FEATURE ARTICLE
Pathogens, Host-Cell Invasion and Disease
Invading pathogens can co-opt even the cells of the immune system. New anti-infective drugs may arise from an understanding of this chemical warfare
Erich Gulbins, Florian Lang
Opposing Forces
As we mentioned above, penetration of the host cell depends not only on the properties of the pathogen but also on the properties of the host. Some individuals have assets that protect their cells from being infected by certain pathogens. Most important to an appropriate defense is the ability of the immune system to kill pathogens before they enter host cells. Consequently, older people with a weaker immune system, as well as patients with an impaired immune system—HIV patients or people with an organ transplant who have to take immunosuppressive medication to suppress rejection of the transplanted organ—are more vulnerable to infectious diseases. Also, the immune system's ability to "remember" pathogens and to mount a faster and stronger defense in case of reinfection confers a strong advantage over time. Young children are particularly vulnerable to many diseases because their immune system is encountering the invading pathogen for the first time.
In addition, some people may be more or less resistant to some pathogens because of their genetic makeup. For instance, a certain mutation in a gene that carries the information for a receptor protein on the surface of white blood cells renders people partly or fully resistant to HIV. HIV uses this protein to attach to and infect white blood cells; the mutation changes the properties of the receptor, so that HIV is less able to infect those cells. It is a rare mutation, but it will eventually become more common in Africa and South Asia because it gives a clear evolutionary advantage for individuals in those areas where AIDS is rampant.
Sickle cell disease is the result of a mutation that changes a single amino acid—swapping glutamate for valine—in hemoglobin, the oxygen-storing protein in red blood cells. A patient who receives this mutation from both parents is severely ill, because hemoglobin precipitates and deforms the erythrocytes as soon as it is deprived of oxygen. However, an individual who carries only one mutant allele does not suffer from the disease; rather, the mutation impedes the intracellular survival of Plasmodium when the person is exposed to the pathogen. It is not entirely clear how the mutated hemoglobin protects against malaria.
In any case, the malaria pathogen has apparently never been able to overcome this resistance through evolution. Thus, individuals carrying the mutation have better survival chances in those areas where malaria is endemic, particularly in Africa and Southeast Asia. As a result, the incidence of the sickle cell trait and of sickle cell disease is particularly high in those areas. Similarly, thalassemia and glucose-6 phosphate dehydrogenase deficiency confer some resistance to malaria. Again, those diseases are particularly frequent in malaria-infested areas.
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