Of the Antigenicanalysis of Plasmodia*
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Bull. Org. mond. Sant) 1969, Bull. Wld Hlth Org. 40, 55-56 Current Status of the Immunology of Malaria and of the Antigenic Analysis of Plasmodia* A Five-Year Review AVIVAH ZUCKERMAN 1 The immunology of malaria has been intensively studied, and many reviews ofseparate topics have appeared. Among hostfactors contributing to susceptibility to malaria, thefol- lowing are studied in the present paper: (1) genetic factors affecting susceptibility to human and rodent plasmodia; (2) physiological and nutritional factors affecting suscep- tibility of vertebrate and vector hosts; (3) sterile immunity in malaria as exemplified by radical cure and by modification of challenge infection following exposure to non-living parasiteproducts; (4) the role ofthe lymphoid-macrophage system in malaria ; and (S) the excessive anaemia of malaria and its etiology. Gamma-globulin levels rise in malaria and remain high during latency. Protection is associated with IgG, which ispassively transferable via the human placenta. Not allgamma- globulin is antibody, and not all antibody is protective. The fluorescent antibody technique and double diffusion in gel have been extensively used in exploring the kinetics ofantibody production. New methods of harvesting plasmodia attempt to avoid protein degradation and to minimize contamination by host antigens. Plasmodia have proven to consist ofa mosaic of antigens, and comparative studies by most of the accepted techniques have been started. Exoantigens have been described in fowl- and rodent-malarias. Relapse-variants of primate plasmodia have been shown to differ antigenicallyfrom their parent strains. INTRODUCTION Reed Army Institute of Research, Washington, USA; 3 and the report of a WHO Scientific During the past 5 years there has been very Group on the Immunology of Malaria (1968). active interest in malarial immunology, and nu- Chapters dealing with important aspects of merous reviews have covered various aspects of malarial immunology are included in the following the field. These will be referred to in their contexts books: Immunity to Protozoa (Garnham et al., below. Several international meetings dealing with 1963); Infectious Blood Diseases of Man and this topic have been held, and their deliberations Animals (Weinman & Ristic, 1968); Immunity to have been or are in the process of being published. Parasites (Taylor, 1968); and Immunity to Parasitic These include a review of papers on malaria Animals (Jackson & Singer, 1969). The Seventh presented at the Seventh International Congresses International Congresses on Tropical Medicine and on Tropical Medicine and Malaria, Rio de Janeiro, Malaria and the WHO Scientific Group on the 1963; 2 two meetings sponsored by the Walter Immunology of Malaria (1968) specifically re- commended that work on malarial immunology * This study was aided by grant no. 1 RO1 A108100-01 from the US Public Health Service. should be encouraged. I Professor of Parasitology, Hebrew University, Jerusa- Wherever possible, the present study is based lem, Israel. on the reviews which appeared during the past ' An unpublished document WHO/Mal/417, with 5 years. In general, only papers not previously Annexes 1 and 2, compiled by L. J. Bruce-Chwatt. A limited number of copies of this document is available to persons officially or professionally interested on request to Distribu- 3 Reported in Amer. J. trop. Med. Hyg., 1964, 13, Suppl., tion and Sales, World Health Organization, 1211 Geneva, pp. 145-241, and in Milit. Med., 1966, 131, Suppl., pp. 847- Switzerland. 1272. 2276 -55 56 A. ZUCKERMAN reviewed are cited, and the reader is referred to the That genetic factors may play a role in rodent reviews for full bibliographic coverage. malarial immunity as well was discussed by Acquired immunity to malaria, as well as to Allison (1963) and confirmed in a review by other blood-parasitic protozoa, was dealt with by Bruce-Chwatt (1965), and in another by Zuckerman Targett (1968), who discussed cellular and humoral (1967). factors, antigenic analysis, excessive anaemia and other aspects of the problem. Basis of specificity in susceptibility to malaria A bird's-eye picture of the current status of malarial immunology was given by Benex (1966). Our knowledge in this important area is frag- He stressed the opinion, which is rapidly gaining mentary and inadequate. The available scattered support among many workers, that acquired references were assembled by Zuckerman (1968). immunity to malaria is qualitatively similar to in an attempt to fit the few pieces of available immunity to other microbial diseases, and pointed information into a logical framework. out that premunition and true immunity with The physiological and nutritional condition of radical cure need not necessarily be mutually the host may play a role in determining suscepti- exclusive. The importance of the newer immuno- bility. Abnormally low host temperatures depressed chemical techniques was stressed. A point with parasitaemia, due to Plasmodium berghei, in rats which other workers would probably disagree is and mice. Similarly, pyrexia induced lowered Benex's denial of the production of protective susceptibility of rats to P. berghei. Dietary defi- antibody in malaria. ciencies may alter the host as a milieu, and affect The rodent malarias continue to be among the susceptibility to malaria: the well-documented most convenient models for the study of mam- effect of para-aminobenzoic acid (PABA) is a malian malarial immunity. Immune processes in case in point. Animals reared on a diet deficient the rodent malarias were reviewed by Yoeli in PABA are thereby rendered less susceptible to (1966), Corradetti (1967) and Zuckerman (1967). their homologous plasmodia; and even hosts Among the topics they discussed are innate and which normally succumb to infection can establish acquired immune mechanisms; the problem of effective immunity under such circumstances. radical cure; humoral and cellular aspects of Other dietary substances that depress susceptibility immunity; intrinsic and extraneous factors affect- to various plasmodia are ascorbic acid and sugar. ing immunity; the antigenic analysis of rodent The effects of the host's diet on susceptibility to plasmodia; the case for autoimmunization, etc. malaria were reviewed by Jacobs (1964). The interactions between host metabolites and parasites and the reciprocal interactions between HOST REACTIONS TO PLASMODIAL INFECTION parasite metabolites and hosts are obvious factors in susceptibility. Apart from the specific inter- Inherited factors conferring resistance to malaria actions generally defined as immune mechanisms, Allison (1963) reviewed the inherited erythro- others, such as those determined by the age and cytic characters suspected of conferring resistance the sex of the host, may also play a role. Younger against human malaria. These include (1) the pres- hosts are generally more susceptible than their ence of the sickle-cell gene, which determines the mature counterparts, but the reasons for this substitution of a single amino-acid residue in the difference are, as yet, largely undefined. In the few haemoglobin molecule, rendering the haemoglobin documented cases, non-virgin female rodents relatively insoluble in an acid medium; and (2) tended to be somewhat less susceptible to P. berghei an inherited deficiency in the production of than males. Many recent attempts have been made glucose-6-phosphate dehydrogenase, leading to the to maintain plasmodia, and particularly human presence of reduced amounts of glutathione in the plasmodia, in unusual hosts. Thus, for example, erythrocytes. The view that this inherited defi- P. falciparum develops in splenectomized chim- ciency may be linked with malarial incidence panzees, which develop resistance to superinfection has been supported by Flatz & Springam (1964). with the same strain. Human immune serum Human haematopathies associated with malarial from persons infected with the same strain (but anaemia were further discussed by Zuckerman not with a geographically distant one) had a (1966). protective effect in chimpanzees (Sadun et al., ANTIGENIC ANALYSIS OF PLASMODIA AND IMMUNOLOGY OF MALARIA 57 1966). In view of the current wave of interest a measure of sterile immunity may also occur in in malaria in unusual hosts, it is well to bear in this disease. mind the fact that trypanosomes undergo marked biological modification when they are maintained Radical cure in malaria for some time in unusual hosts (Desowitz, 1963). On the basis of half a century of unremitting We have a few intriguing glimpses into the ways work in malarial immunology, Sergent (1963) in which plasmodial metabolites may affect host meticulously defined various concepts relating to erythrocytes. Augmented titres of phospholipids, sterilizing and non-sterilizing immunity, which he ATP, fatty acids, adenine, folic acid and folinic considered to be separate entities. Among those acid are all recorded for parasitized erythrocytes. with non-sterilizing immunity he listed a series Host liver mitochondria are damaged in malarial of microbial diseases, including malaria, that rodents and monkeys, and host cell respiration " show a long, metacritical stage of chronic, latent is thus impaired both in vitro and probably in vivo infection ". By his definition, premunition, the by a plasmodial metabolite. The adaptive range non-sterilizing immunity, "accompanies the in- of host susceptibilities, undoubtedly influenced by fection, disappearing with the infection ". factors