Sunday, 13 March 2011

Physiological regulation

Hormones can act as immunomodulators, altering the sensitivity of the immune system. For example, female sex hormones are known immunostimulators of both adaptive[95] and innate immune responses.[96] 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.[97] Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D.[98][99]

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.[100][101]

It is conjectured that a progressive decline in hormone levels with age is partially responsible for weakened immune responses in aging individuals.[102] Conversely, some hormones are regulated by the immune system, notably thyroid hormone activity.[103] The age-related decline in immune function is also related to dropping 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.[104]

The immune system is affected by sleep and rest,[105] and sleep deprivation is detrimental to immune function.[106] 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.[107] 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.[108]
[edit] Nutrition and diet

The functioning of the immune system, like most systems in the body, is dependent on proper nutrition. It has been long known that severe malnutrition leads to immunodeficiency. Overnutrition is also 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.[109]

Specific foods may also affect the immune system; for example, fresh fruits, vegetables, and foods rich in certain fatty acids may foster a healthy immune system.[110] Likewise, fetal undernourishment can cause a lifelong impairment of the immune system.[111] In traditional medicine, some herbs are believed to stimulate the immune system,[112] such as echinacea, licorice, ginseng, astragalus, sage, garlic, elderberry, and hyssop, as well as honey although further research is needed to understand their mode of action.

Medicinal mushrooms like Shiitake,[113] Lingzhi mushrooms,[114][115] the Turkey tail mushroom,[116] Agaricus blazei,[117] and Maitake[118] have shown some evidence of immune system up-regulation in in vitro and in vivo studies, as well as in a limited number of clinical studies. Research suggests that the compounds in medicinal mushrooms most responsible for up-regulating the immune system are a diverse collection of polysaccharides, particularly beta-glucans, and to a lesser extent, alpha-glucans (such as Active Hexose Correlated Compound isolated from Shiitake[119][120][121]). The mechanisms by which beta-glucans stimulate the immune system is only partially understood. One mechanism by which beta-glucans are thought affect immune function is through interaction with the complement receptor 3 (CD18), which is expressed on several types of immune cells.[122] Other receptors–such as Toll-like receptor 2,[123] Dectin-1, lactosylceramide, and scavenger receptors–have also been identified as being able to receive signals from beta-glucan

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