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- Ismail, Hodan Ahmed, et al.
(author)
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Subclass responses and their half-lives for antibodies against EBA175 and PfRh2 in naturally acquired immunity against Plasmodium falciparum malaria
- 2014
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 13
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Journal article (peer-reviewed)abstract
- Background: Plasmodium falciparum EBA175 and PfRh2 belong to two main families involved in parasite invasion, and both are potential vaccine candidates. Current knowledge is limited regarding which target antigens and subclasses of antibodies are actually important for protection, and how naturally acquired immunity is achieved. Methods: Repeated blood samples were collected from individuals in Nigeria over a period of almost one year. ELISA was used to analyse subclasses of IgG responses. Results: For both EBA175 (region III-V) and (a fragment of) PfRh2, the dominant antibody responses consisted of IgG1 and IgG3 followed by IgG2, while for PfRh2 there was also a relatively prominent response for IgG4. High levels of IgG1, IgG2 and IgG3 for EBA175 and total IgG for PfRh2 correlated significantly with a lower parasitaemia during the study period. Children with HbAS had higher levels of some subclasses compared to children with HbAA, while in adults the pattern was the opposite. The half-lives of IgG2 and IgG4 against EBA175 were clearly shorter than those for IgG1 and IgG3. Conclusion: EBA175 and PfRh2 are potential targets for protective antibodies since both correlated with lower parasitaemia. The shorter half-lives for IgG2 and IgG4 might explain why these subclasses are often considered less important in protection against malaria. Triggering the right subclass responses could be of critical importance in a successful vaccine. Further studies are needed to evaluate the role of haemoglobin polymorphisms and their malaria protective effects in this process.
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- Kaddumukasa, Mark, et al.
(author)
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Parasite Specific Antibody Increase Induced by an Episode of Acute P. falciparum Uncomplicated Malaria.
- 2015
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Journal article (peer-reviewed)abstract
- There is no approved vaccine for malaria, and precisely how human antibody responses to malaria parasite components and potential vaccine molecules are developed and maintained remains poorly defined. In this study, antibody anamnestic or memory response elicited by a single episode of P. falciparum infection was investigated.
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- Lugaajju, Allan, et al.
(author)
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Development of Plasmodium falciparum specific naïve, atypical, memory and plasma B cells during infancy and in adults in an endemic area
- 2017
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 16:1
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Journal article (peer-reviewed)abstract
- Background: B-cells are essential in immunity against malaria, but which sub-sets of B-cells specifically recognize Plasmodium falciparum and when they appear is still largely unknown. Results: Using the flow cytometry technique for detection of P. falciparum specific (Pf+) B-cells, this study for the first time measured the development of Pf+ B cell (CD19+) phenotypes in Ugandan babies from birth up to nine months, and in their mothers. The babies showed increases in Pf+ IgG memory B-cells (MBCs), atypical MBCs, and plasma cells/blasts over time, but the proportion of these cells were still lower than in the mothers who displayed stable levels (5, 18, and 3%, respectively). Pf+ non-IgG+ MBCs and naïve B-cells binding to P. falciparum antigens were higher in the babies compared to the mothers (12 and 50%). In ELISA there was an increase in IgG and IgM antibodies over time in babies, and stable levels in mothers. At baby delivery, multigravidae mothers had a higher proportion of Pf+ IgG MBCs and less Pf+ naïve B-cells than primigravidae mothers. Conclusions: In newborns, naïve B-cells are a major player in recognizing P. falciparum. In adults, the high proportion of Pf+ atypical MBCs suggests a major role for these cells. Both in infants and adults, non-IgG+ MBCs were higher than IgG MBCs, indicating that these cells deserve more focus in future.
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- Lugaajju, Allan, et al.
(author)
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Novel flow cytometry technique for detection of Plasmodium falciparum specific B-cells in humans: increased levels of specific B-cells in ongoing infection.
- 2015
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14:1
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Journal article (peer-reviewed)abstract
- Malaria caused by Plasmodium falciparum is still a major health threat in endemic areas especially for children below 5 years of age. While it is recognized that antibody immunity plays an important role in controlling the disease, knowledge of the mechanisms of sustenance and natural boosting of immunity is very limited. Before, it has not been possible to investigate malaria specific B-cells directly in flow cytometry, making it difficult to know how much of a B cell response is due to malaria, or how much is due to other immunological stimulators.
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- Persson, Kristina, 1965-
(author)
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Svensk brevkultur på 1800-talet : Språklig och kommunikationsetnografisk analys av en familjebrevväxling
- 2005
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Doctoral thesis (other academic/artistic)abstract
- In this dissertation, I examine the correspondence of an upper middle-class family from the early part of the nineteenth century. My aim is to answer questions about correspondence and letter-writing as an everyday event and as a social activity. My principal theoretical framework has been ethnograpy of communication. My main source is the Eurén-Snellman manuscript collection at Uppsala University Library (UUB, G65). The central figure of this collection is Axel Eurén (1803−1879), who was a clergyman in Dalarna and also a member of the Swedish parliament. The material expands over three generations and includes Axel, his mother, his sister, his wife and Axel’s and his wife Sophie’s three children. In each generation the letter-writing is reciprocal in nearly all relations.By creating a database of the 2,267 letters that remain from the family correspondence and by extracting meta-commentary about letter-writing I have studied how the family organized their correspondence. From the total collection I have chosen 293 letters during the period 1825−1858. These letters constitute a digitalized corpus that consists of approximately 160,000 words. With this corpus as my principal source, I have examined two different aspects of language use: a structural analysis of each writer’s total sum of letters and a study on address. Certain findings confirm that letter-writing was based on routine. Traits of orality appear less often in the latter part of the material, a result that is in line with earlier investigations.The dimension of formal−informal language has been interesting to examine in relation to gender. Whereas the women’s writing at a lexico-grammatical level is more informal and natural in style, their need to portray themselves in a virtuous Christian manner seems at the same time to promote a certain kind of formality in expression. The opposite seems to be true for the men.
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- Reddy, Sreenivasulu B., et al.
(author)
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Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth
- 2021
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Plasmodium falciparum parasites cause malaria and co-exist in humans together with B-cells for long periods of time. Immunity is only achieved after repeated exposure. There has been a lack of methods to mimic the in vivo co-occurrence, where cells and parasites can be grown together for many days, and it has been difficult with long time in vitro studies. Methods and results: A new method for growing P. falciparum in 5% CO2 with a specially formulated culture medium is described. This knowledge was used to establish the co-culture of live P. falciparum together with human B-cells in vitro for 10 days. The presence of B-cells clearly enhanced parasite growth, but less so when Transwell inserts were used (not allowing passage of cells or merozoites), showing that direct contact is advantageous. B-cells also proliferated more in presence of parasites. Symbiotic parasitic growth was verified using CESS cell-line and it showed similar results, indicating that B-cells are indeed the cells responsible for the effect. In malaria endemic areas, people often have increased levels of atypical memory B-cells in the blood, and in this assay it was demonstrated that when parasites were present there was an increase in the proportion of CD19 + CD20 + CD27 − FCRL4 + B-cells, and a contraction of classical memory B-cells. This effect was most clearly seen when direct contact between B-cells and parasites was allowed. Conclusions: These results demonstrate that P. falciparum and B-cells undoubtedly can affect each other when allowed to multiply together, which is valuable information for future vaccine studies.
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- Reddy, Sreenivasulu B., et al.
(author)
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High Affinity Antibodies to Plasmodium falciparum Merozoite Antigens Are Associated with Protection from Malaria
- 2012
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
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Journal article (peer-reviewed)abstract
- Background: Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown. Methodology/Principal Findings: In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as kd) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up. Conclusions/Significance: This study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations.
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