Sex differences in immune responses, 2016, Klein and Flanagan

[SNT Gatchaman]

Sex differences in immune responses
Klein SL, Flanagan KL

Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.

PubMed | PDF (Nature Reviews: Immunology)

 

[SNT Gatchaman]

 

[SNT Gatchaman]

In humans, sex chromosomes are heterologous in males (XY) and homologous infemales (XX). The human Y chromosome contains approximately 100 genes, including SRY, which encodes for the testis determining factor, and regulatory genes that may be important for immune responses in autoimmune and infectious diseases.

The human X chromosome contains over 1,100 annotated genes, representing approximately 5% of the human genome, and includes a significant number of immune related genes, such as interleukin 2 (IL-2) receptor-γ chain, IL-3 receptor-α chain, IL-13 receptor-α chains, Toll-like receptor 7 (TLR7), TLR8, GATA1, IL-1 receptor-associated kinase 1 (IRAK1), CD40 ligand and FOXP3. Several crucial transcriptional and translational control effectors, that function downstream of activated cytokine receptors, are encoded on the X chromosome. The implications are that X‐linked genes are determinants of sex differential immune responses. For genes on the X chromosome, outside of the pseudoautosomal regions, one copy has to be silenced to ensure only a single copy functions in each sex. Inactivation is initiated by the X-inactive specific transcript (XIST) gene. Approximately 15% of X genes in humans and 3% in mice escape X inactivation and are found in higher copy number in females than males. For X-linked genes that are inactivated in females, the random process of inactivation of copies derived from the maternal or paternal X chromosome results in a mosaic in females, but not in males. Genomic imprinting is an epigenetic mechanism that is responsible for an imbalance in expression of maternal and paternal inherited genes according to the parent-of-origin. It varies in different tissues and at different developmental stages. In mice, the expression levels of certain imprinted genes vary between the sexes. In addition to sex differences in transcription, there are also sex differences in post-transcriptional mechanisms.