Week 11 - Genes Nutrients ImmuneSystem

Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Click to edit Master title style Click to edit Master subtitle style * * * Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of arterial endothelial cells beginning to express adhesion molecules (VCAM-1) which bind to certain leukocytes (monocytes and T lymphocytes). The leukocytes then penetrate into the intima; this transmigration is facilitated by certain chemoattractant molecules (MCP-1) Genes, Nutrients & Immunity: Research Tidbits Macrophage colony-stimulating factor (M-CSF) contributes to the differentiation of the blood monocyte into the macrophage foam cell. As the inflammatory process continues, alterations in the fibrous cap render the vessel wall weal and susceptible to rupture. Cross-talk between T lymphocytes and macrophages enhances the expression of the potent procoagulant tissue factor. Genes, Nutrients & Immunity: Research Tidbits Then, when the plaque ruptures, the tissue factor induced by the inflammatory signalling triggers the blood clot that causes the complications of atherosclerosis (heart attack, stroke). Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients & Immunity: Research Tidbits The triggers for inflammation in atherogenesis are: Oxidized LDL – not proven Very low density lipoproteins and intermediate density lipoproteins – may undergo oxidation or activate inflammatory functions of vascular endothelial cells Hypertension – Angiotensin II is a vasoconstrictor, but can also instigate intimal inflammation via reactive oxygen species, proinflammatory cytokines such as IL-6, and VCAM-1. Genes, Nutrients & Immunity: Research Tidbits Diabetes – hyperglycemia can lead to the formation of advance glycation end (AGE) products that when bound to surface receptors (RAGE) can augment the production of proinflammatory cytokines Obesity – in addition to obesity’s usual role in atherogenesis, adipose tissue can synthesize cytokines such as TNF-? and IL-6 Infection Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of arterial endothelial cells beginning to express adhesion molecules (VCAM-1) which bind to certain leukocytes (monocytes and T lymphocytes). The leukocytes then penetrate into the intima; this transmigration is facilitated by certain chemoattractant molecules (MCP-1) Genes, Nutrients & Immunity: Research Tidbits Macrophage colony-stimulating factor (M-CSF) contributes to the differentiation of the blood monocyte into the macrophage foam cell. As the inflammatory process continues, alterations in the fibrous cap render the vessel wall weal and susceptible to rupture. Cross-talk between T lymphocytes and macrophages enhances the expression of the potent procoagulant tissue factor. Genes, Nutrients & Immunity: Research Tidbits Then, when the plaque ruptures, the tissue factor induced by the inflammatory signalling triggers the blood clot that causes the complications of atherosclerosis (heart attack, stroke). Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients & Immunity: Research Tidbits The triggers for inflammation in atherogenesis are: Oxidized LDL – not proven Very low density lipoproteins and intermediate density lipoproteins – may undergo oxidation or activate inflammatory functions of vascular endothelial cells Hypertension – Angiotensin II is a vasoconstrictor, but can also instigate intimal inflammation via reactive oxygen species, proinflammatory cytokines such as IL-6, and VCAM-1. Genes, Nutrients & Immunity: Research Tidbits Diabetes – hyperglycemia can lead to the formation of advance glycation end (AGE) products that when bound to surface receptors (RAGE) can augment the production of proinflammatory cytokines Obesity – in addition to obesity’s usual role in atherogenesis, adipose tissue can synthesize cytokines such as TNF-? and IL-6 Infection The SOFIA project is attempting to determine how omega-3 fatty acids and cytokine genotype influence the course and severity of atherosclerosis Genes, Nutrients & Immunity: Research Tidbits Researchers at the University of California, San Diego School of Medicine have directly linked an enzyme that initiates inflammation to insulin resistance and the resulting type 2 diabetes. Inhibition of the enzyme, IkB kinase â, in the immune system’s macrophages may prove to be a new diabetes therapy eventually. Genes, Nutrients & Immunity: Research Tidbits Efforts are underway to understand the non-calcemic roles of vitamin D in the immune system, and in particular, on T cell-mediated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of arterial endothelial cells beginning to express adhesion molecules (VCAM-1) which bind to certain leukocytes (monocytes and T lymphocytes). The leukocytes then penetrate into the intima; this transmigration is facilitated by certain chemoattractant molecules (MCP-1) Genes, Nutrients & Immunity: Research Tidbits Macrophage colony-stimulating factor (M-CSF) contributes to the differentiation of the blood monocyte into the macrophage foam cell. As the inflammatory process continues, alterations in the fibrous cap render the vessel wall weal and susceptible to rupture. Cross-talk between T lymphocytes and macrophages enhances the expression of the potent procoagulant tissue factor. Genes, Nutrients & Immunity: Research Tidbits Then, when the plaque ruptures, the tissue factor induced by the inflammatory signalling triggers the blood clot that causes the complications of atherosclerosis (heart attack, stroke). Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients & Immunity: Research Tidbits The triggers for inflammation in atherogenesis are: Oxidized LDL – not proven Very low density lipoproteins and intermediate density lipoproteins – may undergo oxidation or activate inflammatory functions of vascular endothelial cells Hypertension – Angiotensin II is a vasoconstrictor, but can also instigate intimal inflammation via reactive oxygen species, proinflammatory cytokines such as IL-6, and VCAM-1. Genes, Nutrients & Immunity: Research Tidbits Diabetes – hyperglycemia can lead to the formation of advance glycation end (AGE) products that when bound to surface receptors (RAGE) can augment the production of proinflammatory cytokines Obesity – in addition to obesity’s usual role in atherogenesis, adipose tissue can synthesize cytokines such as TNF-? and IL-6 Infection The SOFIA project is attempting to determine how omega-3 fatty acids and cytokine genotype influence the course and severity of atherosclerosis Genes, Nutrients & Immunity: Research Tidbits Researchers at the University of California, San Diego School of Medicine have directly linked an enzyme that initiates inflammation to insulin resistance and the resulting type 2 diabetes. Inhibition of the enzyme, IkB kinase â, in the immune system’s macrophages may prove to be a new diabetes therapy eventually. Genes, Nutrients & Immunity: Research Tidbits Efforts are underway to understand the non-calcemic roles of vitamin D in the immune system, and in particular, on T cell-mediated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. Highest concentrations found in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. Genes, Nutrients & Immunity: Research Tidbits 1, 25-dihydroxyvitamin D3 is thought to be an immunosuppressant. In animal models, it has prevented or markedly suppressed several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease and lupus. A normal or high calcium diet is necessary for these functions of vitamin D to be realized. The vitamin D hormone may stimulate transforming growth factor TGF?-1 and IL-4 production, which in turn, may suppress inflammatory T cell activity. Genes, Nutrients & Immunity: Research Tidbits The vitamin D hormone may be involved in the development of self-tolerance. Autoimmune diseases are a Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of arterial endothelial cells beginning to express adhesion molecules (VCAM-1) which bind to certain leukocytes (monocytes and T lymphocytes). The leukocytes then penetrate into the intima; this transmigration is facilitated by certain chemoattractant molecules (MCP-1) Genes, Nutrients & Immunity: Research Tidbits Macrophage colony-stimulating factor (M-CSF) contributes to the differentiation of the blood monocyte into the macrophage foam cell. As the inflammatory process continues, alterations in the fibrous cap render the vessel wall weal and susceptible to rupture. Cross-talk between T lymphocytes and macrophages enhances the expression of the potent procoagulant tissue factor. Genes, Nutrients & Immunity: Research Tidbits Then, when the plaque ruptures, the tissue factor induced by the inflammatory signalling triggers the blood clot that causes the complications of atherosclerosis (heart attack, stroke). Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients & Immunity: Research Tidbits The triggers for inflammation in atherogenesis are: Oxidized LDL – not proven Very low density lipoproteins and intermediate density lipoproteins – may undergo oxidation or activate inflammatory functions of vascular endothelial cells Hypertension – Angiotensin II is a vasoconstrictor, but can also instigate intimal inflammation via reactive oxygen species, proinflammatory cytokines such as IL-6, and VCAM-1. Genes, Nutrients & Immunity: Research Tidbits Diabetes – hyperglycemia can lead to the formation of advance glycation end (AGE) products that when bound to surface receptors (RAGE) can augment the production of proinflammatory cytokines Obesity – in addition to obesity’s usual role in atherogenesis, adipose tissue can synthesize cytokines such as TNF-? and IL-6 Infection The SOFIA project is attempting to determine how omega-3 fatty acids and cytokine genotype influence the course and severity of atherosclerosis Genes, Nutrients & Immunity: Research Tidbits Researchers at the University of California, San Diego School of Medicine have directly linked an enzyme that initiates inflammation to insulin resistance and the resulting type 2 diabetes. Inhibition of the enzyme, IkB kinase â, in the immune system’s macrophages may prove to be a new diabetes therapy eventually. Genes, Nutrients & Immunity: Research Tidbits Efforts are underway to understand the non-calcemic roles of vitamin D in the immune system, and in particular, on T cell-mediated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. Highest concentrations found in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. Genes, Nutrients & Immunity: Research Tidbits 1, 25-dihydroxyvitamin D3 is thought to be an immunosuppressant. In animal models, it has prevented or markedly suppressed several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease and lupus. A normal or high calcium diet is necessary for these functions of vitamin D to be realized. The vitamin D hormone may stimulate transforming growth factor TGF?-1 and IL-4 production, which in turn, may suppress inflammatory T cell activity. Genes, Nutrients & Immunity: Research Tidbits The vitamin D hormone may be involved in the development of self-tolerance. Autoimmune diseases are the result of targeted destruction of self-tissue. The vitamin D hormone regulates Th1 cells and dendritic cell function while inducing regulatory T cell function. The net result is a decrease in the Th1-driven autoimmune response and decreased severity of symptoms, making vitamin D a potential beneficial and complementary therapy in diseases such as multiple sclerosis. Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. In short, what I learned in school was that impaired immunity was a result of undernutrition. Nutrition and Immunity: The Basics Fish oil, which is high in omega-3 fatty acids, is being investigated for its anti-inflammatory properties. Atherosclerosis is now thought to be at least partly an inflammatory disease. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity, which appears to be one of ameliorating autoimmune/inflammatory diseases. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of arterial endothelial cells beginning to express adhesion molecules (VCAM-1) which bind to certain leukocytes (monocytes and T lymphocytes). The leukocytes then penetrate into the intima; this transmigration is facilitated by certain chemoattractant molecules (MCP-1) Genes, Nutrients & Immunity: Research Tidbits Macrophage colony-stimulating factor (M-CSF) contributes to the differentiation of the blood monocyte into the macrophage foam cell. As the inflammatory process continues, alterations in the fibrous cap render the vessel wall weak and susceptible to rupture. Cross-talk between T lymphocytes and macrophages enhances the expression of the potent procoagulant tissue factor. Genes, Nutrients & Immunity: Research Tidbits Then, when the plaque ruptures, the tissue factor induced by the inflammatory signalling triggers the blood clot that causes the complications of atherosclerosis (heart attack, stroke). Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients & Immunity: Research Tidbits The triggers for inflammation in atherogenesis are: Oxidized LDL – not proven Very low density lipoproteins and intermediate density lipoproteins – may undergo oxidation or activate inflammatory functions of vascular endothelial cells Hypertension – Angiotensin II is a vasoconstrictor, but can also instigate intimal inflammation via reactive oxygen species, proinflammatory cytokines such as IL-6, and VCAM-1. Genes, Nutrients & Immunity: Research Tidbits Diabetes – hyperglycemia can lead to the formation of advance glycation end (AGE) products that when bound to surface receptors (RAGE) can augment the production of proinflammatory cytokines Obesity – in addition to obesity’s usual role in atherogenesis, adipose tissue can synthesize cytokines such as TNF-? and IL-6 Infection The SOFIA project is attempting to determine how omega-3 fatty acids and cytokine genotype influence the course and severity of atherosclerosis Genes, Nutrients & Immunity: Research Tidbits Researchers at the University of California, San Diego School of Medicine have directly linked an enzyme that initiates inflammation to insulin resistance and the resulting type 2 diabetes. Inhibition of the enzyme, IkB kinase â, in the immune system’s macrophages may prove to be a new diabetes therapy eventually. Genes, Nutrients & Immunity: Research Tidbits Efforts are underway to understand the non-calcemic roles of vitamin D in the immune system, and in particular, on T cell-mediated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. Highest concentrations found in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. Genes, Nutrients & Immunity: Research Tidbits 1, 25-dihydroxyvitamin D3 is thought to be an immunosuppressant. In animal models, it has prevented or markedly suppressed several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease and lupus. A normal or high calcium diet is necessary for these functions of vitamin D to be realized. The vitamin D hormone may stimulate transforming growth factor TGF?-1 and IL-4 production, which in turn, may suppress inflammatory T cell activity. Genes, Nutrients & Immunity: Research Tidbits The vitamin D hormone may be involved in the development of self-tolerance. Autoimmune diseases are the result of targeted destruction of self-tissue. The vitamin D hormone regulates Th1 cells and dendritic cell function while inducing regulatory T cell function. The net result is a decrease in the Th1-driven autoimmune response and decreased severity of symptoms, making vitamin D a potential beneficial and complementary therapy in diseases such as multiple sclerosis. Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. In short, what I learned in school was that impaired immunity was a result of undernutrition. Nutrition and Immunity: The Basics Zinc, iron and copper are involved in the selection, maturation and early activation events of immune cells Zinc supplementation has been shown to enhance immunocompetence and decrease the incidence and severity of some infections in individuals with mild zinc deficiency The specific cellular and molecular functions of trace elements on host defense cells are more likely to be determined with new tools of molecular and cell biology. Nutrition and Immunity: The Basics A major discovery is that changes in the intracellular environment that are induced by alterations in micronutrient status can directly influence the virulence of pathogens and can cause immune system dysfunction. Deficient or excess levels of some of the micronutrients promotes the genomic alteration that enhances virulence of a virus so that it subsequently causes myocarditis. Nutrition and Immunity: The Basics Fish oil, which is high in omega-3 fatty acids, is being investigated for its anti-inflammatory properties. Atherosclerosis is now thought to be at least partly an inflammatory disease. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity, which appears to be one of ameliorating autoimmune/inflammatory diseases. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response” Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-? Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of arterial endothelial cells beginning to express adhesion molecules (VCAM-1) which bind to certain leukocytes (monocytes and T lymphocytes). The leukocytes then penetrate into the intima; this transmigration is facilitated by certain chemoattractant molecules (MCP-1) Genes, Nutrients & Immunity: Research Tidbits Macrophage colony-stimulating factor (M-CSF) contributes to the differentiation of the blood monocyte into the macrophage foam cell. As the inflammatory process continues, alterations in the fibrous cap render the vessel wall weak and susceptible to rupture. Cross-talk between T lymphocytes and macrophages enhances the expression of the potent procoagulant tissue factor. Genes, Nutrients & Immunity: Research Tidbits Then, when the plaque ruptures, the tissue factor induced by the inflammatory signalling triggers the blood clot that causes the complications of atherosclerosis (heart attack, stroke). Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients & Immunity: Research Tidbits The triggers for inflammation in atherogenesis are: Oxidized LDL – not proven Very low density lipoproteins and intermediate density lipoproteins – may undergo oxidation or activate inflammatory functions of vascular endothelial cells Hypertension – Angiotensin II is a vasoconstrictor, but can also instigate intimal inflammation via reactive oxygen species, pro-inflammatory cytokines such as IL-6, and VCAM-1. Genes, Nutrients & Immunity: Research Tidbits Diabetes – hyperglycemia can lead to the formation of advance glycation end (AGE) products that when bound to surface receptors (RAGE) can augment the production of proinflammatory cytokines Obesity – in addition to obesity’s usual role in atherogenesis, adipose tissue can synthesize cytokines such as TNF-? and IL-6 Infection The SOFIA project is attempting to determine how omega-3 fatty acids and cytokine genotype influence the course and severity of atherosclerosis Genes, Nutrients & Immunity: Research Tidbits Researchers at the University of California, San Diego School of Medicine have directly linked an enzyme that initiates inflammation to insulin resistance and the resulting type 2 diabetes. Inhibition of the enzyme, IkB kinase â, in the immune system’s macrophages may prove to be a new diabetes therapy eventually. Genes, Nutrients & Immunity: Research Tidbits Efforts are underway to understand the non-calcemic roles of vitamin D in the immune system, and in particular, on T cell-mediated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. Highest concentrations found in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. Genes, Nutrients & Immunity: Research Tidbits 1, 25-dihydroxyvitamin D3 is thought to be an immunosuppressant. In animal models, it has prevented or markedly suppressed several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease and lupus. A normal or high calcium diet is necessary for these functions of vitamin D to be realized. The vitamin D hormone may stimulate transforming growth factor TGF?-1 and IL-4 production, which in turn, may suppress inflammatory T cell activity. Genes, Nutrients & Immunity: Research Tidbits The vitamin D hormone may be involved in the development of self-tolerance. Autoimmune diseases are the result of targeted destruction of self-tissue. The vitamin D hormone regulates Th1 cells and dendritic cell function while inducing regulatory T cell function. The net result is a decrease in the Th1-driven autoimmune response and decreased severity of symptoms, making vitamin D a potential beneficial and complementary therapy in diseases such as multiple sclerosis. Genes, Nutrients, and the Immune System Milly Ryan-Harshman, PhD, RD Nutrition and Immunity: The Basics Protein-energy malnutrition is associated with significant impairment of: Cell-mediated immunity Phagocyte function Complement system Secretory IgA antibody concentration Cytokine production Micronutrients involved in immunity include zinc, selenium, iron, copper, vitamins A, C, E, B6 and folic acid. In short, what I learned in school was that impaired immunity was a result of undernutrition. Nutrition and Immunity: The Basics Zinc, iron and copper are involved in the selection, maturation and early activation events of immune cells. Zinc supplementation has been shown to enhance immunocompetence and decrease the incidence and severity of some infections in individuals with mild zinc deficiency. The specific cellular and molecular functions of trace elements on host defense cells are more likely to be determined with new tools of molecular and cell biology. Nutrition and Immunity: The Basics A major discovery is that changes in the intracellular environment that are induced by alterations in micronutrient status can directly influence the virulence of pathogens and can cause immune system dysfunction. For example, deficient or excess levels of some of the micronutrients promotes the genomic alteration that enhances virulence of a virus so that it subsequently causes myocarditis. Nutrition and Immunity: The Basics Fish oil, which is high in omega-3 fatty acids, is being investigated for its anti-inflammatory properties. Atherosclerosis is now thought to be at least partly an inflammatory disease. Scientists have only recently begun to examine the role of extrarenal vitamin D in immunity, which appears to be one of ameliorating autoimmune/inflammatory diseases. Genes and Immunity: The Basics Regulation of the immune response Human leukocyte antigen (HLA) family of genes Cytokine family of genes Polymorphisms are common in the HLA genes, resulting in functional differences in expressed HLA molecules. Certain HLA polymorphisms have well-defined associations with numerous immunologically-mediated diseases, including some that have known dietary risk factors such as celiac disease. Genes and Immunity: The Basics Cytokine polymorphisms may influence susceptibility to and prognosis re: certain types of cancer, including prostate cancer which is responsive to diet. Preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy people may be genotype dependent. Genes, Nutrients & Immunity: Research Tidbits HLA molecules are the critical initiating event in the T cell immune response. The vast majority of HLA polymorphisms result in functional amino acid substitutions in the expressed HLA molecules. The substitutions mostly occur with the peptide-binding grooves of the molecules, resulting in different peptide-binding specificities and inter-individual differences in immune responses. Genes, Nutrients & Immunity: Research Tidbits Celiac disease has long been thought to be an abnormal immune response to wheat gluten, but also to the related proteins of rye and barley. The response to the gliadin component of gluten is a “pathological intestinal T lymphocyte response”. Individuals with certain specific HLA genotypes have a 250-fold risk of celiac disease. Genes, Nutrients & Immunity: Research Tidbits The presence of these same alleles have been detected in individuals with enteropathy-associated T cell lymphoma, suggesting that these two conditions are genetically related Some individuals have a genotype that results in a delayed clinical presentation of celiac disease, and therefore an extended period of gluten-derived antigen stimulation, with increased risk of developing a neoplastic T cell population Genes, Nutrients & Immunity: Research Tidbits The evidence is strong that both diet and genotype can modulate immune function, but whether they interact in modulating the immune response in health and disease is uncertain. Fish oil, which is rich in n-3 PUFAs, has been shown to have anti-inflammatory effects in rheumatoid arthritis and psoriasis. Some studies show a complex interaction between supplementation with fish oil and genotype that affects production of TNF-?. Genes, Nutrients & Immunity: Research Tidbits Individuals who had a high inherent production of TNF-? were more sensitive to the anti-inflammatory effects of fish oil. Other individuals needed to have a combined set of alleles to benefit from the anti-inflammatory effects of fish oil. While the molecular mechanism is unknown, based upon genetic tests, one could predict the responsiveness of individuals to diet therapy using fish oil. Genes, Nutrients & Immunity: Research Tidbits Atherosclerosis is now believed to be both a lipid storage disease and an ongoing inflammatory response. An atherogenic diet results in patches of arterial endothelial cells beginning to express adhesion molecules (VCAM-1) which bind to certain leukocytes (monocytes and T lymphocytes). The leukocytes then penetrate into the intima; this transmigration is facilitated by certain chemoattractant molecules (MCP-1). Genes, Nutrients & Immunity: Research Tidbits Macrophage colony-stimulating factor (M-CSF) contributes to the differentiation of the blood monocyte into the macrophage foam cell. As the inflammatory process continues, alterations in the fibrous cap render the vessel wall weak and susceptible to rupture. Cross-talk between T lymphocytes and macrophages enhances the expression of the potent procoagulant tissue factor. Genes, Nutrients & Immunity: Research Tidbits Then, when the plaque ruptures, the tissue factor induced by the inflammatory signalling triggers the blood clot that causes the complications of atherosclerosis (heart attack, stroke). Genes, Nutrients & Immunity: Research Tidbits Genes, Nutrients & Immunity: Research Tidbits The triggers for inflammation in atherogenesis are: Oxidized LDL – not proven Very low density lipoproteins and intermediate density lipoproteins – may undergo oxidation or activate inflammatory functions of vascular endothelial cells Hypertension – Angiotensin II is a vasoconstrictor, but can also instigate intimal inflammation via reactive oxygen species, pro-inflammatory cytokines such as IL-6, and VCAM-1. Genes, Nutrients & Immunity: Research Tidbits Diabetes – hyperglycemia can lead to the formation of advance glycation end (AGE) products that when bound to surface receptors (RAGE) can augment the production of proinflammatory cytokines Obesity – in addition to obesity’s usual role in atherogenesis, adipose tissue can synthesize cytokines such as TNF-? and IL-6 Infection The SOFIA project is attempting to determine how omega-3 fatty acids and cytokine genotype influence the course and severity of atherosclerosis. Genes, Nutrients & Immunity: Research Tidbits Researchers at the University of California, San Diego School of Medicine have directly linked an enzyme that initiates inflammation to insulin resistance and the resulting type 2 diabetes. Inhibition of the enzyme, IkB kinase â, in the immune system’s macrophages may prove to be a new diabetes therapy eventually. Genes, Nutrients & Immunity: Research Tidbits Efforts are underway to understand the non-calcemic roles of vitamin D in the immune system, and in particular, on T cell-mediated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. Highest concentrations found in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. Genes, Nutrients & Immunity: Research Tidbits 1, 25-dihydroxyvitamin D3 is thought to be an immunosuppressant. In animal models, it has prevented or markedly suppressed several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease and lupus. A normal or high calcium diet is necessary for these functions of vitamin D to be realized. The vitamin D hormone may stimulate transforming growth factor TGF?-1 and IL-4 production, which in turn, may suppress inflammatory T cell activity. Genes, Nutrients & Immunity: Research Tidbits The vitamin D hormone may be involved in the development of self-tolerance. Autoimmune diseases are the result of targeted destruction of self-tissue. The vitamin D hormone regulates Th1 cells and dendritic cell function while inducing regulatory T cell function. The net result is a decrease in the Th1-driven autoimmune response and decreased severity of symptoms, making vitamin D a potential beneficial and complementary therapy in diseases such as multiple sclerosis.