Protective immunity and specificity of antibody responses elicited in cattle by irradiated <i>Trypanosoma brucei</i>

Morrison, W. Ivan; Black, Samuel J.; Paris, J; Hinson, C. A.; Wells, P.W.

doi:10.1111/j.1365-3024.1982.tb00451.x

Cited by 44 publications

(25 citation statements)

References 15 publications

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“…Such a linear relationship between the antibody response and the quantity of trypanosome antigen is inconsistent with experimental findings (8). Furthermore, by extrapolation from experiments carried out with cattle, it would appear that the smallest inoculum sizes used in our experiment would be insufficient to elicit an anti-variant-specific surface glycoprotein response (32).…”

Section: Discussioncontrasting

confidence: 77%

Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate

Mamman¹,

Gettinby²,

Murphy³

et al. 1995

Antimicrob Agents Chemother

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The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25 mg/kg of body weight was investigated for populations of Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10 2 , 10 3 , 10 4 , 10 5 , and 10 6 trypanosomes per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 mice functioned as untreated controls. Thereafter, all animals were monitored for 100 days for the presence of trypanosomes. In each group, trypanosomes were detected in 50 of 50 control mice, indicating 100% infectivity for all five inoculum sizes. In contrast, in the groups of 50 mice infected with 10 2 , 10 3 , 10 4 , 10 5 , and 10 6 trypanosomes and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regression, a good fit was found between the number of mice identified as parasitemic and the inoculum sizes. Maximum likelihood estimates for the proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body weight for the inoculum of 10 2 , 10 3 , 10 4 , 10 5 , and 10 6 organisms were 8.335 ؋ 10 ؊4 , 2.485 ؋ 10 ؊4 , 3.02 ؋ 10 ؊5 , 8.3 ؋ 10 ؊6 , and 1.6 ؋ 10 ؊6 , respectively. These findings indicate that the majority of the relapse trypanosomes were susceptible to the drug dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varied inversely with the inoculum size. Further experiments with mice indicated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The data therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazeneresistant trypanosomes in populations of T. congolense occurring in vivo.

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Section: Discussioncontrasting

confidence: 77%

Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate

Mamman¹,

Gettinby²,

Murphy³

et al. 1995

Antimicrob Agents Chemother

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“…There is another VSGtriggered immune response, which activates macrophages to yield trypanocidal agents (38), but it is not known whether this response kills trypanosomes variant-specifically. Because this response is mainly extravascular (43), and order is not influenced by trypanosomes in that compartment (17,39), it is unlikely to (37), switching between variants and the density-dependent variables of differentiation to the nonproliferating stumpy stage (33), immune response onset (46,47), and removal of variants. The simulation began with 1,000 trypanosomes (akin to natural transmissions from tsetse) and involved a computationally feasible archive of 30 VSGs; the output provides a sample of events rather than simulating an entire infection.…”

Section: T Rypanosomes Switch Antigens Primarily By Duplication Ofmentioning

confidence: 99%

“…The immune response against variant i grows at an intrinsic rate determined by the number of cells of variant i. The intrinsic growth rate of the immune response x leads to a threshold of effectiveness, above which there is killing of the parasite, as occurs in vivo (46,47). Whether trypanosomes can resist antibodies during switching or at low antibody levels (24,48) would be included in these empirical profiles of immunity and do not need to be factored.…”

Section: [4]mentioning

confidence: 99%

Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation

Lythgoe

Morrison

Read

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Pathogens often persist during infection because of antigenic variation in which they evade immunity by switching between distinct surface antigen variants. A central question is how ordered appearance of variants, an important determinant of chronicity, is achieved. Theories suggest that it results directly from a complex pattern of transition connectivity between variants or indirectly from effects such as immune cross-reactivity or differential variant growth rates. Using a mathematical model based only on known infection variables, we show that order in trypanosome infections can be explained more parsimoniously by a simpler combination of two key parasite-intrinsic factors: differential activation rates of parasite variant surface glycoprotein (VSG) genes and densitydependent parasite differentiation. The model outcomes concur with empirical evidence that several variants are expressed simultaneously and that parasitaemia peaks correlate with VSG genes within distinct activation probability groups. Our findings provide a possible explanation for the enormity of the recently sequenced VSG silent archive and have important implications for field transmission.mathematical model ͉ Typanosoma brucei ͉ variant surface glycoprotein ͉ switching ͉ hierarchy

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“…Within the mammalian host, their cell membrane is covered by a variant surface glycoprotein (VSG) coat; termed variable because each parasite has an estimated 1000 VSG genes (Van der Ploeg et al 1982), each encoding an antigenically distinct surface coat. Cattle immunized with irradiated trypanosomes or purified VSG are protected against a homologous (trypanosomes expressing the same antigenic repertoire), but not a heterologous, challenge (Wellde et al 1975, Morrison et al 1982. Thus, the potential of African trypanosomes to express different VSG coats reduces the likelihood of an effective VSG-based vaccine.…”

mentioning

confidence: 99%

Immune Response of Cattle Infected with African Trypanosomes

Taylor

Mertens

1999

Mem. Inst. Oswaldo Cruz

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Protective immunity and specificity of antibody responses elicited in cattle by irradiated Trypanosoma brucei

Cited by 44 publications

References 15 publications

Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate

Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate

Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation

Immune Response of Cattle Infected with African Trypanosomes

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