scholarly journals Heme concentration-dependently modulates the production of specific antibodies in murine

2016 ◽  
Author(s):  
Guofu Li ◽  
Haiyan Xue ◽  
Zeng Fan ◽  
Yun Bai

Free heme is an endogenous danger signal to provoke innate immunity. Active innate immunity is a precondition of an effective adaptive immune response. However, heme catabolites, CO, biliverdin and bilirubin trigger immunosuppression. Furthermore, free heme induces the expression of heme oxygenase-1 to reinforce the production of CO, biliverdin and bilirubin. As such, free heme can drive two antagonistic mechanisms to affect adaptive immunity. What is the outcome of animal immune response to an antigen in the presence of free heme? The question remains to be explored. Here we report the immunization results by intraperitoneal injection of the formulations containing BSA and heme. When the used heme concentrations were about less than 1μM, the production of anti-BSA IgG and IgM was unaffected; when the used heme concentrations were about more than 1μM but less than 5μM, the production of anti-BSA IgG and IgM was enhanced; when the used heme concentrations were about more than 5μM, the production of anti-BSA IgG and IgM was suppressed. The results demonstrate that heme can modulate adaptive immunity (at least humoral immunity) by the mode of double concentration-thresholds. If heme concentrations are below the first threshold, there is no effect on adaptive immunity; if between the first and second thresholds, there is promotive effect; if over the second threshold, there is inhibitive effect. A hypothesis is also presented here to explain the mode.

Author(s):  
Paul Klenerman

Following the innate immune response, which acts very rapidly, the adaptive immune response plays a critical role in host defence against infectious disease. Unlike the innate response, which is triggered by pattern recognition of pathogens, i.e. features that are common to many bacteria or viruses, the adaptive response is triggered by structural features—known as antigens or epitopes—that are typically unique to a single organism....


2020 ◽  
pp. 325-336
Author(s):  
Paul Klenerman

The adaptive immune response is distinguished from the innate immune response by two main features: its capacity to respond flexibly to new, previously unencountered antigens (antigenic specificity), and its enhanced capacity to respond to previously encountered antigens (immunological memory). These two features have provided the focus for much research attention, from the time of Jenner, through Pasteur onwards. Historically, innate and adaptive immune responses have often been treated as separate, with the latter being considered more ‘advanced’ because of its flexibility. It is now clear this not the case, and in recent years the molecular basis for these phenomena has become much better understood.


1999 ◽  
Vol 67 (4) ◽  
pp. 2001-2004 ◽  
Author(s):  
Sing Sing Way ◽  
Alain C. Borczuk ◽  
Marcia B. Goldberg

ABSTRACT Shigella flexneri cydC, which is deficient in cytochrome bd, was rapidly cleared from the lungs of intranasally inoculated mice and was Sereny negative, yet it induced 93% protection against challenge with wild-type S. flexneri. Mice that lack immunoglobulin A (IgA) were fully protected, suggesting that IgA may not be required for adaptive immunity in this model system.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Elias J. Sayour ◽  
Duane A. Mitchell

Although cancer immunotherapy has shown significant promise in mediating efficacious responses, it remains encumbered by tumor heterogeneity, loss of tumor-specific antigen targets, and the regulatory milieu both regionally and systemically. Cross talk between the innate and adaptive immune response may be requisite to polarize sustained antigen specific immunity. Cancer vaccines can serve as an essential fulcrum in initiating innate immunity while molding and sustaining adaptive immunity. Although peptide vaccines have shown tepid responses in a therapeutic setting with poor correlates for immune activity, RNA vaccines activate innate immune responses and have shown promising effects in preclinical and clinical studies based on enhanced DC migration. While the mechanistic insights behind the interplay between innate and adaptive immunity may be unique to the immunotherapeutic being investigated, understanding this dynamic is important to coordinate the different arms of the immune response in a focused response against cancer antigens.


mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Jhansi L. Leslie ◽  
Kimberly C. Vendrov ◽  
Matthew L. Jenior ◽  
Vincent B. Young

ABSTRACTClostridium(Clostridioides)difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor forClostridium difficileinfection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance ofC. difficilehas yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance ofC. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance ofC. difficilefrom the murine gastrointestinal tract.IMPORTANCEClostridium difficileinfection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels ofC. difficilecolonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance ofC. difficilefrom the GI tract. Our results show that clearance ofC. difficilecan occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.


2019 ◽  
Author(s):  
Jhansi L. Leslie ◽  
Kimberly C. Vendrov ◽  
Matthew L. Jenior ◽  
Vincent B. Young

AbstractClostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium is the leading single cause of nosocomial infections in the United States. A major risk factor for C. difficile infection (CDI) is prior exposure to antibiotics as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80-90% success rate of fecal microbial transplants in treating recurrent infection. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, Random Forest analysis using only 2 members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract.ImportanceC. difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens as inherent differences in the baseline community structure of animals may bias findings.


1998 ◽  
Vol 10 (5) ◽  
pp. 349-350 ◽  
Author(s):  
Charles A. Janeway Jr. ◽  
Ruslan Medzhitov

Author(s):  
Sean F. Monaghan ◽  
Alfred Ayala

The development of sepsis remains a significant morbid event facing the critically-ill/severely-injured patient and while substantial improvements in supportive care have been made, a true molecular pharmacological treatment directed at mitigating the development of this condition has remained elusive. This is due, at least in part, to our lack of appreciation of the complex and intertwined changes in the nature of not only the innate, but also the adaptive immune response and how they affect our response to septic challenge. Here, we consider some of the aspects of the adaptive immune response, how it changes in the response to sepsis, possible pathological processes contributing to patient/experimental animal susceptibility to poorer outcomes and where novel immune-therapeutic targets/biomarkers may exist.


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