Immune Plasma Research Articles

Immune Plasma Algorithm: A Novel Meta-Heuristic for Optimization Problems.

The recent global health crisis also known as the COVID-19 or coronavirus pandemic has attracted the researchers’ attentions to a treatment approach called immune plasma or convalescent plasma once more again. The main idea lying behind the immune plasma treatment is transferring the antibody rich part of the blood taken from the patients who are recovered previously to the critical individuals and its efficiency has been proven by successfully using against great influenza of 1918, H1N1 flu, MERS, SARS and Ebola. In this study, we modeled the mentioned treatment approach and introduced a new meta-heuristic called Immune Plasma (IP) algorithm. The performance of the IP algorithm was investigated in detail and then compared with some of the classical and state-of-art meta-heuristics by solving a set of numerical benchmark problems. Moreover, the capabilities of the IP algorithm were also analyzed over complex engineering optimization problems related with the noise minimization of the electro-encephalography signal measurements. The results of the experimental studies showed that the IP algorithm is capable of obtaining better solutions for the vast majority of the test problems compared to other commonly used meta-heuristic algorithms.

Identification of immunodominant Trypanosoma musculi antigens recognized by monoclonal antibody and curative immunoglobulin G2a antibody

Shaw K. T. Y., Shaw I. T., Ryan P., Stevenson M. M. and Kongshavn P. A. L. 1992. Identification of immunodominant Trypanosoma musculi antigens recognized by monoclonal antibody and curative immunoglobulin G2a antibody. International Journal for Parasitology 22: 603–612. Trypanosoma musculi obtained from normal or irradiated (900 rad) hosts or from in vitro cultures were lysed and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Similar protein banding patterns with a molecular weight (mol. wt) range from 34 to 68 kDa were observed between the two bloodstream forms. In comparison, lysates of cultured parasites showed a unique banding pattern of antigens within the same mol. wt range. Western blot of bloodstream form lysates, probed with immune plasma (IP), revealed a wide range of parasite proteins. However, when probed with the IgG2a-enriched fraction of IP, a major band of approximately 66 kDa was detected on the blot. Several bands of higher mol. wt were also observed. When anti- T. musculi monoclonal antibodies were used to probe the blot, the 66 kDa protein was again recognized. Using indirect fluorescence, live bloodstream form parasites were analysed by flow cytometry and the p66 protein was determined to be a surface molecule. Finally, lysates of 35S-methionine-labelled trypanosomes were immunoprecipitated with Sepharose linked anti- T. musculi monoclonal antibodies and the eluted ligand analysed by SDS-PAGE and autoradiographed. The 66 kDa band was identified, therefore confirming that this protein was of parasite origin.

Cells within the vascular system capable of mediating trypanocidal activity in vitro

Cure of Trypanosoma musculi infection involves an effector mechanism mediated by immunoglobulin G2a antibody, C3, and an unidentified effector cell. In the present study, experiments were designed to identify the cell(s) within the vascular system that may be responsible for cure of trypanosomiasis. The ability of various cell populations to mediate killing of trypanosomes in the presence of C3 and immune plasma (IP) was tested in vitro. Blood-derived platelets or leukocytes or Bio-Gel-elicited macrophages or neutrophils were incubated at various concentrations with T. musculi, C3, and IP diluted up to 1 in 8. Trypanocidal activity was dependent upon the presence and concentration of IP and on the number of cells in the wells. Macrophages, neutrophils, and platelets were shown to kill with different potencies. With a 2:1 cell-to-parasite ratio, both macrophages and neutrophils reduced parasite numbers by 2 log, while platelets at a 40:1 ratio mediated a 1 log decrease. In addition, even in the absence of C3, the phagocytes were capable of killing trypanosomes while platelet trypanocidal activity was abrogated. The time course of trypanocidal activity was monitored for macrophages and neutrophils. The number of parasites decreased by 0.5 log by 4 h and 1 to 2 log by 8 h and by 20 h was reduced to zero. Cultured monolayers of endothelial cells were also tested for trypanocidal activity and shown to kill the parasites in the presence of IP and C3. The level of trypanocidal activity was dependent on the concentration of IP.

Failure to demonstrate a major role for Kupffer cells and radiosensitive leukocytes in immunoglobulin-mediated elimination of Trypanosoma musculi

Previous studies have indicated that elimination of parasitemia in Trypanosoma musculi infection is brought about by immunoglobulin G2a antibodies, C3, and an effector cell. Experiments were designed to identify the putative effector cell by using several approaches. Infected C5-deficient or C5-sufficient mice treated with silica particles or given 900 rads of radiation 3 days earlier effectively eliminated trypanosomes following administration of immune plasma (IP). Silica-treated, noninfected mice given T. musculi preincubated with IP also cleared the parasites. Radiolabeling studies revealed that uptake of the cleared trypanosomes by the liver in normal mice was relatively low (24%) and fell only slightly (19%) in silica-treated mice. In contrast, uptake of radiolabeled sheep erythrocytes by the liver was normally much higher (47%) and fell drastically (7%) in silica-treated mice. Mice were then immunocompromised by 900 rads of radiation, silica particles, and anti-platelet serum combined before IP-sensitized trypanosomes were given. Leukocyte and platelet counts were both reduced by 95% and sheep erythrocyte uptake by the liver fell from 77 to 5%; however, greater than 99% of the injected trypanosomes were cleared in these mice and uptake of radiolabeled trypanosomes by the liver was similar to that of normal mice. Lastly, in anesthetized mice in which Kupffer cells were excluded surgically from the circulation, greater than 99% of the IP-sensitized trypanosomes disappeared rapidly from the blood. Only 7% of the radiolabel was found in the liver versus 60% in sham-operated mice. The results are interpreted as showing that hepatic Kupffer cells play a minor role in the immune elimination of T. musculi. Likewise, radiosensitive leukocytes and platelets are unlikely to be sole candidates for the putative effector cell that mediates a cure of murine trypanosomiasis.

Further characterization of the curative antibodies in Trypanosoma musculi infection.

The ability of immune plasma (IP) taken from different donor strains of mice to cure Trypanosoma musculi infection in various recipient mouse strains, when given during the plateau phase of infection, was examined. C57BL/6, B10.A/SgSn, B10.D2/oSn, B10.D2/nSn, DBA/2, and BALB/c strains could be cured of parasitemia (giving 0.4 to 0.8 ml of IP per mouse), whereas A/J and C3H/HeN strains could not (giving up to 1.2 ml of IP per mouse). Noncure appeared to be associated with the high-plateau parasitemias (approximately 10(8] that developed in the latter strains since IP administered early in infection, when the parasite burden was similar to the plateau parasitemias (approximately 10(6] of strains that could be cured, was at least partially effective in A/J and C3H/HeN mice. The IP of any strain tested (C57BL/6, B10.D2/oSn, B10.D2/nSn, DBA/2, A/J, or C3H/HeN) could bring about elimination of trypanosomes in strains able to be cured. The potency of IP from different strains varied, being greater in the strains that developed higher-plateau parasitemias. Potency of IP appears to correlate positively with the titers of trypanosome-specific antibody of the immunoglobulin G2a isotype (the curative antibody). The role of the late-acting complement components was examined. In C5-deficient mice the course of infection was normal, although the elimination phase was delayed by a few days. Cure of parasitemia by IP administered during the plateau phase was equally effective in the presence or absence of C5 in either the donor or the recipient. When tested in vitro, however, IP only exhibited antitrypanosomal activity when added to infected blood taken from C5-sufficient strains of mice. We conclude that in vitro, under the conditions used in the assay, antibody-mediated destruction of the trypanosomes is brought about by complement-mediated lysis. This process, although it probably occurs to some extent, is unlikely to be the major mechanism of trypanosome elimination in vivo.