Sometimes human immune cells manage to create antibodies that seriously prevent the malaria parasite from living.
In their complex life cycle, malaria parasites, plasmodia, travel between mosquitoes and humans (or some other vertebrate – it all depends on the specific plasmodium). Once inside a person, the plasmodium rushes to the liver, where it multiplies and moves on to the next phase of the life cycle. Then this next phase enters the blood and penetrates the red blood cells, in which it begins to multiply again. The symptoms of malaria – fever, joint pain, headaches, anemia, etc. – are associated precisely with the erythrocyte stage: when multiplying, the parasites destroy red blood cells, but, in addition, they force them to attach to the walls of blood vessels. Normally, red blood cells do not live long, ending their existence in the spleen, but for plasmodia it is important that the red blood cell in which they settle lives as long as possible, so they stick them to the walls of blood vessels. You can imagine what will happen to the vessel and the blood supply if a lot of red blood cells adhere to the vascular wall. That is why severe attacks of malaria often end in death – for example, when malarial red blood cells clog the blood vessels of the brain.
But over time, many people develop a certain resistance to malaria: attacks occur less frequently, and symptoms during attacks are not as severe. Immunity softens malaria, and how this happens, in the article in Nature say employees of the University of Copenhagen, European Molecular Biological Laboratorythe University of Texas Medical Center at San Antonio and other research centers. In red blood cells infected with plasmodium, the plasmodium protein PfEMP1 appears on the surface, which interacts with the EPCR receptor of the cells lining the blood vessels – that is why they stick to them. The immune system would have to react to the PfEMP1 protein and create antibodies against it, but it is quite variable in Plasmodium. In other words, Plasmodium synthesizes many varieties of PfEMP1 that are similar enough to interact well with the vascular cell receptor, and at the same time different enough to prevent the immune system from effectively destroying diseased red blood cells along with Plasmodium.
However, it happens that a person develops immune cells (B lymphocytes) that produce antibodies against a whole set of PfEMP1. The researchers found such antibodies in two donors who had mild cases of their malaria; the antibodies of one donor were called C7, the antibodies of the other were called C74. The same molecule (C7 or C74) could interact with several varieties of PfEMP1, despite the fact that C7 and C74 themselves were different from each other. With all the diversity of the plasmodium protein, there are unchanged sections of the amino acid sequence – if something changes in them, then the red blood cells will most likely not attach well to the walls of blood vessels. The antibodies were targeted specifically against this conserved region; By interacting with it, they most likely prevented the plasmodium protein from binding to the EPCR receptor.
In fact, the effect of such antibodies has yet to be proven. The researchers used a laboratory simulation of a brain blood vessel in which red blood cells with different variants of the PfEMP1 protein moved past cells with the EPCR receptor. Antibodies actually prevented diseased red blood cells from sticking to the walls of the “vessel.” But still, such a system is only to a certain extent similar to real blood vessels. In addition, much may depend on the amount of the parasite itself and the protein that it exposes on the surface of the red blood cell.
Although the detected antibodies interacted with several variants of the plasmodium protein, they did not see some of its varieties. And in general, it cannot be said that they completely saved their owners from malaria: attacks of the disease still occurred. On the other hand, if malaria loses its strength, then this is already something. In the future, based on such multispecific antibodies, it is possible to create more advanced molecules using protein design methods that will interact with all variants of the plasmodium protein. There is still no effective and safe vaccine against malaria, plasmodia are gradually developing resistance to drugs, and in the meantime, tens and hundreds of thousands of people die from malaria every year, so we have to carefully study every possibility, every trick that can be use against her.
Source: www.nkj.ru
