Figure 2.
The diagram is divided into three sections: Dysregulation of Innate Immunity, Dysregulation of Adaptive T cell Immunity, and Dysregulation of Adaptive B cell Immunity. Each section lists decreased and increased components, functional differences, and clinical impacts. The Dysregulation of Innate Immunity section includes decreased classical monocytes and increased non-classical monocytes, basophils, and activated NK cells. Functional differences include impaired neutrophil chemotaxis, decreased bactericidal activity, interferon hypersensitivity, and dysregulated TLR signaling. Clinical impacts include early-onset periodontitis, complications from sinopulmonary infections, bacterial pneumonia, sepsis, HLH, and atypical inflammatory syndromes. The Dysregulation of Adaptive T cell Immunity section includes decreased total T cells, thymic output, naive subsets, and TCR excision circles, and increased CD8/CD4 ratio, effector and memory subsets, exhausted subsets, and γδ T cells. Functional differences include interferon hypersensitivity, increased cytokine production upon TCR stimulation, resistance to Treg-mediated suppression, differential VDJ usage, and Th17 polarization. Clinical impacts include autoimmunity. The Dysregulation of Adaptive B cell Immunity section includes decreased total B cells, total memory B cells, class-switch memory B cells, and IgE production, and increased age-associated B cells, plasmablasts, CD11c expression, and Tbet expression. Functional differences include interferon hypersensitivity, increased autoreactivity, and differential VDJ usage. Clinical impacts include autoimmunity, decreased vaccine responses, susceptibility to bacterial infections, CVID phenotype, and lower allergic sensitization.
Mechanisms and clinical manifestations of dysregulated innate and adaptive immunity in DS.