Genetics of resistance to bacterial and parasitic infection / edited by D. Wakelin and J.M. Blackwell.

Date:
1988
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Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Genetics of resistance to bacterial and parasitic infection / edited by D. Wakelin and J.M. Blackwell. Source: Wellcome Collection.

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    Introduction 7 1.4.4. Failure to undergo normal growth and development because of the absence of correct developmental stimuli or of inadequate nutritional supply The ability to gain entry into the body of a potential host, or even to penetrate cells successfully, is merely the initial step in parasitic development. Many parasites, particularly those entering the intestine as a specialized infective stage (cyst, egg, larva), require triggering by host-derived signals to continue their development. Absence of the correct signals will effectively prevent this development and thus confer resistance upon the host. Such a phenomenon is the basis of host specificity of many intestinal protozoan and helminth parasites. Inadequate nutritional supply may be both quantitative and qualitative. Qualitative inadequacies can be quite subtle, and involve relatively small discrepancies in availability of nutrients. For example, guinea pigs are resistant to infection with certain strains of Yersinia pestis because their serum lacks asparagine, needed for bacterial growth. Certain malaria parasites fail to grow when the host is deficient in/?íírd-aminobenzoic acid, others appear inhibited in red cells containing mutant haemoglobins or with specific enzyme deficiencies (e.g. glucose-6-phosphate dehydrogenase). In many cases it is quite clear that growth and development is inhibited but the underlying mechanism has yet to be determined, e.g. the poor development of Leishmania spp. in macrophages of certain mouse strains. 1.4.5. Destruction after entry into tissues by cells of the granulocyte and phagocyte series In practical terms it is unlikely that natural resistance operating in this way can be divorced from mechanisms of acquired resistance. Invading organisms are foreign bodies both in the sense of being intruders and in the sense of being antigenically different from the host. Under normal conditions, non- immunological and immunological defence mechanisms therefore combine to protect the body against infection. Nevertheless, the action of granulocytes and phagocytes does not require the cooperation of immunological factors. Adherence of phagocytes to microparasites can occur purely on the basis of molecular interactions between the two and it is also facilitated by activation of complement, a property which many parasite surfaces show. Adherence may then be followed by phagocytosis and digestion in phagolysosomes. The effectiveness of this form of natural resistance is reflected in the many strategies adopted by microparasites to prevent it taking place. These include release of toxins, inhibition of phagocyte Chemotaxis, prevention of phagocytosis by surface adaptations and resistance to digestion; indeed certain microparasites capitalize upon phagocytosis and use it as a means of invading host cells. Larger parasites, such as platyhelminths and nematodes, may also be vulnerable to the extracellular killing mechanisms of granulocytes and macrophages and similarly show adaptations for survival.