scholarly journals Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection

2015 ◽  
Vol 83 (5) ◽  
pp. 2185-2196 ◽  
Author(s):  
Joshua M. Obiero ◽  
Seif Shekalaghe ◽  
Cornelus C. Hermsen ◽  
Maxmillian Mpina ◽  
Else M. Bijker ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intradermal Injection ◽  
Content Type ◽  
Human Malaria ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Controlled Human Malaria Infection ◽  
Circulating Lymphocytes ◽  
Ifn Γ

To understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreservedPlasmodium falciparumsporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection ofP. falciparumsporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexualP. falciparumlysate and another that, based onP. falciparumserology, resembled the malaria-naive Dutch cohort. PositiveP. falciparumserology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparumantibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increaseP. falciparum-specificin vitrorecall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower inP. falciparumlysate-seropositive individuals than in seronegative individuals. In conclusion, positiveP. falciparumlysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is endemic.

scholarly journals Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

2013 ◽  
Vol 81 (12) ◽  
pp. 4626-4634 ◽  
Author(s):  
Ediane B. Silva ◽  
Andrew Goodyear ◽  
Marjorie D. Sutherland ◽  
Nicole L. Podnecky ◽  
Mercedes Gonzalez-Juarrero ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Strain ◽  
Protective Immunity ◽  
Burkholderia Pseudomallei ◽  
Partial Protection ◽  
Content Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immune Correlates ◽  
Draining Lymph Nodes

ABSTRACTInfections with the Gram-negative bacteriumBurkholderia pseudomallei(melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections withB. pseudomallei. At present, our understanding of what constitutes effective protective immunity againstB. pseudomalleiinfection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acuteB. pseudomalleiinfection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excludedpurMdeletion mutant ofB. pseudomallei(strain Bp82) and then subjected to intranasal challenge with virulentB. pseudomalleistrain 1026b. Immunization with Bp82 generated significant protection from challenge withB. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuatedBurkholderiavaccine strain was dependent primarily on generation of effective humoral immune responses.

scholarly journals REGULATION OF THE IMMUNE RESPONSE

1973 ◽  
Vol 137 (3) ◽  
pp. 721-739 ◽  
Author(s):  
Michael Hoffmann ◽  
John W. Kappler
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Immune Suppression ◽  
Antigen Recognition ◽  
Helper T Cells ◽  
Antibody Specificity ◽  
Humoral Immune ◽  
Functional Assays ◽  
Humoral Immune Responses

The specificity of antigen recognition by thymus-derived helper cells (T cells) and antibody was examined in mice, heterologous erythrocyte antigens from sheep (SRBC), goat (GRBC), burro (BRBC), chicken (CRBC), and toad (TRBC) being used. Antibody specificity was tested by a number of functional assays: hemagglutination, hemolysis, and immune suppression. The specificity of T cells was determined by titrating their ability to help the in vitro antitrinitrophenol (TNP) responses of mouse spleen cultures immunized with the hapten coupled to the various test erythrocytes as carrier. Anti-SRBC antibody cross-reacted with GRBC, but not with BRBC, CRBC, or TRBC. In contrast, SRBC-primed helper T cells cross-reacted with both GRBC and BRBC, but not with CRBC or TRBC, indicating a difference in the specificity of antigen recognition between the cellular and the humoral immune responses.

scholarly journals Immunostimulatory Effects of Recombinant Erysipelothrix rhusiopathiae Expressing Porcine Interleukin-18 in Mice and Pigs

2012 ◽  
Vol 19 (9) ◽  
pp. 1393-1398 ◽  
Author(s):  
Yohsuke Ogawa ◽  
Yu Minagawa ◽  
Fang Shi ◽  
Masahiro Eguchi ◽  
Yoshihiro Muneta ◽  
...  
Keyword(s):  
Immune Responses ◽  
Peritoneal Macrophages ◽  
Erysipelothrix Rhusiopathiae ◽  
Interleukin 18 ◽  
Murine Splenocytes ◽  
Content Type ◽  
Immunostimulatory Effect ◽  
Ifn Γ ◽  
Acquired Immune Responses

ABSTRACTInterleukin-18 (IL-18), which was originally called gamma interferon (IFN-γ)-inducing factor, has been shown to play an important role in innate and acquired immune responses. In this study, attenuatedErysipelothrix rhusiopathiaestrains were engineered to produce porcine IL-18 (poIL-18) and evaluated for their potential immunostimulatory effect in animals. Recombinant poIL-18 was successfully expressed in the recombinantE. rhusiopathiaestrains YS-1/IL-18 and KO/IL-18. The culture supernatant of YS-1/IL-18 was confirmed to induce IFN-γ production in murine splenocytesin vitro, and this production was inhibited by incubation with anti-poIL-18 monoclonal antibodies. Furthermore, more IFN-γ production was induced upon stimulation of splenocytes with concanavalin A for splenocytes from mice that were intraperitoneally inoculated with YS-1/IL-18 than for splenocytes from control mice inoculated with the parent strain YS-1. Peritoneal macrophages from mice preinoculated with YS-1/IL-18 exhibited enhanced phagocytosis ofSalmonella entericasubsp.entericaserovar Typhimurium compared with peritoneal macrophages from control mice preinoculated with YS-1. We also confirmed the immunostimulatory effect on humoral immune responses against antigens ofE. rhusiopathiaeandMycoplasma hyopneumoniaein gnotobiotic pigs that were orally preinoculated with KO/IL-18. Thus, these results provide evidence thatE. rhusiopathiaeis a promising vector for the expression of host cytokines and suggest the potential utility ofE. rhusiopathiaevector-encoded cytokines in the activation of host innate and acquired immune responses.

scholarly journals Humoral Immune Responses in a Human Case of Glanders

2012 ◽  
Vol 19 (5) ◽  
pp. 814-816 ◽  
Author(s):  
David M. Waag ◽  
Marilyn J. England ◽  
David DeShazer
Keyword(s):  
Immune Responses ◽  
Burkholderia Pseudomallei ◽  
Human Case ◽  
Burkholderia Mallei ◽  
Baseline Serum ◽  
Content Type ◽  
Whole Cells ◽  
Humoral Immune ◽  
Diagnostic Antigen ◽  
Humoral Immune Responses

ABSTRACTWithin 2 months of acquiring glanders, a patient developed 8-, 16-, and 4-fold increases, respectively, in specific IgA, IgG, and IgM serological titers againstBurkholderia mallei. Within 14 months of infection, the titers decreased to the baseline. Serum from this patient was also highly reactive againstBurkholderia pseudomalleiwhole cells.Burkholderia malleiwhole cells did not react with sera from patients with other diseases. Therefore, an assay using aB. malleicellular diagnostic antigen may be useful for the serodiagnosis of glanders.

Chondroitin sulfate activates B cells in vitro, expands CD138+cells in vivo, and interferes with established humoral immune responses

2014 ◽  
Vol 96 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Hilke Brühl ◽  
Josef Cihak ◽  
Nicole Goebel ◽  
Yvonne Talke ◽  
Kerstin Renner ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Chondroitin Sulfate ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Intranasal Immunization with Gal-Inhibitable Lectin plus an Adjuvant of CpG Oligodeoxynucleotides Protects against Entamoeba histolytica Challenge

2007 ◽  
Vol 75 (10) ◽  
pp. 4917-4922 ◽  
Author(s):  
Catherine P. A. Ivory ◽  
Kris Chadee
Keyword(s):  
Immune Responses ◽  
Entamoeba Histolytica ◽  
Mucosal Vaccine ◽  
Target Cells ◽  
Cpg Odn ◽  
Mucosal Vaccination ◽  
Humoral Immune ◽  
Cpg Oligodeoxynucleotides ◽  
Humoral Immune Responses

ABSTRACT The development of an effective amebiasis vaccine could improve child health in the developing world, reducing cases of amebic colitis and liver abscess. An ideal vaccine would be comprised of a well-characterized parasite antigen and an adjuvant, which would have high potency while driving the immune response in a Th1 direction. This study describes a mucosal vaccine composed of the Entamoeba histolytica galactose/N-acetyl-d-galactosamine-inhibitable lectin (Gal-lectin) and CpG oligodeoxynucleotides (CpG-ODN). The Gal-lectin is a protein involved in parasite virulence and adherence and is known to activate immune cells, while CpG-ODN are known to be potent inducers of type 1-like immune responses. We demonstrated that intranasal administration of the vaccine resulted in strong Gal-lectin-specific Th1 responses and humoral responses. Vaccination induced the production of Gal-lectin-specific T cells and the production of the proinflammatory cytokine gamma interferon. Vaccinated animals had detectable serum anti-Gal-lectin immunoglobulin G (IgG) and stool anti-Gal-lectin IgA capable of blocking parasite adherence to target cells in vitro. One week after immunization, gerbils were challenged intrahepatically with live trophozoites. Vaccinated gerbils had no detectable abscesses after day 5, whereas control gerbils developed larger abscesses. These results show that mucosal vaccination with Gal-lectin and CpG-ODN can induce both systemic and humoral immune responses.

scholarly journals Live Oral Typhoid Vaccine Ty21a Induces Cross-Reactive Humoral Immune Responses against Salmonella enterica Serovar Paratyphi A andS. Paratyphi B in Humans

2012 ◽  
Vol 19 (6) ◽  
pp. 825-834 ◽  
Author(s):  
Rezwanul Wahid ◽  
Raphael Simon ◽  
Shah J. Zafar ◽  
Myron M. Levine ◽  
Marcelo B. Sztein
Keyword(s):  
Immune Responses ◽  
Salmonella Enterica ◽  
Outer Membrane Proteins ◽  
Serum Antibody ◽  
Significant Proportion ◽  
Field Trials ◽  
Content Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Paratyphi B

ABSTRACTEnteric fever caused bySalmonella entericaserovar Paratyphi A infection has emerged as an important public health problem. Recognizing that in randomized controlled field trials oral immunization with attenuatedS. entericaserovar Typhi live vaccine Ty21a conferred significant cross-protection againstS. Paratyphi B but notS. Paratyphi A disease, we undertook a clinical study to ascertain whether humoral immune responses could explain the field trial results. Ty21a immunization of adult residents of Maryland elicited predominantly IgA antibody-secreting cells (ASC) that recognizeS. Typhi lipopolysaccharide (LPS). Cross-reactivity toS. Paratyphi A LPS was significantly lower than that toS. Paratyphi B LPS. ASC producing IgG and IgA that bind LPS from each of theseSalmonellaserovars expressed CD27 and integrin α4β7 (gut homing), with a significant proportion coexpressing CD62L (secondary lymphoid tissue homing). No significant differences were observed in serum antibody against LPS of the different serovars. Levels of IgA B memory (BM) cells toS. Typhi LPS were significantly higher than those againstS. Paratyphi A or B LPS, with no differences observed betweenS. Paratyphi A and B. The response of IgA BMto outer membrane proteins (OMP) fromS. Typhi was significantly stronger than that to OMP ofS. Paratyphi A but similar to that to OMP ofS. Paratyphi B. The percentages of IgG or IgA BMresponders to LPS or OMP from theseSalmonellastrains were similar. Whereas cross-reactive humoral immune responses toS. Paratyphi A or B antigens are demonstrable following Ty21a immunization, they cannot explain the efficacy data gleaned from controlled field trials.

Leukemia Specific Humoral Immune Responses in Immunotherapy with Leukemia Cell-Derived HSP70 in Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5192-5192
Author(s):  
Junko Jimbo ◽  
Kazuya Sato ◽  
Takaaki Hosoki ◽  
Motohiro Shindo ◽  
Katsuya Ikuta ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Leukemia Cell ◽  
Leukemia Cells ◽  
Specific Antibodies ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Mice Liver ◽  
Igg Level

Abstract Background: Tumor-derived heat shock proteins (HSPs), which bind the tumor specific antigenic peptides and carry them onto MHC molecules, are used for the vaccination against cancers. We previously reported that immunotherapy using leukemia cell-derived HSPs against minimal residual leukemia in mice prolonged survival by leukemia-specific CD8 + cytotoxic T lymphocyte induction. In addition, we showed that CD4+ as well as CD8+ T cell is indispensable for survival prolongation (Sato et al. Blood, 2001), which suggests that humoral immune response by CD4+ T cell is also important to eradicate leukemia cells. Contributions of humoral immune responses in anti-leukemia immunity induced by HSP-based immunotherapy remain unknown and are important information to induce effective anti-leukemia immunity. In this study, we investigated the humoral immune responses and cytotoxic activities against leukemia cells in the leukemia cell-derived HSP70 immunization mice model in vitro. Methods: Balb/c mice and syngeneic A20 B-cell leukemia cell line were used in this study. HSP70 was purified from A20 cells or healthy mice liver tissue. After subcutaneous administration of A20-derived HSP70 (A20-HSP), liver-derived HSP70 (liver-HSP) to the healthy mice, the sera were harvested to perform following experiments. To detect anti-A20 antibodies, mean fluorescence intensity (MFI) of A20 cells with mice sera and FITC-conjugated anti-mouse-IgG was analyzed by flowcytometry. The sera were subjected to ELISA to detect the specific IgG against A20-HSP, or IgG secreted by A20 cells (A20 Ig) as putative A20-specific antigen. Complement dependent cytotoxicity (CDC) activities were determined by trypan blue uptake of mouse target cells (A20, YAC1: lymphoma, or T27A: myeloid leukemia) after incubation with mice sera and rabbit complement. Results: MIF of A20 with the sera from A20-HSP immunized mice (A20-HSP mice) was significantly higher than that from liver-HSP immunized mice (liver-HSP mice). IgG level against A20-HSP by ELISA was significantly increased in the A20-HSP mice compared with liver-HSP mice. The reactivities of A20-HSP mice sera against A20-HSP were completely lost by ATP treatment, which treatment dissociates the antigenic peptide from A20-HSP. In addition, IgG level against A20 Ig in the A20-HSP mice was significantly higher than that in the liver-HSP mice, and this reactivity against A20 Ig were inhibited by preincubation of sera with A20 Ig-idiotipe-derived peptide (A20 IP) DYWGQGTEL, which is known as the A20-specific peptide. The sera from A20-HSP mice showed no cytotoxic activity itself but showed significantly high CDC activity with complement against A20 but not to YAC-1 or T27A in vitro. Conclusions: Immunization with leukemia cell-derived HSP70 induces the leukemia specific antibodies against peptides bound with leukemia cell-derived HSP70, including an idiotipic peptide of IgG secreted by leukemia cells. In addition, CDC by these leukemia specific antibodies is though to be one of the mechanisms of anti-leukemia immunity induced by leukemia cell-derived HSP70 immunization. These findings enable the effective monitoring of therapeutic effects on the HSP-based immunotherapy for patients with leukemia by using the leukemia specific antibodies, and might develop a new strategy to enhance the leukemia specific CDC activities induced by HSP70-immunization.

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