mortality from infectious diseases. Despite this success, infectious diseases remain an enigmatic public health threat, where effective vaccines for influenza, human immunodeficiency virus (HIV), tuberculosis, and malaria, among others remain elusive. In addition to the immune evasion tactics employed by complex pathogens, our understanding of immunopathogenesis and the development of effective vaccines is also complexified by the inherent variability of human immune responses. Lymph nodes (LNs) are the anatomical sites where B cell responses develop. An important, but understudied component of immune response complexity is variation in LN immune dynamics and in particular variation in germinal center follicular helper T cells (Tfh) and B cells which can be impacted by genetic variation, aging, the microbiome and chronic infection. We describe the contribution of genetic variation, aging, microbiome and chronic infection on LN immune dynamics and associated Tfh responses and offers perspective on how inclusion of LN immune subset and cytoarchitecture analyses, along with peripheral blood biomarkers can supplement systems vaccinology or immunology approaches for the development of vaccines or other interventions to prevent infectious diseases.

Human lymph node immune dynamics as driver of vaccine efficacy: an understudied aspect of immune responses