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Nutrients and Immune system Innate immunity a)Macrophages , monocytes,eosinophils,Dc,basophils,… b)Complement c)Acute phase proteins d)Cytokines e)Other proteins f)Interferons Adaptive immunity a)Complement b)Cytokines c)B & T cells d)Antigen presenting cells e)Antibodies Nutrition Nutrition is a critical determinant of immune responses and malnutrition the most common cause of immunodeficiency worldwide. Protein –energy malnutrition is associated with a significant impairment of: CMI phagocyte function complement system secretory IgA concentration cytokine production. Of the micronutrients :zn,slenium,iron,cu,vit.A,C,E,B6 and folic acid have important influences on immune responses. Overnutrition and obesity also reduce immunity. Malnutrition Undernourished a)consuming too few essential nutrients b) using or excreting them more rapidly than they can be replaced c)Loss of appetite d)chronic diseases especially disease of the intestinal tract, kidneys, and liver e)drug or alcohol dependencies Overnourished(dietary imbalances ) Nutrient deficiencies The 5 aspects of immunity affected by malnutrition are: a)CMI b)Phagocyte function c)Complement system d) Secretory antibody e)Cytokine production Micronutrients Micronutrient deficiencies and infectious diseases often coexist micronutrients are significant immunomodulators and thus are critical in determining the outcome of host microbe interactions Infections, in turn, aggravate micronutrient deficiencies by a)reducing nutrient intake b)increasing losses c)and interfering with utilization by altering the metabolic pathways Antioxidant Micronutrient Deficiency Micronutrients such as beta-carotene, vitamin C, selenium,copper, and riboflavin are powerful antioxidants and are found to significantly in•fluence infection-related morbidity in humans. Beck and Levander in their recent critical review describe the possibility of serious effects of antioxidant-deficient status on viral infections. Micro-nutrients like iron, copper, zinc, folic acid, and vitamins A, C, E and B-6 all have important influences on immune response Vitamin A • As early as 1928, Green and Mellanby named vitamin A as an anti-infective vitamin Apart from its effects on vision, the role of vitamin A in maintaining the structural and functional integrity of mucosal epithelial cells through its actions on gene expression • vitamin A controls cellular proliferation and *differentiation The effect of vitamin A deficiency reduced number of lymphocytes low immunoglobulin (Ig) concentrations Decreased antibody responses to viral and bacterial antigens impaired T-cell responses in vivo and in vitro Abnormal cytokine production Thus, vitamin A deficiency leads to a suppression of many of the effector functions of the immune system and consequently to a state of immunodeficiency Hydrogen peroxide generation by neutrophils and IL-1 production and cytotoxic functions in macrophages and leukocyte lysozyme content of phagocytic cells was found to be low in vitamin A– deficient children. Keratinizing metaplasia with decreased mucus production caused by disappearance of goblet cells is the most important change observed on epithelial linings in vitamin A– deficient children. Such a change has been shown to increase bacterial adherence, thus promoting colonization and subsequent invasion by pathogenic microbes. Vitamin A also helps to maintain the mucous membrane and skin, thus improving defense to infection Immune Adjuvant Effects of Vitamin A Administration of 100,000 to 200,000 IU of vitamin A as a single dose has been found to enhance phagocytic functions in macrophages. Enhancement of seroconversion rates to measles vaccine when coadministered with vitamin A (84%) The immunopotentiating effects of large dose administrations of vitamin A have led to their routine use in reducing the severity and complications of infectious diseases like measles and diarrhea. Supplementation of beta-carotene or vitamin A in HIV-positive pregnant women was also found to reduce verticaltransmission of the virus. The effects of vitamin A administration in reducing the load of malarial parasitemia in countries having endemic malaria is of clinical relevance Iron Besides being a hemopoietic factor, iron is essential for: a) cell proliferation b)oxidative metabolism of various tissues c) alter cell-mediated immune functions in children as well as in pregnant women d) Circulating T-cell numbers were found to be significantly impaired in children having iron deficiency and anemia. e) Increased susceptibility to predominantly intracellular microbial infections and also raise concerns about the success of immunization programs among children living in communities having widely prevalent iron deficiency Zinc Zinc is a biologically essential trace element: critical for cell growth cell development and differentiation It is required for DNA synthesis RNA transcription cell division cell activation Zinc Zinc deficiency affects multiple aspects of innate and adaptive immunity : lymphopenia increased infection prolonged healing time both of which are indicators of compromised immunity lymphoid atrophy decreased delayed cutaneous hypersensitivity responses and lower thymic hormone activity. Zinc Zinc deficiency : decreases production of the Th1 cell cytokines, IFN-[gamma], IL-2, and tumor necrosis factor (TNF)-[alpha], which play major roles in tumor suppression. These in turn inhibit the functional capacity of these cells Zinc Several investigators reported a significant association between low plasma zinc levels and respiratory tract infections in children Zinc-deficient individuals have been observed to exhibit decreased thymulin levels and impaired cellmediated immune functions. Copper A medical publication in 1867 reported that, during the cholera epidemics in Paris of 1832, 1849 and 1852, copper workers did not develop cholera. Another observation was that persons with Menke's disease died from frequent and severe infections due to an inadequate immune response. Menke's is an inherited disease causing defective copper absorption and severe copper deficiency1. Copper Some of the recent research showed that interleukin 2 is reduced in copper deficiency and is likely the mechanism by which T cell proliferation is reduced. The number of neutrophils in human peripheral blood is reduced in cases of severe copper deficiency. Not only are they reduced in number, but their ability to generate superoxide anion and kill ingested microorganisms is also reduced in both overt and marginal copper deficiency -Carotene -Carotene and other carotenoids may enhance immune function by quenching singlet oxygen and other reactive oxygen species, including free radicals. -Carotene PMN reactive oxygene and free radicals killing of bacteria human PMN incubated with -carotene and bacteria, the bacteria were killed efficiently and the PMN were not damaged or destroyed by the free radicals. -Carotene *T helper cell numbers were significantly increased in individuals given -carotene supplementation. *A large body of epidemiological evidence has shown that diets rich in carotenoids have been associated with lower risk of developing many types of cancer *it was shown that human natural killer cells killed significantly more tumor cells when incubated with carotene than human cells not exposed to -caroten -Carotene Carotenoids may increase the tumoricidal activity of the cytotoxic T cells, macrophages and/or natural killer cells by any of these mechanisms of action. T and B lymphocyte proliferation induction of specific effector cells capable of killing tumor cells and the secretion of factors required for the communication between immunologically competent cells. Vitamin C Vitamin C (ascorbic acid) is a powerful antioxidant and immune booster, an antiviral and anticancer nutrient. The white blood cells utilize vitamin C to fight microbes, infections and inflammation; during which levels of vitamin C are depleted. Animals; except for guinea pigs have the necessary enzyme to synthesize vitamin C in their liver. But humans lack this vitamin C synthesizing enzyme. During high stress situations, our requirement for vitamin C increases. Vitamin C is a good example of a nutrient where experimental deficiencies have shown consistently increased susceptibility to infections Human milk Advantages of human milk Human milk provides the newborn with: a) nutrients b)growth factors c)anti-infectious substances Breastfeeding to account for the decrease in number and severity of infants’ intestinal and respiratory infections ,as well as of septicemia and meningitis the enhancement of maternal-infant bonding and avoidance of allergic diseases The protective activity of breastfeeding against infections is explained by antimicrobial factors such as the: immunoglobulins Leucocytes Lysozyme Lactoferrin and bifidus factor Human milk contains IgA antibodies Human milk also directly affects the neonate’s immune system, because it contains a factor that stimulates IgA synthesis in the infant cell-mediated immunity is transferred from mother to infant through human milk First ,Human milk shows antimicrobial activity.A lower incidence of infections may in turn reduce risk for sensitisation Secondly,breastfeeding has been proposed to affect the gastrointestinal flora in a direction that may be favourable in terms of prevention of sensitisation, since introduction of cow’s milk promotes the growth of gram-negative endotoxin producing bacteria with adjuvant properties that enhance sensitisation Thirdly, certain hormones, identified in human milk, such as cortisol, growth factors such as epidermal growth factor ,insulin-like growth factor ,milk growth factor ,and transforming growth factor (TGF), may support the anatomic integrity of the mucosal barrier in the infant.