Immunity In Malnutrition Research Articles

Impact of childhood malnutrition and intestinal microbiota on MDR infections.

The global burden of infection from MDR organisms (MDROs) disproportionately affects children residing in low- and middle-income countries and those with increased healthcare exposure. These populations have high rates of malnutrition making them increasingly vulnerable to infection with intestinal-derived pathogens. Malnourished children experience increased incidence of intestinal carriage and invasive infection with intestinal-derived MDROs including ESBL- and carbapenemase-producing Enterobacterales. However, the relationship between malnutrition and MDRO infection remains to be clearly defined. Impairment in intestinal barrier function and innate and adaptive immunity in malnutrition increases the risk for infection with intestinal-derived pathogens, and there is an increasing appreciation of the role of the intestinal microbiota in this process. Current evidence from human studies and animal models suggests that diet and the intestinal microbiota influence each other to determine nutritional status, with important implications for infectious outcomes. These insights are crucial to developing microbiota-targeted strategies aimed at reversing the growing burden of MDRO infections in malnourished populations worldwide.

Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses

The thymus gland, where T lymphocyte development occurs, is targeted in malnutrition secondary to protein energy deficiency. There is a severe thymic atrophy, resulting from massive thymocyte apoptosis (particularly affecting the immature CD4+CD8+ cell subset) and decrease in cell proliferation. The thymic microenvironment (the non-lymphoid compartment that drives intrathymic T-cell development) is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production, as well as an increase of intrathymic contents of extracellular proteins. Profound changes in the thymus can also be seen in deficiencies of vitamins and trace elements. Taking Zn deficiency as an example, there is a substantial thymic atrophy. Importantly, marginal Zn deficiency in AIDS subjects, children with diarrhoea and elderly persons, significantly impairs the host's immunity, resulting in an increased risk of opportunistic infections and mortality; effects that are reversed by Zn supplementation. Thymic changes also occur in acute infectious diseases, including a severe thymic atrophy, mainly due to the depletion of CD4+CD8+ thymocytes, decrease in thymocyte proliferation, in parallel to densification of the epithelial network and increase in the extracellular matrix contents, with consequent disturbances in thymocyte migration and export. In conclusion, the thymus is targeted in several conditions of malnutrition as well as in acute infections. These changes are related to the impaired peripheral immune response seen in malnourished and infected individuals. Thus, strategies inducing thymus replenishment should be considered as adjuvant therapeutics to improve immunity in malnutrition and/or acute infectious diseases.

Mucosal immunity in malnutrition.

Mucosal immunity in malnutrition.

Interleukin-1 in malnutrition.

The effect of malnutrition on the in vitro production of interleukin-1 by lipopolysaccharide stimulated circulating monocytes has been investigated in children suffering from kwashiorkor and marasmus. The interleukin-1 activity was significantly lower in children with severe malnutrition. Furthermore, macrophages from children with kwashiorkor produced factors that suppressed mouse thymocyte proliferation. These observations show a significant impairment of macrophage function and provide a mechanism for the suppression of cellular immunity in malnutrition.

Inducer and suppressor T cell subsets in protein-energy malnutrition: Analysis by monoclonal antibodies

Malnutrition results in impaired cell-mediated immune responses. We have examined various subsets of T lymphocytes reactive with monoclonal antibodies against cell-surface antigens using flourescein-triggered cell sorting technique. There was a reduction in the absolute number of T lymphocytes reactive with anti-T3. Both inducer cells identified by anti-T4 and suppressor cells identified by anti-T8 were decreased in number, particularly the former. The inducer/suppressor ratio was low. These alterations in lymphocyte subset numbers were reversed to normal following nutritional therapy for 4–8 weeks. Changes in T lymphocyte subpopulations may partly explain depressed cell-medicated immunity in malnutrition.

Effects of levamisole on the immune responses of experimentally malnourished rats.

Levamisole (Ketrax), and anthelmintic drug commonly used in the tropics, has been found to restore the impaired spontaneous rosette-forming lymphocytes and delayed cutaneous hypersensitivity reactions in experimentally malnourished rats. It, however, has no effects on plaque-forming cells. The drug was also found to reconstitute the histologic integrity of the thymus in malnutrition.

Microbial—Phagocytic Interactions

The laboratory and clinical evidence is overwhelming that the phagocytic system is essential for protection against and for recovery from microbial disease (Table 1). Mobile phagocytic polymorphonuclear cells and mononuclear cells accumulate rapidly and in massive numbers in areas of inflammation such as the joint space of patients with septic arthritis. Active factors released by microbes or from tissue in response to material recognized as ‘non-self’ attract neutrophils by a process termed chemotaxis. These chemotactic factors have a small molecular weight, are freely diffusible and achieve highest concentration at the centre of an inflammatory process. Phagocytic cells migrate in a unidirectional fashion (chemotax) in response to this gradient. In addition a highly complex system of humoral factors termed opsonins increase the affinity of microbes for phagocytic cells by neutralizing antiphagocytic factors on the microbial surface and bind microbes to the plasma membranes of phagocytes. A normal opsonization system is necessary for efficient phagocytosis and killing of most microorganisms. Examples of dysfunction of the opsonin system are hypogammaglobulinaemia and complement deficiency. Greatly increased susceptibility to microbial disease is a clinical characteristic of patients with disorders of the phagocytic system. Septic lesions do occur as a result of overwhelming challenge in normal hosts but patients with phagocytic cell dysfunction have unusually severe and frequent septic lesions. Fortunately, antimicrobial capacity of the phagocytic system in patients with disordered function is usually not completely absent and therefore recovery from microbial disease is the rule with optimal medical management. Patients without any circulating phagocytic cells, however, usually do not recover from sepsis. The recent appreciation that dysfunction of the phagocytic system increases the susceptibility to, and severity of, disease and delays recovery has prompted the use of clinical modalities which attempt to restore function. An example is the transfusion of leucocytes in patients with granulocytopenia secondary to chemotherapy in malignancy. Another practical consideration should be attention to the nutritional status of patients since there is clear evidence for dysfunction of cell-mediated immunity in malnutrition and accumulating evidence that nutritional status is related to phagocytic function.

Lymphocyte Subpopulations in Human Malnutrition: Cytotoxic and Suppressor Cells

Lymphocytes in the peripheral blood of young children with protein-calorie undernutrition were evaluated for surface markers and function. Thymus-dependent lymphocytes were reduced and the immunoglobulin-bearing B lymphocytes were unchanged. The relative proportion of the remaining "null" lymphoid cells was increased. Null cells and, to a lesser extent, B lymphocytes showed cytotoxic activity against xenogeneic target cells and suppressed phytohemagglutinin-induced DNA synthesis by normal T lymphocytes. It is suggested that these alterations in lymphoid subpopulations contribute to depressed cell-mediated immunity in malnutrition.

Rosette-forming T lymphocytes and cell-mediated immunity in malnutrition: Chandra, R. K.: Br. Med. J. 3: 608, 1974

Rosette-forming T lymphocytes and cell-mediated immunity in malnutrition: Chandra, R. K.: Br. Med. J. 3: 608, 1974

Rosette-forming T lymphocytes and cell-mediated immunity in malnutrition.

The frequency of rosette-forming thymus-dependent lymphocytes was reduced in the peripheral blood of malnourished infants and children. The reduced frequency parallelled the impairment of delayed hypersensitivity response to 2, 4-dinitrochlorobenzene and decreased DNA synthesis by lymphocytes challenged with phytohaemagglutinin. The abnormalities were reversed on nutritional improvement.

An evaluation of factors associated with the depression of immunity in malnutrition and in measles

In a previous communication (I) attention was drawn to the effects of protein-calorie malnutrition (PCM) on immunological responses in children and the way in which this may alter tile pattern and response to infection. In this further study is reported: 1) the pattern of immunological ehabiitation during recovery from PCM and how this correlates with tile biochemical pattern of recovery; 2) the role of some specific nutritional deficiencies in PCM in depressing immunity; 3) the proportion of bursal (“B”) lymphocytes in the peripheral blood and depression of humoral immunity; and 4) the role of infection (as represented by measles) in depressing immunity and how this compares with the depression due to PCM.

Influence of Protein Deficiency on 19S Antibody-forming Cells in Rats and Mice

Influence of protein deficiency on immune response to sheep red blood cells was investigated in rats and mice with Jerne's plaque-forming cell technique. Protein deficiency resulted in a reduction in the number of antibody-producing cells consequent upon a prolongation of cell generation time in rats. Injection of syngeneic thymocytes brings about better improvement in the immune response of the X-radiated protein-deficient mice as compared to the controls. It is suggested that depressed immunity in malnutrition may be partly due to a disturbance in thymic function.

Isohemagglutinins and Immunity in Malnutrition

Isohemagglutinins and Immunity in Malnutrition