scholarly journals Mucosally Induced Immunoglobulin E-Associated Inflammation in the Respiratory Tract

2000 ◽  
Vol 68 (2) ◽  
pp. 672-679 ◽  
Author(s):  
Jerry W. Simecka ◽  
Raymond J. Jackson ◽  
Hiroshi Kiyono ◽  
Jerry R. McGhee

ABSTRACT The purpose of the present study was to determine the immunologic responses, particularly immunopathologic reactions, associated with nasal immunization with the mucosal adjuvant, cholera toxin (CT). BALB/c mice were nasally immunized with tetanus toxoid (TT) combined with CT, and the responses of these mice were determined. After nasal immunization, mice produce a serum antibody response, primarily of the immunoglobulin G (IgG) isotype of predominantly IgG1 subclass, against both TT and CT. Along with the antibody responses, we also found that inflammatory reactions, which could be potentially fatal, developed within the lung. Furthermore, IgE responses were also induced after nasal immunization, and these responses were associated with the detection of interleukin 5 in the serum. Thus, nasal immunization with TT plus CT likely results in the activation of Th2 cells, which may contribute to serious immunopathologic reactions in the lung.

2004 ◽  
Vol 72 (6) ◽  
pp. 3350-3358 ◽  
Author(s):  
Nicholas H. Carbonetti ◽  
Galina V. Artamonova ◽  
Charlotte Andreasen ◽  
Edward Dudley ◽  
R. Michael Mays ◽  
...  

ABSTRACT Pertussis toxin (PT), a virulence factor secreted by Bordetella pertussis, contributes to respiratory tract infection and disease caused by this pathogen. By comparing a wild-type (WT) B. pertussis strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (ΔPT), we recently found that the lack of PT confers a significant defect in respiratory tract colonization in mice after intranasal inoculation. In this study, we analyzed serum antibody responses in mice infected with the WT or ΔPT strain and found that infection with the ΔPT strain elicited greater responses to several B. pertussis antigens than did infection with the WT, despite the lower colonization level achieved by the ΔPT strain. The same enhanced antibody response was observed after infection with a strain expressing an enzymatically inactive PT; but this response was not observed after infection with B. pertussis mutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered with the ΔPT inoculum, indicating a specific role for PT activity in this immunosuppressive effect. In particular, there were consistent strong serum antibody responses to one or more low-molecular-weight antigens after infection with the ΔPT strain. These antigens were Bvg independent, membrane localized, and also expressed by the closely related pathogens Bordetella parapertussis and Bordetella bronchiseptica. Two-dimensional gel electrophoresis and mass spectrometry were used to identify one of the immunodominant low-molecular-weight antigens as a protein with significant sequence homology to peptidoglycan-associated lipoprotein in several other gram-negative bacterial species. However, a serum antibody response to this protein alone did not protect mice against respiratory tract infection by B. pertussis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tybbysay P. Salinas ◽  
Jose L. Garrido ◽  
Jacqueline R. Salazar ◽  
Publio Gonzalez ◽  
Nicole Zambrano ◽  
...  

BackgroundNew World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections.MethodsFor this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry.ResultsHigh titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals.ConclusionA Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies.


2005 ◽  
Vol 73 (6) ◽  
pp. 3471-3478 ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Christoph Aebi ◽  
Sanjay Sethi

ABSTRACT Moraxella catarrhalis is an important respiratory tract pathogen, causing otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Adults with COPD make antibody responses to M. catarrhalis following infection, but little is known about the identity of the antigens to which these antibodies are directed. In this study, 12 serum samples obtained from adults with COPD who had cleared M. catarrhalis from the respiratory tract following infection and who had developed new serum immunoglobulin G (IgG) to their infecting strain were subjected to a series of assays to identify the antigens to which potentially protective antibodies were directed. Sera were adsorbed with intact bacterial cells, and antibodies were eluted from the surfaces of the bacteria. Analysis by flow cytometry established that adsorption and elution effectively detected antibodies specifically directed to surface-exposed epitopes. Immunoblot assays of adsorbed and eluted serum fractions were performed with purified outer membranes and purified lipooligosaccharide of homologous infecting strains and with a series of mutants deficient in expression of individual outer membrane proteins (OMPs). While heterogeneity in antibody responses among individuals was observed, five major OMPs, UspA1, UspA2, Hag, TbpB, and OMP CD, were identified as targets of antibodies to surface epitopes in the majority of adults with COPD who cleared the organism. These results have important implications in understanding human immune responses to M. catarrhalis and in elucidating the elements of a protective immune response.


Parasitology ◽  
1998 ◽  
Vol 116 (5) ◽  
pp. 463-469 ◽  
Author(s):  
J. MATSUMOTO ◽  
K. YAGI ◽  
N. NONAKA ◽  
Y. OKU ◽  
M. KAMIYA

The kinetics of serum antibody response against infection with Echinococcus multilocularis eggs was evaluated in AKR mice. The animals were infected by oral inoculation with 300 parasite eggs, and necropsied at 1, 2, 4, 6, 9, 12 and 16 weeks post-infection (p.i.), respectively. The parasite formed the laminated layer at 4 weeks p.i., the brood capsule with a massive proliferation of germinal cells at 9 weeks p.i. and protoscoleces at 16 weeks p.i. Serum antibody responses of the mice to antigen preparations from metacestodes of different stages and protoscoleces were evaluated by ELISA, immunoblotting and immunohistochemistry. In ELISA, the antibody responses began to increase at 4 weeks and became more apparent at 9 weeks p.i. and thereafter. Immunoblots using sera collected at 16 weeks p.i. showed some common bands among the 3 different antigen preparations. In addition to this, the germinal cells and brood capsules of mature metacestodes were stained strongly in an immunohistochemical study. From above, it is suggested that some antigen molecules are expressed in the parasite through these stages and stimulated host antibody responses.


2010 ◽  
Vol 18 (3) ◽  
pp. 380-386 ◽  
Author(s):  
Kristina Crothers ◽  
Kieran R. Daly ◽  
David Rimland ◽  
Matthew Bidwell Goetz ◽  
Cynthia L. Gibert ◽  
...  

ABSTRACTSerologic studies can provide important insights into the epidemiology and transmission ofPneumocystis jirovecii. Exposure toP. jiroveciican be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses toP. jiroveciiin comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses toP. jiroveciiMsgC fragments were significantly and independently decreased in current smokers. Antibodies toP. jiroveciialso tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific toP. jiroveciiand did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreasedP. jiroveciiantibody responses. Whether smoking exerts an immunosuppressive effect that affects theP. jiroveciiantibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.


2004 ◽  
Vol 72 (2) ◽  
pp. 810-817 ◽  
Author(s):  
David Abraham ◽  
Ofra Leon ◽  
Silvia Schnyder-Candrian ◽  
Chun Chi Wang ◽  
Ann Marie Galioto ◽  
...  

ABSTRACT Mice immunized with irradiated Onchocerca volvulus third-stage larvae developed protective immunity. Eosinophil levels were elevated in the parasite microenvironment at the time of larval killing, and measurements of total serum antibody levels revealed an increase in the immunoglobulin E (IgE) level in immunized mice. The goal of the present study was to identify the role of granulocytes and antibodies in the protective immune response to the larval stages of O. volvulus in mice immunized with irradiated larvae. Immunity did not develop in mice if granulocytes, including both neutrophils and eosinophils, were eliminated, nor did it develop if only eosinophils were eliminated. Moreover, larvae were killed in naïve interleukin-5 transgenic mice, and the killing coincided with an increase in the number of eosinophils and the eosinophil peroxidase (EPO) level in the animals. To determine if EPO was required for protective immunity, mice that were genetically deficient in EPO were immunized, and there were no differences in the rates of parasite recovery in EPO-deficient mice and wild-type mice. Two mouse strains were used to study B-cell function; μMT mice lacked all mature B cells, and Xid mice had deficiencies in the B-1 cell population. Immunity did not develop in the μMT mice but did develop in the Xid mice. Finally, protective immunity was abolished in mice treated to eliminate IgE from the blood. We therefore concluded that IgE and eosinophils are required for adaptive protective immunity to larval O. volvulus in mice.


1999 ◽  
Vol 67 (6) ◽  
pp. 2884-2890 ◽  
Author(s):  
Anna Rudin ◽  
Gerdt C. Riise ◽  
Jan Holmgren

ABSTRACT Nasal vaccine delivery is superior to oral delivery in inducing specific immunoglobulin A (IgA) and IgG antibody responses in the upper respiratory tract. Although an antibody response in the nasal passages is important in protecting against primary colonization with lung pathogens, antibodies in the lungs are usually required as well. We immunized 15 male volunteers twice nasally or orally with cholera toxin B subunit (CTB) and determined the specific antibody levels in serum, bronchoalveolar lavage (BAL) fluid, and urine before and 2 weeks after immunization. Nasal immunization induced fivefold increases in the levels of specific IgA antibodies in BAL fluid of most volunteers, whereas there were no significant specific IgA responses after oral immunization. The specific IgG antibody level increased eightfold in BAL fluid in the nasally vaccinated subjects, and the major part of IgG had most probably been transferred from serum. Since the specific IgG response in serum was lower in the individuals vaccinated orally, the IgG response in BAL fluid in this group was also lower and not significant. In conclusion, nasal immunization is also preferable to the oral route when vaccinating against lower respiratory tract infections, and a systemic immune response is considerably more important in the lower than in the upper respiratory tract. Moreover, both nasal and oral immunizations were able to stimulate 6- to 10-fold specific IgA and IgG responses in urine in about half of the individuals, which indicates that distant mucosal vaccination might be used to prevent adhesion of pathogens to the urogenital tract.


1988 ◽  
Vol 34 (3) ◽  
pp. 312-318 ◽  
Author(s):  
Irving E. Salit ◽  
James Hanley ◽  
Lorraine Clubb ◽  
Susan Fanning

Urinary tract infections caused by Escherichia coli are associated with a local and systemic antibody response. We have studied the serum and urine antibody responses to Escherichia coli in men and women with pyelonephritis, cystitis, and asymptomatic bacteriuria. Protein immunoblots consistently demonstrated serum antibody response to lipopolysaccharide (LPS). Anti-LPS antibody titres rose significantly and progressively when comparing acute with convalescent sera in those who have had their first urinary infection. For those with repeated infections, high titre LPS antibodies were present and did not change significantly between acute and convalescent sera. Antibody responses to the major outer membrane proteins were present but did not differ significantly when compared with normal human serum. A specific anti-P pilus antibody response was demonstrated by immunoblotting. Anti-P pilus antibody was quantitated using ELISA and the titres were found to be very low. Three other techniques were also used to demonstrate the presence of serum antibody. Antibody was detectable by immunofluorescence, but the antigenic specificity of the antibody was more difficult to ascertain. Immunoprecipitation was more specific for determining the nature of the antibody response. Lastly, immunoelectron microscopy was valuable in demonstrating antipilus and antiflagellar antibodies. Immunoelectron microscopy and immunoblotting provided evidence that human antiserum to P pili was modestly cross-reactive and could bind heterologous P pili. These studies indicated that the major antibody response in humans occurs after pyelonephritis and is directed against LPS. An anti-P pilus response is frequently present and is cross-reactive to some extent with other P pili.


2005 ◽  
Vol 12 (12) ◽  
pp. 1387-1392 ◽  
Author(s):  
Hamid R. Haghighi ◽  
Jianhua Gong ◽  
Carlton L. Gyles ◽  
M. Anthony Hayes ◽  
Babak Sanei ◽  
...  

ABSTRACT Probiotic bacteria, including Lactobacillus acidophilus and Bifidobacterium bifidum, have been shown to enhance antibody responses in mammals. The objective of this study was to examine the effects of a probiotic product containing the above bacteria in addition to Streptococcus faecalis on the induction of the chicken antibody response to various antigens, both systemically and in the gut. The birds received probiotics via oral gavage and subsequently were immunized with sheep red blood cells (SRBC) and bovine serum albumin (BSA) to evaluate antibody responses in serum or with tetanus toxoid (TT) to measure the mucosal antibody response in gut contents. Control groups received phosphate-buffered saline. Overall, BSA and SRBC induced a detectable antibody response as early as week 1 postimmunization (p.i.), which lasted until week 3 p.i. Probiotic-treated birds had significantly (P ≤ 0.001) more serum antibody (predominantly immunoglobulin M [IgM]) to SRBC than the birds that were not treated with probiotics. However, treatment with probiotics did not enhance the serum IgM and IgG antibody responses to BSA. Immunization with TT resulted in the presence of specific IgA and IgG antibody responses in the gut. Again, treatment with probiotics did not change the level or duration of the antibody response in the gut. In conclusion, probiotics enhance the systemic antibody response to some antigens in chickens, but it remains to be seen whether probiotics have an effect on the generation of the mucosal antibody response.


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