Studies in infantile marasmus. IV. Impairment of immunologic responses in the marasmic pig.

Abstract

Extract: We investigated the immunologic responses in an experimental model, the marasmic piglet. Two litters of miniature piglets of the Pitman Moore strain [46] were divided into two groups with five of the animals given normal diet and eight subjected to dietary restriction. The dietary intake of the experimental piglets was restricted to prevent further significant weight gain after the age of 35 days. The experimental animals displayed a well developed characteristic picture of severe undernutrition after 3 months of dietary restriction. Concentrations of immunoglobulins G and M (IgG and IgM) in both experimental and control pigs were similar. Antibody titers against erythrocyte A-antigen of experimental pigs were consistently lower (Table IV). Antibody responses after immunization to tetanus toxoid, sheep erythrocytes, and bacterio-phage πX 174 were remarkably similar in both groups (Tables V and VI). The experimental animals had a delay in appearance of IgG antibody after primary immunization with bacteriophage πX 174. The physiologic lymphecytosis found in the control animals was absent in the experimental group. All lymphoid organs examined in the marasmic pigs displayed marked atrophy as compared to the control animals. No tissues were identified grossly as thymus in the neck or anterior mediastinum of the experimental animals. The germinal centers of the spleen and lymph nodes were poorly formed in the experimental animals. Delayed hypersensitivity to 2,4-dinitro-fluorobenzene was demonstrated in only one of the five experimental animals while all four control animals demonstrated delayed hypersensitivity when tested at the same age. Four experimental pigs and three control pigs were immunized with BCG vaccine at 10 months of age. The mean diameter of tuberculin reaction of the experimental group was 6.5 mm; that of the controls was 27 mm when tested 4 weeks later. Both full thickness skin grafts and split thickness grafts underwent a delayed rejection in the experimental group. Lymphocyte transformation with phytohemagglutinin was studied at 6, 9, and 14 months of age in both control and experimental animals with similar results in both groups (Table VIII). Leukocytes from three experimental pigs had no increase in uptake of thymidine when tested in mixed leukocyte culture. Leukocytes from five experimental animals and three control pigs had normal leukocyte bactericidal activity against Staphylococcus aureus and Serratia marcescens. These studies provide presumptive evidence that marasmic pigs have defects in both humoral and cellular immunity. The deficiency in cellular immunity seemed greater and was manifest by thymic involution, lymphopenia, a decreased capacity to express delayed hypersensitivity, delayed homograft rejection, and absence of reactivity in the mixed leukocyte culture. Speculation: Clinical experience and recent experimental studies indicate that malnutrition decreases resistance to infection. The results presented show that cell-mediated immunity is impaired in malnutrition. Much of the immunodeficiency in malnutrition may be mediated by hyperadrenocorticism.