Evaluation of immune responses raised againstTc13 antigens ofTrypanosoma cruziin the outcome of murine experimental infection

Parasitology ◽  
2007 ◽  
Vol 135 (3) ◽  
pp. 347-357 ◽  
Author(s):  
G. A. GARCÍA ◽  
M. R. ARNAIZ ◽  
M. I. ESTEVA ◽  
S. A. LAUCELLA ◽  
P. A. GARAVAGLIA ◽  
...  
Keyword(s):  
Immune Responses ◽  
Terminal Segment ◽  
T Cell Epitopes ◽  
Genetic Immunization ◽  
Cellular Immune Responses ◽  
Family Protein ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Efficient Memory

SUMMARYWe have previously reported that genetic immunization withTc13Tul antigen ofTrypanosoma cruzi, the aetiological agent of Chagas' disease, triggers harmful effects and non-protective immune responses. In order to confirm the role ofTc13 antigens duringT. cruziinfection, herein we studied the humoral and cellular immune responses to theTc13Tul molecule and its EPKSA C-terminal portion in BALB/cT. cruzi-infected mice or mice immunized with recombinantTc13Tul. Analysis of the antibody response showed that B-cell epitopes that stimulate a sustained IgM production along the infection and high levels of IgG in the acute phase are mainly located at theTc13 N- and C-terminal domains, respectively. DTH assays showed that T-cell epitopes are mainly at theTc13 N-terminal segment and that they do not elicit an efficient memory response. RecombinantTc13Tul did not induce IFN-γ secretion in either infected or immunized mice. However, a putative CD8+Tc13Tul-derived peptide was found to elicit IFN-γ production in chronically infected animals. Immunization with recombinantTc13Tul did not induce pathology in tissues and neither did it protect against the infection. Our results show that in the outcome ofT. cruziinfection theTc13 family protein mainly triggers non-protective immune responses.

Immunological and pathological responses in BALB/c mice induced by genetic administration ofTc13 Tul antigen ofTrypanosoma cruzi

Parasitology ◽  
2006 ◽  
Vol 132 (6) ◽  
pp. 855-866 ◽  
Author(s):  
G. A. GARCÍA ◽  
M. R. ARNAIZ ◽  
S. A. LAUCELLA ◽  
M. I. ESTEVA ◽  
N. AINCIART ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Encoding ◽  
Genetic Immunization ◽  
Humoral Immune ◽  
Specific Memory ◽  
Family Protein ◽  
Ifn Γ

Tc13 is atrans-sialidase family protein ofTrypanosoma cruzi, the aetiological agent of Chagas' disease. Recently,in vitrostudies had suggested thatTc13 might participate in the pathogenesis of the disease. In order to study the role ofTc13 antigens in anin vivomodel, we administered plasmid DNA encoding aTc13 antigen from the Tulahuén strain (Tc13 Tul) to BALB/c mice and evaluated the immunological and pathological manifestations as well as the capacity of this antigen to confer protection againstT. cruziinfection.Tc13 Tul immunization did not elicit a detectable humoral immune response but induced specific memory T-cells with no capacity to produce IFN-γ. Five months after DNA-immunization withTc13 Tul, signs of hepatotoxicity and reactive changes in the heart, liver and spleen were observed in 40–80% of mice. WhenTc13 Tul DNA-immunized animals were challenged with trypomastigotes, a significant decrease in parasitaemia in early and late acute phase was observed without modification in the survival rate. Surprisingly,Tc13 Tul-immunized mice chronically infected withT. cruzishowed a decrease in the severity of heart damage. We conclude that, in BALB/c mice, genetic immunization withTc13 Tul mainly induces immune responses associated with pathology.

scholarly journals Simultaneous Administration of Recombinant Measles Viruses Expressing Respiratory Syncytial Virus Fusion (F) and Nucleo (N) Proteins Induced Humoral and Cellular Immune Responses in Cotton Rats

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 27 ◽  
Author(s):  
Yoshiaki Yamaji ◽  
Akihito Sawada ◽  
Yosuke Yasui ◽  
Takashi Ito ◽  
Tetsuo Nakayama
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Simultaneous Administration ◽  
Cellular Immune Responses ◽  
Immunization Group ◽  
Cotton Rats ◽  
Ifn Γ ◽  
Syncytial Virus ◽  
Cellular Immune

We previously reported that recombinant measles virus expressing the respiratory syncytial virus (RSV) fusion protein (F), MVAIK/RSV/F, induced neutralizing antibodies against RSV, and those expressing RSV-NP (MVAIK/RSV/NP) and M2-1 (MVAIK/RSV/M2-1) induced RSV-specific CD8+/IFN-γ+ cells, but not neutralizing antibodies. In the present study, MVAIK/RSV/F and MVAIK/RSV/NP were simultaneously administered to cotton rats and immune responses and protective effects were compared with MVAIK/RSV/F alone. Sufficient neutralizing antibodies against RSV and RSV-specific CD8+/IFN-γ+ cells were observed after re-immunization with simultaneous administration. After the RSV challenge, CD8+/IFN-γ+ increased in spleen cells obtained from the simultaneous immunization group in response to F and NP peptides. Higher numbers of CD8+/IFN-γ+ and CD4+/IFN-γ+ cells were detected in lung tissues from the simultaneous immunization group after the RSV challenge. No detectable RSV was recovered from lung homogenates in the immunized groups. Mild inflammatory reactions with the thickening of broncho-epithelial cells and the infiltration of inflammatory cells were observed in lung tissues obtained from cotton rats immunized with MVAIK/RSV/F alone after the RSV challenge. No inflammatory responses were observed after the RSV challenge in the simultaneous immunization groups. The present results indicate that combined administration with MVAIK/RSV/F and MVAIK/RSV/NP induces humoral and cellular immune responses and shows effective protection against RSV, suggesting the importance of cellular immunity.

scholarly journals Humoral and Cellular Immune Responses to Trypanosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease

2003 ◽  
Vol 71 (6) ◽  
pp. 3165-3171 ◽  
Author(s):  
Vladimir Michailowsky ◽  
Keith Luhrs ◽  
Manoel Otávio C. Rocha ◽  
David Fouts ◽  
Ricardo T. Gazzinelli ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Chagas Disease ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Cellular Responses ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4+ CD25+ and CD4+ CD69+ lymphocytes, as well as that of small CD8+ CD25+ lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-γ) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-γ upon stimulation with PFR. PFR enhanced the percentages of IFN-γ-producing cells in both CD3+ and CD3− populations. Within the T-cell population, large CD4+ T lymphocytes were the main source of IFN-γ.

scholarly journals Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies

2002 ◽  
Vol 76 (12) ◽  
pp. 6093-6103 ◽  
Author(s):  
Eishiro Mizukoshi ◽  
Michelina Nascimbeni ◽  
Joshua B. Blaustein ◽  
Kathleen Mihalik ◽  
Charles M. Rice ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Hepatitis C ◽  
Immune Responses ◽  
Cellular Immune Responses ◽  
Functional Homology ◽  
Histocompatibility Complex ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several candidate vaccines and immunotherapies for these infections aim at the induction or enhancement of cellular immune responses against viral epitopes presented by common human major histocompatibility complex (MHC) alleles. To identify and characterize chimpanzee MHC class I molecules that are functionally related to human alleles, we sequenced 18 different Pan troglodytes (Patr) alleles of 14 chimpanzees, 2 of them previously unknown and 3 with only partially reported sequences. Comparative analysis of Patr binding pockets and binding assays with biotinylated peptides demonstrated a molecular homology between the binding grooves of individual Patr alleles and the common human alleles HLA-A1, -A2, -A3, and -B7. Using cytotoxic T cells isolated from the blood of hepatitis C virus (HCV)-infected chimpanzees, we then mapped the Patr restriction of these HCV peptides and demonstrated functional homology between the Patr-HLA orthologues in cytotoxicity and gamma interferon (IFN-γ) release assays. Based on these results, 21 HCV epitopes were selected to characterize the chimpanzees' cellular immune response to HCV. In each case, IFN-γ-producing T cells were detectable in the blood after but not prior to HCV infection and were specifically targeted against those HCV peptides predicted by Patr-HLA homology. This study demonstrates a close functional homology between individual Patr and HLA alleles and shows that HCV infection generates HCV peptides that are recognized by both chimpanzees and humans with Patr and HLA orthologues. These results are relevant for the design and evaluation of vaccines in chimpanzees that can now be selected according to the most frequent human MHC haplotypes.

scholarly journals THE ROLE OF HUMORAL ANTIBODIES IN REJECTION OF SKIN HOMOGRAFTS IN RABBITS

1961 ◽  
Vol 114 (4) ◽  
pp. 509-520 ◽  
Author(s):  
Roberto R. Kretschmer ◽  
Ruy Peréz-Tamayo
Keyword(s):  
Immune Responses ◽  
Skin Graft ◽  
Local Administration ◽  
Cellular Immune Responses ◽  
Humoral Antibodies ◽  
Skin Homograft ◽  
Cellular Immune ◽  
Control Skin

Gross and microscopic observations of skin homograft rejection carried out in cortisone-conditioned and non-conditioned rabbits seem to indicate that humoral antibodies play an important role in the phenomenon. Thus, local administration of isoimmune serum to animals bearing skin homografts resulted in a significantly earlier rejection of that particular test graft without modifying the course of a neighboring control-skin graft. This result appears to support the idea that homograft rejection is not only due to cellular antibodies but to a combination of both humoral and cellular immune responses, which should not be regarded as completely unrelated.

scholarly journals Profiling CD8+ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants

Cell Reports ◽  
2021 ◽  
Vol 36 (11) ◽  
pp. 109708
Author(s):  
Hang Zhang ◽  
Shasha Deng ◽  
Liting Ren ◽  
Peiyi Zheng ◽  
Xiaowen Hu ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cell ◽  
T Cell Epitopes ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Detection of a gamma interferon-induced protein IP-10 in psoriatic plaques.

1988 ◽  
Vol 168 (3) ◽  
pp. 941-948 ◽  
Author(s):  
A B Gottlieb ◽  
A D Luster ◽  
D N Posnett ◽  
D M Carter
Keyword(s):  
Immune Responses ◽  
Cdna Probe ◽  
Gamma Interferon ◽  
Activated T Cells ◽  
Cellular Immune Responses ◽  
Hla Dr ◽  
Pathologic Features ◽  
Dermal Infiltrate ◽  
Cellular Immune

The pathologic features of psoriatic plaques are inflammation and increased epidermal turnover. IP-10, a cytokine the expression of which is induced by gamma-interferon, is a member of a family of soluble mediators with inflammatory and growth-promoting activities. IP-10 protein was detected in keratinocytes and the dermal infiltrate from active psoriatic plaques using an affinity-purified rabbit anti-IP-10 antibody in immunoperoxidase studies. Successful treatment of active plaques decreased IP-10 expression in plaques. These results were corroborated by Northern blot analysis with an IP-10 cDNA probe. We have previously detected activated T cells and HLA-DR keratinocytes in active psoriatic plaques. Since IP-10 is detected in delayed cellular immune responses, the present study further points to the role of ongoing cellular immune responses in the pathogenesis of psoriasis.

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