scholarly journals Corrected and Republished from: A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Fabian Uddén ◽  
Jonas Ahl ◽  
Nils Littorin ◽  
Kristoffer Strålin ◽  
Simon Athlin ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Acute Phase ◽  
Pneumococcal Infection ◽  
Adaptive Immune Response ◽  
Invasive Disease ◽  
Community Acquired Pneumonia ◽  
Phase Response ◽  
Antibody Activity ◽  
Convalescent Phase

ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. The remaining individuals exhibited either an increased convalescent-phase OPA titer (n  =  24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). Invasive pneumococcal disease (i.e., bacteremia) was significantly more common among patients with a nonfunctional convalescent-phase response than in patients with other convalescent-phase responses. Anticapsular Ig concentrations were higher among patients with detectable convalescent-phase OPA titers (P = 0.003), and the greatest Ig concentration increase was observed among patients with an increased convalescent-phase response (P = 0.002). Our findings indicate that an episode of pneumococcal infection may act as an immunizing event. However, in some cases when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations determine opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response may fail after CAP, predominantly among patients with simultaneous bacteremia.

scholarly journals A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Fabian Uddén ◽  
Jonas Ahl ◽  
Nils Littorin ◽  
Kristoffer Strålin ◽  
Simon Athlin ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Acute Phase ◽  
Pneumococcal Infection ◽  
Adaptive Immune Response ◽  
Invasive Disease ◽  
Community Acquired Pneumonia ◽  
Antibody Activity ◽  
Adaptive Immune ◽  
Convalescent Phase

ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. A nonfunctional convalescent-phase response was significantly more common among patients with invasive pneumococcal disease (i.e., bacteremia) than in patients without invasive disease (53%; P = 0.019). Remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). No correlation was found between anticapsular Ig concentrations and OPA titers. Our findings indicate that an episode of pneumococcal infection may act as an immunizing event, leading to an improved antipneumococcal adaptive immune status. However, in some cases, when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations are important for opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response frequently fails to occur after CAP, predominantly among patients with simultaneous bacteremia.

scholarly journals Effects of supplementing mid-lactation dairy cows with seaweed and vitamin E on plasma and milk α-tocopherol and antibody response to immunization

2015 ◽  
Vol 153 (5) ◽  
pp. 929-942 ◽  
Author(s):  
A. KIDANE ◽  
I. L. NESHEIM ◽  
H. J. S. LARSEN ◽  
E. THUEN ◽  
S. K. JENSEN ◽  
...  
Keyword(s):  
Immune Response ◽  
Vitamin E ◽  
Antibody Response ◽  
Dairy Cows ◽  
Control Diet ◽  
Adaptive Immune Response ◽  
The Other ◽  
Tocopheryl Acetate ◽  
Significant Group ◽  
Adaptive Immune

SUMMARYThe objective of the current experiment was to compare the effects of supplementing mid-lactation dairy cows with all-rac-α-tocopheryl acetate (SyntvE), RRR-α-tocopheryl acetate (NatvE) or seaweed meal (Seaweed) in the presence of a Control group (no supplemental vitamin E or seaweed) on the concentration of α-tocopherol in plasma and milk, and antibody response following immunization. The hypothesis was that supplementation of dairy cows with vitamin E, regardless of its form, would increase plasma and milk α-tocopherol compared to the control diet and this incremental response would be bigger with NatvE than SyntvE. Furthermore, it was hypothesized that vitamin E, regardless of its form, will provide an improved adaptive immune response to immunization than the Control diet, and cows supplemented with Seaweed meal would produce better adaptive immune response following immunization than cows in the Control group. Twenty-four Norwegian Red (NR) dairy cows in their mid-lactation were allocated randomly to the four treatments in a replicated Latin square design. The cows were fed on a basal diet of silage and concentrate on top of which the experimental supplements were provided. Plasma and milk α-tocopherol concentrations were higher in NatvE and SyntvE groups than in the other two groups. The RRR-α-tocopherol stereoisomer was the predominant form (>0·86), in both plasma and milk, whereas the remaining part was largely made up of the other three 2R stereoisomers (RRS, RSR and RSS). In cows fed the Control, Seaweed and NatvE, the proportion of the RRR-α-tocopherol stereoisomer in plasma and milk constituted >0·97 of the total α-tocopherol. Mid-lactation NR dairy cows had higher than adequate levels of plasma α-tocopherol (9·99 mg/l) even when not supplemented with external source of vitamin E, suggesting that with a good quality silage these cows may not be at risk of vitamin E deficiency. Furthermore, the present study shows that dairy cows in mid to late lactation have preferential uptake of RRR stereoisomer of α-tocopherol compared with other stereoisomers. All cows responded well to immunization with different antigens, but there were no significant group effects of the diet on the immune response measured.

scholarly journals Selenium controls the sex-specific immune response and selenoprotein expression during the acute-phase response in mice

2010 ◽  
Vol 429 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Mette Stoedter ◽  
Kostja Renko ◽  
Antonia Hög ◽  
Lutz Schomburg
Keyword(s):  
Immune Response ◽  
Acute Phase ◽  
Clinical Studies ◽  
Acute Phase Response ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Cell Activity ◽  
Selenium Supplementation ◽  
Phase Response ◽  
Serum Selenium

Selenium modifies inflammatory reactions in rodents and humans. The liver controls metabolism and transport of selenium via hepatically-derived SEPP (selenoprotein P). Intracellular SEPS (selenoprotein S) modifies endoplasmic-reticulum function and immune-cell activity. Polymorphisms in SEPS have been associated with cytokine levels and inflammatory diseases in a subset of clinical studies. In the present study, we hypothesized that sex and selenium represent decisive parameters controlling the immune response and regulation of SEPS expression in vivo. Male and female mice fed a selenium-poor diet were supplemented or not with selenite for 3 days and injected with saline or LPS (lipopolysaccharide) 24 h before analysis. Selenium supplementation mitigated the LPS-induced rise in circulating cytokines in male mice. Serum SepP and selenium concentrations decreased in response to LPS, whereas hepatic SepS was specifically up-regulated despite declining selenium concentrations in the liver. Hepatic SepS induction was mainly controlled by post-transcriptional mechanisms and attributed to hepatocytes by analysing transgenic mice. Notably, selenium supplementation was essential for an optimal SepS induction. We conclude that selenoprotein biosynthesis becomes redirected in hepatocytes during the acute-phase response at the expense of dispensable selenoproteins (e.g. SepP) and in favour of SepS expression, thereby causing declining serum selenium and improving liver function. The selenium status and sex control SepS expression and modify cytokine response patterns in serum, which might explain contradictory results on associations of SEPS genotype and inflammatory diseases in clinical studies.

scholarly journals Metabolic Cost of the Activation of Immune Response in the Fish-Eating Myotis (Myotis vivesi): The Effects of Inflammation and the Acute Phase Response

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164938 ◽  
Author(s):  
Aída Otálora-Ardila ◽  
L. Gerardo Herrera M. ◽  
José Juan Flores-Martínez ◽  
Kenneth C. Welch
Keyword(s):  
Immune Response ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Metabolic Cost ◽  
Phase Response ◽  
Myotis Myotis

scholarly journals The Murine Polyomavirus MicroRNA Locus Is Required To Promote Viruria during the Acute Phase of Infection

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
James M. Burke ◽  
Clovis R. Bass ◽  
Rodney P. Kincaid ◽  
Emin T. Ulug ◽  
Christopher S. Sullivan
Keyword(s):  
Immune Response ◽  
Acute Phase ◽  
Adaptive Immune Response ◽  
Natural Host ◽  
Mutant Virus ◽  
Adaptive Immune ◽  
Mirna Locus ◽  
Murine Polyomavirus ◽  
Serious Disease

ABSTRACTPolyomaviruses (PyVs) can cause serious disease in immunosuppressed hosts. Several pathogenic PyVs encode microRNAs (miRNAs), small RNAs that regulate gene expression via RNA silencing. Despite recent advances in understanding the activities of PyV miRNAs, the biological functions of PyV miRNAs duringin vivoinfections are mostly unknown. The studies presented here used murine polyomavirus (MuPyV) as a model to assess the roles of the PyV miRNAs in a natural host. This analysis revealed that a MuPyV mutant that is unable to express miRNAs has enhanced viral DNA loads in select tissues at late times after infection. This is consistent with the PyV miRNAs functioning to reduce viral replication during the persistent phase of infection in a natural host. Additionally, the MuPyV miRNA locus promotes viruria during the acute phase of infection as evidenced by a defect in shedding during infection with the miRNA mutant virus. The viruria defect of the miRNA mutant virus could be rescued by infectingRag2−/−mice. These findings implicate the miRNA locus as functioning in both the persistent and acute phases of infection and suggest a role for MuPyV miRNA in evading the adaptive immune response.IMPORTANCEMicroRNAs are expressed by diverse viruses, but for only a few is there any understanding of theirin vivofunction. PyVs can cause serious disease in immunocompromised hosts. Therefore, increased knowledge of how these viruses interact with the immune response is of clinical relevance. Here we show a novel activity for a viral miRNA locus in promoting virus shedding. This work indicates that in addition to any role for the PyV miRNA locus in long-term persistence, it also has biological activity during the acute phase. As this mutant phenotype is alleviated by infection of mice lacking an adaptive immune response, our work also connects thein vivoactivity of the PyV miRNA locus to the immune response. Given that PyV-associated disease is associated with alterations in the immune response, our findings help to better understand how the balance between PyVs and the immune response becomes altered in pathogenic states.

scholarly journals Differing antibody responses toHaemophilus influenzaetype b after meningitis or epiglottitis

1996 ◽  
Vol 116 (1) ◽  
pp. 21-26 ◽  
Author(s):  
P. D. R. Johnson ◽  
M. Hanlon ◽  
D. Isaacs ◽  
G. L. Gilbert
Keyword(s):  
Antibody Response ◽  
Haemophilus Influenzae ◽  
Confidence Intervals ◽  
Age Differences ◽  
Geometric Mean ◽  
Invasive Disease ◽  
Antibody Responses ◽  
Type B ◽  
Convalescent Phase ◽  
Antibody Levels

SummaryTwo common forms of invasive disease due toHaemophilus influenzaetype b (Hib) are epiglottitis and meningitis. It is not known why some children develop epiglottitis and others meningitis. To examine the hypothesis that epiglottitis occurs in children who may have been previously exposed to Hib, and who would therefore exhibit a more vigorous antibody response in convalescence, we measured levels of antibody to Hib capsule in 92 children. Geometric mean convalescent-phase IgG, IgA, IgM and total antibody levels were significantly higher in 45 children with epiglottitis than in 47 with meningitis, even after adjustment for age differences (mean total antibody, 95% confidence intervals: meningitis 0·38, 0·34–0·43; epiglottitis: 2·25, 2·0–2·54 μg/ml). However, contrary to previous reports, a poor antibody response was only observed in a minority of children with meningitis; the antibody response of the majority was indistinguishable from that observed in children with epiglottitis.

scholarly journals Dynamics of the Immune Response against Extracellular Products of Group A Streptococci during Infection

2006 ◽  
Vol 14 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Linda Maripuu ◽  
Anna Eriksson ◽  
Björn Eriksson ◽  
Karlis Pauksen ◽  
Stig Holm ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Phase ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Streptococcal Toxic Shock Syndrome ◽  
Convalescent Phase ◽  
Extracellular Products ◽  
Group A

ABSTRACT The immune response against the infecting group A streptococcus (GAS) extracellular products (EP) was determined in acute- and convalescent-phase sera from 75 patients with different clinical manifestations of GAS infection. All EP elicited a high proliferative response in human peripheral blood mononuclear cells. In patients with bacteremia, low neutralization in acute-phase sera was associated with development of streptococcal toxic shock syndrome. Lack of neutralization in acute-phase sera was more common in patients infected with the T1emm1 serotype. The majority of patients did not develop the ability to neutralize the mitogenic activity of their infecting isolate despite a significant increase in enzyme-linked immunosorbent assay titer in early convalescent-phase sera. In patients with the ability to neutralize GAS EP, the immune response remained high over at least 3 years. In contrast, the neutralization capacity conferred by intravenous immunoglobulin and/or plasma treatment disappeared within 3 months.

scholarly journals Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Davor Brinc ◽  
Alan H. Lazarus
Keyword(s):  
Immune Response ◽  
Animal Models ◽  
Antibody Response ◽  
B Cell ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
B Cell Activation ◽  
Hemolytic Disease ◽  
Inhibit Antibody

Abstract Anti-D is routinely and effectively used to prevent hemolytic disease of the fetus and newborn (HDFN) caused by the antibody response to the D antigen on fetal RBCs. Anti-D is a polyclonal IgG product purified from the plasma of D-alloimmunized individuals. The mechanism of anti-D has not been fully elucidated. Antigenic epitopes are not fully masked by anti-D and are available for immune system recognition. However, a correlation has frequently been observed between anti-D-mediated RBC clearance and prevention of the antibody response, suggesting that anti-D may be able to destroy RBCs without triggering the adaptive immune response. Anti-D-opsonized RBCs may also elicit inhibitory FcγRIIB signaling in B cells and prevent B cell activation. The ability of antigen-specific IgG to inhibit antibody responses has also been observed in a variety of animal models immunized with a vast array of different antigens, such as sheep RBCs (SRBC). This effect has been referred to as antibody-mediated immune suppression (AMIS). In animal models, IgG inhibits the antibody response, but the T-cell response and memory may still be intact. IgG does not mask all epitopes, and IgG-mediated RBC clearance or FcγRIIB-mediated B-cell inhibition do not appear to mediate the AMIS effect. Instead, IgG appears to selectively disrupt B cell priming, although the exact mechanism remains obscure. While the applicability of animal models of AMIS to understanding the true mechanism of anti-D remains uncertain, the models have nevertheless provided us with insights into the possible IgG effects on the immune response.

scholarly journals Antibody Response to SARS-CoV-2 Membrane Protein in Patients of the Acute and Convalescent Phase of COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Philipp Jörrißen ◽  
Paula Schütz ◽  
Matthias Weiand ◽  
Richard Vollenberg ◽  
Inga Marie Schrempf ◽  
...  
Keyword(s):  
Antibody Response ◽  
Acute Phase ◽  
Nucleocapsid Protein ◽  
M Protein ◽  
Plasma Samples ◽  
Convalescent Phase ◽  
Protein Encoding ◽  
Linear Epitopes ◽  
Specific Reactivity ◽  
Control Plasma

Understanding the course of the antibody response directed to individual epitopes of SARS-CoV-2 proteins is crucial for serological assays and establishment of vaccines. Twenty-one synthetic peptides were synthesized that have ten amino acids overlap and cover the complete membrane (M) protein. Plasma samples from 32 patients having acute disease and 30 patients from the convalescent phase were studied. Only peptide M01 (aa 1–20) and to a lesser extent peptide M21 (aa 201–222) showed specific reactivity as compared to historical control plasma samples. Peptide M01 was recognized by IgM- (71.9%) and IgG-specific antibodies (43.8%) during the acute phase as early as day 8 PIO. In a longitudinal analysis, a higher reactivity was observed for the IgM response directed to peptide M01 following day 20 PIO as compared to earlier time points of the acute phase. In the convalescent phase, antibody reactivity to the two M-specific peptides was significantly lower (<30% seropositivity). A fusion protein encoding major parts of RBD also showed higher rates of recognition during acute (50.0%) and lower rates in the convalescent phase (23.3%). Taken together, our results suggest that during the acute phase of COVID-19 antibodies are raised to two linear epitopes of the SARS-CoV-2 M protein, located at the very N- and C-termini, showing almost similar levels of reactivity as immunodominant linear epitopes derived from the spike and nucleocapsid protein. Anti-M is also present in the convalescent phase of COVID-19 patients, however at lower levels, with the N-terminus of the M protein as a preferred target.

scholarly journals MAVS regulates the quality of the antibody response to West-Nile Virus

2020 ◽  
Vol 16 (10) ◽  
pp. e1009009
Author(s):  
Marvin O’Ketch ◽  
Spencer Williams ◽  
Cameron Larson ◽  
Jennifer L. Uhrlaub ◽  
Rachel Wong ◽  
...  
Keyword(s):  
Immune Response ◽  
West Nile Virus ◽  
Antibody Response ◽  
Adaptive Immunity ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Neutralizing Antibody ◽  
West Nile ◽  
Humoral Immune

A key difference that distinguishes viral infections from protein immunizations is the recognition of viral nucleic acids by cytosolic pattern recognition receptors (PRRs). Insights into the functions of cytosolic PRRs such as the RNA-sensing Rig-I-like receptors (RLRs) in the instruction of adaptive immunity are therefore critical to understand protective immunity to infections. West Nile virus (WNV) infection of mice deficent of RLR-signaling adaptor MAVS results in a defective adaptive immune response. While this finding suggests a role for RLRs in the instruction of adaptive immunity to WNV, it is difficult to interpret due to the high WNV viremia, associated exessive antigen loads, and pathology in the absence of a MAVS-dependent innate immune response. To overcome these limitations, we have infected MAVS-deficient (MAVSKO) mice with a single-round-of-infection mutant of West Nile virus. We show that MAVSKO mice failed to produce an effective neutralizing antibody response to WNV despite normal antibody titers against the viral WNV-E protein. This defect occurred independently of antigen loads or overt pathology. The specificity of the antibody response in infected MAVSKO mice remained unchanged and was still dominated by antibodies that bound the neutralizing lateral ridge (LR) epitope in the DIII domain of WNV-E. Instead, MAVSKO mice produced IgM antibodies, the dominant isotype controlling primary WNV infection, with lower affinity for the DIII domain. Our findings suggest that RLR-dependent signals are important for the quality of the humoral immune response to WNV.

Sign in / Sign up

Export Citation Format

Share Document