HIV and Malnutrition: Effects on Immune System
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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 [ 1617 ].
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 ]. Immunology of Malnutrition 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. PEM Protein-energy malnutrition PEMnow 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.
Journal of Immunology Research
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 sIgAwhich 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 ].
Essential Fatty Acids 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 ]. Vitamins 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.
Breastfeeding plays a key role in optimally supplying all the nutrients and energy needs of infants in the first six months of life. However in resource constrained countries, replacement feeding actually causes equal or more infant deaths due to malnutrition and infection when compared to the number of deaths due to HIV as a result of postnatal transmission through breastfeeding. Understanding the relationship of breastfeeding and child survival is a key to successful counselling of HIV positive mothers on how to optimally feed their babies.
This section addresses important issues with regard to infant feeding in the context of HIV in Ethiopia. However, replacement feeding, if not carried out properly, is associated with increased risk of morbidity and mortality at a young age. This is particularly the case in low-resource settings. Exclusive breastfeeding during the first six months of life is associated with lower transmission of HIV and improved child survival compared to non-exclusive breastfeeding children in developing countries.
There are a number of common terms used to describe infant feeding practices. You may already be familiar with these terms. Giving only breastmilk and no other drinks or foods, not even water, with the exception of drops or syrups consisting of vitamins, mineral supplements or medicine.
The use of breastmilk substitute totally avoiding breastmilk.The Aids Myth and Deception, The Real Disease is Malnutrition and Drugs
Giving breastmilk with non-human milk and solids and other fluids. Addition of semi-solid or solid food in addition to breastmilk or formula at six months. Mothers who are able to give exclusive replacement feeding can usually do this successfully if a number of factors are in place.
The mother has no barrier in choosing a feeding option for cultural or social reasons, or for fear of stigma and discrimination Feasible: The mother or family has adequate time, knowledge, skills, and other resources to prepare feeds and to feed her infant, and the support to cope with any family, community and social pressure Affordable: Birr per month Sustainable: The mother has access to the continuous and uninterrupted supply of all ingredients and commodities needed to implement the feeding option safely for as long as the infant needs it.
Replacement foods are correctly and hygienically prepared and stored in nutritionally adequate quantities; infants are fed with clean hands using clean cups. Why do you think that exclusive replacement feeding might be difficult for some mothers in your community? Exclusive replacement feeding is difficult, especially in rural situations because it is expensive for families on low incomes and because preparing formula milk in consistently hygienic conditions is almost impossible.
In this section we will discuss how you can help mothers decide the preferred feeding options for her child. First, as you have learnt, breastmilk is very important for the survival of the child.
The difficult thing in recommending continuing breastfeeding is that HIV infection is present in breastmilk. So when you advise the mother to continue with exclusive breastfeeding, she needs to know she is possibly exposing the child to HIV infection. If, on the other hand, you advise the mother on exclusive replacement feeding, the positive thing is that there will be no exposure of the child to the HIV virus.
So the child will probably remain HIV-free. The difficult thing with this option is that not giving a child breastmilk, but relying on infant formula, is associated with a high rate of morbidity and mortality.
The high risk of malnutrition and diarrhoeal diseases are very common in children who are not breastfed, especially in resource-limited countries.
Mixed feeding Studies have shown that mixed feeding carries both a risk of HIV transmission from mother to child and a high risk of malnutrition. Therefore you must counsel parents to avoid mixed feeding and continue either with exclusive breastfeeding or exclusive replacement feeding.
Nutrition Module: Nutrition and HIV: View as single page
Exclusive replacement feeding The use of exclusive replacement feeding using commercial infant formula eliminates the transmission of HIV from breastfeeding. Exclusive replacement feeding means that the mother completely avoids breastfeeding her baby. However, as you read earlier, there are risks as well as benefits associated with exclusive replacement feeding.
These are set out in Box Benefits Less likelihood of HIV transmission from mother to child if entirely exclusive replacement feeding. Because of the difficulties of exclusive replacement feeding, avoidance of breastfeeding is not safe in countries with limited resources like Ethiopia.
Exclusive breastfeeding Several studies have demonstrated that babies who are exclusively breastfed are at a lower risk of acquiring HIV infection compared with infants who have mixed feeding. However, there are risks associated with exclusive breastfeeding.
HIV is present in the breastmilk of infected mothers and can be transmitted to infants by breastfeeding. This poses a substantial risk for acquisition of HIV infection for the infant. Women with advanced disease are at highest risk of transmitting the virus to their babies during breastfeeding. Stopping breastfeeding earlier than this should be avoided since this is associated with increased risk of death from diarrheal illnesses, malnutrition and pneumonia.
Exclusive replacement feeding formula feeding is the second possible option for a minority of mothers. If this is the option chosen by a mother you have to make every effort to ensure that she does this safely. Some mothers may choose this option first but because of economic problems or cultural influences, they may end up mixing the formula with breastmilk, which will increase the risk of transmission.
If this is not chosen, you should do your best to ensure safety before you agree with a mother that she uses the exclusive replacement feeding option. Only very few mothers could make it safe. Good theories do not necessarily provide an evidence base for good practice. We would like to see greater attention to documenting [the effects of various nutritional interventions].
She also voiced concerns about the financial implications both to the individual and, possibly, health systems. What if they are not working? What about orphans and other vulnerable groups. The same cycle of malnutrition and infection see figure 1 that occurs with macronutrients is seen with micronutrients as well. People with serious infections or diseases, may have altered intake, absorption and metabolism of various micronutrients. These deficiencies in turn can weaken the immune system and increase the risk of infection.
Micronutrient supplementation can improve health — for example, vitamin A supplementation reduces mortality from a variety of causes in children under 5.
Nutrition Module: 12. Nutrition and HIV
Moreover, vitamin and minerals can be relatively easy and inexpensive to administer — but they should not be seen as a magic bullet.
He told the audience at the WHO meeting of a variety of methodological problems that make designing or deciphering vitamin and mineral studies difficult.
There is clear evidence that micronutrient status affects both susceptibility to and progression of HIV infection as well as general health, pregnancy outcomes, growth in children, etc. In severe cases, micronutrient deficiency leads to a complex known as NAIDS or nutritionally acquired immunodeficiency syndrome — which, like AIDS, increases susceptibility to secondary infections.
In addition, poor micronutrient status also leads to oxidative stress, which has been directly shown to increase HIV replication — potentially speeding progression. Much of the data on micronutrients and HIV and AIDS has been based on observational studies — but their findings are not always reliable. For one thing, it is difficult to assess micronutrient intake in these studies. In addition, it is difficult to study just one micronutrient on its own because bioavailability may depend on intake of other nutrients.
Also, biomarkers used to measure nutrient status in the blood are not always trustworthy when there is an infection in the patient.