Thymus-dependency of the immune response of mice to a primary infection with the nematode Trichuris muris

SUMMARYCortisone acetate, given to mice on two days during a primary infection with the nematodeTrichuris muris, suppressed the development of acquired immunity to the parasite. The proportion of mice in which suppression occurred was greatest when the drug was given (at 2.5 mg per mouse) on days 14 and 15 of the infection. Suppression of the response prevented the elimination of larvae, which otherwise occurs during the third week, and allowed the parasite population to mature and survive for at least a further 3 weeks. Similar treatment given during a challenge infection in resistant mice prevented the elimination of the challenge larvae for 2 or 3 days only. Mice in which cortisone treatment had prevented the elimination of a primary infection were not only found to be fully susceptible to subsequent challenge, but showed no development of immunity to the challenge infection itself. This long-lasting suppression of the immune response toT. murisis discussed and the possibility of the induction of a specific immunological unresponsiveness to the parasite is considered.

Download Full-text

Suppression of the immune response to Trichuris muris in lactating mice

Parasitology ◽

10.1017/s0031182000053166 ◽

1975 ◽

Vol 71 (1) ◽

pp. 77-85 ◽

Cited By ~ 16

Author(s):

Gwendoline R. Selby ◽

D. Wakelin

Keyword(s):

Immune Response ◽

Lymphoid Cell ◽

Primary Infection ◽

Secondary Infection ◽

Suppressive Effect ◽

Acquired Immunity ◽

Serum Antibodies ◽

Trichuris Muris ◽

Worm Expulsion

Mice infected with Trichuris muris during lactation were unable to expel the infection at the normal time, but expulsion occurred when lactation was terminated. Suppression of expulsion was uniform in mice suckling more than five young but variable with smaller litters. Mice exposed to a primary infection while lactating were shown to have serum antibodies capable of passively transferring immunity to recipient mice and showed near normal immunity to a secondary infection given after lactation had ceased.Acquired immunity to T. muris was also suppressed by lactation, but the worms which became established in lactating resistant mice were fewer and smaller than those in non-lactating, non-resistant controls.It is suggested that the suppressive effect of lactation in this hostparasite relationship is exerted on the second, lymphoid cell-mediated phase of worm expulsion.

Download Full-text

The effects of H-2 and non-H-2 genes on the expulsion of the nematode Trichuris muris from inbred and congenic mice

Parasitology ◽

10.1017/s0031182000080173 ◽

1988 ◽

Vol 96 (3) ◽

pp. 543-550 ◽

Cited By ~ 87

Author(s):

Kathryn Else ◽

D. Wakelin

Keyword(s):

Immune Response ◽

Large Intestine ◽

Genetic Background ◽

Primary Infection ◽

Differential Resistance ◽

Protective Immune Response ◽

Trichuris Muris ◽

Rate Of Development ◽

Congenic Mice ◽

Congenic Strains

SUMMARYTwo groups of H-2 congenic strains of mice were compared for their susceptibility to a primary infection with the nematode Trichuris muris. Mice of the BALB genetic background were markedly more resistant than mice of the BIO genetic background, as reflected by the rate of expulsion of T. muris from the large intestine. Within each of the two groups of H-2 congenic strains mice possessing the H-2k haplotype (BALB/k, B10.BR) were more susceptible to infection than mice expressing other haplotypes; B10 background strains expressing H-2b (B10) or H-2q (B10.G) alleles were the most resistant of the four congenic strains studied. Differential resistance was observed within three of the four BIO congenic strains and this is discussed in terms of rate of development of the protective immune response in relation to worm development. The results support the conclusion that both H-2-linked and non-H-2 genes play important roles in controlling the immune response which expels worms from the gut.

Download Full-text

Genetically-determined influences on the ability of poor responder mice to respond to immunization against Trichuris muris

Parasitology ◽

10.1017/s0031182000078793 ◽

1990 ◽

Vol 100 (3) ◽

pp. 479-489 ◽

Cited By ~ 20

Author(s):

K. J. Else ◽

D. Wakelin

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Primary Infection ◽

Protective Immunity ◽

Rapid Development ◽

Poor Responder ◽

Post Challenge ◽

Good Responder ◽

Trichuris Muris ◽

Genetically Determined

SUMMARYStrains of mice poorly (B10) or non-responsive (B10.BR) to a primary infection with Trichuris muris were protected against infection by vaccination with excretory/secretory (E/S) antigen in Complete Freund's Adjuvant (CFA). Protection in these mice was slow to be expressed compared to that in good responder strains. Vaccination boosted the IgG and IgG1 antibody responses to E/S antigen and altered the antigen recognition profiles, three high molecular weight antigens (80–85, 90–95, 105–110 kDa) being recognized by antibodies in sera from vaccinated but not control mice. B10. BR mice which had experienced a patent primary infection could not be protected against challenge infections by vaccination and this was correlated with depressed levels of IgG1, but not total IgG, to E'S antigen early post-challenge compared with vaccinated infected mice which had not seen an adult primary infection. There was also lack of recognition of the three high molecular weight antigens recognized by antibodies in sera from mice infected after vaccination. It is suggested that the rapid development of high levels of IgG1 antibodies, and the recognition of the three high molecular weight antigens, may reflect events that are important in protective immunity. Immunomodulation of host immunity by T. muris may therefore be achieved, at least in part, by the suppression of specific IgG1 levels, the production of an irrelevant IgG isotype and prevention of the recognition of critical antigens.

Download Full-text

Seropositivity to Nucleoprotein to detect SARS-CoV-2 infections: a tool to detect breakthrough infections after COVID-19 vaccination

10.1101/2021.10.05.21264555 ◽

2021 ◽

Author(s):

Lotus Leonie van den Hoogen ◽

Gaby Smits ◽

Cheyenne CE van Hagen ◽

Denise Wong ◽

Eric RA Vos ◽

...

Keyword(s):

Immune Response ◽

Primary Infection ◽

Spike Protein ◽

Multiplex Immunoassay ◽

Specific Immunoglobulin ◽

Vaccination History ◽

Specific Igg ◽

Exposure History ◽

Asymptomatic Individuals ◽

Roll Out

Background With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. Methods Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) with a primary infection and no vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). Results The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥7 days after the second dose (p=0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in naïve participants. Conclusions Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.

Download Full-text

Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection

10.21203/rs.3.rs-101480/v1 ◽

2020 ◽

Author(s):

Jianmin Zuo ◽

Alex Dowell ◽

Hayden Pearce ◽

Kriti Verma ◽

Heather Long ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Immune Responses ◽

Antibody Level ◽

Primary Infection ◽

Natural Infection ◽

T Cell Responses ◽

Symptomatic Infection ◽

Cell Responses ◽

Cell Immunity

Abstract The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection.

Download Full-text

Fluctuations in rat liver alanine-amino-transferase activity during experimental nippostrongylosis

Parasitology ◽

10.1017/s0031182000062223 ◽

1989 ◽

Vol 98 (2) ◽

pp. 301-306

Author(s):

Lucy J. Robertson

Keyword(s):

Immune Response ◽

Primary Infection ◽

Parasitic Infection ◽

Transferase Activity ◽

Nippostrongylus Brasiliensis ◽

Alanine Amino Transferase ◽

A Value ◽

Gluconeogenic Enzyme ◽

Alt Activity

SUMMARYThe activity of the gluconeogenic enzyme, alanine-amino-transferase (ALT), in a preparation from the liver of rats was studied by means of an in vitro assay throughout the course of a primary infection of Nippostrongylus brasiliensis, established by a subcutaneous injection of approximately 4000 3rd-stage larvae. The activity was measured on days 1–14 p.i. in both uninfected and infected rats and a marked pattern in the enzyme's activity was observed. In infected rats, the activity increased from 1·46±0·19 U/g liver on day 1 p.i. to a peak on day 4 p.i. of 10·75±1·62 U/g liver, then decreased to a trough of 0·44±0·18 U/g liver on day 10 p.i. before returning to original levels by day 14 p.i., by which time the infection had been largely eliminated. In uninfected rats the activity of the liver enzyme remained constant throughout this period with a value of 2·54±0·12 U/g liver. The activity of the enzyme in vitro was found to be related to the size of the inoculum on days 4 and 10 p.i. It was proposed that these observations could be due to either (1) a direct effect of the parasite, or (2) a consequence of the host immune response to the infection. In order to investigate the second proposition more fully, liver ALT activity was investigated by in vitro assay on selected days p.i. in rats experiencing a secondary N. brasiliensis infection. In these rats the liver ALT activity was observed to reach a peak on day 2 p.i., with an activity of 3·87 ± 0-28 U/g liver, and a trough on day 4 p.i. with an activity of 0·11 ±0·03 U/g liver, returning to similar levels to those measured in uninfected rats by day 7 p.i. When serum prepared from rats having secondary N. brasiliensis infections collected on day 4 p.i. was added to the assay, a reduction in the activity of liver ALT activity from both the infected and uninfected rats was measured by in vitro assay. The results are discussed in relation to protein metabolism and gluconeogenesis in rats infected with N. brasiliensis, and also in relation to the host’s immune response to the parasitic infection.

Download Full-text

Sepsis

10.1093/med/9780199568741.003.0309 ◽

2018 ◽

Author(s):

Graham Cooke

Keyword(s):

Immune Response ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Primary Infection ◽

Clinical Manifestations ◽

Host Immune Response ◽

Organ Damage ◽

Clinical Syndrome ◽

Systemic Inflammatory Response ◽

Physiological Status

Sepsis is a clinical syndrome defined by the presence of both infection and a systemic inflammatory response with or without organ damage. The pathogenesis of sepsis is complex and may differ according to the infecting microbe, the site of primary infection, and the host’s immunological and physiological status prior to infection. The term ‘systemic inflammatory response syndrome’ refers to the clinical manifestations of a dysregulated host immune response, while ‘bacteraemia’, in contrast, refers to the presence of viable organisms that can be cultured from blood.

Download Full-text

The Innate Immune Responses of Colonic Epithelial Cells to Trichuris muris Are Similar in Mouse Strains That Develop a Type 1 or Type 2 Adaptive Immune Response

Infection and Immunity ◽

10.1128/iai.01609-05 ◽

2006 ◽

Vol 74 (11) ◽

pp. 6280-6286 ◽

Cited By ~ 20

Author(s):

Matthew L. deSchoolmeester ◽

Harinder Manku ◽

Kathryn J. Else

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Immune Responses ◽

Adaptive Immune Response ◽

Subsequent Development ◽

Trichuris Muris ◽

Adaptive Immune ◽

Ifn Γ

ABSTRACT Trichuris muris resides in intimate contact with its host, burrowing within cecal epithelial cells. However, whether the enterocyte itself responds innately to T. muris is unknown. This study investigated for the first time whether colonic intestinal epithelial cells (IEC) produce cytokines or chemokines following T. muris infection and whether divergence of the innate response could explain differentially polarized adaptive immune responses in resistant and susceptible mice. Increased expression of mRNA for the proinflammatory cytokines gamma interferon (IFN-γ) and tumor necrosis factor and the chemokine CCL2 (MCP-1) were seen after infection of susceptible and resistant strains, with the only difference in expression being a delayed increase in CCL2 in BALB/c IEC. These increases were ablated in MyD88−/− mice, and NF-κB p65 was phosphorylated in response to T. muris excretory/secretory products in the epithelial cell line CMT-93, suggesting involvement of the MyD88-NF-κB signaling pathway in IEC cytokine expression. These data reveal that IEC respond innately to T. muris. However, the minor differences identified between resistant and susceptible mice are unlikely to underlie the subsequent development of a susceptible type 1 (IFN-γ-dominated) or resistant type 2 (interleukin-4 [IL-4]/IL-13-dominated) adaptive immune response.

Download Full-text