Lysosome activity in immunogenesis during experimental protein-calorie malnutrition

Several structural characteristics of the lysosome apparatus in the liver and the spleen of 80 mature (4-month old) female albino Wistar rats subjected to ad libitum feeding (17.5% protein = control) and to chronic (16 weeks) highly restricted diet (5.7% protein) were studied electron-microscopically. The beta-glucosaminidase and alpha-mannosidase serum activity, assessing lysosome membrane permeability, was also determined. Results obtained in these studies are compared with data from quantitative and semi-qualitative immunoelectrophoretic analysis of IgG and IgM in the serum as well as with the existing capacities for the production of specific precipitating antibodies post antigen stimulation with 10% human gamma-globulin and incomplete Freund's adjuvant. Distinctly disturbed IgM synthesis and precipitating antibody production was observed in rats subjected to restricted diet. Inhibition of humoral immunogenesis probably begins as early as endocytosis, and is determined by the ineffective heterophagic function of the lysosomes against the introduced antigen. It can be assumed that this is a result of pathologically enhanced autophagy due to increased endogenic nutrition, exhausting the lysosome system's functional capacity and affecting not only hepatocytes and macrophages, but also some other immunocompetent cells.