THE ZINC AND IMMUNE SYSTEM

The Zinc

Zinc is an essential trace element. Zinc intake is closely related to protein intake; as a result, it is an important component of nutritionally related morbidity worldwide. Symptoms attributable to severe zinc depletion include growth failure, primary hypogonadism, skin disease, impaired taste and smell, and impaired immunity and resistance to infection. Zinc supplementation in populations likely at risk for zinc deficiency appears to have beneficial effects on the incidence and outcome of serious childhood infectious diseases 

 THE ZINC AND IMMUNE SYSTEM

The immune system is highly proliferative, and thus particularly susceptible to Zn deficiency. The immune response can be divided into two major systems: the innate and the adaptive immunity. In the case of pathogens entering the body, the first cells acting in pathogen recognition and elimination are the cells of the innate immune system, notably polymorphonuclear cells (PMNs), macrophages and natural killer (NK) cells. PMNs are the first cells to actively enter the site of infection. They take up pathogens by phagocytosis and kill them through the production of reactive oxygen species (ROS) 

The adaptive immune response is orchestrated by highly specialized cells, the T and B lymphocytes. B lymphocytes play a role in the humoral immune response by the production of antibodies specifically directed against an antigen, whereas Tlymphocytes are involved in cell-mediated immune responses by activation of other immune cells (T helper lymphocytes) and by the production of toxic granules in cytotoxic T lymphocytes. Dendritic cells (DCs) serve as a link between the innate and adaptive immune systems. They circulate as immature cells and after coming into contact with the antigen, DCs start expressing major histocompatibility complex (MHC) molecules and co-receptors on their cell surface for the activation and stimulation of T cells 

THE ZINC AND INNATE IMMUNITY SYSTEM

Zn regulates several crucial processes implicated in the innate immune response via mechanisms not yet completely understood (Fig. 2). First, Zn ions function as chemoattractants for some immune cells. Zn deficiency leads to reduced PMN chemotaxis and, inversely, a super-physiological Zn concentration (500 μM) induces PMN chemotaxis in vitro  

Zn deficiency decreases phagocytosis while Zn supplementation has the opposite effect (50). The effect of Zn on phagocytosis is probably mediated by Zn proteins involved in this process, such as the early endosome antigen 1 (EEA1). EEA1 binds directly to the phospholipid phosphatidylinositol 3-phosphate (PI3K) at its Cterminal and binds to Rab5 via its N-terminal zinc finger domain enabling membrane tethering and fusion critical for phagosome and endosome maturation For the neutralization of pathogens, Zn is equally important: both Zn deficiency and Zn excess inhibit nicotinamide adenine dinucleotide phosphate (NAPDH), which regulates superoxide anion production responsible for the destruction of pathogens after phagocytosis  

Chronic diseases due to zinc deficency 

Altered production of cytokines during Zn deficiency can lead to inflammation. It induces IL-1-β release and subsequently inhibits the inflammation depending on the transcription factor NF-κB. These data suggest that Zn deficiency contributes to diseases in which there is an IL-1β-dependent inflammatory response and that Zn supplementation could potentially have a beneficial effect
Moreover, simultaneous evaluation of circulating cytokines and Zn status showed that the reduced circulating Zn correlates with increased IL-6, IL-8 and TNF-α levels. In addition, cytokine signaling pathways are influenced by the Zn status. For example, the proliferative response of T and B lymphocytes following IL-6 and IL-2 stimulation increases in Zn deficiency, whereas it adversely influences the IL-4 signaling, causing an impairment of the immune system In summary, Zn deficiency affects all aspects of the immune system indicating that the availability of Zn is essential for the proper development and function of the immune system, even if some mechanisms of action are not yet decrypted.