Antimalarial red cells.
It is difficult to overestimate the evolutionary pressures exerted over the past few thousand years by endemic malaria. For most of hominid evolution, these parasites probably caused little morbidity and mortality. However, as Livingstone (1964, 1967, 1971) has pointed out, the advent of slash and burn horticulture and associated sedentary living patterns dramatically changed this situation. For many human populations, endemic malaria became an evolutionary emergency. In such pressing circumstances, genetic traits which ordinarily would carry with them an intolerable genetic load actually increase in frequency. Thus, although a few antimalarial red cell characteristics such as Duffy negativity are evidently innocuous, the majority of malaria-selected traits are not. Ovalocytosis, the abnormal hemoglobins and G-6-PD deficiencies are all quite deleterious in the homo- or hemizygote. This, more than anything else, bespeaks the extraordinary evolutionary pressures exerted by malaria. Needless to say, the mechanisms by which these various red cell traits protect are incompletely known. Although our discussion of such mechanisms has revolved about parasite/host cell relationships, the actual antimalarial effect may involve more distal interactions, especially of infected erythrocytes with the immune and reticuloendothelial systems. Protection exerted by modifications of such interactions would not be revealed by in vitro culture experiments upon which we rely for much of our information. For example, as normal red cells age and senesce, they express novel surface antigens which are recognized by specific immunoglobulins (Kay, 1983). Cells which have bound such antibodies are likely recognized and destroyed rapidly by the reticuloendothelial system. The expression of such senescence antigens may be hastened in already abnormal cells subject to the additional burden of an internal parasite. Therefore, it is quite possible that congenital defects of the red cell membrane, hemoglobin and metabolism may afford protection against malaria via immunologic mechanisms rather than by blocking penetration or predisposing the cell to spontaneous intravascular lysis. To be successful in the mammalian host, erythrocytic phase of malaria must recognize and attach to the host red cell, successfully penetrate, and replicate within. Remarkably, there are antimalarial red cells which impair each one of these individual steps. In this case, the ingenuity of natural selection has been almost--but not quite--a match for that of the malaria parasite.
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D004375:Duffy Blood-Group System; D004910:Erythrocyte Membrane / Q000469:parasitology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood; D006021:Glycophorins / Q000502:physiology; D006455:Hemoglobins, Abnormal / Q000502:physiology; D006801:Humans; D008288:Malaria / Q000097:blood* / Q000235:genetics / Q000469:parasitology; D011110:Polymorphism, Genetic
D004375:Duffy Blood-Group System; D006021:Glycophorins; D006455:Hemoglobins, Abnormal; D000255:Adenosine Triphosphate