Indeed, the female immune system is more active, it copes with sepsis faster and helps to heal wounds faster, but, on the other hand, the risk increases that the immune system will begin to attack the body’s own cells: women are more likely to suffer from lupus erythematosus, multiple sclerosis, Sjogren’s syndrome and other autoimmune diseases. Why is female immunity different from male immunity? By itself, the immune system, its cells (lymphocytes, macrophages, plasmocytes) and humoral agents (antibodies, cytokines, lymphokines) have no sexual characteristics. However, the immune system is closely linked to the nervous and endocrine systems, and there are more than enough sexual differences in them. Over 1,100 genes have been found to be more or less associated with differences in immune responses in women and men. If we talk about the nervous system, now the features in the structure of the brain, determined by gender, are already quite well known. Men have more white matter in them, and women have more gray matter. Because of this, the cortex of the brain in women is slightly thicker, and therefore has a slightly more complex landscape (since more gray matter needs to be somehow arranged and laid using convolutions). In addition, there is a difference in the size of individual brain structures: for example, the hippocampus, which is considered one of the main memory centers, is on average larger in men. They also have a larger amygdala, which is responsible for processing emotions and, again, for memory. As men age, the total volume of the brain decreases, but at the same time the size of the frontal and temporal lobes increases, while in women, the size of the hippocampus and the cortex of the parietal region decreases with age. The volume of gray matter in both sexes decreases linearly with age, but in men this process is more intense. Finally, not so long ago, neuroscientists found differences in intracerebral connections.: for women, the advantage is given to interhemispheric connections, and for men — to intrahemispheric ones. Although it is not always clear how structural features affect (and whether they affect) the cognitive functions and behavior of both sexes. As for the intracerebral connections, the structural data are quite consistent with the results of psychological experiments, according to which women are better able to control attention, better remember words and faces, and better navigate the group, that is, show good social skills. Men, on the other hand, win in the corresponding tests in sensorimotor tasks and in the ability to navigate in space. And such cognitive-behavioral differences appear just by the age of 12-14, when specifics begin to arise in the structure of the brain’s pathways. One of the most important functions of the nervous system is the response to stress, including psychological stress. It manifests itself in different ways: a person can become depressed, or he can become aggressive, preferring an attack to withdrawal. In any case, stress suppresses the immune system, and since we have sexual differences in the nervous system, the stress effect of immune suppression in men and women should be different. Indeed, depression is more harmful to women’s immunity than men’s. Negative emotional stress causes an increase in the level of inflammatory cytokine proteins, which increases the risk of developing tissue immunity to insulin in women with a low anger threshold (i.e., irritated by trifles), which is one of the characteristic features of type 2 diabetes. For men, this issue has not been sufficiently studied. But why do differences in the nervous system affect the immune system? Here we need to remember through which intermediaries the brain and nerves can act on the immune system. Firstly, these are neurotransmitters, substances that are involved in the transmission of impulses from one nerve cell to another. They can act not only on neurons, but also on other cells. Secondly, it’s hormones. Thus, chronic stress stimulates the release of adrenal hormones — glucocorticoids, as well as prolactin and PHF (nerve growth factor), which act on the immune system, slowing wound healing, impairing the response to vaccination and reducing the anti-cancer abilities of the immune system. Analyzing the relationship between gender and hormonal status in acute psychological stress, researchers have found that two important endocrine glands, the hypothalamus and pituitary gland, work differently in men and women. Gender differences in their work affect the level of the stress glucocorticoid cortisol, the secretion of which in the adrenal glands is controlled by the hypothalamic-pituitary axis.: In women, the amplitude of cortisol reached its maximum during social stress, and in men, it reached its maximum during motivational stress related to solving problems. That is, the nature of stress (which in itself refers to higher cognitive activity), refracted through different gender perceptions, had different effects on the state of the endocrine system. Speaking of hormones, it is impossible to get past sex steroids, androgens and estrogens. Everyone knows that men and women have different groups of sex hormones and that in women, estrogen activity follows a periodic cycle. However, do not think that these steroids control only the reproductive system — androgens and estrogens are in close and reciprocal relationship with the nervous system, other hormones, and the immune system. The effect of sex steroids on the nervous system leads to the activation of many systems responsible for our emotions and behavior. Estradiol contributes to anxiety and depression, while testosterone is often associated with aggressive behavior. Animal studies have demonstrated the association of estrogens with increased body sensitivity to stress and impaired cognitive function. On the other hand, laboratory and clinical data indicate protective, neuroprotective properties of estrogens, which can be at least partially explained by the interaction of the endocrine and immune systems. For example, estrogen suppresses the production of inflammatory factors in brain damage and inhibits neurodegenerative diseases such as Parkinson’s syndrome and Alzheimer’s syndrome. (Androgens, like estrogens in women, exhibit neuroprotective properties in men. One of the mechanisms of this action may be the stimulation of metabolism in the central nervous system.) The different dynamics of male and female sex steroids also contributes to the sex differences. In men, androgen levels decrease slowly with age, so that they do not experience dramatic changes in both the nervous system and the immune system. In women, stress reactions worsen during menopause, when steroid levels change dramatically and hormone replacement therapy helps mitigate this “stress tolerance.” In addition, the immune system’s responses to stress depend on the phase of the menstrual cycle and pregnancy. In general, in women of reproductive age, the amplitude of the stress response is lower than in men, but in the luteal phase (when bp is destroyed in the ovaries?The mammary gland, called the corpus luteum, which synthesizes progesterone and some estrogen, approaches the male gland. Fluctuations in the levels of estrogens and progesterone during the female sexual cycle are naturally reflected in fluctuations in the levels of immunoregulatory factors. In women on the verge of menopause, estrogen causes mood swings and increased anxiety, acting through neural pathways that use serotonin, dopamine, gamma-aminobutyric acid (GABA), adrenaline and norepinephrine as neurotransmitters. Sex steroids can affect the immune system not only through the nervous system, but also directly by acting directly on immune cells. Thus, estrogen receptors are found in many types of immune cells, including B and T lymphocytes, dendritic and NK cells. Estrogens affect innate immune responses and stimulate the synthesis of so—called adhesion molecules (thanks to which lymphocytes can gain a foothold in the lesion) and chemokines, substances that control the local immune response, such as inflammation. In general, sex steroids can be both immunostimulants and immunosuppressants, depending on the specific hormone, its concentration at a given time and the number of receptors for it. In general, it is believed that androgens, male steroid hormones, and pregnancy hormones progestins work as immunosuppressants, whereas estrogens are associated with an increased immune response, and they act not only on the immune cells themselves, but also on the service cells of the stroma (supporting structure) of lymph nodes synthesizing regulatory immune proteins cytokines. The direct interaction of sex hormones with the immune system has a noticeable effect during menopause. During this period, the risk of bone damage due to osteopenia and osteoporosis increases especially, when bone mass and its mineral density decrease. On the one hand, estrogens themselves are necessary to maintain proper mineralization of the bone system. On the other hand, it is known that inflammation, infection, and autoimmune diseases are also associated with systemic and local bone loss. The direct involvement of immune T cells and cytokines in the formation and functioning of osteoclasts (cells that destroy bone) and osteoblasts (cells that generate bone matter) has now been proven. Estrogen deficiency causes T cells to increase the level of osteoclastogenic factors. The aging of the body also affects the state of the immune system, which is manifested, in particular, in a decrease in the thymus (thymus gland), in which maturation, differentiation and immunological “training” of T cells occur. As a result, the cellular response decreases not only to new pathogens, but also to those that should already be known to the immune system, which leads to a decrease in protection against infectious diseases. Although the mechanisms responsible for age-related weakening of the thymus are not fully known, there is evidence that sex steroids are essential. The elimination of hormones is accompanied by rejuvenation of the old thymus with a marked increase in its mass and the release of T cells into circulation. The changes persist for a very long time, moreover, even a temporary decrease in steroids can significantly stimulate thymic activity and expand the activity of circulating T cells, which may be important in immunodeficiency conditions associated either with age or with the results of toxic treatment (chemotherapy and radiotherapy, HIV treatment). We have been discussing sex hormones for so long that it may seem that only estrogens and androgens are responsible for the “bond” of the nervous, immune and endocrine systems. However, this is not the case. Earlier, we also mentioned glucocorticoids (adrenal steroid hormones), prolactin, neuropeptide PHN (nerve growth factor), neurotransmitters; to these can be added insulin, growth hormone somatotropin, somatostatin, peptides leptin, ghrelin, opioids and many, many others. In addition to the central nervous system, there is also the peripheral nervous system, which is also involved in regulating the activity of the immune system. Finally, not only the nervous and endocrine systems affect the immune system, but also vice versa. We have already discussed how estrogen fluctuations affect emotional state and cognitive functions; there is evidence that cytokines and growth factors secreted by immune cells during inflammation or stress can affect the functioning of the endocrine and central nervous systems. For example, cytokines with anti-inflammatory effects interfere with hormonal signaling pathways and are therefore capable of provoking hormonal resistance when tissues stop feeling one or another active substance (we mentioned that in the case of insulin, such resistance leads to type 2 diabetes). A detailed analysis of all the substances that bind the endocrine, nervous and immune systems and cause sex differences between them would take up too much space, so we will finally focus on two hormonal peptides, leptin and ghrelin. Leptin is synthesized primarily by adipocyte fat cells and is released into the bloodstream during meals, as you get full. It serves as an anorexic (appetite suppressant) mediator, sending appropriate signals to the brain and simultaneously stimulating fat burning. But leptin is not only a “satiety hormone”: there is evidence that it is involved in the development and maintenance of immune and inflammatory reactions. The level of leptin increases during infections, acute and chronic inflammatory processes, which indicates its role in the body’s immune defense. Leptin is involved in the pathogenesis of autoimmune diseases (encephalomyelitis, type 1 diabetes, inflammatory diseases of the gastrointestinal tract and arthritis). Although its exact role in these diseases is not clear, it is obvious that it works as a powerful immunomodulator, hormone, and cytokine with a pro-inflammatory nature, capable of regulating innate and adaptive immune responses. Another metabolic hormone with the opposite function to leptin, ghrelin, is synthesized primarily in the stomach and serves as a powerful orexigenic (appetite-stimulating) factor that controls energy expenditure, obesity, and the secretion of growth hormones. An increase in the level of leptin in the blood usually signals to the brain that a person is full, while an increase in the level of acetylated ghrelin indicates hunger. Their signals intersect in immune cells in a similar way: unlike leptin, ghrelin has an anti-inflammatory effect. That is, obesity caused by an imbalance in the leptin-ghrelin system can provoke immunological disorders. But it’s not limited to leptin and ghrelin: in a recent article in the journal Immunity, a group of researchers from the Weizmann Institute of Technology (Israel) reports that obesity and its associated high blood pressure, high blood cholesterol and diabetes symptoms occur against the background of the disappearance of dendritic immune cells. They monitor the balance of their “colleagues” — T cells, which, having lost control from the outside, provoke obesity in experimental mice. In these examples illustrating the relationship between immunity and energy metabolism, it is clearly seen what difficulties doctors have to face: it is obvious that a medical drug that should act on intermediary molecules of one system (for example, a sedative) will to some extent act on substances belonging to associated “departments” (immune and endocrine). And in order to improve the quality of treatment and avoid side effects, we need to understand the metabolic relationships in our immune-neuro-endocrine supersystem as fully as possible. Source: Science and life Photo: www.davidwygant.com