Stress: Its Effect on Nutrition and Immunity
A sick person's nutrition is further aggravated by diarrhea, malabsorption, loss of appetite, diversion of nutrients for the immune response, and urinary nitrogen loss, all of which lead to nutrient losses and further damage to defense mechanisms. Supplementation with selenium in deficient HIV-positive people has been shown to improve selenium status. For instance, too much dietary methionine will suppress the immune system. The Institute of Food and Agricultural Sciences IFAS is an Equal Opportunity Institution authorized to provide research, educational information and other services only to individuals and institutions that function with non-discrimination with respect to race, creed, color, religion, age, disability, sex, sexual orientation, marital status, national origin, political opinions or affiliations. My own abiding interest in this field is a direct consequence of meeting Nevin in
Even when the hypertrophy of the liver and the massive production of acute phase proteins are included, the amount of nutrients diverted to protective processes accounts for very little of the depression in growth or reproduction that occurs during the response. More recently we have examined the ideal balance of amino acids for the immune response to a pathogen and found that lysine needs are lower for immunity relative to growth or egg production and use of sulfur amino acids, especially cysteine, gives a better estimate Table 1.
This large difference in the balance of amino acids needed for the immune response relative to accretion of body tissue or egg protein greatly increases the protein cost of an immune response.
Ongoing research indicates that fever, decreased intake of food, and less efficient digestion that accompanies a robust immune response are, together, more important than the diversion of nutritional resources to the immune system Figure 2. Quantitatively, a decrease in digestion of nutrients, especially fat and some amino acids Table 2 is the most important physiological change when the nutritional impact is used as a metric.
Appropriation of nutrients when the immune system responds. In the initial stages of an immune response against a novel pathogen, phagocytes are the early responders and release pro-inflammatory cytokines in sufficient amounts that they have endocrine-like effects throughout the body. This cytokine storm induces metabolic changes, including increased protein degradation and insulin resistance, which divert nutrients from skeletal muscle and other tissues so that they become available for the increased demands of the liver and responding leukocytes Sirimongkolkasem, In the case of amino acids, the balance of essential and semi-essential amino acids is very different in leukocytes, protective proteins and the hypertrophying liver compared to the balance in muscle and other tissues.
Recent work indicates that cysteine is the most limiting amino acid during the acute phase response in chickens Table 1. Iseri and Klasing, ; Sirimongkolkasem, and also in rats Breuille et al. This is due to a mismatch between muscle cysteine release and hepatic demand for the markedly enhanced production of acute phase proteins and glutathione, which serves as an antioxidant.
The role of constraints and limitation in driving individual variation in immune response. Functional Ecology 25, Beneficial effect of amino acid supplementation, especially cysteine, on body nitrogen economy in septic rats. Cysteine and glutathione in catabolic states. Nestle Nutrition Workshop Series. Dynamics of the systemic components of the chicken Gallus gallus domesticus immune system following activation by Escherichia coli; implications for the costs of immunity.
Implications for the Nutritional Costs of Immunity. Integrative and Comparative Biology Toll-like receptors and innate immunity. Nat Rev Immunol 1, Ecological Immunology, Evolutionary Parasitology.
Without the ability to make new DNA and RNA for cell division the host response sputters, and this is clearly documented in a variety of in vitro studies. It has been more difficult to demonstrate these effects in vivo in humans, however, and the clinical importance of zinc and iron deficiency remains in doubt. Interestingly, iron excess also appears to impair immune function, in this instance because of iron-catalyzed toxic oxidative reactions that physically damage immunocompetent cells.
Interesting studies on Keshan disease, the cardiomyopathy ascribed to Coxsackie B virus infections in selenium-deficient individuals in Keshan province in China, demonstrated that the antioxidant deficiency acted to select for a more virulent form of the causative virus. As is the case for many RNA viruses, including HIV, the relatively common infidelity of RNA replication leads to the production of an array of slightly different genotypes, commonly known as quasi-species.
Alterations in certain specific nucleotide positions also correlate with increases or decreases in viral virulence, as tested in a mouse cardiomyopathy model. Infection of normal mice with fully virulent, but not avirulent, forms of the virus results in disease and death. Infection of selenium-deficient mice with avirulent virus also causes disease, and when the progeny virus is reinfected into normal mice, severe disease results. Analysis of this virus before and after this serial passage in animals demonstrates the selection of virulent virus associated with nucleotide changes in the relevant virulence positions in the genome 3.
Although the precise nature of this selection for virulence in selenium deficiency remains to be determined, these studies have established another mechanism of micronutrient influence on infection. During this decade, further studies of the catabolic wasting syndrome in AIDS have suggested that the underlying mechanism involves an imbalance in the levels of pro- and antiinflammatory cytokines produced by mononuclear cells.
Why these particular subjects were able to balance the increase in proinflammatory cytokines with antiinflammatory cytokines is not known at present, but of interest not only for this situation but also to the possible use of antiinflammatory cytokines in other clinical settings. What does the new millennium portend for these areas of research? Opening on a positive note, a textbook dedicated to nutrition and immunology was published 5 , demonstrating not only the general interest in the field, but also the involvement of increasing numbers of serious immunologists as research partners.
It is certainly not too much to expect that there will be an improvement in existing methods and the development of better methods to assess nutritional status as well as immune function.
As a part of this, assessment of RNA and protein synthesis can help track the activation of genes during immune responses and production of the relevant proteins that mediate the ultimate responses of the host. Interest in regulatory mechanisms, and the role of newly described cytokines in the control of nutritional status and immune activation will continue to yield new insights 7.
Explorations are much easier now with the new microchip array technology, which allows the rapid and simultaneous analysis of multiple pathways, at both the transcriptional and translational levels 8 , 9. Although there are some possibilities to use excreted samples such as saliva or urine for analysis, standardization is a problem and invasive sampling of cells and body fluids remains the standard. Nonetheless, it is conceivable that new photolabeling and imaging techniques could make possible real-time noninvasive sampling methods.
The biological revolution initiated by the Human Genome Project and the development of rapid sequencing methods have created the possibility of identifying minor sequence variations in specific genes that predict expression patterns of the proteins they encode, and thus the nature of the response at the protein and phenotypic levels Single nucleotide variations or SNPs , now readily detected, can indicate functional differences in genes between individuals.
There is a major ongoing collaborative international effort to map and identify the truly important variances. Because gene sequence reveals protein sequence, the level of functional action, a new science, proteomics, has emerged This will ultimately lead to new products that block, enhance, delay activation or deviate the locus of action of individual response proteins including receptor and regulatory membrane proteins.
This may permit the selective activation or inhibition of specific pathways that mediate disease or host responses to exogenous challenges, such as infections. In the context of nutrition, it may be possible to determine the specific mechanisms by which individual nutrients affect the immune system, and thus to target activation and regulation of immune pathways.
Because the acute-phase response is so crucial to host defense, the application of these methods of molecular analysis and the identification of ways to affect the regulatory pathways is of the highest immediate priority. All that is necessary is that there are investigators trained and ready to move down this route, and that sources of research funding become available. The path ahead is clear; what is not clear, however, is the time frame for making progress.
We need only to find a few scientists with the dedication of Nevin Scrimshaw to begin this journey. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
Sign In or Create an Account. Close mobile search navigation Article navigation. The History of Nutrition: Malnutrition, Infection and Immunity Gerald T. Antioxidants and viral infections: Relationship of cytokine and cytokine antagonist plasma levels to disease progression in African women with HIV-1 infection. Leptin regulation of the immune response and the immunodeficiency of malnutrition.
Email alerts New issue alert. Receive exclusive offers and updates from Oxford Academic. More on this topic Nutrition and Immune Function: Related articles in Google Scholar. Related articles in PubMed Vaccine-preventable severe morbidity and mortality caused by meningococcus and pneumococcus: A population-based study in France.
Infection occurs commonly through the respiratory tract. Bacteria that survive mucociliary escalator of the upper respiratory tract are ingested by alveolar macrophages that contain numerous acidic phagocytic vacuoles and hydrolytic enzymes. Macrophage activation results in a drastic reduction in the number of viable bacteria that may be completely eradicated. However, some mycobacteria may survive the powerful microbicidal onslaught and escape into the cytoplasm where they multiply unhindered, leading ultimately to cell death, and release into the tissues where they enter other cells including macrophages.
Persistent organisms provide the antigenic stimulation and cell-mediated hypersensitivity reaction that leads to local accumulation of inflammatory cells and formation of granulomas. This process limits the spread of mycobacteria but is associated with tissue necrosis, fibrosis, and functional impairment. This stereotypic hide-and-seek game of evasion, activation, attack, and death is played out in response to many intracellular pathogens, e.
Bloom and colleagues 12 — 16 have conducted a number of studies to elucidate the principal mechanisms by which murine mononuclear phagocytes kill M. Now, Bloom and colleagues take us one major step forward by examining the effects of a low protein diet on anti-mycobacterial immunity Interestingly, these changes were observed in the lungs but not in the liver, and the effects wore off after 2 weeks after challenge. There was no significant effect on total nitric acid production in vivo.
Granulomatous inflammation was studied at the light, immunohistochemical, and electron microscopic levels, and was impaired in the low-protein group, confirming and extending earlier observations The immunologic changes and risk of death could be reversed by reverting to a normal high-protein diet. The seminal work of Bloom and colleagues raises many new questions. Are the findings nutrient-specific? Did body weight and lymphoid organ weight differ in the two animal groups?
It is possible that at least some of the observed effects may be the result of concomitant deficiencies of micronutrients such as zinc. It is recognized that inadequate diets result in poor appetite, malabsorption, and decreased growth. Thus, the consumption and absorption of nutrients that are critical for optimum immune responses e. This confounding variable can be sorted out by including a pair-fed comparison group.
Would the quality of dietary protein make a difference? In general, animal proteins are superior to vegetable proteins in sustaining growth and maintaining immunity; there are subtle differences in immune responses of animals fed casein-based and whey-based diets. What is the threshold of nutritional deficiency that results in a significant impairment of anti-mycobacterial defenses? What is the explanation for the marked heterogeneity of survival time in genetically similar mice challenged with the same mycobacterial burden?
What is the basis of tissue specificity of macrophage handling of the microorganisms? It has been shown that CD8 T cells specific for listeriolysin O mediate significant immunity in the liver but not in the spleen Is one cell type essential for antibacterial defense at one site but not at another location, as has been shown for neutrophils and Listeria Would deficiencies of other nutrients result in impaired anti-mycobacterial immunity similar to that observed in mice on low-protein diet?
For instance, deficiencies of vitamin A 1 , 21 , 22 and zinc 1 , 23 — 25 alter a wide range of immune responses. Both in small-for-gestation low-birth-weight infants 26 , 27 and in animal models of intrauterine undernutrition or zinc deficiency 28 , 29 , the immunologic impairment is profound and long lasting. What is the status of other immunologic mechanisms that play an important role in defense against intracellular pathogens, e.
Neutralizing antibodies 42 , gene knockout mice 43 , and adoptive transfer assays 19 with bone marrow chimeric or transgenic rodent hosts can be deployed to study the specific role of individual immune processes. What is the impact of genetic host factors on antigen recognition and immunologic defense 44? Finally, it would be useful to confirm the interesting observations reported in the study by Chan et al. There is exciting new information on another face of host—parasite interaction.
Viruses can mutate and show altered virulence because of nutritional deficiencies in the hosts they infect. Beck and coworkers 45 showed that selenium deficiency enhanced the heart-damaging potential of coxsackievirus. Virus strain recovered from selenium-deficient animals was capable of inducting damage in well-nourished animals. Most interestingly, there were six nucleotide changes between the avirulent input virus strain and the virulent virus recovered from selenium-deficient animals.
This report of a specific nutritional deficiency associated with changes in a viral genome and virulence needs confirmation in other viruses and in other nutritional deficiency states.