scholarly journals Comparative Immune Response to PE and PE_PGRS Antigens of Mycobacterium tuberculosis

2001 ◽  
Vol 69 (9) ◽  
pp. 5606-5611 ◽  
Author(s):  
Giovanni Delogu ◽  
Michael J. Brennan

ABSTRACT Sequencing of the entire genome of Mycobacterium tuberculosis identified a novel multigene family composed of two closely related subfamilies designated PE and PE_PGRS. The major difference between these two families is the presence of a domain containing numerous Gly-Ala repeats extending to the C terminus of the PE_PGRS genes. We have used a representative PE_PGRS gene fromM. tuberculosis, Rv1818c(1818PE_PGRS), and its amino-terminal PE region (1818PE), to investigate the immunological response to these proteins during experimental tuberculosis and following immunization with DNA constructs. During infection of mice with M. tuberculosis, a significant humoral immune response was observed against recombinant 1818PE_PGRS but not toward the 1818PE protein. Similarly, immunization with a 1818PE_PGRS DNA construct induced antibodies directed against 1818PE_PGRS but not against 1818PE proteins, and no humoral response was induced by 1818PE DNA. These results suggest that certain PE_PGRS genes are expressed during infection of the host with M. tuberculosis and that an antibody response is directed solely against the Gly-Ala-rich PGRS domain. Conversely, splenocytes from 1818PE-vaccinated mice but not mice immunized with 1818PE_PGRS secreted gamma interferon following in vitro restimulation and demonstrated protection in the mouse tuberculosis challenge model. These results suggest that the PE vaccine can elicit an effective cellular immune response and that immune recognition of the PE antigen is influenced by the Gly-Ala-rich PGRS domain.

2000 ◽  
Vol 192 (7) ◽  
pp. 953-964 ◽  
Author(s):  
Richard K.G. Do ◽  
Eunice Hatada ◽  
Hayyoung Lee ◽  
Michelle R. Tourigny ◽  
David Hilbert ◽  
...  

B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine. It has been implicated in the development of autoimmunity, and functions as a potent costimulator with antiimmunoglobulin M in B cell proliferation in vitro. Here we demonstrate that BLyS prominently enhances the humoral responses to both T cell–independent and T cell–dependent antigens, primarily by attenuation of apoptosis as evidenced by the prolonged survival of antigen-activated B cells in vivo and in vitro. BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis. Moreover, although BLyS alone cannot activate the cell cycle, it is sufficient to prolong the survival of naive resting B cells in vitro. Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL. In either resting or CD40L-activated B cells, the NF-κB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival. Together, these results provide direct evidence for BLyS enhancement of both T cell–independent and T cell–dependent humoral immune responses, and imply a role for BLyS in the conservation of the B cell repertoire. The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response.


2021 ◽  
Vol 67 (3) ◽  
pp. 251-258
Author(s):  
A.E. Kniga ◽  
I.V. Polyakov ◽  
A.V. Nemukhin

Effective personalized immunotherapies of the future will need to capture not only the peculiarities of the patient’s tumor but also of his immune response to it. In this study, using results of in vitro high-throughput specificity assays, and combining comparative models of pMHCs and TCRs using molecular docking, we have constructed all-atom models for the putative complexes of all their possible pairwise TCR-pMHC combinations. For the models obtained we have calculated a dataset of physics-based scores and have trained binary classifiers that perform better compared to their solely sequence-based counterparts. These structure-based classifiers pinpoint the most prominent energetic terms and structural features characterizing the type of protein-protein interactions that underlies the immune recognition of tumors by T cells.


2019 ◽  
Vol 7 (5) ◽  
pp. 125
Author(s):  
Ryan M. Moreno ◽  
Victor Jimenez ◽  
Fernando P. Monroy

Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Currently, no experimental studies have investigated the effects of binge alcohol on the adaptive immune system during an active infection. In this study, we used B. thailandensis and B. vietnamiensis, to investigate the impact of a single binge alcohol episode on the humoral response during infection. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking (4.4 g/kg) or PBS intraperitoneally 30 min before intranasal infection. Mice infected with B. thailandensis had a 100% survival rate, while those infected with B. vietnamiensis had a 33% survivability rate when a binge alcohol dose was administered. B. thailandensis was detected in blood of mice administered alcohol at only 7 days post infection (PI), while those infected with B. vietnamiensis and receiving alcohol were found throughout the 28-day infection as well as in tissues at day 28 PI. Binge alcohol elevated IgM and delayed IgG specific to the whole cell lysate (WCL) of B. vietnamiensis but not B. thailandensis infections. Differences in immunogenicity of B. pseudomallei near-neighbors provide a framework for novel insights into the effects of binge alcohol’s suppression of the humoral immune response that can cause opportunistic infections in otherwise healthy hosts.


2005 ◽  
Vol 65 (2) ◽  
pp. 203-209 ◽  
Author(s):  
J. M. Barreto-Medeiros ◽  
E. G. Feitoza ◽  
K. Magalhães ◽  
R. R. da Silva ◽  
F. M. Manhães-de-Castro ◽  
...  

The repercussion on the immune response of the expression of intraspecific aggressiveness in the face of a stressor agent was investigated in rats. Ninety-day-old animals were divided into three groups: the control group (only immunological measurements were performed), the foot-shock (FS) (animals individually receiving FS), and the intraspecific aggressive response (IAR) group (animals receiving FS and presenting IAR). For immunological measurements, blood samples were collected promptly at 7 and 15 days after FS or IAR. The FS reduced the total leukocyte amount presented. However, aggressiveness triggered not only reduction of the leukocytes, but also lymphocyte decrease and neutrophil increase. Moreover, an elevation in total leukocytes associated with an increase in the humoral immune response was also observed one week after IAR. In this study, the expression of intraspecific aggressiveness in the face of a stressor seemed to activate the immune system and to potentiate the antigen specific humoral response.


2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Dan Ren ◽  
Tuofan Li ◽  
Xinyu Zhang ◽  
Xiaohui Yao ◽  
Wei Gao ◽  
...  

ABSTRACT Although astroviruses causes enteric diseases and encephalitis in humans and nephritis and hepatitis in poultry, astrovirus infection is thought to be self-limiting. However, little is known about its molecular mechanism. In this study, we found that a novel goose astrovirus (GAstV), GAstV-GD, and its open reading frame 2 (ORF2) could efficiently activate the innate immune response and induce a high level of OASL in vitro and in vivo. The truncation assay for ORF2 further revealed that the P2 domain of ORF2 contributed to stimulating OASL, whereas the acidic C terminus of ORF2 attenuated such activation. Moreover, the overexpression and knockdown of OASL could efficiently restrict and promote the viral replication of GAstV-GD, respectively. Our data not only give novel insights for elucidating self-limiting infection by astrovirus but also provide virus and host targets for fighting against astroviruses. IMPORTANCE Astroviruses cause gastroenteritis and encephalitis in human, and nephritis, hepatitis, and gout disease in poultry. However, the host immune response activated by astrovirus is mostly unknown. Here, we found that a novel goose astrovirus, GAstV-GD, and its ORF2 protein could efficiently induce a high level of OASL in vitro and in vivo, which could feed back to restrict the replication of GAstV-GD, revealing novel innate molecules triggered by astroviruses and highlighting that the ORF2 of GAstV-GD and OASL can be potential antiviral targets for astroviruses.


Author(s):  
Hyun Soo Lee ◽  
Sehyun Han ◽  
Jeong-Won Seo ◽  
Ki-Joon Jeon

Ambient particulate matter (PM), a major component of air pollution, aggravates ocular discomfort and inflammation, similarly to dry eye disease (DED) or allergies. However, the mechanism(s) by which PM induces the ocular inflammatory response is unknown. This study investigated the immunological response of traffic-related fine particulate matter (PM2.5) on the ocular surface in a murine model. C57BL/6 mice were exposed by topical application to PM2.5 or vehicle for 14 days to induce experimental environmental ocular disease. Corneal fluorescein staining and the number of ocular inflammatory cells were assessed in both groups. The expression of IL-1β, IL-6, tumor necrosis factor (TNF)-α, and mucin 5AC (MUC5AC) in the ocular surface were evaluated by real-time PCR. An immunohistochemical assay evaluated apoptosis and goblet cell density. ELISA was used to determine the levels of serum IgE and cytokines of Type 1 helper (Th1) and Type 2 helper (Th2) cells after in vitro stimulation of T cells in the draining lymph nodes (LNs). Exposure to traffic-related PM2.5 significantly increased corneal fluorescein staining and cellular toxicity in the corneal epithelium compared with the vehicle control. A significant increase in the number of CD11b+ cells on the central cornea and mast cells in the conjunctiva was observed in the PM2.5 group. Exposure to PM2.5 was associated with a significant increase in the corneal or conjunctival expression of IL-1β, IL-6, TNF, and MUC5AC compared to the vehicle, and increased maturation of dendric cells (DCs) (MHC-IIhighCD11c+) in draining LNs. In addition, PM2.5 exposure increased the level of serum IgE and Th2 cytokine production in draining LNs on day 14. In conclusion, exposure to traffic-related PM2.5 caused ocular surface damage and inflammation, which induced DC maturation and the Th2-cell-dominant allergic immune response in draining LNs.


1981 ◽  
Vol 16 (5) ◽  
pp. 556-563 ◽  
Author(s):  
Hiromasa Yoshie ◽  
Takashi Mitsuma ◽  
Keniti Kozima ◽  
Kohji Hara

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Ana Jolly ◽  
Silvia Beatriz Colavecchia ◽  
Bárbara Fernández ◽  
Eloy Fernández ◽  
Silvia Leonor Mundo

Lipoarabinomannan (LAM) is a major glycolipidic antigen on the mycobacterial envelope. The aim of this study was to characterize the humoral immune response induced by immunization with a LAM extract in bovines and to evaluate the role of the generated antibodies in thein vitroinfection of macrophages withMycobacterium aviumsubsp.paratuberculosis(MAP). Sera from fourteen calves immunized with LAM extract or PBS emulsified in Freund's Incomplete Adjuvant and from five paratuberculosis-infected bovines were studied. LAM-immunized calves developed specific antibodies with IgG1 as the predominant isotype. Serum immunoglobulins were isolated and their effect was examined in MAP ingestion and viability assays using a bovine macrophage cell line. Our results show that the antibodies generated by LAM immunization significantly increase MAP ingestion and reduce its intracellular viability, suggesting an active role in this model.


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