SUMMARY

The prevalence and intensity of infections caused by protozoa, nematodes, trematodes, cestodes, and arthropods is higher in males than females. The primary thesis of this review is that immunological differences exist between the sexes that may underlie increased parasitism in males compared to females. Several field and laboratory studies link sex differences in immune function with circulating steroid hormones; thus, the roles of sex steroids, including testosterone, oestradiol, and progesterone, as well as glucocorticoids will be discussed. Not only can host hormones affect responses to infection, but parasites can both produce and alter hormone concentrations in their hosts. The extent to which changes in endocrine–immune interactions following infection are mediated by the host or the parasite will be considered. Although males are more susceptible than females to many parasites, there are parasites for which males are more resistant than females and endocrine–immune interactions may underlie this sex reversal. Finally, although immunological differences exist between the sexes, genetic and behavioural differences may explain some variability in response to infection and will be explored as alternative hypotheses for how differences between the sexes contribute to dimorphic responses to parasites.

http://www.higiene.edu.uy/ubp/ubp_files/papers/2-7%20Hormonal.pdf

Hormonal and immunological mechanisms mediating sex differences in parasite infection

Natural killer (NK) cells survey host tissues for signs of infection, transformation or stress and, true to their name, kill target cells that have become useless or are detrimental to the host. For decades, NK cells have been classified as a component of the innate immune system. However, accumulating evidence in mice and humans suggests that, like the B and T cells of the adaptive immune system, NK cells are educated during development, possess antigen-specific receptors, undergo clonal expansion during infection and generate long-lived memory cells. In this Review, we highlight the many stages that an NK cell progresses through during its remarkable lifetime, discussing similarities and differences with its close relative, the cytotoxic CD8(+) T cell.

https://www.ufjf.br/imunologia/files/2012/06/Aula-3-Poliana-Jerusa-e-Isabella-REV-12-NK-cell-development.pdf

NK cell development, homeostasis and function: parallels with CD8 + T cells

Natural killer (NK) cells play important roles in immunological processes, including early defense against viral infections. This review provides an overview of the dynamic in vivo life of NK cells from their development in the bone marrow to their mature peripheral responses and their ultimate demise, with particular emphasis on mouse NK cells and viral infections.

The Dynamic Life of Natural Killer Cells

Liver natural killer (NK) cells were recently reported to possess memory-like properties in contact hypersensitivity (CHS) models. However, the phenotype and origin of these “memory” NK cells cannot be distinguished from other NK cell subpopulations. Here, we define the transcriptional, phenotypic, and functional features of liver NK cell subsets and their roles in mediating CHS. Liver NK cells can be divided into two distinct subsets: CD49a+DX5– and CD49a–DX5+. Substantial transcriptional and phenotypic differences existed between liver CD49a+DX5– NK cells and other NK cell subsets. CD49a+DX5– NK cells possessed memory potential and conferred hapten-specific CHS responses upon hapten challenge. Importantly, CD49a+DX5– NK cells were liver resident and were present in the liver sinusoidal blood, but not the afferent and efferent blood of the liver. Moreover, they appeared to originate from hepatic hematopoietic progenitor/stem cells (HPCs/HSCs) but not from the bone marrow, and maintained their phenotypes in the steady state. Our findings of liver-resident NK cells shed new light on the acquisition of memory-like properties of NK cells.

/pdf/liver-resident-nk-cells-confer-adaptive-immunity-in-skin-10yvsv5edp.pdf

Liver-resident NK cells confer adaptive immunity in skin-contact inflammation.

Numerous epidemiological and clinical studies have noted differences in the incidence and severity of parasitic diseases between males and females. Although in some instances this may be due to gender-associated differences in behavior, there is overwhelming evidence that sex-associated hormones can also modulate immune responses and consequently directly influence the outcome of parasitic infection. Animal models of disease can often recreate the gender-dependent differences observed in humans, and the role of sex-associated hormones can be confirmed by experimentally altering their levels. Under normal circumstances, levels of sex hormones not only differ between males and females but vary according to age. Furthermore, not only are females of reproductive age subject to the regular hormonal cycles which control ovulation, they are also exposed to dramatically altered levels during pregnancy. It is thus not surprising that the severity of many diseases, including those caused by parasites, has been shown to be affected by one or more of these circumstances. In addition, infection with many pathogens has been shown to have an adverse influence on pregnancy. In this article we review the impact of sex-associated hormones on the immune system and the development and maintenance of immunity to the intracellular protozoan parasites Toxoplasma gondii, Plasmodium spp., and Leishmania spp.

Sex-Associated Hormones and Immunity to Protozoan Parasites

beta-estradiol was administered to mice continuously by diffusion from a silastic tube that was implanted subcutaneously at 4 weeks of age. Four to 6 weeks of estrogen administration caused a substantial reduction in natural killer cell activity in the spleens from mice of either sex. Androgen (5alpha-dihydrotestosterone) did not. Castration of male or female mice did not affect natural killing and did not alter the effect of beta-estradiol. Estradiol did not affect natural killing in vitro and the loss of natural killing was not due to a soluble or a cellular suppressor of natural killing. The effects of estradiol were not dependent on the thymus, since estradiol reduced natural killing in mice that had been neonatally thymectomized. After removal of the estrogen implant, natural killing recovered over a period of 8 weeks. The loss of natural killing may reflect a loss of bone marrow secondary to estrogen-induced osteosclerosis.

John M. Loeb

Papers

Beta-estradiol reduces natural killer cells in mice.