Importance of Zinc to Innate Immunity
The mammalian immune system actually is comprised of two complementary systems, referred to as the innate system and the adaptive system. The adaptive system has been studied extensively over the past 50 years, and consequently, the the components of the system have become well-known. The adaptive system depends upon humoral agents (antibodies) that are produced by B-lymphocytes, whose production, release, and activities are modified by T-lymphocytes. Although the adaptive system is better known and studied, it is a relatively new development in the evolution of “higher” mammalian species. The adaptive system evolved as a coordinated system of molecules and cells that is “recruited” upon exposure to foreign substances in our environment. This initial exposure provides an “imprint” on the T- and B-lymphocytes, allowing them to recognize and combat the particular foreign substance the “next” time we are exposed to it. Unlike this adaptive system, the innate system is a more primitive system that evolved in lower life forms. The innate system also functions to protect the host from foreign substances, and although it is less efficient than the adaptive system in more evolved species, the components of the system are in place and ready to detect foreign substances the first time the host is exposed.
The importance of zinc in the maturation and function of T- and B-lymphocytes has been known for decades. Although the presence of the innate system also has been known, only recently have researchers discovered specific components of the innate system that complement the adaptive immune system. In fact, recent studies suggest that lack components of the innate system are susceptible to certain diseases, despite the fact that their adaptive system is fully functional. Importantly, some of these components also are zinc metalloproteins.
Like the highly evolved mammalian species, microbial species also depend upon bioavailable zinc for survival. Consequently, certain components of the innate system have developed high-affinity zinc binding sites which effectively reduce the concentration of zinc that is available for the growth of invading pathogens in the microenvironment.
Although these zinc-sequestering components of the innate immune system evolved to protect the host from foreign substances and microbes in its environment, for some people, this system is somewhat of a “double-edge sword”. In fact, for these people, the system works so well, that the components of the system not only starve the microbes of zinc, but they prevent the host itself from accessing the zinc that it needs. These individuals that possess a “hyperactive” innate immune system develop specific diseases that are due, in part, to deficiencies of zinc in the affected tissues.
The components of the innate system often are released in a highly localized manner, where the extent of their actions are limited to a specific tissue or organ. For those individuals with a hyperactive innate system, the production and/or release of the substances that sequester zinc largely are limited to the particular vicinity in which they are produced and released. This localized activation of the innate system results in a localized deficiency of zinc, and is in marked contrast to a “systemic” zinc deficiency, that typically results when dietary sources are inadequate. This is an important concept when considering an approach to treat and/or prevent illnesses that are due to a hyperactive innate system. Dietary zinc supplementation occasionally has produced improvements in the symptoms but has not been uniformly successful. The reason for these disparate results is that a small portion of the dietary zinc gets to the tissues where deficiency has been produced, but the majority of the supplement is taken up by tissues that already have adequate amounts of zinc present. Delivery of zinc to the tissues with adequate amounts of zinc induces the production of metallothionein (MT), a protein produced by the cell to bind the excess zinc to reduce its effective concentration, and store it for future release if a deficiency occurs. The net effect of taking a “nonspecific” supplement is to cause a further depletion of zinc in the tissues that already suffer from a local deficiency.
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