Fig. 3.

Sex-specific immune responses to vaccination. Innate and adaptive immune responses to vaccination are overall different in males and females, including sex chromosomal and hormonal differences. Sex-based effects of vaccination are more pronounced in females than males. At the first step of immune responses, neutrophils and macrophages release more inflammatory cytokines and chemokines in females. Actually, females have more levels of neutrophils and macrophages, but in contrast NK cell frequencies are more in males than females. Sex hormones of estrogen mostly influence responses to vaccination. Major histocompatibility complex (MHCII) that exists on antigen-presenting cells of dendritic cells, macrophages and B cells, is upregulated by estrogen. Also, while testosterone has an inhibitory effect on the expression of TLR7, estrogen exerts a stimulatory impact on them. Also, estrogen leads to more expression of IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) in the dendritic cells. In adaptive immunity, estrogen result in antibody glycosylation levels. X-chromosome encodes the genes involved in immune responses to vaccination. TLR7 and CD40L locate on the X-chromosome and more expressed in females than males.