Review
The influence of sex and gender on the immune response

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Abstract

The immune system and its orchestrated response are affected by a multitude of endogenous and exogenous factors, modulators and challenges. One of the most frequent differences described in the immune response is its vigor and activity in females compared to males, leading to the consequent increase in autoimmune conditions seen in the female population as well as differences in the immune response to pathogens and viruses. The following review summarizes our present knowledge on sex differences in the immune response, detailing the hormonal and genetic effects that have been proposed as explanatory mechanisms. Sexual hormones, mostly estrogen but also progesterone and testosterone, affect immune cells quantitatively and qualitatively. Relevant research has focused on the impact of hormones on cytokine production by the different effector cells, as well as impact on immunoglobulin production by B lymphocytes and activity of granulocytes and NK cells. The biological aspects are complemented by research data on the possible modulatory role of the X chromosome. In addition to biological differences, the frequently neglected role of gender as an immunomodulator is introduced and explored. Gender affects all areas of human life and consequently affects the different steps of an immune response. Exposure to various types of antigens, access to health promotion programs and health care, as well as prioritization of health needs and household resource allocation all affect the different response of females and males to immunologic challenges.

Introduction

Differences between women and men can be identified at many levels of the immune response and might affect its eventual outcome. While these differences are generally analyzed from a biological point of view, gender aspects are seldom incorporated. In the medical field “sex differences” are defined as biologically conditioned dissimilarities between female and male subjects, while psychosocial, cultural and economic factors determine “gender differences” [1]. Applying the methods commonly used in biomedical research biological differences might appear forthright in detection, while gender aspects are frequently more elusive and complex to define and identify. As both factors act in concert and cannot be separated at times (Table 1), the following review will consider both aspects; biological and genetic differences in the immune response and gender aspects that condition exposure, modulation and access to immunomodulatory agents. The reader will notice how research methodology; theoretical assumptions and focus vary between these two sections, nonetheless, an integration of both areas is possible as demonstrated by the constantly increasing number of publications in the field [2] and essential for the understanding of this complex issue.

Section snippets

Biological differences

Research about sex differences in immunology as in any other medical discipline has been centered on two main influences: endocrinology, i.e. the effect of sex hormones, and genetics, i.e. the effect of the X chromosome.

Gender differences

In addition to their influence on biological differences in the immune response, gender differences are especially relevant in the exposure to the challenges that will determine and modulate an immune response. The exposure to the immunological challenge of viral, bacterial, chemical or any other nature is the first step towards an orchestrated immune response, thus, these differences should be considered in addition to the biological and genetic ones described above. Degree and timing of

Conclusions and further directions

Sex and gender interact at several levels to determine the entity and effectiveness of the immune response and should be considered in concert whenever possible (Fig. 1). Further investigation into both dimensions and especially their interaction could broaden our knowledge about sex and gender differences in immunology substantially and potentially identify unknown pathogentic pathways and novel therapeutic approaches for both women and men.

Conflicts of interest

None to declare.

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