Induction of humoral immunity in response to immunization with recombinantMycobacterium bovisBCG expressing the S1 subunit ofBordetella pertussistoxin

2005 ◽  
Vol 51 (12) ◽  
pp. 1015-1020 ◽  
Author(s):  
Marco A Medeiros ◽  
Geraldo R.G Armôa ◽  
Odir A Dellagostin ◽  
Douglas McIntosh
Keyword(s):  
Immune Responses ◽  
Pertussis Toxin ◽  
Whooping Cough ◽  
Low Cost ◽  
Long Term Memory ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Specific Igg

Two recombinant Mycobacterium bovis BCG (rBCG) vaccine strains were developed for the expression of cytoplasmically located S1 subunit of pertussis toxin, with expression driven by the hsp60 promoter of M. bovis (rBCG/pPB10) or the pAN promoter of Mycobacterium paratuberculosis (rBCG/pPB12). Both strains showed stable expression of equivalent levels of recombinant S1 in vitro and induced long-term (up to 8 months) humoral immune responses in BALB/c mice, although these responses differed quantitatively and qualitatively. Specifically, rBCG/pPB12 induced markedly higher levels of IgG1 than did rBCG/pPB10, and mice immunized with the former strain developed specific long-term memory to S1, as indicated by the production of high levels of S1-specific IgG in response to a sublethal challenge with pertussis toxin 15 months after initial immunization. When considered in combination with previous studies, our data encourage further evaluation of rBCG as a potential means of developing a low-cost whooping cough vaccine based on defined antigens.Key words: recombinant BCG, humoral immune response, B. pertussis.

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.

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 Leukocyte Immunoglobulin-Like Receptor 1-Expressing Human Natural Killer Cell Subsets Differentially Recognize Isolates of Human Cytomegalovirus through the Viral Major Histocompatibility Complex Class I Homolog UL18

2016 ◽  
Vol 90 (6) ◽  
pp. 3123-3137 ◽  
Author(s):  
Kevin C. Chen ◽  
Richard J. Stanton ◽  
Jareer J. Banat ◽  
Mark R. Wills
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Natural Killer ◽  
Cytomegalovirus Infection ◽  
Hcmv Infection ◽  
Nk Cell ◽  
Long Term Memory ◽  
Term Memory

ABSTRACTImmune responses of natural killer (NK) cell are controlled by the balance between activating and inhibitory receptors, but the expression of these receptors varies between cells within an individual. Although NK cells are a component of the innate immune system, particular NK cell subsets expressing Ly49H are positively selected and increase in frequency in response to cytomegalovirus infection in mice. Recent evidence suggests that in humans certain NK subsets also have an increased frequency in the blood of human cytomegalovirus (HCMV)-infected individuals. However, whether these subsets differ in their capacity of direct control of HCMV-infected cells remains unclear. In this study, we developed a novelin vitroassay to assess whether human NK cell subsets have differential abilities to inhibit HCMV growth and dissemination. NK cells expressing or lacking NKG2C did not display any differences in controlling viral dissemination. However, whenin vitro-expanded NK cells were used, cells expressing or lacking the inhibitory receptor leukocyte immunoglobulin-like receptor 1 (LIR1) were differentially able to control dissemination. Surprisingly, the ability of LIR1+NK cells to control virus spread differed between HCMV viral strains, and this phenomenon was dependent on amino acid sequences within the viral ligand UL18. Together, the results here outline anin vitrotechnique to compare the long-term immune responses of different human NK cell subsets and suggest, for the first time, that phenotypically defined human NK cell subsets may differentially recognize HCMV infections.IMPORTANCEHCMV infection is ubiquitous in most populations; it is not cleared by the host after primary infection but persists for life. The innate and adaptive immune systems control the spread of virus, for which natural killer (NK) cells play a pivotal role. NK cells can respond to HCMV infection by rapid, short-term, nonspecific innate responses, but evidence from murine studies suggested that NK cells may display long-term, memory-like responses to murine cytomegalovirus infection. In this study, we developed a new assay that examines human NK cell subsets that have been suggested to play a long-term memory-like response to HCMV infection. We show that changes in an HCMV viral protein that interacts with an NK cell receptor can change the ability of NK cell subsets to control HCMV while the acquisition of another receptor has no effect on virus control.

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 Analytical treatment interruption after short-term anti-retroviral therapy in a postnatally SHIV infected infant rhesus macaque model

2019 ◽  
Author(s):  
Ria Goswami ◽  
Ashley N. Nelson ◽  
Joshua J. Tu ◽  
Maria Dennis ◽  
Liqi Feng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rhesus Macaque ◽  
Treatment Interruption ◽  
Viral Rebound ◽  
Short Term ◽  
Analytical Treatment ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Infant Rhesus

ABSTRACTTo achieve long-term viral remission in HIV-infected children, novel strategies beyond early anti-retroviral therapy (ART) will be necessary. Identifying clinical predictors of time to viral rebound upon ART interruption will streamline the development of novel therapeutic strategies and accelerate their evaluation in clinical trials. However, identification of these biomarkers is logistically challenging in infants, due to sampling limitations and potential risks of treatment interruption. To facilitate identification of biomarkers predicting viral rebound, we have developed an infant rhesus macaque (RM) model of oral SHIV.CH505.375H.dCT challenge and analytical treatment interruption (ATI) after short-term ART. We used this model to characterize SHIV replication kinetics and virus-specific immune responses during short-term ART or post-ATI and demonstrated plasma viral rebound in 5 out of 6 (83%) infants. We observed a decline in humoral immune responses and partial dampening of systemic immune activation upon initiation of ART in these infants. Furthermore, we documented that infant and adult macaques have similar SHIV replication and rebound kinetics and equally potent virus-specific humoral immune responses. Finally, we validated our models by confirming a well-established correlate of time to viral rebound, namely pre-ART plasma viral load, as well as identified additional potential humoral immune correlates. Thus, this model of infant ART and viral rebound can be used and further optimized to define biomarkers of viral rebound following long-term ART as well as to pre-clinically assess novel therapies to achieve a pediatric HIV functional cure.IMPORTANCENovel interventions that do not rely on daily adherence to ART are needed to achieve sustained viral remission for perinatally infected children who currently rely on lifelong ART. Considering the risks and expense associated with ART-interruption trials, identification of biomarkers of viral rebound will prioritize promising therapeutic intervention strategies, including anti-HIV Env protein therapeutics. However, comprehensive studies to identify those biomarkers are logistically challenging in human infants, demanding the need for relevant non-human primate models of HIV rebound. In this study, we developed an infant RM model of oral Simian/Human Immunodeficiency virus infection expressing clade C HIV Env, and short-term ART followed by ATI, longitudinally characterizing immune responses to viral infection during ART and post-ATI. Additionally, we compared this infant RM model to an analogous adult RM rebound model and identified virologic and immunologic correlates of time to viral rebound post-ATI.

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.

scholarly journals Augmentation of in vitro humoral immune responses in the mouse by an antibody to IgD.

1980 ◽  
Vol 152 (3) ◽  
pp. 493-506 ◽  
Author(s):  
F D Finkelham ◽  
V L Woods ◽  
S B Wilburn ◽  
J J Mond ◽  
K E Stein ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Total Serum ◽  
Adjuvant Effect ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Almost All ◽  
T Cell Help

Heterologous anti-delta-chain antibodies have an adjuvant effect on specific in vivo humoral immune responses to simultaneously, or subsequently, injected antigens in the rat and rhesus monkey. We have used a hybridoma-secreted antibody that binds murine delta-chain of the allotype (4.22aM delta a) to study this phenomenon in the mouse and to investigate the mechanism of this effect. Injection of 4.22aM delta a into BALB/c mice removes almost all surface IgD (sIgD) from splenic B lymphocites. sIgD does not reappear until the serum level of 4.22aM delta a decreased 5-7 d after injection. 4.22aM delta a fails to induce detectable proliferation or to raise total serum Ig levels substantially above control values. However, 4.22aM dalta a injected 24 h before antigen elicits an approximately twofold enhancement of serum IgM and a 3- to 10-fold enhancement of serum IgG anti-trintriphenyl (TNP) antibodies in response to immunization with optimal doses of TNP-Ficoll or TNP-sheep red blood cells (TNP-SRBC). 4.22aM delta a injected 1 wk before or 3 d after TNP-SRBC, however, has no effect on IgG anti-TNP levels. The adjuvant effect of anti-delta-chain antibody was markedly decreased when suboptimal antigen doses were used. Furthermore, even in the case of TNP-Ficoll, a relatively T-independent antigen, the ability of 4.22aM dalta a to enhance the anti-TNP antibody response was T cell dependent. Our data suggest that the binding of anti-delta-chain antibody to cell sIgD may partially activate B lymphocytes and make them more capable of differentiating into antibody-secreting cells when stimulated by antigen-specific T cell help.

Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

2007 ◽  
Vol 81 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Debabrata Ghosh ◽  
Soma Datta ◽  
Shelley Bhattacharya ◽  
Shibnath Mazumder
Keyword(s):  
Immune Responses ◽  
Head Kidney ◽  
Clarias Batrachus ◽  
Humoral Immune ◽  
Humoral Immune Responses
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