Erythrocytes immunologic system

Erythrocyte Entrapment of Enzymes. Erythrocytes have been used as carriers for therapeutic enzymes in the treatment of inborn errors (249). Exogenous enzymes encapsulated in erythrocytes may be useful both for dehvery of a given enzyme to the site of its intended function and for the degradation of pathologically elevated, diffusible substances in the plasma. In the use of this approach, it is important to determine that the enzyme is completely internalized without adsorption to the erythrocyte membrane. Since exposed protein on the erythrocyte surface may ehcit an immune response following repeated sensitization with enzyme loaded erythrocytes, an immunologic assessment of each potential system in animal models is required prior to human trials (250). 

Many microorganisms minimize the effects of the host s defence system against them by mimicking the antigenic stmcture of the host tissne. The eventual immunological response of the host to infection then leads to the autoimmune destmction of itself. Thus, infections with Mycoplasma pneumoniae can lead to production of antibody against normal Group 0 erythrocytes with concomitant haemolytic anaemia. 

Immunological Effects. The effects of carbon tetrachloride on the immune system have not been evaluated in humans. Immune responses were not affected in rats orally exposed to carbon tetrachloride (Smialowicz et al. 1991). Parenteral exposure of animals to carbon tetrachloride has been reported to impair the immune system (Kaminski et al. 1989 Muro et al. 1990 Tajima et al. 1985), and oral exposure caused depletion of lymphocytes, hemorrhage, and hemosiderin deposition in the pancreaticoduodenal lymph node (Doi et al. 1991). These findings are supported by in vitro studies in which the IgM antibody formation response of isolated mouse splenocytes to sheep erythrocytes was inhibited in a dose-dependent manner when the splenocytes were exposed to carbon tetrachloride for 1-3 hours in the presence of cocultured hepatocytes (Kaminski and Stevens 1992). No effects were observed in the absence of cocultured hepatocytes. Mice appear to be more sensitive than rats to carbon tetrachloride-induced immunosuppression, but the biological significance to humans of these reported effects are yet ascertainable from the available data. 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

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