The in vivo antibody response in rat gut-associated lymphoid tissue (GALT) after immunization with bacterial polysaccharide antigen

1993 ◽  
Vol 144 (2) ◽  
pp. 121-128 ◽  
Author(s):  
M. Soesatyo ◽  
G.P.J.M. Van den Dobbelsteen ◽  
E.P. Van Rees ◽  
J. Biewenga ◽  
T. Sminia
1967 ◽  
Vol 168 (1012) ◽  
pp. 244-262 ◽  

The aim of these studies was to examine the possible immunological significance of the process of lymphocyte recirculation. For this purpose a technique for perfusing the isolated spleen of the rat was developed. Antigen (sheep erythrocytes) was added to the perfusate and, after 3 to 6 h periods of perfusion, the spleens were cut into fragments and implanted into the peritoneal cavities of X-irradiated syngeneic recipients to determine the magnitude of the haemolysin response. The lymphocyte concentration in the blood perfusing the spleen was varied within wide limits to determine whether a migration of lymphocytes through the spleen influenced its ability to respond to antigenic stimulation. Normal spleens perfused for 3 h with blood containing a normal concentration of lymphocytes gave substantial haemolysin titres in the recipients when sheep erythrocytes had been added initially to the perfusate. Spleens depleted of lymphocytes in vivo by either X-irradiation or chronic drainage from a thoracic duct fistula produced very low titres after perfusion with lymphocyte-free blood and antigen, but their responses were restored by adding lymphocytes to the perfusate. The antibody response of normal spleens was significantly depressed following perfusion for 3 h with lymphocyte-free blood to which antigen had been added initially. However, normal responses were obtained in this experiment if the addition of antigen to the perfusate was delayed for 5 h and perfusion then continued for one further hour. The delay allowed lymphocytes to migrate from the normal spleens into the perfusate and to build up the concentration in the initially lymphocyte-free blood to normal levels. The conclusion drawn from this paradoxical finding was that the magnitude of the haemolysin response depended upon the concentration of lymphocytes in the perfusate at the time of antigen addition and not upon the total number of lymphocytes in the spleen. The rate of migration of small lymphocytes from the blood into the spleen was found to be directly proportional to the concentration of lymphocytes in the perfusate. The most acceptable explanation of all the data is that the magnitude of the haemolysin response is proportional to the concentration of lymphocytes in a limited compartment of the splenic lymphoid tissue into which lymphocytes have recently migrated from the blood. This compartment is probably located in the central area of the periarteriolar lymphocyte sheath.


2009 ◽  
Vol 83 (23) ◽  
pp. 12355-12367 ◽  
Author(s):  
Mohammed Rafii-El-Idrissi Benhnia ◽  
Megan M. McCausland ◽  
John Laudenslager ◽  
Steven W. Granger ◽  
Sandra Rickert ◽  
...  

ABSTRACT Antibodies against the extracellular virion (EV or EEV) form of vaccinia virus are an important component of protective immunity in animal models and likely contribute to the protection of immunized humans against poxviruses. Using fully human monoclonal antibodies (MAbs), we now have shown that the protective attributes of the human anti-B5 antibody response to the smallpox vaccine (vaccinia virus) are heavily dependent on effector functions. By switching Fc domains of a single MAb, we have definitively shown that neutralization in vitro—and protection in vivo in a mouse model—by the human anti-B5 immunoglobulin G MAbs is isotype dependent, thereby demonstrating that efficient protection by these antibodies is not simply dependent on binding an appropriate vaccinia virion antigen with high affinity but in fact requires antibody effector function. The complement components C3 and C1q, but not C5, were required for neutralization. We also have demonstrated that human MAbs against B5 can potently direct complement-dependent cytotoxicity of vaccinia virus-infected cells. Each of these results was then extended to the polyclonal human antibody response to the smallpox vaccine. A model is proposed to explain the mechanism of EV neutralization. Altogether these findings enhance our understanding of the central protective activities of smallpox vaccine-elicited antibodies in immunized humans.


2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S10-S10
Author(s):  
Artemis Gogos ◽  
Michael J Federle

Abstract Background Streptococcus pyogenes is a human-restricted pathogen most often found in the human nasopharynx. Multiple bacterial factors have been found to contribute to persistent colonization of this niche, and many of these factors are important in mucosal immunity and vaccine development. In this work, we infected mice intranasally with transcriptional regulator mutants of the Rgg2/3 quorum sensing (QS) system—a peptide-based signaling system conserved in all sequenced isolates of S. pyogenes. Methods Three-week-old CD1 mice were intranasally infected with ~107 CFU of S. pyogenes strain MGAS315. Calcium alginate throat swabs were used to monitor nasopharyngeal colonization by the bacteria over time. Luciferase reporters used alongside an IVIS camera were able to show quorum sensing activity levels after inoculation into the mouse nose. Bacterial RNA was isolated from the throat of the mice and quantitative RT–PCR was performed on the samples to corroborate the luciferase reporter data. The nasal-associated lymphoid tissue (NALT) was excised and its supernatants were subjected to 32-plex murine cytokine and chemokine analysis (Millipore). Results Deletion of the QS system’s transcriptional activator (Δrgg2) dramatically diminished the percentage of colonized mice. Deletion of the transcriptional repressor (Δrgg3) increased the percentage of colonized mice compared with wild type. Stimulation of the QS system using synthetic pheromones prior to inoculation did not significantly increase the percentage of animals colonized, indicating that activity of the QS system is responsive to conditions of the host nasopharynx. Mice inoculated with QS-dependent luciferase reporters were subjected to in vivo imaging and showed activation within 1 hour. Bacterial RNA extracted directly from oropharyngeal swabs and evaluated by quantitative RT–PCR subsequently confirmed QS upregulation within 1 hour of inoculation. In the nasal-associated lymphoid tissue (NALT), a muted inflammatory response to the Δrgg2 bacteria suggests that their rapid elimination fails to elicit the previously characterized response to intranasal inoculation of GAS. Conclusions Deletion of the Rgg2 transcriptional activator of the Rgg 2/3 quorum sensing system eliminates colonization of the murine nasopharynx and changes the transcriptional profile of the bacteria in this niche. An existing small-molecule inhibitor of the Rgg2/3 system was unable to inhibit QS activation in vivo, likely due to the suboptimal achievable doses; however, results of our study indicate inhibition of QS may diminish the oropharyngeal colonization of S. pyogenes and argue for further development.


1980 ◽  
Vol 29 (2) ◽  
pp. 633-641 ◽  
Author(s):  
Thuang S. Lim ◽  
Juneann W. Murphy ◽  
Larry K. Cauley

Inbred CBA/J mice were used in developing a defined in vivo model for studying host-parasite relationships in cryptococcosis. Mice were infected either intranasally or intraperitoneally with 10 3 viable Cryptococcus neoformans cells. At weekly intervals over a 92-day period, C. neoformans growth profiles in the lungs, spleens, livers, and brains of the infected animals were determined. In addition, humoral and delayed-type hypersensitivity responses and cryptococcal antigen levels were assayed in these mice. Intranasally infected mice developed strong delayed-type hypersensitivity reactions in response to cryptococcal culture filtrate (CneF) antigen, and there was good correlation between acquisition of delayed-type hypersensitivity and the reduction of C. neoformans cell numbers in infected tissues. In contrast, intraperitoneally infected mice displayed greater numbers of C. neoformans cells in tissues and had somewhat suppressed delayed-type hypersensitivity responses to CneF antigen. Anticryptococcal antibodies were not detected in intranasally or intraperitoneally infected mice, but cryptococcal polysaccharide antigen titers were relatively high in both groups. The transfer of sensitized spleen cells from intranasally infected mice to syngeneic naive recipient mice resulted in the transfer of delayed-type hypersensitivity responsiveness to cryptococcal antigen in the recipients. The intranasally induced infection in mice was similar to the naturally acquired infection in humans; therefore we are proposing that this murine-cryptococcosis model would be useful in gaining a greater understanding of host-etiological agent relationships in this disease.


1994 ◽  
Vol 8 (4) ◽  
pp. 327-340 ◽  
Author(s):  
L.G. Krymskaya ◽  
N.Y. Gromykhina ◽  
A.A. Tinnikov ◽  
V.A. Kozlov

2021 ◽  
Author(s):  
Marta Calvet-Mirabent ◽  
Daniel T. Claiborne ◽  
Maud Deruaz ◽  
Serah Tanno ◽  
Carla Serra ◽  
...  

Effective function of CD8+ T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8+ T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4+ T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to secondary lymphoid organs and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies.


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