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Genetic resistance to disease, of which malaria is a specific example, is an inherited change in the genome of an organism that confers a selective survival advantage due to conferring or increasing resistance to disease. In the case of malaria, an infection of the erythrocytes (red blood cells), the genetic change is an alteration of the hemoglobin molecule or cellular proteins or enzymes of erythrocytes that inhibits invasion by or replication of ''Plasmodia'', the microorganisms that cause the disease. This article focuses on mechanisms of human innate resistance to malaria. Malaria has placed the strongest known selective pressure on the human genome since the origination of agriculture within the past 10,000 years. ''Plasmodium falciparum'' was probably not able to gain a foothold among African populations until larger sedentary communities emerged in association with the evolution of domestic agriculture in Africa (the agricultural revolution). Several inherited variants in erythrocytes have become common in formerly malarious parts of the world as a result of selection exerted by this parasite. This selection was historically important as the first documented example of disease as an agent of natural selection in humans. It was also the first example of genetically controlled innate immunity that operates early in the course of infections, preceding adaptive immunity which exerts effects after several days. In malaria, as in other diseases, innate immunity leads into, and stimulates, adaptive immunity. One of the key reasons for the high fatality rate in ''P. falciparum malaria'' is the occurrence of so-called cerebral malaria. Patients become confused, disoriented and often lapse into a terminal coma. Clumps of malaria-infested red cells adhere to the endothelium and occlude the microcirculation of the brain with deadly consequences. The ''P. falciparum'' parasite alters the characteristics of the red cell membrane, making them more "sticky". Clusters of parasitized red cells exceed the size of the capillary circulation blocking blood flow and producing cerebral hypoxia. Cerebral malaria accounts for 80% of malaria deaths. Thalassemic erythrocytes adhere to parasitized red cells much less readily than do their normal counterparts. This alteration would lessen the chance of developing cerebral malaria. ''P. vivax'' is clearly a less potent agent of natural selection that is ''P. falciparum''. However, the morbidity of ''P. vivax'' is not negligible. For example, ''P. vivax'' infections induce a greater inflammatory response in the lungs than is observed in ''P. falciparum'' infections, and progressive alveolar capillary dysfunction is observed after the treatment of ''vivax'' malaria. Epidemiological studies in the Amazonian region of Brazil have shown that the number and rate of hospital admissions for ''P. vivax'' infections have recently increased while those of ''P. falciparum'' have decreased. These inherited changes to hemoglobin or other characteristic erythrocyte proteins which are critical and rather invariant features of mammalian biochemistry, usually result in some kind of anemia, a disease or defect of red blood cells. These changes are referred to by the names of the diseases resulting from them including sickle cell disease, thalassemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and others. These blood disorders cause increased morbidity and mortality in areas of the world where malaria is no longer prevalent. == A primer on hemoglobin and red blood cells == Blood is composed of red and white cells suspended in plasma, a liquid composed of water in which various substances, mostly proteins, are suspended or dissolved. White blood cells are part of the body's immune system. Red blood cells transport oxygen from the lungs to the tissues of the body. The principal component of red blood cells is hemoglobin, an organic molecule that carries oxygen and gives blood its red color. Hemoglobin is a large complex molecule composed of heme, an iron-based part to which oxygen can bind, and globin, a structural protein chain. Each hemoglobin molecule is composed of four globin chains, two each of α-globin and β-globin. A molecule of heme is attached to each globin chain. Each globin chain has a characteristic compact shape it assumes based on the chemical bonds it contains: it twists around itself, then coils up, and finally ties itself into a kind of knot. The final shape of the hemoglobin molecule is a compact clump of the four knotted globin chains together with their attached heme molecules. The bonding of the proteins in a hemoglobin molecule and throughout red blood cells is so particular that even a very small change in one of them can result in serious effects. Most of these changes or defects result in some kind of anemia, because the oxygen-delivery function of hemoglobin has been impaired. These small changes are effected by alterations that occur occasionally in the genes (units of DNA associated with particular traits) which code for the globin chains or other cellular proteins as the result of an error (mutation) in the replication of DNA during cell division. There are also many other proteins and enzymes in a red blood cell with very specific constitutions and shapes conducive to their different functions in the cell. Not only human cellular biochemistry, but also infectious organisms, in particular malaria which infects red blood cells, depend on the specific constitution and shape of these proteins, or the action of specific enzymes. Many possible defects that cause anemia may also result in resistance to infectious organisms. Some of these defects cause globin chains (and therefore the hemoglobin molecules) to assume less compact shapes. Red blood cells with these defective hemoglobins or other proteins, particularly ones in the cell membrane, may assume elliptical (egg-shaped), spherical, or sickle shapes instead of the normal flattened disk shape. Other kinds of protein defects that confer some resistance to malaria may not result in abnormally shaped red blood cells, but still impair the function of the cells, such as ones that cause premature death, or hemolysis. Some of these disorders are classified as anemias, and some as other diseases. Abnormal hemoglobins and other red cell disorders are common in parts of the world where malaria is or was formerly endemic. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「genetic resistance to malaria」の詳細全文を読む スポンサード リンク
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