Physiological regulation
The immune system is involved in many aspects of physiological regulation in the body. The immune system interacts intimately with other systems, such as the endocrine and the nervous systems. The immune system also plays a crucial role in embryogenesis (development of the embryo), as well as in tissue repair and regeneration.
Hormonesedit
Hormones can act as immunomodulators, altering the sensitivity of the immune system. For example, female sex hormones are known immunostimulators of both adaptive and innate immune responses. Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their onset often coincides with puberty. By contrast, male sex hormones such as testosterone seem to be immunosuppressive. Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D.
Vitamin Dedit
When a T-cell encounters a foreign pathogen, it extends a vitamin D receptor. This is essentially a signaling device that allows the T-cell to bind to the active form of vitamin D, the steroid hormone calcitriol. T-cells have a symbiotic relationship with vitamin D. Not only does the T-cell extend a vitamin D receptor, in essence asking to bind to the steroid hormone version of vitamin D, calcitriol, but the T-cell expresses the gene CYP27B1, which is the gene responsible for converting the pre-hormone version of vitamin D, calcidiol into the steroid hormone version, calcitriol. Only after binding to calcitriol can T-cells perform their intended function. Other immune system cells that are known to express CYP27B1 and thus activate vitamin D calcidiol, are dendritic cells, keratinocytes and macrophages.
It is conjectured that a progressive decline in hormone levels with age is partially responsible for weakened immune responses in aging individuals. Conversely, some hormones are regulated by the immune system, notably thyroid hormone activity. The age-related decline in immune function is also related to decreasing vitamin D levels in the elderly. As people age, two things happen that negatively affect their vitamin D levels. First, they stay indoors more due to decreased activity levels. This means that they get less sun and therefore produce less cholecalciferol via UVB radiation. Second, as a person ages the skin becomes less adept at producing vitamin D.
Sleep and restedit
The immune system is affected by sleep and rest, and sleep deprivation is detrimental to immune function. Complex feedback loops involving cytokines, such as interleukin-1 and tumor necrosis factor-α produced in response to infection, appear to also play a role in the regulation of non-rapid eye movement (REM) sleep. Thus the immune response to infection may result in changes to the sleep cycle, including an increase in slow-wave sleep relative to REM sleep.
When suffering from sleep deprivation, active immunizations may have a diminished effect and may result in lower antibody production, and a lower immune response, than would be noted in a well-rested individual. Additionally, proteins such as NFIL3, which have been shown to be closely intertwined with both T-cell differentiation and our circadian rhythms, can be affected through the disturbance of natural light and dark cycles through instances of sleep deprivation, shift work, etc. As a result, these disruptions can lead to an increase in chronic conditions such as heart disease, chronic pain, and asthma.
In addition to the negative consequences of sleep deprivation, sleep and the intertwined circadian system have been shown to have strong regulatory effects on immunological functions affecting both the innate and the adaptive immunity. First, during the early slow-wave-sleep stage, a sudden drop in blood levels of cortisol, epinephrine, and norepinephrine induce increased blood levels of the hormones leptin, pituitary growth hormone, and prolactin. These signals induce a pro-inflammatory state through the production of the pro-inflammatory cytokines interleukin-1, interleukin-12, TNF-alpha and IFN-gamma. These cytokines then stimulate immune functions such as immune cells activation, proliferation, and differentiation. It is during this time that undifferentiated, or less differentiated, like naïve and central memory T cells, peak (i.e. during a time of a slowly evolving adaptive immune response). In addition to these effects, the milieu of hormones produced at this time (leptin, pituitary growth hormone, and prolactin) support the interactions between APCs and T-cells, a shift of the Th1/Th2 cytokine balance towards one that supports Th1, an increase in overall Th cell proliferation, and naïve T cell migration to lymph nodes. This milieu is also thought to support the formation of long-lasting immune memory through the initiation of Th1 immune responses.
In contrast, during wake periods differentiated effector cells, such as cytotoxic natural killer cells and CTLs (cytotoxic T lymphocytes), peak in order to elicit an effective response against any intruding pathogens. As well during awake active times, anti-inflammatory molecules, such as cortisol and catecholamines, peak. There are two theories as to why the pro-inflammatory state is reserved for sleep time. First, inflammation would cause serious cognitive and physical impairments if it were to occur during wake times. Second, inflammation may occur during sleep times due to the presence of melatonin. Inflammation causes a great deal of oxidative stress and the presence of melatonin during sleep times could actively counteract free radical production during this time.
Nutrition and dietedit
Overnutrition is associated with diseases such as diabetes and obesity, which are known to affect immune function. More moderate malnutrition, as well as certain specific trace mineral and nutrient deficiencies, can also compromise the immune response.
Foods rich in certain fatty acids may foster a healthy immune system. Likewise, fetal undernourishment can cause a lifelong impairment of the immune system.
Repair and regenerationedit
The immune system, particularly the innate component, plays a decisive role in tissue repair after an insult. Key actors include macrophages and neutrophils, but other cellular actors, including γδ T cells, innate lymphoid cells (ILCs), and regulatory T cells (Tregs), are also important. The plasticity of immune cells and the balance between pro-inflammatory and anti-inflammatory signals are crucial aspects of efficient tissue repair. Immune components and pathways are involved in regeneration as well, for example in amphibians. According to one hypothesis, organisms that can regenerate could be less immunocompetent than organisms that cannot regenerate.
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