Parasites have evolved an extraordinary variety of mechanisms for surviving in the face of the natural and acquired immune responses of their hosts. A selection of the mechanisms serves to illustrate the challenge involved in developing strategies for immunising against parasites.

Games parasites play: how parasites evade immune surveillance

Theileria parva and T. annulata provide intriguing models for the study of parasite-host interactions. Both parasites possess the unique property of being able to transform the cells they infect; T. parva transforms T and B cells, whereas T. annulata affects B cells and monocytes/macrophages. Parasitized cells do not require antigenic stimulation or exogenous growth factors and acquire the ability to proliferate continuously. In vivo, parasitized cells undergo clonal expansion and infiltrate both lymphoid and non-lymphoid tissues of the infected host. Theileria-induced transformation is entirely reversible and is accompanied by the expression of a wide range of different lymphokines and cytokines, some of which may contribute to proliferation or may enhance spread and survival of the parasitized cell in the host. The presence of the parasite in the host-cell cytoplasm modulates the state of activation of a number of signal transduction pathways. This, in turn, leads to the activation of transcription factors, including nuclear factor-kappa B, which appear to be essential for the survival of Theileria-transformed T cells.

Transformation of Leukocytes by Theileria parva and T. annulata

Three spleen cell lines derived from 3 calves experimentally infected withTheileria parva have been established. After an apparent disappearance of parasitized cells from the cultures there was a resurgence of infected lymphoblasts in 5 to 6 weeks. The infected lymphoblasts can be readily subcultured without feeder layers in a medium consisting of Eagle’s Minimal Essential Medium and 20 per cent foetal calf serum. The plating of infected cells was greatly enhanced by implanting the cells on preformed monolayers. No evidence was obtained by the methods employed which might indicate the existence of an extracellular form of the parasite capable of reinfecting new cellsin vitro.

East coast fever: Cultivationin vitro of bovine spleen cell lines infected and transformed byTheileria parva

The MHC restriction and parasite strain specificity of cytotoxic cells elicited in a group of Theileria parva (Muguga)-immunized cattle following homologous challenge, were investigated. The cytotoxic cells were specific for parasitized target cells and in 9 of the 10 animals examined, they were clearly genetically restricted. Cytotoxicity could be inhibited by monoclonal antibodies (MoAb) to class I MHC molecules but not by MoAb to class II molecules, indicating that a large component of the response was restricted by class I MHC determinants. Low levels of inhibition of cytotoxicity were also obtained with a MoAb to the T-cell subset marker BoT8, suggesting that at least part of the response was mediated by BoT8+ lymphocytes. When cytotoxic cells from individual cattle were assayed on panels of parasitized target cells, there was a close correlation between susceptibility of the target cells to lysis and sharing of BoLA-A locus-encoded specificities with the effectors. This observation, taken together with the knowledge that within several of the sets of BoLA-A-matched targets the relevant BoLA-A specificities were on different MHC haplotypes, indicated that the responses were restricted predominantly by BoLA-A products. In individual cattle there was a striking bias in the restriction of the response to one or other BoLA-A specificity. Among the six specificities represented, responses restricted by w6, w8 and KN18 consistently predominated over responses restricted by w7, w10 and w11. In the three cattle tested for parasite strain specificity, two showed complete specificity and one partial specificity for cells infected with the parasite stock used for immunization, T. parva (Muguga).

Cytotoxic T-cells elicited in cattle challenged with Theileria parva (Muguga): evidence for restriction by class I MHC determinants and parasite strain specificity

Alteration of host cell phenotype by Theileria annulata and Theileria parva: mining for manipulators in the parasite genomes.

weight did occur, albeit at a slower rate than with complete diet, and there was no mortality. The a.ddition of L-penicilla.mino to the drinking water of the group maintained on pyridoxine-deficient diet retarded their normal weight gain still further within the first 30 days, but thero was no actual weight loss. It was only during the second 30 days of oral L-penicillamine therapy with pyridoxinedeficient diet that a 15 per cent loss in body-weight and 20 per cent mortality occurred. This was attributed to the reinforcing action of L-penicillamine on the vitamin deficiency induced by pyridoxine-deficient diet. Baseline data demonstrate tha.t within the first 30 days maintenance on pyridoxine-deficient diet, with or without daily oral treatment with L-penicillamine, does not causo either weight loss or mortality in CF! mice.

Mode of multiplication of theileria in cultures of bovine lymphocytic cells.

Theileria parva is responsible for East Coast fever of cattle—a disease which is usually fatal and which is characterized by an acute thermal reaction, a lymphoid hyperplasia followed by exhaustion of the lymphoid tissues and leucopenia.

J. K. H. Wilde

Papers

Mode of multiplication of theileria in cultures of bovine lymphocytic cells.

Transition of Developmental Stages of Theileria parva in vitro at High Temperature