HIV and Malnutrition: Effects on Immune System
T lymphocyte subpopulations in protein-energy malnutrition. Synergism of nutrition, infection, and immunity: If caught early enough, several of the effects of malnutrition can be reversed. Secretory IgA in protein-calorie malnutrition. Antimicrobial systems in the neutrophils are affected by malnutrition. If the problem lies with the amount and type of food the child eats, a dietitian will come up with a food plan and may recommend vitamin and mineral supplements. Body Mass Changes Lean body mass is naturally lost as you age but it can also be lost when you are malnourished.
Continuous research is being done in many parts of the world regarding its treatment and vaccine development, and a lot of money has flown into this.
However, fully understanding the mechanisms of immune depletion has still not been possible. Malnutrition further reduces the capacity of the body to fight this infection by compromising various immune parameters. Knowledge of essential components of nutrition and incorporating them in the management goes a long way in improving quality of life and better survival in HIV-infected patients. HIV accounts for significant immunosuppression in an infected individual.
If the corroboratory indices of good health are satisfactory, the suppression of immune defences can be mitigated. One such index is nutrition. HIV, immune expression, and nutrition interactions are complex and related to each other. Nutrition and HIV are strongly related and complement each other. A malnourished person after acquiring HIV is likely to progress faster to AIDS, because his body is weak to fight infection whereas a well-nourished person can fight the illness better.
It has been proved that good nutrition increases resistance to infection and disease, improves energy, and thus makes a person stronger and more productive. Nutritional improvement measures must be initiated before a patient reaches this stage. One of the factors responsible for malnutrition in an HIV-infected person is reduced appetite, which could be due to difficulty in ingesting food as a result of infections like oral thrush or oesophagitis caused by Candida, a common opportunistic infection in HIV-infected people and fever, side effects of medicines, or depression.
Poor absorption of nutrients may be due to accompanying diarrhea which may be because of bacterial infections like Salmonella or Mycobacterium avium intercellular ; viral like CMV or parasitic infections like Giardia, C. Gastrointestinal tract is the largest lymphoid organ in the body and is directly affected by HIV infection. HIV causes damage to the intestinal cells by causing villus flattening and decreased D-xylose absorption. This leads to carbohydrate and fat malabsorption thereby affecting fat soluble vitamins like vitamins A and E, which are important for proper functioning of immune system.
Whereas larger amounts of nutrients are required during fever and infections that accompany an HIV infection, they are utilised poorly by the body. This leads to loss of weight and lean muscle tissue, further causing damage to the immune system. Lack of iron in the diet and infections such as malaria and hookworm lead to anaemia. Anaemia causes lethargy, further reduces food intake and nutrient absorption, and also causes disruption of metabolism, chronic infections, muscle wasting, or loss in lean body tissue [ 4 ].
AIDS-related dementia or neuropsychiatric impairment may make the patients unable to care for themselves, forget to eat, or unable to prepare balanced meals. Even in households with HIV-infected members, nutritional impacts can be seen if the infected adult becomes too sick to work and provide food for themselves and their families [ 5 , 6 ].
Dietary intake also varies inversely with level of virus, suggesting that viral replication directly or indirectly suppresses appetite [ 7 ]. Malnutrition is frequent and is considered a marker for poor prognosis among HIV-infected subjects [ 8 ].
Also, in acute viral infections such responses could be seen but they were generally not present in patients with chronic progressive infections. Antiviral immunity involves both the arms of the immune system. The protective component of cell-mediated immunity involves the cytotoxic CD8 T-lymphocytes.
Schmitz and colleagues had demonstrated the effects of CD8 T lymphocytes in monkeys experimentally infected with simian immunodeficiency virus SIV. Humoral immunity to HIV is expressed by neutralising antibodies.
Anti-HIV antibodies are able to bind cell-free virus and potentially prevent established infection in the challenged host. Neutralising antibodies attaching to CD4 binding site of HIV have been identified which appear to prevent the virus from attaching to and infecting T cells.
Though HIV-specific humoral immune responses can be detected during primary infection, they mostly comprise low-avidity env specific IgG antibodies with little or no neutralising activity [ 12 ]. Significant neutralising titers are believed to take place after chronicity has set in.
HIV evolves various strategies to establish chronicity in human body. Initial CTL responses cause downregulation of viremia and prevent disease progression, but later it induces the selection of virus mutants capable of escaping the immune response [ 14 ].
Immune activation in HIV is supported by an experiment by Pandrea et al. High T-cell turnover in chronic HIV infection is attributed to overlapping and nonsynchronized bursts of proliferation, differentiation, and death in response to T-cell receptor- TCR- mediated stimulation and inflammation [ 16 , 17 ]. Antiretroviral therapy ART results in a marked reduction of T-cell activation and apoptosis and helps to decrease naive T-cell consumption and restore their numbers [ 18 ].
Chronic HIV infection also causes immunological or direct virotoxic effects on gastrointestinal tract which shows blunted villi, crypt hyperplasia, and damaged epithelial barrier with increased permeability and malabsorption of bile acid and vitamin B12, microbial translocation, and enterocyte apoptosis. There is a decrease of luminal defensins and massive CD4 T-cell depletion but high concentration of infected CD4 T cells [ 19 ].
Malnutrition is considered to be the most common cause of immunodeficiency worldwide [ 20 ]. Malnutrition, immune system, and infectious diseases are interlocked in a complex negative cascade [ 1 ]. Malnutrition elicits dysfunctions in the immune system and promotes increased vulnerability of the host to infections [ 21 ].
Every type of immunological deficiency induced by malnutrition can be included under the NAIDS umbrella. Protein-energy malnutrition PEM , now known as protein-energy undernutrition, is an energy deficit due to chronic deficiency of all macronutrients [ 22 ]. In children, PEM causes widespread atrophy of lymphoid tissues, particularly T-lymphocyte areas. The thymus involutes causing a reduction in the thymus-derived lymphocyte growth and maturation factors, arrest of lymphocyte development, reduced numbers of circulating mature CD4 helper cells, and impairment of antibody production to T-dependent antigens.
Imbalance in Th1-Th2 activation occurs depending on nature of stimuli and altered regulatory pathways, including responses mediated by the nuclear factor-kB NF-kB [ 23 ], a major transcription factor involved in the development of innate and adaptive immunity. However, CD8 suppressor cells are relatively preserved.
The lymphocytes not only get reduced in blood, but also impaired show T-lymphocyte mitogenesis and diminished activity in response to mitogens [ 24 ]. According to Chandra [ 25 ], in children with PEM, there is a decrease or reversal of the T-helper-suppressor cell ratio and total numbers of T-lymphocytes decrease due to reduced numbers of these T-cell subpopulations.
In malnourished children, changes such as dermal anergy, loss of delayed dermal hypersensitivity DDH reactions, and loss of the ability of killer lymphocytes to recognize and destroy foreign tissues were noted [ 20 ]. Necropsy studies on malnourished patients have also shown profound depletion of the thymolymphatic system and severe depression of cell-mediated immunity.
Chronic thymic atrophy with peripheral lymphoid tissue wasting along with depletion of paracortical cells and loss of germinal centres was noted. This was suggested to have led to various types of infections from which these patients actually died [ 26 ].
B-lymphocyte numbers and functions generally appear to be maintained though immunoglobulin concentrations get reduced including secretory IgA sIgA , which is responsible for mucosal immunity. This may be due to increased bacterial adherence to nasopharyngeal and buccal epithelial cells or altered expression of membrane glycoprotein receptors [ 27 ].
It has been speculated that the existing antibody production is conserved or even increased during generalized malnutrition but new primary antibody responses to T-cell-dependent antigens and antibody affinity are impaired [ 20 ]. The failure of antibody formation is reversed within a few days of protein therapy as amino acids become available for the synthesis of immune proteins [ 28 ].
It also reduces complement formation, and interferon and lower interleukin 2 receptors [ 26 ]. In patients with severe generalized malnutrition, functional status of the immune system should be assessed by simply looking at the tonsils in young children.
In adequately nourished children they are usually huge but are virtually undetectable in children with severe PEM. Deficiencies of other nutrients also adversely affect the immune mechanisms. Deficiencies of essential amino acids can depress the synthesis of proteins responsible for production of cytokines released by lymphocytes, macrophages, and other body cells, complement proteins, kinins, clotting factors, and tissue enzymes activated during acute phase responses [ 24 ]. Arginine deficiency diminishes the production of nitric oxide, and hence, the antioxidants, allowing damaging effects of free oxygen radicals [ 24 ].
Arginine has also been shown to enhance phagocytes of alveolar macrophages, depress T suppressor cells, and stimulate T helper cells [ 29 ]. Particularly the omega-3 fatty acids, serve as the key precursors for the production of eicosanoids like prostaglandins, prostacyclins, thromboxanes, and leukotrines that play a variety of host defensive roles.
Thus their deficiency in the diet can impair cytokine synthesis [ 30 ]. Vitamin A has an important role in nucleic acid synthesis, and its deficiency is also characterized by lymphoid tissue atrophy, depressed cellular immunity, impaired IgG responses to protein antigens, and pathologic alterations of mucosal surfaces. Experimental animals with vitamin A deficiency have decreased thymus and spleen sizes, reduced natural killer cell, macrophage and lymphocyte activity, lower production of interferon, and weak response to stimulation by mitogens [ 31 ].
B-group vitamins like thiamin, riboflavin, pantothenic acid, biotin, folic acid, and cobalamin can influence humoral immunity by diminishing antibody production.
Pyridoxine deficiency has also been associated with reduced cell-mediated immunity. Folic acid and vitamin B are essential to cellular replication. Experimental deficiencies of these vitamins were shown to interfere with both replication of stimulated leukocytes and antibody formation.
In anemia due to folic acid deficiency, cell-mediated immunity is depressed [ 32 ]. In vitamin C deficiency, phagocytic cells cannot produce tubulin, therefore, with impaired chemotaxis, microorganisms cannot be engulfed and destroyed [ 33 ].
Vitamin D acts as an immunoregulatory and a lymphocyte differentiation hormone [ 34 ]. It is not a substitute for professional care. If you have or suspect you may have a health problem, consult your health care provider. People with HIV often take micronutrient supplements, but the research has not yet proven what the most useful dosages are for these individuals.
Certain nutrients may directly influence the immune system's ability to fight infection. For example, cells that are supplemented with vitamin D appear to prevent Mycobacterium avium complex MAC from growing in macrophages from HIV-positive patients.
This article will briefly review selected micronutrients and their known functions in the complex immune system. Malnutrition and Immune Function It has long been known that malnourished individuals are at higher risk for infectious disease due to an inadequate immune response.
Infection then leads to inflammation and worsening nutritional status, which further compromises the immune system. This has been called the "vicious cycle. Protein-calorie malnutrition has a significant negative effect on various components of the immune system. Studies have shown decreased function of the organs thymus, spleen, lymph nodes of the immune system in malnourished humans. The branch of the immune system that produces antibodies is depressed in malnutrition, specifically with a decreased number of circulating B-cells and antibody responses.
Other mechanisms that kill infectious organisms are also depressed in malnutrition. The functions of cytokines, chemicals that act as cell messengers, are altered in malnourished individuals. Vitamin A deficiency can interfere with how epithelial cells function, which is vital in maintaining tissue structure.
The ability of certain immune cells to kill infectious organisms and the production of B-cells and T-cells are also dependent on vitamin A status. Blood levels of vitamin A have been shown to be lower in HIV-positive individuals compared to healthy individuals in both developing and developed countries. This is especially true in HIV-positive individuals with an opportunistic infection or cancer.
Beta-carotene, a predecessor to vitamin A, has also been shown to be deficient in HIV-positive individuals despite vitamin supplementation. How Antiretrovirals May Affect Birth.
In the Hallways of the U. Science Alone Is Not the Solution. Zinc, selenium and magnesium have been shown to be deficient in some studies. When zinc was supplemented with vitamin A, an increased number of immune cells were seen in humans. Blood levels of zinc in an HIV-positive individual may not accurately reflect how much zinc is stored in the body or immune function, so supplementation is controversial.
Furthermore, because of the complex interplay between nutrients in the body, excessive intake of zinc may interfere with copper absorption. Other Nutrients and Immunity Omega-3 n-3 fatty acids, normally found in fish oils, have been shown to effect immune function. Two fatty acids, eicosapentanoic acid EPA and docosahexanoic acid DHA , have been shown to decrease inflammation by modulating and influencing the cytokine production of T-cells. Other studies have shown that n-3 fatty acids reduce the ability of some immune cells to react to infectious organisms.
DHA may also slow down natural killer cell activity. Alpha-lipoic acid, an antioxidant that has been studied in HIV infection, appears to be able to regenerate vitamins C and E, further enhancing the overall antioxidant effect. Certain amino acids, specifically glutamine and arginine, may also play immune-related roles. Glutamine is important in maintaining the structure of the intestinal wall, which prevents infectious organisms from migrating across and into the bloodstream.