Recognition of self and nonself, the crucial role of phagocytosis and lysosomal destruction of antigen.

Primitive animals possess the ability to take up foreign matter and degrade it intracellularly. It is unlikely that during the evolution of the immune apparatus this mode of dealing with the foreign material would be bypassed. It is suggested that phagocytosis and intracellular digestion of the antigen is the primary mode of defense, and that failing complete digestion of the antigen an antibody response occurs. Phagocytosis of the antigen is known to be a necessary step in the process of antibody formation. Following the uptake by macrophages, the antigen is concentrated within the lysosome and subjected to the action of hydrolytic enzymes. Lysosomes are also the sites of catabolism of body constituents, and are believed to contain enzymes necessary for complete digestion of self constituents. If the lysosomal enzymes can completely degrade the antigen, the latter's possible harmful effects would be destroyed. The organism then does not need to waste energy in the synthesis of specific antibody, the function of which now is redundant. If the lysosomal enzymes cannot hydrolyze the antigen completely, the hydrolysis-resistant fragment can be transferred to lymphocytes, where it can induce antibody synthesis. Thus, the ability of the host hydrolytic enzymes to degrade a substance completely constitutes the recognition of self and the inability to do so amounts to the recognition of nonself.