Mode of multiplication of theileria in cultures of bovine lymphocytic cells.
TL;DR: 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.
Abstract: 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.
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TL;DR: A selection of the mechanisms serves to illustrate the challenge involved in developing strategies for immunising against parasites.
Abstract: 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.
207 citations
TL;DR: The presence of the parasite in the host-cell cytoplasm modulates the state of activation of a number of signal transduction pathways, including nuclear factor-kappa B, which appear to be essential for the survival of Theileria-transformed T cells.
Abstract: 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.
161 citations
TL;DR: There was a resurgence of infected lymphoblasts in 5 to 6 weeks after an apparent disappearance of parasitized cells from the cultures and no evidence was obtained by the methods employed which might indicate the existence of an extracellular form of the parasite capable of reinfecting new cells in vitro.
Abstract: 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.
113 citations
TL;DR: 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 and indicated that the responses were restricted predominantly by BoLA‐A products.
Abstract: 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).
100 citations
TL;DR: The most widely used method of theileriosis control has involved tick control with acaricides and with the development of methods of immunisation, vaccination is being used more widely, particularly to control T. annulata and T. parva.
Abstract: Summary: Theileriasis is a protozoan infection of wild and domestic Bovidae which occurs throughout much of the world. The Theileria spp. are transmitted by ixodid ticks and have complex life cycles in both vertebrate host and vector, with sexual reproduction occurring in the tick. The classification and distribution of the different species are reviewed, followed by a description of the pathology, immunology, chemotherapy and control of the important species causing disease in domestic animals. The most widely used method of theileriosis control has involved tick control with acaricides. For many reasons this form of control has become less reliable and with the development of methods of immunisation, vaccination is being used more widely, particularly to control T. annulata. Biological differences between Theileria spp. have dictated different methods of vaccination, with an in vitro cultured schizont infected cell being used for T. annulata and T. hirci, and infection with sporozoites followed by drug treatment for T. parva. These live vaccines have limitations and considerable research is being directed towards identifying parasite antigens which may form the basis of newer killed vaccines. The broad immunising capacity of T. annulata isolates contrasts strongly with the antigenic complexity of T. parva. There is an urgent need for in vitro tests which will distinguish between stocks ofT. parva with different immunising capacities. In view of the relatively limited distribution of T. parva and the importance of the disease it causes, an effective system of information exchange and some co-operation and co-ordination in research towards its control have been instituted. The very wide distribution of T. annulata, and the variety of languages and cultures within its distribution, have limited exchange and co-operation but this situation needs to be corrected.
89 citations
References
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TL;DR: Polyoma virus induced transformation in four fibroblast clones derived from a culture of baby hamster kidney cells is found to be low, not due to these populations consisting of a mixture of genetically stable insusceptible and susceptible cells.
1,203 citations
TL;DR: The evidence presented does not support the current conception that the parasites serve as a powerful stimulus to the multiplication of lymphocytes, and is unable to substantiate the view, which has apparently never been seriously questioned, that they undergo schizogony in this situation.
Abstract: The history of the ticks (Rhipicephalus appendiculatus) employed for transmission of East Coast fever is detailed in Part I. During the 1st day the ticks generally become attached and are partly held in place by a kind of cement substance (Fig. 1).Penetration usually occurs at some time during the 2nd day, and the cellular elements of the corium quickly respond. There is a local swelling of the capillary endothelium, an infiltration with polymorphonuclear leucocytes and a slight increase in eosinophiles. More cement substance is produced which hardens about the edges. Some of it enters through the wound and spreads out in the corium along lines of least resistance (Fig. 2).Later on the eosinophiles increase greatly in number and in turn give place to macrophages which ingest some of the cement substance. Mast cells also become more numerous. The area of reaction extends 2 or 3 mm. from the tip of the proboscis. Marked cytolysis of fibroblasts, of histiocytes and of the swollen endothelial cells occurs. The latter leads to haemorrhage (Figs. 6, 8, 9). The red blood cells and leucocytes are, however, not destroyed. They are sucked up by the tick, the leucocytes first because they accumulate before the haemorrhages take place.Twenty-five of the sixty-six ticks examined were found to contain parasites in their salivary glands, but no parasites were seen in the sixty-six pieces of skin excised while the ticks were attached. Soon after the parasites enter the blood stream and spread throughout the system the corium of the skin is invaded by them like other parts of the body (Table III).The medium-sized lymphocytes are the principal cells parasitised; but parasites are also found in lymphoblasts, large and small lymphocytes and occasionally in parenchymatous liver cells. We never saw them in vascular endotheial cells. For this reason we are unable to substantiate the view, which has apparently never been seriously questioned, that they undergo schizogony in this situation. The first agamonts were noted in lymphocytes in gland smears the day the fever first exceeded 103° F. The gamonts appeared about a day later and the intra-erythrocytic forms soon after. Taking the average of a number of cases: (1) The temperature first surpassed 103° F. on the 9·8th day after infestation with ticks. (2) The first Koch bodies within lymphocytes were observed on the 14·8th day, that is to say, 5 days after the fever commenced. (3) The first parasites within the red cells were noted 1·6 days later, on the 16·4th day after infestation.The cycle which the parasite undergoes in changing from the agamonts to the intra-erythrocytic forms is illustrated in Diagram II (fully described on p. 36).The alterations in the tissues caused directly or indirectly by the parasitic invasion were studied principally in specimens secured at autopsy from animals killed in extremis. The changes which apparently dominate relate to the lymphatic system. The medium-sized lymphocytes and to a less extent the small and large lymphocytes and lymphoblasts, first in the lymph glands and later in all parts of the body, become infested with Koch bodies which grow in their interior apparently without causing any severe injury. The distribu tion of Koch bodies is recorded in Table III, and their incidence in the lymph glands and in the liver in Tables IV and V. The evidence presented does not support the current conception that the parasites serve as a powerful stimulus to the multiplication of lymphocytes. The enlargement of lymph glands is caused more by oedema than by increase in their number. But there is a marked redistribution of lymphocytes. Their number is reduced in the lymph glands and in the peripheral blood stream and increased in the blood vessels of the liver and some other organs. Perivascular lymphocytic infiltrations are also a notable feature of the reaction in the liver, kidneys, adrenals and several other organs, but they are of rare occurrence in the nervous system. It is uncertain how far they are formed by the emigration of lymphocytes from the blood stream and by the proliferation of lymphocytes previously present perivascularly.Small haemorrhages constitute a second alteration of importance. They are particularly prone to occur in the epicardium and endocardium, but may be found in almost any part of the body. Evidence is lacking that these haemorrhages play a part in the genesis of the perivasoular lymphocytic infiltrations. The latter are far more widespread and are chiefly observed in locations where haemorrhages are seldom seen.Oedema is a third type of reaction. It is constantly found in the lymph glands and occasionally in the lungs, especially in the later stages of the disease.Generally speaking, therefore, the lesions reported in this paper are acute in type. The functional activity of the several organs (except the lymph glands) has not been impaired sufficiently severely or over a time long enough to leave distinct structural changes in the parenchymatous organs; but the specimens examined were not collected from protracted cases of East Coast fever or from animals under suspicion of having undergone repeated attacks of the disease.It is the parasites in the red blood cells which are capable of continuing the cycle if they are ingested by ticks able to act as vectors. We have recog nised three principal groups: (1) small spherical-ovoid parasites which are the first to make their appearance, (2) tailed parasites, and (3) plunip forms, both of which develop later and become more numerous than the spherical-ovoid parasites. Possible stages of transition are represented in Diagram I (p. 37). Though many parasites undergo differentiation and some probably divide, a variable number degenerate within the erythrocytes.We question the validity of the genera into which the family Theileriidae are customarily divided on account of the inadequacy of the data on which they are based.
52 citations
TL;DR: The addition of glutamine, pyridoxin, and riboflavine to the mixture of serum and Tyrode induced multiplication of Koch bodies, which was observed in ten successive fragments of normal calf spleen during a period of two months.
Abstract: THE following simple method modified from Jacoby (1944) was found suitable for the growth in vitro of Theileria annulata. A small fragment of infected calf's spleen or lymphatic gland is placed on a sterile glass coverslip and a drop each of calf plasma and chickens' embryonic extract are added. After coagulation the coverslip is sealed to the bottom of a large Carrel flask by a drop of plasma and embryonic extract; 3–5 c.c. of a mixture of 30–40 per cent calf serum in Tyrode is then added and the flask closed and incubated. On this medium Koch bodies survive for at least twelve days, but do not multiply. If fragments of normal spleen are placed in juxtaposition to the infected fragment at intervals of 3–5 days, Koch bodies survive for 15–18 days, but there is no obvious multiplication. The addition of glutamine (3 γ per c.c), pyridoxin (0·6 γ per c.c.), inositol (4 γ per c.c.) and riboflavine (0·4 γ per c.c.) to the mixture of serum and Tyrode induces multiplication of Koch bodies, which was observed in ten successive fragments of normal calf spleen during a period of two months. The addition of these factors to the transplant, in which Koch bodies have survived without multiplication for eighteen days, immediately induced multiplication of the surviving parasites.
40 citations
32 citations
TL;DR: Theileria annulata was grown in tissue culture from implants of infected spleen, lymph node or liver and the cultures were infective for cattle when tested after 17 and 42 days and T. parva appeared to exert a toxic influence over the adjacent cells.
Abstract: 1.
1) Theileria annulata was grown in tissue culture for over 59 days from implants of infected spleen, lymph node or liver. Multiplication of the parasites occurred and the cultures were infective for cattle when tested after 17 and 42 days. This confirms earlier work by TsUR (Tchernomoretz), 1945.
2.
2) T. parva was maintained in tissue culture up to 14 days. Some multiplication of the parasites occurred during the first few days. The parasites occurred mostly in lymphoid cells ; they were restricted to the cells of the initial implant and did not spread out into the cells of the outgrowth.
3.
3) T. parva appeared to exert a toxic influence over the adjacent cells ; and if the initial implant of spleen or lymph node contained many parasites, growth of all types of cell was inhibited.
17 citations