Leishmania are digenetic protozoa which inhabit two highly specific hosts, the sandfly, where they grow as motile flagellated promastigotes in the gut, and the mammalian macrophage, where they survive and grow intracellularly as non-flagellated amastigotes in the phagolysosome. Leishmaniasis is the outcome of an evolutionary 'arms race' between the host's immune system and the parasite's evasion mechanisms, which ensure survival and transmission in the population. The diverse spectrum of patterns and severity of disease reflect the varying contributions of parasite virulence factors and host responses, some of which act in a host protective manner while others exacerbate disease. This chapter describes the interaction of the Leishmania with their hosts, with emphasis on the molecules and mechanisms evolved by the parasites to avoid, subvert or exploit the environments in the sandfly and the macrophage, and to move from one to the other.

Cell biology of Leishmania.

Isolation and characterization of infective and non-infective clones of Leishmania tropica.

Although Entamoeba histolytica induces humoral and cellular immune responses in both human and animal hosts, there is no indication of postinfection immunity in humans; in contrast, several other mammals are protected by prior infection or immunization. The exacerbation of the disease by immunosuppression suggests a protective function of still-unknown defense mechanisms. Specific local and circulating antibodies are produced regularly during invasive amebiasis. Although serum antibodies, together with complement, are lytic to the trophozoites in vitro, the poor correlation of these antibodies with resistance contradicts a protective capacity in vivo. The parasite may evade harm by shedding antigen-antibody complexes from its surface. Demonstration of immediate-type skin reactions, elevated IgE titers, and specific antiamebic IgE suggests that anaphylaxis occurs. The function of the anaphylactic reaction in pathology and resistance remains to be studied. Delayed hypersensitivity parallels healing or resistance and is retarded in human hepatic amebiasis. This observation is consistent with a protective role of cell-mediated immunity.

Immunology of Entamoeba histolytica in Human and Animal Hosts

The polymerase chain reaction (PCR) is a simple, rapid procedure that has been adapted for the diagnosis of leishmaniasis. In the present study, 85 blood samples and seven bone marrow aspirates from 85 patients with clinical symptoms suggestive of visceral leishmaniasis from the metropolitan region of Belo Horizonte in the Brazilian State of Minas Gerais were screened using molecular and serological techniques. Samples that were negative (N = 12) and positive (N = 19) in parasitological and serological tests were used as controls. Of the 85 samples analyzed by PCR, 61 (71.7%) showed the expected amplification products in agarose gels. However, when the technique was combined with molecular hybridization, 72 samples (83.5%) gave a positive signal on film. Nineteen patients with Leishmania parasites in bone marrow cultures (positive controls) showed PCR hybridization in whole-blood samples, as did the seven bone marrow aspirates positive for Leishmania. None of the negative controls reacted in PCR or in an indirect immunofluorescent assay. These results indicate that PCR could replace the conventional parasitological examination in the diagnosis of leishmaniasis since it provides very satisfactory results with blood samples spotted on filter paper.

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Diagnosis of human visceral leishmaniasis by PCR using blood samples spotted on filter paper

Using rabbit erythrocyte-derived neutral glycosphingolipids enriched for a defined ceramide pentasaccharide as antigens, we have detected elevated anti-galactosyl-alpha(1-3)galactose (anti-G alpha G) antibody values in patients with American cutaneous leishmaniasis (ACL), chronic Chagas' disease, and Trypanosoma rangeli infections compared with normal subjects or with patients suffering from any of 15 other infectious diseases. The specificity of the G alpha G antibodies was determined by inhibition enzyme-linked immunosorbent assays, which revealed that several alpha-galactosyl- but not beta-galactosyl-bearing sugars blocked absorption of G alpha G antibodies to the specific antigen used. G alpha G antibodies were mainly distributed between immunoglobulin classes G and M in three Kinetoplastida infections studied, with a lower increase in reactivity detected in immunoglobulin A. Absorption of highly reactive G alpha G antibodies with purified murine laminin and nidogen, two basement membrane proteins, almost abolished G alpha G reactivity, suggesting the identity of anti-G alpha G with laminin and nidogen antibodies previously reported as elevated in Kinetoplastida infections. In ACL, G alpha G antibodies were detected in 71% of patients having skin lesions with a clinical evolution time of 0.5 month. This percentage increased with the time of evolution of skin lesions, reaching 93% in lesions older than 3 months, and tended to decrease inversely to the induration diameter in the skin leishmanin test. It is proposed that similar epitopes may exist on kinetoplast protozoa and that the determination of G alpha G antibodies may be a highly sensitive assay for the detection of humoral responses to Kinetoplastida infections.

Serological activity against galactosyl-alpha(1-3)galactose in sera from patients with several kinetoplastida infections.

Abstract Literature dealing with the immunology and immunopathology of infections with Plasmodium spp. in avian, rodent, and primate hosts is reviewed for the period between 1969 and 1974. A considerable amount of current work is with three of the chief target organs in the immunopathology of malaria, namely the erythron, the spleen, and the kidney. Serodiagnosis was developed as an epidemiological tool during this period. Work has focused also on the relapse problem, particularly in conjunction with the emergence of antigenic variants in response to the production of nonsterilizing amounts of anti-plasmodial antibody. Antigenic analysis of plasmodia, actively studied during the review period, is still fragmentary and incomplete. In particular, protection-inducing antigens still need to be isolated and characterized. Progress has been made in attempts at vaccination against various plasmodial stages but, although promising, advances are still rudimentary. Humoral and cell-mediated contributions to the development of functional protection against malaria have been studied. Antibody alone can neutralize small plasmodial inocula both in vitro and in vivo, and the merozoite is suspected as the stage vulnerable to this neutralization. While humoral protection is therefore not in doubt, it is widely believed that cell-mediated reactions fortify the humoral response via a helper-cell function. However, a total consensus on this view has not yet been reached.

A. Zuckerman

Papers

Current status of the immunology of blood and tissue protozoa. I.