A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

PubMed

Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

2005-08-01

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

Effect of anthrax immune globulin on response to BioThrax (anthrax vaccine adsorbed) in New Zealand white rabbits.

PubMed

Malkevich, Nina V; Basu, Subhendu; Rudge, Thomas L; Clement, Kristin H; Chakrabarti, Ajoy C; Aimes, Ronald T; Nabors, Gary S; Skiadopoulos, Mario H; Ionin, Boris

2013-11-01

Development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a component of anthrax toxins. We evaluated the interaction between AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits. While pharmacokinetics of AIGIV were not altered by vaccination, the vaccine-induced immune response was abrogated in AIGIV-treated animals.

WinRho: Rh immune globulin prepared by ion exchange for intravenous use.

PubMed Central

Bowman, J M; Friesen, A D; Pollock, J M; Taylor, W E

1980-01-01

An Rh immune globulin [Rh IgG] for intravenous use, WinRho, has been prepared by the Winnipeg Rh Institute by a modification of the ion-exchange column method of Hoppe and colleagues. When administered to Rh-negative male and nonpregnant female volunteers WinRho was found to be nonpyrogenic, nontoxic, safe and protective against Rh alloimmunization. In a clinical trial with 240 microgram given at about 28 weeks' gestation and 120 microgram given after delivery to Rh-negative women at risk of Rh immunization WinRho was effective in preventing Rh immunization. Of the 870 women carrying Rh-positive fetuses who were treated with WinRho during pregnancy and were not tested several months after delivery 14 would have shown evidence of Rh immunization by the time of delivery if WinRho had been ineffective; none showed such evidence. Of the 1122 women carrying Rh-positive fetuses who were retested 4 to 6 months after delivery 83 would have shown evidence of Rh immunization at that time if WinRho had been ineffective; only 1 showed such evidence. The efficiency of yield of anti-D with the modified method of production, the fct that it can be given intravenously (a route that causes the patient less discomfort and immediately results in high anti-D levels) and the lower levels of contaminating IgA and IgM make WinRho the preparation of choice for preventing Rh immunization. PMID:6161687

Immune reconstitution with two different rabbit polyclonal anti-thymocytes globulins.

PubMed

Bamoulid, Jamal; Crepin, Thomas; Gaiffe, Emilie; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Courivaud, Cécile; Ducloux, Didier

2017-12-01

Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. Currently, two different ATG are used in clinical practice, Thymoglobulin and Grafalon. Due to differences in the immunization source, these products contain different specificities and quantity of antibodies. These differences may have clinical consequences. We conducted a nested study in a large prospective multicentric cohort of kidney transplant to determine whether Grafalon-treated and Thymoglobulin-treated patients experience different lymphocyte reconstitution and clinical outcomes. 182 patients matched for age, gender, CMV status, CMV prophylaxis, number of previous transplantation, and maintenance immunosuppressive treatment were included (Thymoglobulin, [n=91]; Grafalon®, [n=91]). One-year post-transplant, recent thymic emigrants were significantly decreased (12±10% vs 21±12%; p<0.001) in Grafalon-treated patients. By contrast, T cell activation (CD38+DR+Ki67+) and senescence (CD8+CD57+CD28-) was increased in Thymoglobulin-treated patients. Compared to Grafalon, Thymoglobulin was not associated with a significantly different rate of acute rejection. CMV disease (p=0.013) was more frequent in Thymoglobulin-treated patients. Grafalon and Thymoglobulin seem to be equivalent to prevent acute rejection. CMV disease is more frequent in Thymoglobulin-treated patients. One year post-transplant immune profile profoundly differs according to the type of ATG. Copyright © 2017 Elsevier B.V. All rights reserved.

Globulin Test

MedlinePlus

... of cancer Why do I need a globulin test? Your health care provider may order globulin tests as part your ... Globulin tests are blood tests. During a blood test, a health care professional will take a blood sample from a ...

What the world's religions teach, applied to vaccines and immune globulins.

PubMed

Grabenstein, John D

2013-04-12

For millennia, humans have sought and found purpose, solace, values, understanding, and fellowship in religious practices. Buddhist nuns performed variolation against smallpox over 1000 years ago. Since Jenner developed vaccination against smallpox in 1796, some people have objected to and declined vaccination, citing various religious reasons. This paper reviews the scriptural, canonical basis for such interpretations, as well as passages that support immunization. Populous faith traditions are considered, including Hinduism, Buddhism, Jainism, Judaism, Christianity, and Islam. Subjects of concern such as blood components, pharmaceutical excipients of porcine or bovine origin, rubella strain RA 27/3, and cell-culture media with remote fetal origins are evaluated against the religious concerns identified. The review identified more than 60 reports or evaluations of vaccine-preventable infectious-disease outbreaks that occurred within religious communities or that spread from them to broader communities. In multiple cases, ostensibly religious reasons to decline immunization actually reflected concerns about vaccine safety or personal beliefs among a social network of people organized around a faith community, rather than theologically based objections per se. Themes favoring vaccine acceptance included transformation of vaccine excipients from their starting material, extensive dilution of components of concern, the medicinal purpose of immunization (in contrast to diet), and lack of alternatives. Other important features included imperatives to preserve health and duty to community (e.g., parent to child, among neighbors). Concern that 'the body is a temple not to be defiled' is contrasted with other teaching and quality-control requirements in manufacturing vaccines and immune globulins. Health professionals who counsel hesitant patients or parents can ask about the basis for concern and how the individual applies religious understanding to decision-making about

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

PubMed

Wittek, Riccardo

2006-05-01

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009-2010.

PubMed

Cui, Xizhong; Nolen, Leisha D; Sun, Junfeng; Booth, Malcolm; Donaldson, Lindsay; Quinn, Conrad P; Boyer, Anne E; Hendricks, Katherine; Shadomy, Sean; Bothma, Pieter; Judd, Owen; McConnell, Paul; Bower, William A; Eichacker, Peter Q

2017-01-01

We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009-2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0-5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6-11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak.

SHBG (Sex Hormone Binding Globulin)

MedlinePlus

... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

Human antibodies to bovine alpha-globulin.

PubMed

Foucard, T; Bennich, H; Johansson, S G; Lundkvist, U

1975-01-01

Antibodies to bovine gamma-globulin (anti-BGG antibodies) were detectable by a radio-immunoassay in 70% of healthy blood donors but, generally, the titres were low. Significantly increased concentrations of anti-BGG antibodies were found in patients lacking IgA but not in patients with allergic disorders. The anti-BGG antibodies were shown to give rise to falsely high IgE values in the radio-immunosorbent test for IgE determination (RIST) when a sheep anti-IgE antiserum was used. Furthermore, falsely positive results can sometimes be caused by such antibodies in the determination of cow-dander- or cow's-milk-specific IgE by the radio-allergosorbent test (RAST). When a rabbit anti-IgE antiserum was used instead of the sheep anti-IgE, normal IgE levels and negative RAST results were obtained. The difference is explained by the higher degree of cross-reactivity between the anti-BGG antibodies and sheep alpha-globulin than between anti-BGG antibodies and rabbit alpha-globulin.

Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis.

PubMed

Nelson, Noele P

2017-09-15

GamaSTAN S/D (Grifols Therapeutics, Inc., Research Triangle Park, North Carolina) is a sterile, preservative-free solution of immune globulin (IG) for intramuscular administration and is used for prophylaxis against disease caused by infection with hepatitis A, measles, varicella, and rubella viruses (1). GamaSTAN S/D is the only IG product approved by the Food and Drug Administration for hepatitis A virus (HAV) prophylaxis. In July 2017, GamaSTAN S/D prescribing information was updated with changes to the dosing instructions for hepatitis A preexposure and postexposure prophylaxis indications. These changes were made because of concerns about decreased HAV immunoglobulin G antibody (anti-HAV IgG) potency, likely resulting from decreasing prevalence of previous HAV infection among plasma donors, leading to declining anti-HAV antibody levels in donor plasma (2). No changes in dosing instructions were made for measles, varicella, or rubella preexposure or postexposure prophylaxis.

Classification of Blood-Group Antibodies as β2M or γ Globulin

PubMed Central

Adinolfi, M.; Polley, Margaret J.; Hunter, Denise A.; Mollison, P. L.

1962-01-01

Thirty selected blood-group antibodies (excluding anti-A and anti-B) have been classified as β2M (19S γ) globulin, γ (7S γ) globulin or mixtures, using the following three methods: fractionation on a DEAE-cellulose column; indirect anti-globulin tests, using specific anti-β2M-globulin and anti-γ-globulin sera; and treatment with 2-mercapto-ethanol. With only minor exceptions, results obtained with the three methods were in agreement. Most blood-group antibodies within the Le, MNSs and P systems appear to be `naturally occurring' and these were found to be β2M globulin. Blood-group antibodies within the Rh, K and Jk systems, which had arisen after an antigenic stimulus, were usually γ globulin but were occasionally β2M globulin. Antibodies composed of β2M globulin usually behave as agglutinins but may behave as incomplete antibodies (e.g. some examples of anti-Jka); conversely, antibodies composed of γ globulin usually behave as incomplete antibodies but may behave as agglutinins (e.g. an example of anti-M). The ability to bind complement seems to be related more to the blood-group specificity of the particular antibody than to its molecular size. For example, anti-Jka, when composed either of γ or β2M globulin, seems invariably to bind complement, whereas potent anti-M or anti-Rh, whether composed of γ or β2M globulin, do not bind complement. PMID:14011076

Intravenous Immune Globulin in Children with Streptococcal Toxic Shock Syndrome

PubMed Central

Shah, Samir S.; Hall, Matthew; Srivastava, Raj; Subramony, Anupama; Levin, James E.

2009-01-01

Background Streptococcal toxic shock syndrome (TSS) is a rare and severe manifestation of group A streptococcal infection. The role of intravenous immune globulin (IVIG) for streptococcal TSS in children is controversial. Objective To describe the epidemiology of streptococcal TSS in children and to determine whether adjunctive therapy with IVIG is associated with improved outcomes. Methods A multicenter retrospective cohort study of children with streptococcal TSS from 2003-2007 was conducted. Propensity scores were used to determine each child's likelihood of receiving IVIG. Differences in the primary outcomes of death, hospital length of stay, and total hospital costs were compared after matching IVIG-recipients and non-recipients on propensity score. Results The median age was 8.2 years. IVIG was administered to 84 (44%) of 192. Overall mortality was 4.2% (95% confidence interval: 1.8% to 8.0%). Differences in mortality between IVIG recipients (n=3, 4.5%) and non-recipients (n=3, 4.5%) were not statistically significant (P=1.00). While patients receiving IVIG had higher total hospital and drug costs than non-recipients, differences in hospital costs were not significant once drug costs were removed (median difference between matched patients, $6,139; interquartile range: -$8,316 to $25,993; P=0.06). There were no differences in length of stay between matched IVIG recipients and non-recipients. Conclusion This multicenter study is the largest to describe the epidemiology and outcomes of children with streptococcal TSS and the first to explore the association between IVIG use and clinical outcomes. IVIG use was associated with increased costs of caring for children with streptococcal TSS but was not associated with improved outcomes. PMID:19788359

Polyclonal antithymocyte globulin and cardiovascular disease in kidney transplant recipients.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

2014-06-01

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. Copyright © 2014 by the American Society of Nephrology.

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

PubMed Central

Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

2014-01-01

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)–induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8+ T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. PMID:24511120

Should cell-free DNA testing be used to target antenatal rhesus immune globulin administration?

PubMed

Ma, Kimberly K; Rodriguez, Maria I; Cheng, Yvonne W; Norton, Mary E; Caughey, Aaron B

2016-01-01

To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model. A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed. In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States. Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.

Vitamin B6 status, immune response and inflammation markers in kidney transplant recipients treated with polyclonal anti-thymocyte globulin.

PubMed

Jankowska, M; Trzonkowski, P; Dębska-Ślizień, A; Marszałł, M; Rutkowski, B

2014-10-01

Vitamin B6 status has an impact on the body's inflammatory and immune responses. Immunosuppressive therapy may influence vitamin B6 metabolism in kidney transplant recipients. Treatment with polyclonal anti-thymocyte globulin (ATG) is associated with long-term changes in inflammatory and immune parameters. It is not known if ATG therapy also may have an impact on vitamin B6 status in kidney transplant recipients. We aimed to analyze the impact of therapy with ATG on vitamin B6 status, immune response, and the profile of inflammatory cytokines. This was a retrospective, observational study that included 44 kidney allograft recipients. Twenty patients received induction therapy with ATG (6 to 24 months before enrollment). Twenty-four patients constituted the control group, matched with respect to time since transplantation. The B6 vitamers, total lymphocyte count, CD3 percentage, interleukin (IL)-6, -7, and -10, transforming growth factor β, interferon γ, and chemokine ligand 21 were analyzed in a study group. All indicators of vitamin B6 status were lower in the ATG group than in the control group. There were also significant differences with respect to immune response (significantly lower total lymphocyte count and CD3 in the ATG group) and inflammatory status (significantly higher IL-6 and IL-10 in the ATG group). Vitamin B6 vitamers and derivatives were not related to lymphocyte count and cytokine levels or to estimated glomerular filtration rate and age of the study population. Vitamin B6 stores and active forms are lower in kidney transplant recipients treated with ATG. ATG therapy promotes CD3 and total lymphocyte depletion and increases indicators of inflammation. We found no associations between vitamers of B6, immune response cells, and inflammatory cytokines in study population.

Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

PubMed

Vora, Neil M; Orciari, Lillian A; Bertumen, J Bradford; Damon, Inger; Ellison, James A; Fowler, Vance G; Franka, Richard; Petersen, Brett W; Satheshkumar, P S; Schexnayder, Stephen M; Smith, Todd G; Wallace, Ryan M; Weinstein, Susan; Williams, Carl; Yager, Pamela; Niezgoda, Michael

2018-02-09

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.

PubMed

Fisher, R W; Reed, J L; Snoy, P J; Mikolajczyk, M G; Bray, M; Scott, D E; Kennedy, M C

2011-01-01

A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV.

PROPERTIES OF VARIOUS ANTI-γ-GLOBULIN FACTORS IN HUMAN SERA

PubMed Central

Harboe, Morten; Rau, Barbara; Aho, Kimmo

1965-01-01

The serological and physicochemical properties of the following three forms of human anti-γ-globulin factors were compared: (a) rheumatoid factors; (b) Milgrom type anti-γ-globulin factors; and (c) factors directed against an antigen in human γG-globulin that is hidden in the intact molecule and revealed by enzymatic digestion at low pH. The property common to these factors is ability to interact with human γG-globulin; they are distinguishable because they react with different antigenic groups on this molecule. In all of five sera, the Milgrom type anti-γ-globulin factors were γM-globulins. They reacted with various human γG-globulin antibodies but failed to interact with γM-globulin type antibodies in agglutination and absorption experiments. When isolated from other anti-γ-globulin factors, they agglutinated red cells coated with intact anti-Rh antibodies, but failed to react with cells cells coated with pepsin-digested anti-Rh antibody. These observations indicate that the agglutinator reacts with the crystallizable, inert fragment of γG-globulin. Anti-γ-globulin activity directed against an antigen in human γG-globulin revealed by pepsin digestion was demonstrated in γG-, γA-, and γM-globulins. This anti-γ-globulin factor could be absorbed by antigen-antibody precipitates containing human antibody, which shows that the hidden antigen in human γG-globulin is revealed not only by enzymatic digestion at low pH, but also when γG-globulin is present as antibody in an antigen-antibody precipitate. Rheumatoid factors and Milgrom type anti-γ-globulin factors were also absorbed by antigen-antibody precipitates containing human antibody. The results indicate that the three distinct forms of antiγ-globulin factors may all be produced as a result of antigenic stimulation by autologous antigen-antibody complexes. PMID:14276773

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

Lack of association between Rh status, Rh immune globulin in pregnancy and autism.

PubMed

Miles, Judith H; Takahashi, T Nicole

2007-07-01

Though causes of autism are considered largely genetic, considerable concern remains that exposure to Rh immune globulin (RhIg), which until 2001 in the United States contained the preservative thimerosal, can cause autism. To determine whether mothers of children with autism are more likely to be Rh negative (Rh(-)) or to have received RhIg preserved with thimerosal, which is 49.6% ethyl mercury, we surveyed families of children with an autism spectrum disorder (ASD) ascertained through a University-based autism clinic considered free of ascertainment biases related to type of autism or severity. Between 2004 and 2006, 305 mothers of 321 children with an ASD agreed to participate in a telephone interview. Analysis of complete records including the blood group status and RhIg exposure of 214 families showed that Rh(-) status is no higher in mothers of children with autism than in the general population, exposure to antepartum RhIg, preserved with thimerosal is no higher for children with autism and pregnancies are no more likely to be Rh incompatible. This was also true for autism subgroups defined by behavioral phenotype, gender, IQ, regressive onset, head circumference, dysmorphology, birth status, essential, or complex phenotype. These findings support the consensus that exposure to ethylmercury in thimerosal is not the cause of the increased prevalence of autism. These data are important not only for parents in this country but also for the international health community where thimerosal continues to be used to preserve multi-dose vials which in turn makes vaccines affordable. (c) 2007 Wiley-Liss, Inc.

Local application of antirabies gamma-globulin in dried form for the prevention of rabies

PubMed Central

Soloviev, V. D.; Kobrinski, G. D.

1962-01-01

The authors report on guinea-pig experiments conducted to determine the effect of dried antirabies gamma-globulin in the local treatment of wounds infected with street rabies. The results showed that local application of dried gamma-globulin within 30 minutes of the time of infection of the wound protected the majority of animals and resulted in a considerably longer incubation period in the remainder than in the controls. When the preparation was applied later than 30 minutes after infection, the therapeutic effect was slight or absent. Optimum protection in these experiments was obtained through rapid application of gamma-globulin, followed by vaccination every other day for six days. Dried antirabies gamma-globulin exerts a specific, local action on the rabies virus and is entirely painless and non-destructive to body tissues. PMID:13915039

Comparative study of two human diploid rabies vaccines administered with antirabies globulin.

PubMed

Vodopija, I; Sureau, P; Smerdel, S; Lafon, M; Baklaic, Z; Ljubicic, M; Svjetlicic, M

1988-12-01

The association of human rabies immune globulin (HRIG) to the vaccine is recommended for postexposure rabies treatment in cases of severe exposure. In a previous study using an abbreviated postexposure vaccination schedule it was observed that passive immunization could partially inhibit the active immune response, with three cell-culture purified vaccines but not with the concentrated human diploid cell vaccine (HDCV). In order to see if this difference was related to the purification process, the present study was designed comparing two HDCV, one concentrated and the other concentrated and purified, both of them administered in association with HRIG. The neutralizing antibody response in the vaccines was found to be identical with both vaccines, ruling out the role of the purification and confirming the excellent immunogenicity of both human diploid cell vaccines and the absence of inhibition of the active immune response by the association of HRIG to HDCV.

Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

PubMed Central

Sparks, Susan; Rakocevic, Goran; Joe, Galen; Manoli, Irini; Shrader, Joseph; Harris-Love, Michael; Sonies, Barbara; Ciccone, Carla; Dorward, Heidi; Krasnewich, Donna; Huizing, Marjan; Dalakas, Marinos C; Gahl, William A

2007-01-01

Background Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM. Methods We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. Results For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. Conclusion The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM. PMID:17261181

A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

PubMed Central

Konduru, Krishnamurthy; Virata-Theimer, Maria Luisa; Yu, Mei-ying W; Kaplan, Gerardo G

2008-01-01

Background Hepatitis A virus (HAV), the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA) based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd) resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG) preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the endpoint dilution ELISA

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Globulin. (a) Proper name and definition. The proper name of this product shall be Anti-Human Globulin... in tissue cultures or in secondary hosts. [50 FR 5579, Feb. 11, 1985, as amended at 65 FR 77499, Dec...

Multihormonal induction of hepatic α2u-globulin mRNA as measured by hybridization to complementary DNA

PubMed Central

Kurtz, David T.; Feigelson, Philip

1977-01-01

A procedure is presented for the preparation of a 3H-labeled complementary DNA (cDNA) specific for the mRNA coding for α2u-globulin, a male rat liver protein under multihormonal control that represents approximately 1% of hepatic protein synthesis. Rat liver polysomes are incubated with monospecific rabbit antiserum to α2u-globulin, which binds to the nascent α2u-globulin chains on the polysomes. These antibody-polysome complexes are then adsorbed to goat antiserum to rabbit IgG that is covalently linked to p-aminobenzylcellulose. mRNA preparations are thus obtained that contain 30-40% α2u-globulin mRNA. A labeled cDNA is made to this α2u-globulin-enriched mRNA preparation by using RNA-dependent DNA polymerase (reverse transcriptase). To remove the non-α2u-globulin sequences, this cDNA preparation is hybridized to an RNA concentration × incubation time (R0t) of 1000 mol of ribonucleotide per liter × sec with female rat liver mRNA, which, though it shares the vast majority of mRNA sequences with male liver, contains no α2u-globulin mRNA sequences. The cDNA remaining single-stranded is isolated by hydroxylapatite chromatography and is shown to be specific for α2u-globulin mRNA by several criteria. Good correlation was found in all endocrine states studied between the hepatic level of α2u-globulin, the level of functional α2u-globulin mRNA as assayed in a wheat germ cell-free translational system, and the level of α2u-globulin mRNA sequences as measured by hybridization to the α2u-globulin cDNA. Thus, the hormonal control of hepatic α2u-globulin synthesis by sex steroids and thyroid hormone occurs through modulation of the cellular level of α2u-globulin mRNA sequences, presumably by hormonal control of transcriptive synthesis. PMID:73184

Langerhans Cell Histiocytosis in an Adult with Involvement of the Calvarium, Cerebral Cortex and Brainstem: Discussion of Pathophysiology and Rationale for the Use of Intravenous Immune Globulin

PubMed Central

Dardis, Christopher; Aung, Thandar; Shapiro, William; Fortune, John; Coons, Stephen

2015-01-01

We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin. PMID:25873887

Ultrastructural studies of human and rabbit alpha-M-globulins.

PubMed

Bloth, B; Chesebro, B; Svehag, S E

1968-04-01

Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

ACTIVITY OF DISSOCIATED AND REASSOCIATED 19S ANTI-γ-GLOBULINS

PubMed Central

Schrohenloher, Ralph E.; Kunkel, Henry G.; Tomasi, Thomas B.

1964-01-01

19S anti-γ-globulins were isolated in a high state of purity from the sera of two patients with rheumatoid arthritis. Following reduction with ethyl mercaptan and alkylation by iodoacetamide, fragments were produced which retained the capacity to combine with 7S γ-globulin. The fragments from one of the 19S anti-γ-globulins agglutinated red cells coated with incomplete anti-Rh antibodies. This activity was shown by density gradient ultracentrifugation to be associated with low molecular weight fractions. The agglutination of the coated red cells by the fragments was strongly inhibited by normal and myeloma 7S γ-globulins and showed a greater specificity than the parent 19S material. Analytical ultracentrifuge experiments demonstrated that the fragments from either of the 19S anti-γ-globulins formed complexes with 7S γ-globulin. Reassociation of the dissociated fragments through reformation of disulfide bonds resulted in the formation of fast sedimenting molecules having properties similar to those of the untreated 19S material in respect to precipitation with aggregated γ-globulin and agglutination of coated red cells. PMID:14238936

Role of intravenous immune globulin in streptococcal toxic shock syndrome and Clostridium difficile infection.

PubMed

Shah, Punit J; Vakil, Niyati; Kabakov, Anna

2015-06-15

The use of intravenous immune globulin (IVIG) in the management of streptococcal toxic shock syndrome (STSS) and Clostridium difficile infection (CDI) is reviewed. IVIG has a wide range of uses in clinical practice, including STSS and CDI. It is an attractive option for these two infections because both infections are toxin mediated, and IVIG may contain antibodies that neutralize these toxins. For STSS and CDI, IVIG is often considered for use in critically ill patients who are not responding to traditional therapies. Several encouraging case reports and retrospective chart reviews have been published, highlighting the potential benefit of IVIG in such patients. However, its definitive role remains unclear, mainly due to the lack of high-level evidence. Data supporting its use have been extrapolated from retrospective chart reviews and case reports in which profound heterogeneity in patient populations and treatment modalities exist. The use of IVIG must be weighed carefully because it is not a benign product. As with the use of IVIG for STSS, the role of IVIG for CDI is unclear. Nonetheless, IVIG may serve as a useful adjunct therapy for patients suffering from severe complicated CDI (shock, ileus, or megacolon) who do not respond to conventional treatment. Adverse reactions to IVIG are mild and transitory and occur during or immediately after drug infusion. Although randomized, controlled trials supporting the use of IVIG for STSS and CDI are lacking, IVIG may be considered a last-line adjunct therapy in those patients for whom the clinical benefit outweighs the potential adverse effects of therapy. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Apparent effect of immune serum globulin prophylaxis in the military on viral hepatitis incidence in the civilian population in Israel.

PubMed

Green, M S; Block, C

1989-06-01

Since 1969, extensive use of immune serum globulin in the Israel Defence Force for prophylaxis against hepatitis A virus (HAV) infection has produced a sharp decline in the incidence of the disease. However, it is not clear whether this policy has affected the susceptibility of Israeli adults to HAV infection. In this study, we examined the effect of the immunisation policy on the incidence of hepatitis A virus infection in the civilian population in the 15-44 year age group, which includes all those who have completed compulsory military service since vaccination was introduced. The incidence of viral hepatitis in the Jewish civilian population aged 15-44 increased by approximately 50% 3-4 years after the implementation of the immunisation policy. This rise was not seen in the non-Jewish population of the same age nor among Jews aged 45-64. These findings strongly suggest that the immunisation policy in the military prevents both clinical and sub-clinical disease, but has had the effect of producing more susceptible people at an older age in the civilian population.

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5400 Alpha-globulin immuno-logical test system. (a) Identification. An alpha-globulin immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866...

21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160 Beta-globulin immunolog-ical test system. (a) Identification. A beta-globulin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160...

Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin.

PubMed

Sauter, Craig; Abboud, Michelle; Jia, Xiaoyu; Heller, Glenn; Gonzales, Anne-Marie; Lubin, Marissa; Hawke, Rebecca; Perales, Miguel-Angel; van den Brink, Marcel R; Giralt, Sergio; Papanicolaou, Genovefa; Scaradavou, Andromachi; Small, Trudy N; Barker, Juliet N

2011-10-01

Factors contributing to infection risk after cord blood transplantation (CBT) include the use of anti-thymocyte globulin (ATG), prolonged neutropenia, and failure to transfer immunity. In the present study, we investigated the potential of double-unit CBT without ATG to reduce the risk of infection and evaluated the nature of serious infections in the first year after CBT using this approach. Seventy-two predominantly adult patients underwent CBT for hematologic malignancies; of these, 52 patients received myeloablative conditioning, and 20 received nonmyeloablative conditioning. The peak incidences of bacterial infections (32%), fungal infections (14%), and bacterial/fungal pneumonias (10%) occurred in the first 30 days posttransplantation. Three such infections contributed to early mortality. The peak incidence of viral infections was 31-60 days posttransplantation, affecting 30% of patients. Cytomegalovirus (CMV) was the most common viral infection. CMV infections occurring before day 120 (n = 23) had no relationship with graft-versus-host disease (GVHD), whereas CMV infections occurring after day 120 (n = 5), along with all cases of Epstein-Barr virus viremia (n = 5) and adenoviral enteritis (n = 2), occurred exclusively in the context of GVHD therapy or corticosteroid use for another indication. Viral infections had the highest lethality: 2 were a direct cause of death, and 3 contributed to death. Patients exhibited steady immune recovery, achieving a median CD3(+)4(+) T cell count >200 cells/μL by day 120 post-CBT, and no infection-related deaths occurred after day 120. Our results suggest that double-unit CBT without ATG is associated with prompt T cell recovery, and, unlike in CBT incorporating ATG, infection is rarely a primary cause of death. However, CBT without ATG is associated with a significant risk of GVHD, and serious infections remain a challenge, especially in the setting of GVHD. New strategies are needed to further reduce infectious

Acquired Immunological Tolerance to a Fraction of Bovine Gamma Globulin

PubMed Central

Dresser, D. W.

1961-01-01

A state of acquired immunological tolerance to bovine gamma globulin (BGG) has been observed in CBA mice injected with 10 mg. BGG within 12 hours of birth. Tolerance was demonstrated by a lack of immune elimination of 131I labelled BGG (BGG-131I) after prior challenge with Freund's adjuvant containing BGG. The degree of tolerance was found to diminish when the time between the tolerance injection and the challenge injection with adjuvant was increased. Mice were found to be tolerant 4 months after injection of 10 mg. BGG at birth but other similarly treated mice were found to be partially immune when challenged 6 months after the tolerance injection. This diminution of tolerance could be prevented by injections of antigen into adult mice whilst they were still tolerant. Precipitin and haemagglutination tests showed that antibody to BGG was present in mice shown to be tolerant to BGG by the antigen-elimination technique. The Ouchterlony double-diffusion technique showed that the mice were tolerant to one fraction of BGG but immune to at least one other fraction. The tolerated fraction of BGG was identified by means of starch-gel electrophoresis. ImagesFIG. 2 PMID:13724353

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

STUDIES ON STRUCTURAL UNITS OF THE γ-GLOBULINS

PubMed Central

Edelman, G. M.; Poulik, M. D.

1961-01-01

When human and rabbit 7S γ-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately ⅓ of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S γ-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components. A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal γ-globulins. Reduction of normal and abnormal γ-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules. PMID:13725659

Genomic organization of the rat alpha 2u-globulin gene cluster.

PubMed

McFadyen, D A; Addison, W; Locke, J

1999-05-01

The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

PubMed

Bigham, Mark; Murti, Michelle; Fung, Christina; Hemming, Felicity; Loadman, Susan; Stam, Robert; Van Buynder, Paul; Lem, Marcus

2017-05-09

Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25years was significantly associated with breakthrough clinical measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all <150mIU/ml. The estimated crude IM ISG PEP protective effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. Copyright �

Studies on Red Cell Aplasia. V. PRESENCE OF ERYTHROBLAST CYTOTOXICITY IN γG-GLOBULIN FRACTION OF PLASMA

PubMed Central

Krantz, Sanford B.; Moore, W. H.; Zaentz, S. Donald

1973-01-01

The marrow cells of a patient with pure red cell aplasia markedly increased their rate of heme synthesis when they were freed from the host environment and were incubated in vitro. When the red cell aplasia was treated with cyclophosphamide and prednisone, marrow cell incorporation of 59Fe into heme in vitro increased several weeks before a reticulocytosis was apparent, and was the earliest effect noted. The plasma γG-globulins of this patient inhibited heme synthesis by normal marrow cells or the patient's own marrow cells obtained after remission of the disease. Since the inhibition of heme synthesis could be the result of damage to erythroblasts, the patient's posttreatment marrow cells or normal marrow cells were labeled with 59Fe and were then incubated with the patient's pretreatment, treatment, and posttreatment γG-globulins as well as normal γG-globulins. At the end of this incubation the supernatant and cells were separated and counted. Heme was extracted and also was counted. Treatment of the cells with the patient's pretreatment γG-globulins resulted in a release of 40% of the radioactive heme from the cells. This represented the loss of radioactive hemoglobin and was an index of erythroblast cytotoxicity. A progressive disappearance of the cytotoxic factor in the γG-globulins occurred in the 3 wk period preceding the onset of reticulocytes in the patient's blood. Posttreatment and normal γG-globulins did not produce this effect and increased injury of red cells and lymphocytes was not produced by the patient's pretreatment γG-globulins. These studies demonstrate a method for measuring erythroblast cytoxicity and show that red cell aplasia is associated with γG-globulins that specifically damage erythroblasts. Whether interference with new erythroblast development also occurs and contributes to the inhibition of heme synthesis has not yet been ascertained. Images PMID:4119161

Physicochemical, functional and angiotensin converting enzyme inhibitory properties of amaranth (Amaranthus hypochondriacus) 7S globulin.

PubMed

Quiroga, Alejandra V; Aphalo, Paula; Ventureira, Jorge L; Martínez, E Nora; Añón, María C

2012-01-30

Amaranth 7S globulin is a minor globulin component and its impact on the properties of an amaranth protein ingredient depends on its proportion in the variety of amaranth being considered. Some physicochemical, functional and angiotesin I-converting enzyme (ACE) inhibitory properties of amaranth vicilin were studied in this work and compared with the 11S globulin. Fluorescence spectroscopy results indicated that 7S globulin tryptophans were more exposed to the solvent and, by calorimetry, the 7S globulin denaturation temperature (T(d) ) was found lower than the 11S globulin T(d) , suggesting a more flexible structure. The 7S globulin surface hydrophobicity was higher than that of the 11S globulin, which is in agreement with the better emulsifying properties of the 7S globulin. The solubility in neutral buffer of the 7S globulin (851 ± 25 g kg(-1) ) was also higher than that of the 11S globulin (195 ± 6 g kg(-1) ). Bioinformatic analyses showed the presence of ACE inhibitory peptides encrypted in 7S tryptic sequences and peptides released after in vitro gastrointestinal digestion showed a high ACE-inhibitory capacity (IC(50) = 0.17 g L(-1) ), similar to that of 11S globulin peptides. Compared with the 11S globulin, the 7S globulin presents similar ACE inhibitory activity and some functional advantages, better solubility and emulsifying activity, which suits some food requirements. The functional behavior has been related with the structural properties. Copyright © 2011 Society of Chemical Industry.

Assessment of acquired immune response to Rhipicephalus appendiculatus tick infestation in different goat breeds.

PubMed

Gopalraj, Jeyanthi B P; Clarke, Francoise C; Donkin, Edward F

2013-01-01

Changes in serum gamma globulin levels, numbers of replete female ticks and engorged tick mass were used as parameters to monitor the acquired immune response (antibody mediated immune response) elicited by Rhipicephalus appendiculatus adult tick infestations. Three consecutive Rhipicephalus appendiculatus adult tick infestations were applied to South African Indigenous goats (Nguni), Saanen goats and cross-bred goats (Saanen goats crossed with South African Indigenous goats [Nguni]) under laboratory conditions. During the three consecutive Rhipicephalus appendiculatus adult tick infestations the serum gamma globulin levels increased in all three breeds, whilst the mean replete female tick numbers and engorged tick mass decreased. Even though all three goat breeds exhibited an acquired immune response, the South African Indigenous goats (Nguni) response was significantly higher than that of the Saanen and cross-bred goats. However, the acquired immune response elicited by Saanen goats was significantly lower when compared with cross-bred goats.

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

PubMed

Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

2017-09-01

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

The effects of ALG on the murine immune response to sheep erythrocytes

PubMed Central

Anderson, Hilary R.; Dresser, D. W.; Iverson, G. M.; Lance, E. M.; Wortis, H. H.; Zebra, J.

1972-01-01

Antilymphocyte globulin (ALG), and to a lesser extent normal rabbit globulin (NRG), when given to mice prior to immunization with sheep-RBC suppress both the γM and γG2a responses. Globulin injected after the antigen suppresses the γG2a response, augments the γG1 response and has little effect on the γM response. These effects are also observed in mice partially paralysed to rabbit γ globulin. In another system—the response to hapten—protein conjugates precursors of antibody producing cells were found to be more resistant to ALS treatment in vivo than were helper cells. It is concluded that the suppressive effects of ALG treatment are largely due to the direct action of ALG on helper cells (T-cells). The mechanism of the adjuvant-like effect is unclear. PMID:4550853

[The macrophage disappearance reaction in guinea pigs sensitized with bovine gamma globulin or human scrum albumin (author's transl)].

PubMed

Schimke, R; Bernstein, B; Ambrosius, H

1977-01-01

The macrophage disappearance reaction (MDR) is a suitable test for detection of cell mediated immunity against bovine gamma globulin (BGG) and human serum albumin (HSA) in guinea pigs. The MDR is a technical simple, good manipulable, and quantifiable test. The optimal test conditions for the antigens BGC and HSA are the following: Peritoneal exudat cells (PEC) were stimulated with paraffin oil. On the 5th day after receiving oil the animals were injected with 80 microgram BGG or 30 microgram HSA i.p. 5 hours later the PEC were harvested and counted. With the MDR it is possible to detect differences with respect to degree of cell-mediated immunity. Supernatants of sensitized lymphocytes produces the MDR too.

Structural, Functional and Evolutionary Aspects of Seed Globulins.

PubMed

Kesari, Pooja; Neetu; Sharma, Anchal; Katiki, Madhusudhanarao; Kumar, Pramod; Gurjar, Bhola R; Tomar, Shailly; Sharma, Ashwani K; Kumar, Pravindra

2017-01-01

Globulins are a major class of seed storage proteins which were thought to be enzymatically inactive. These proteins belong to the most ancient cupin superfamily. They can be graded into 11S legumin type and 7S vicilin type based on their sedimentation coefficients. Members from both classes share structural homology are thought to have evolved from either one-domain germin predecessor by duplication or by horizontal gene transfer of two-domain gene from bacteria to eukaryotes. Globulins are known to define the nutritional quality of the seeds, however, they are also involved in sucrose binding, desiccation, defense against microbes, hormone binding and oxidative stress etc. Major drawback with globulins is their tendency to bind to IgE. Studying structural-functional behavior of such protein can help in modifying proteins for enhanced functionality in food processing industries. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

PubMed Central

Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

2012-01-01

BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia.

PubMed

Hayakawa, Jin; Kanda, Junya; Akahoshi, Yu; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Yoshinobu

2017-05-01

Aplastic anemia patients who received rabbit antithymocyte globulin exhibited response and survival rates inferior to those who received horse antithymocyte globulin in several studies. Therefore, we conducted a meta-analysis to compare rabbit and horse antithymocyte globulin as immunosuppressive therapy for aplastic anemia. We searched online databases for studies that compared antithymocyte globulin regimens as first-line treatment for aplastic anemia, including both randomized and non-randomized controlled trials. The early mortality rate at 3 months and overall response rate at 6 months were evaluated. Thirteen studies were included in the analysis. The risk ratio (RR) of early mortality for rabbit vs. horse antithymocyte globulin was 1.33 [95% confidence interval (CI) 0.69-2.57; P = 0.39], with significant heterogeneity. A sensitivity analysis suggested higher early mortality rate in patients who received rabbit antithymocyte globulin. The overall response rate was significantly higher in patients who received horse antithymocyte globulin (RR 1.27; 95% CI 1.05-1.54; P = 0.015). In conclusion, in aplastic anemia patients treated with ATG, early mortality rate was not significantly different in patients receiving horse or rabbit ATG, although a sensitivity analysis showed higher early mortality in the rabbit ATG group. Horse ATG was associated with significantly higher response rate than rabbit ATG.

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

PubMed

Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

2017-07-01

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P <0.001) and chronic (20% versus 9%, P <0.001) graft- versus -host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3-year overall survival, 87% and 92%, P =0.76, respectively. Among recipients of unrelated donor transplants, acute graft- versus -host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P <0.001) but not chronic graft- versus -host disease (38% versus 32%, P =0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P =0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia. Copyright© 2017 Ferrata Storti Foundation.

Posttransplant Immune Activation

PubMed Central

Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-01-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8+ T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8+ T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence. PMID:29113470

Anti-thymocyte globulins in kidney transplantation: focus on current indications and long-term immunological side effects.

PubMed

Bamoulid, Jamal; Staeck, Oliver; Crépin, Thomas; Halleck, Fabian; Saas, Philippe; Brakemeier, Susanne; Ducloux, Didier; Budde, Klemens

2017-10-01

Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Enhanced Efficacy of Cidofovir Combined with Vaccinia Immune Globulin in Treating Progressive Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice

PubMed Central

Dagley, Ashley; Downs, Brittney; Hagloch, Joseph; Tarbet, E. Bart

2014-01-01

The treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so sparing the use of VIG during treatment is an important objective. VIG sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV combined with VIG to determine the effective treatments that delayed the time to death, reduced cutaneous lesion severity, and/or decreased tissue viral titers. SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and VIG) were initiated 2 days postinfection and were given every 3 to 4 days through day 11. The efficacy assessment included survival rate, cutaneous lesion severity, and viral titers. Delays in the time to death and the reduction in lesion severity occurred in the following order of efficacy: triple therapy had greater efficacy than double combinations (CDV plus VIG or topical plus parenteral CDV), which had greater efficacy than VIG alone. Parenteral administration of CDV or VIG was necessary to suppress virus titers in internal organs (liver, lung, and spleen). The skin viral titers were significantly reduced by triple therapy only. The greatest efficacy was achieved by triple therapy. In humans, this regimen should translate to a faster cure rate, thus sparing the amount of VIG used for treatment. PMID:25385098

21 CFR 862.1330 - Globulin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862... other disorders of blood globulins. (b) Classification. Class I (general controls). The device is exempt...

Serum IgG, IgM and slow alpha-globulin levels in carrageenan-treated rats.

PubMed Central

Fowler, E. F.; Thomson, A. W.

1979-01-01

Serum levels of IgM, IgG, slow alpha 1- and slow alpha 2-globulins were measured either by quantitative radial immunodiffusion (IgG) or immunoelectrophoresis (IgM and slow alpha-globulins) during the 3-week period after i.p. injection of 50 mg potassium carrageenan. There was a significant elevation in levels of IgM and slow alpha 1-globulin, maximal on Day 4 and returning to normal by Day 14. Slow alpha 2-globulin was detectable within 24 h, reached a peak at Day 2, and was no longer measurable in most rats by Day 14. Levels of IgG however, were unaffected by carrageenan injection. PMID:92333

Modification of solubility and heat-induced gelation of amaranth 11S globulin by protein engineering.

PubMed

Carrazco-Peña, Laura; Osuna-Castro, Juan A; De León-Rodríguez, Antonio; Maruyama, Nobuyuki; Toro-Vazquez, Jorge F; Morales-Rueda, Juan A; Barba de la Rosa, Ana P

2013-04-10

The primary structure of amaranth 11S globulin (Ah11S) was engineered with the aim to improve its functional properties. Four continuous methionines were inserted in variable region V, obtaining the Ah11Sr+4M construction. Changes on protein structure and surface characteristics were analyzed in silico. Solubility and heat-induced gelation of recombinant amaranth 11S proglobulin (Ah11Sr and Ah11Sr+4M) were compared with the native protein (Ah11Sn) purified from amaranth seed flour. The Ah11Sr+4 M showed the highest surface hydrophobicity, but as consequence the solubility was reduced. At low ionic strength (μ = 0.2) and acidic pH (<4.1), the recombinant proteins Ah11Sr and Ah11Sr+4 M had the highest and lowest solubility values, respectively. All globulins samples formed gels at 90 °C and low ionic strength, but Ah11Sn produced the weakest and Ah11Sr the strongest gels. Differential scanning calorimetry analysis under gel forming conditions revealed only exothermic transitions for all amaranth 11S globulins analyzed. In conclusion, the 3D structure analysis has revealed interesting molecular features that could explain the thermal resistance and gel forming ability of amaranth 11S globulins. The incorporation of four continuous methionines in amaranth increased the hydrophobicity, and self-supporting gels formed had intermediate hardness between Ah11Sn and Ah11Sr. These functional properties could be used in the food industry for the development of new products based on amaranth proteins.

A simplified immune suppression scheme leads to persistent micro-dystrophin expression in Duchenne muscular dystrophy dogs.

PubMed

Shin, Jin-Hong; Yue, Yongping; Srivastava, Arun; Smith, Bruce; Lai, Yi; Duan, Dongsheng

2012-02-01

Highly abbreviated micro-dystrophin genes have been intensively studied for Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus (AAV) gene transfer, robust microgene expression is achieved in murine DMD models in the absence of immune suppression. Interestingly, a recent study suggests that AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued immune suppression is not only costly but also may cause untoward reactions. Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily available. To overcome these limitations, we developed a novel 5-week immune suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase gene, or AV.CMV.μDys that expresses the canine R16-17/H3/ΔC microgene) at 2.85×10(12) vg particles were injected into adult dystrophic dog limb muscles under the new immune suppression protocol. Sustained transduction was observed for nearly half year (the end of the study). The simplified immune suppression strategy described here may facilitate preclinical studies in the dog model.

11S Storage globulin from pumpkin seeds: regularities of proteolysis by papain.

PubMed

Rudakova, A S; Rudakov, S V; Kakhovskaya, I A; Shutov, A D

2014-08-01

Limited proteolysis of the α- and β-chains and deep cleavage of the αβ-subunits by the cooperative (one-by-one) mechanism was observed in the course of papain hydrolysis of cucurbitin, an 11S storage globulin from seeds of the pumpkin Cucurbita maxima. An independent analysis of the kinetics of the limited and cooperative proteolyses revealed that the reaction occurs in two successive steps. In the first step, limited proteolysis consisting of detachments of short terminal peptides from the α- and β-chains was observed. The cooperative proteolysis, which occurs as a pseudo-first order reaction, started at the second step. Therefore, the limited proteolysis at the first step plays a regulatory role, impacting the rate of deep degradation of cucurbitin molecules by the cooperative mechanism. Structural alterations of cucurbitin induced by limited proteolysis are suggested to generate its susceptibility to cooperative proteolysis. These alterations are tentatively discussed on the basis of the tertiary structure of the cucurbitin subunit pdb|2EVX in comparison with previously obtained data on features of degradation of soybean 11S globulin hydrolyzed by papain.

Immune and hormonal activity in adults suffering from depression.

PubMed

Nunes, S O V; Reiche, E M V; Morimoto, H K; Matsuo, T; Itano, E N; Xavier, E C D; Yamashita, C M; Vieira, V R; Menoli, A V; Silva, S S; Costa, F B; Reiche, F V; Silva, F L V; Kaminami, M S

2002-05-01

An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5%) were females and 11 (27.5%) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and beta-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation.

Total Protein and Albumin/Globulin Ratio Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

Humoral and Cellular Immune Response in Canine Hypothyroidism.

PubMed

Miller, J; Popiel, J; Chełmońska-Soyta, A

2015-07-01

Hypothyroidism is one of the most common endocrine diseases in dogs and is generally considered to be autoimmune in nature. In human hypothyroidism, the thyroid gland is destroyed by both cellular (i.e. autoreactive helper and cytotoxic T lymphocytes) and humoral (i.e. autoantibodies specific for thyroglobulin, thyroxine and triiodothyronine) effector mechanisms. Other suggested factors include impaired peripheral immune suppression (i.e. the malfunction of regulatory T cells) or an additional pro-inflammatory effect of T helper 17 lymphocytes. The aim of this study was to evaluate immunological changes in canine hypothyroidism. Twenty-eight clinically healthy dogs, 25 hypothyroid dogs without thyroglobulin antibodies and eight hypothyroid dogs with these autoantibodies were enrolled into the study. There were alterations in serum proteins in hypothyroid dogs compared with healthy controls (i.e. raised concentrations of α-globulins, β2- and γ-globulins) as well as higher concentration of acute phase proteins and circulating immune complexes. Hypothyroid animals had a lower CD4:CD8 ratio in peripheral blood compared with control dogs and diseased dogs also had higher expression of interferon γ (gene and protein expression) and CD28 (gene expression). Similar findings were found in both groups of hypothyroid dogs. Canine hypothyroidism is therefore characterized by systemic inflammation with dominance of a cellular immune response. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of anticonvulsants on plasma testosterone and sex hormone binding globulin levels.

PubMed Central

Barragry, J M; Makin, H L; Trafford, D J; Scott, D F

1978-01-01

Plasma sex hormone binding globulin (SHBG) and testosterone levels were measured in 29 patients with epilepsy (16 men and 13 women), most of them on chronic therapy with anticonvulsant drugs. Sex hormone binding globulin concentrations were increased in both sexes and testosterone levels in male patients. It is postulated that anticonvulsants may induce hepatic synthesis of SHBG. PMID:569688

Follicle stimulating hormone, its novel association with sex hormone binding globulin in men and postmenopausal women.

PubMed

Wang, Ningjian; Zhang, Kun; Han, Bing; Li, Qin; Chen, Yi; Zhu, Chunfang; Chen, Yingchao; Xia, Fangzhen; Zhai, Hualing; Jiang, Boren; Shen, Zhoujun; Lu, Yingli

2017-06-01

Follicle stimulating hormone plays direct roles in a variety of nongonadal tissues and sex hormone binding globulin is becoming the convergence of the crosstalk among metabolic diseases. However, no studies have explored the association between follicle stimulating hormone and sex hormone binding globulin. We aimed to study this association among men and women. SPECT-China is a population-based study conducted since 2014. This study included 4206 men and 2842 postmenopausal women. Collected serum was assayed for gonadotropins, sex hormone binding globulin, sex hormones etc. Regression analyses were performed to assess the relationship between sex hormone binding globulin and follicle stimulating hormone and other variables including metabolic factors, thyroid function and sex hormones. Treatment with follicle stimulating hormone at different concentrations of 0, 5, 50 and 100 IU/L for 24 h was performed in HepG2 cells. In Spearman correlation, sex hormone binding globulin was significantly correlated with FSH, triglycerides, thyroxins, body mass index and blood pressure in men and postmenopausal women (all P < 0.05). In regression analyses, follicle stimulating hormone was a significant predictor of sex hormone binding globulin in men and postmenopausal women (P < 0.05), independent of above variables. Follicle stimulating hormone induced sex hormone binding globulin expression in a dose-dependent fashion in HepG2 cells. Serum follicle stimulating hormone levels were positively associated with circulating sex hormone binding globulin levels in men and postmenopausal women. This association is independent of age, insulin resistance, hepatic function, lipid profile, thyroid function, adiposity, blood pressure, and endogenous sex hormones.

Effects of medicinal herbs "Plantago asiatica", "Houttuynia cordata" and "Mentha haplocalyx" on non-specific immune responses of cobia (Rachycentron canadum).

PubMed

Wu, Yu-Sheng; Chen, Yin-Yu; Ueng, Pien-Sheng; Nan, Fan-Hua

2016-11-01

This study investigated the effects of orally administered Plantago asiatica, Houttuynia cordata, and Mentha haplocalyx on the growth and nonspecific immune responses of cobia (Rachycentron canadum). The nonspecific immune parameters assessed were weight gain, feed conversion ratio, superoxide anion (O 2 - ) production, superoxide dismutase (SOD) activity, phagocytic rate, phagocytic index, lysozyme activity, serum albumin and globulin, and albumin:globulin (A/G) ratio. The growth experiment indicated that 6-week dietary treatments did not significantly affect on the growth of cobia. Nonspecific immune responses showed that O 2 - production, SOD and lysozyme activity, and phagocytosis were significantly increased after the oral administration of P. asiatica and H. cordata, and the serum albumin:globulin ratio (A/G) gradually decreased. In this study, treatment of the Mentha haplocalyx on the cobia didn't present with the inducing of the phagocytosis ability compared with the treatment of P. asiatica and H. cordata. We suggest that oral administration of the 10 g/kg or 20 g/kg of the P. asiatica and H. cordata is exactly inducing the phagocytosis, ROS production, lysozyme activity and SOD production in the cobia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical and economic analysis of delayed administration of antithymocyte globulin for induction therapy in kidney transplantation.

PubMed

McGillicuddy, John W; Taber, David J; Pilch, Nicole A; Kohout, Ryan K; Bratton, Charles F; Chavin, Kenneth D; Baliga, Prabhakar K

2013-03-01

The increasing number of marginal deceased kidney donors and an aging recipient population, prolonged hospitalization, and increased costs have destabilized the economic viability of kidney transplants. To determine if a delay in the administration of the day-of-discharge dose of rabbit antithymocyte globulin would result in equivalent clinical outcomes with cost savings. Single-center, prospective, observational before-and-after study of adult kidney transplant recipients who received induction with rabbit antithymocyte globulin.Intervention-Patients who received a transplant between June 2006 and February 2009 and received rabbit antithymocyte globulin served as the control group. Patients who received a transplant between March 2009 and August 2010 and received rabbit antithymocyte globulin had the day-of-discharge dose delayed to the following day and administered in the clinic. A total of 231 patients (146 in the control group, 85 in the study group) were included. Baseline demographic and clinical characteristics were similar in the 2 groups. Patients who had delayed administration of rabbit antithymocyte globulin had shorter stays (3.9 vs 3.1 days, P< .001) and reduced inpatient costs for rabbit antithymocyte globulin (mean $860/patient); these changes were achieved without affecting acute rejection rates (5% vs 5%, P> .99) or readmission rates. In conclusion, delayed inpatient administration of rabbit antithymocyte globulin provided identical clinical outcomes while helping to reduce inpatient costs and increase timely discharges.

Proteomic analysis of albumin and globulin fractions of pea (Pisum sativum L.) seeds.

PubMed

Dziuba, Jerzy; Szerszunowicz, Iwona; Nałęcz, Dorota; Dziuba, Marta

2014-01-01

Proteomic analysis is emerging as a highly useful tool in food research, including studies of food allergies. Two-dimensional gel electrophoresis involving isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis is the most effective method of separating hundreds or even thousands of proteins. In this study, albumin and globulin tractions of pea seeds cv. Ramrod were subjected to proteomic analysis. Selected potentially alergenic proteins were identified based on their molecular weights and isoelectric points. Pea seeds (Pisum sativum L.) cv. Ramrod harvested over a period of two years (Plant Breeding Station in Piaski-Szelejewo) were used in the experiment. The isolated albumins, globulins and legumin and vicilin fractions of globulins were separated by two-dimensional gel electrophoresis. Proteomic images were analysed in the ImageMaster 2D Platinum program with the use of algorithms from the Melanie application. The relative content, isoelectric points and molecular weights were computed for all identified proteins. Electrophoregrams were analysed by matching spot positions from three independent replications. The proteomes of albumins, globulins and legumin and vicilin fractions of globulins produced up to several hundred spots (proteins). Spots most characteristic of a given fraction were identified by computer analysis and spot matching. The albumin proteome accumulated spots of relatively high intensity over a broad range of pi values of ~4.2-8.1 in 3 molecular weight (MW) ranges: I - high molecular-weight albumins with MW of ~50-110 kDa, II - average molecular-weight albumins with MW of ~20-35 kDa, and III - low molecular-weight albumins with MW of ~13-17 kDa. 2D gel electrophoregrams revealed the presence of 81 characteristic spots, including 24 characteristic of legumin and 14 - of vicilin. Two-dimensional gel electrophoresis proved to be a useful tool for identifying pea proteins. Patterns of spots with similar isoelectric

Association of Central Obesity with Sex Hormonebinding Globulin: A Cross-sectional Study of 1166 Chinese Men.

PubMed

Liu, Fangwei; Shen, Xubo; Wang, Ruifeng; Yu, Na; Shi, Yongjun; Xiong, Shimin; Xiong, Chengliang; Zhou, Yuanzhong

2018-01-01

Background Both sex hormone-binding globulin and central obesity have been found to be associated with metabolic and cardiovascular diseases. However, the direct relation between sex hormone-binding globulin and central obesity has not been demonstrated. Methodology We performed a cross-sectional study of 1166 male participants from Zunyi, Guizhou, western China, in 2013. Each participant completed a questionnaire and had a brief clinical exam with a fasting blood sample taken. All blood samples underwent standard laboratory testing for sex hormone-binding globulin. Level of serum sex hormone-binding globulin was compared by demographic characteristics, and multiple linear regression was used to evaluate the independent association of variables and sex hormone-binding globulin level. Results The mean serum level of sex hormone-binding globulin was increased in old-aged men (older than 40 years; mean 44.68±20.58 nmol/L), low diastolic blood pressure (<90mmHg; 43.76±20.50 nmol/L), waist-to-height ratio <0.5 (48.73±20.59 nmol/L), no education (52.36±22.91 nmol/L), farm occupation (43.58±20.60nmol/L), non-alcohol or former user (44.78±20.94 nmol/L) and long-term medication history (44.79±21.50 nmol/L). Factors independently associated with sex hormone binding globulin level on multiple regression were waist-to-height ratio (β=- 11.84 [95% confidence interval -13.96,-9.72]), age(β=12.40 [9.63,15.17]) and diastolic blood pressure (β=-5.07 [-7.44,-2.71]). Conclusions Central obesity has an independent inverse relation with serum level of sex hormone binding globulin among western Chinese men.

Biosynthesis and Intracellular Transport of 11S Globulin in Developing Pumpkin Cotyledons 1

PubMed Central

Hara-Nishimura, Ikuko; Nishimura, Mikio; Akazawa, Takashi

1985-01-01

In vitro studies to explore the biosynthesis of 11S globulin developing cotyledons of pumpkin (Cucurbita sp.) demonstrated that 11S globulin is synthesized on membrane-bound polysomes. Mr of the translation products (preproglobulin) synthesized by the poly(A)+-RNA isolated from developing cotyledons were determined to be 64,000 and 59,000, which are larger than those of the mature globulin subunit (62,000 and 57,000). Preproglobulin is then cotranslationally processed by cleavage of the signal peptide to produce proglobulin. In vivo pulse-chase experiments showed the sequential transformation of the single-chain proglobulin to mature globulin subunit (disulfide-linked doublet polypeptides) indicating posttranslational modification of the proglobulin. Subcellular fractionation of the pulse-chased intact cotyledons showed that the [35S]methionine label is detectable in proglobulin in rough endoplasmic reticulum shortly after the pulse label. With time, the labeled proteins move into other cellular fractions: proglobulin in the density = 1.24 grams per cubic centimeter fractions after 30 minutes and mature globulin subunit associated with protein bodies after 1 to 2 hours. The distribution of proglobulin in sucrose density gradients did not correspond with those of catalase (microbody marker) or fumarase (mitochondria marker). An accumulation of proglobulin occurred in the density = 1.24 grams per cubic centimeter fractions, whereas the mature globulin was scarcely detectable in this fraction. In contrast, proglobulin was not detected by immunochemical blotting analysis in the protein bodies prepared under the mild conditions from cotyledon protoplasts. The results suggest that the d = 1.24 grams per cubic centimeter fractions are engaged in the translocation of proglobulin into the protein bodies. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:16664128

21 CFR 862.1330 - Globulin test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Globulin test system. 862.1330 Section 862.1330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1330 - Globulin test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Globulin test system. 862.1330 Section 862.1330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

Sex hormone-binding globulin and corticosteroid-binding globulin mRNA levels in infertile women with luteal phase deficiency.

PubMed

Misao, R; Nakanishi, Y; Fujimoto, J; Tamaya, T

1995-09-01

This study was designed to investigate the biological significance in intracellular expression of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNA in uterine endometrium with luteal phase deficiency (designated as out-of-phase endometrium or low serum progesterone level). The levels of such mRNAs were measured by the quantitative reverse transcription-polymerase chain reaction. Under the normal serum 17 beta-estradiol and progesterone levels in the mid-luteal phase, the levels of SHBG and CBG mRNAs in the out-of-phase endometria were not significantly different from those in the normal endometria. On the other hand, SHBG and CBG mRNA levels in the endometria of low serum midluteal progesterone level were significantly (p < 0.05) reduced and raised, respectively, compared with normal levels. These findings suggest that the synthesis of endometrial steroid-binding proteins in the out-of-phase endometrium is conserved, as that in the in-phase endometrium, whereas the decreased progesterone level might up-regulate CBG expression with down-regulation of SHBG expression.

Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine--induced immunity.

PubMed

He, Yong; Manischewitz, Jody; Meseda, Clement A; Merchlinsky, Michael; Vassell, Russell A; Sirota, Lev; Berkower, Ira; Golding, Hana; Weiss, Carol D

2007-10-01

The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27.

Biochemistry of Fern Spore Germination: Globulin Storage Proteins in Matteuccia struthiopteris L. 1

PubMed Central

Templeman, Thomas S.; DeMaggio, Augustus E.; Stetler, David A.

1987-01-01

Two globulin storage proteins have been identified in spores of the ostrich fern, Matteuccia struthiopteris (L.) Todaro. The two proteins comprise a significant amount of the total spore protein, are predominantly salt-soluble, and can be extracted by other solvents to a limited extent. The large 11.3 Svedberg unit (S) globulin is composed of five polypeptides with molecular weights of 21,000, 22,000, 24,000, 28,000 and 30,000. Each polypeptide has several isoelectric point (pI) variants between pH 5 and 7. The small 2.2S storage protein has a pI > 10.5 and is composed of at least two major polypeptides of 6,000 and 14,000 Mr. The amino acid composition of both storage proteins reveals that the 11.3S protein is particularly rich in aspartic and glutamic acid, while the 2.2S protein has few acidic amino acids. During imbibition and germination the globulin fraction declines rapidly, with a corresponding degradation of individual polypeptides of each protein. Polyclonal antibodies against each of the two proteins were produced and used for immunolocalization to determine the site of storage protein deposition within the quiescent spore. The proteins were sequestered in protein bodies of 2 to 10 micrometers, that are morphologically similar to those found in the seeds of flowering plants. The results suggest that spore globulins are biochemically similar to seed globulins, especially those found in some cruciferous seeds. Images Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:16665699

Antitumor effect of degalactosylated gc-globulin on orthotopic grafted lung cancer in mice.

PubMed

Hirota, Keiji; Nakagawa, Yoshinori; Takeuchi, Ryota; Uto, Yoshihiro; Hori, Hitoshi; Onizuka, Shinya; Terada, Hiroshi

2013-07-01

Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF.

Use of the Vettest 8008 and refractometry for determination of total protein, albumin, and globulin concentrations in feline effusions.

PubMed

Papasouliotis, Kostas; Murphy, Kate; Dodkin, Steve; Torrance, Andy G

2002-01-01

Pleural and peritoneal effusion is a common clinical finding in feline practice. Determination of fluid albumin (ALB) and globulin (GLOB) concentrations in addition to total protein (TP) concentration can be helpful in diagnosing or ruling out certain diseases in cats, especially feline infectious peritonitis (FIP). The objective of this study was to compare effusion TP, ALB, and GLOB results obtained by a refractometer and a bench-top dry chemistry analyzer with those results obtained by a reference method. Twenty-six pleural and 14 peritoneal effusion samples were analyzed from 40 cats with various diseases. TP and ALB concentrations were determined by a reference automated wet chemistry analyzer (Kone Specific, Kone Instruments, Espoo, Finland), a bench-top dry chemistry analyzer (Vettest 8008, IDEXX Laboratories Ltd, Chalfont St Peter, UK), and a refractometer (Atago SPR-T2, Atago Co, Tokyo, Japan). GLOB, albumin to globulin (A/G) ratio, and globulins as a percentage of total proteins (GLOB%) were calculated. Results were analyzed by paired t tests, difference plots, and Deming s regression analysis. Correlation coefficients (r) for TP with Vettest versus Kone and refractometer versus Kone methods were.97 and.94, respectively. GLOB and GLOB% values were significantly higher and A/G ratios were significantly lower with Vettest versus Kone methods. Correlation coefficients for ALB, GLOB, GLOB% and A/G ratio with Vettest versus Kone methods were.86,.93,.82, and.73, respectively. Although correlation with other methods was good, the refractometer underestimated TP concentrations in 3 samples. The refractometer is an acceptable method for determination of TP concentration in feline effusions. The Vettest 8008 also is an acceptable method for the determination of TP and ALB concentrations, however, calculated A/G ratios obtained with the Vettest are unacceptable.

Identification of three wheat globulin genes by screening a Triticum aestivum BAC genomic library with cDNA from a diabetes-associated globulin

PubMed Central

Loit, Evelin; Melnyk, Charles W; MacFarlane, Amanda J; Scott, Fraser W; Altosaar, Illimar

2009-01-01

Background Exposure to dietary wheat proteins in genetically susceptible individuals has been associated with increased risk for the development of Type 1 diabetes (T1D). Recently, a wheat protein encoded by cDNA WP5212 has been shown to be antigenic in mice, rats and humans with autoimmune T1D. To investigate the genomic origin of the identified wheat protein cDNA, a hexaploid wheat genomic library from Glenlea cultivar was screened. Results Three unique wheat globulin genes, Glo-3A, Glo3-B and Glo-3C, were identified. We describe the genomic structure of these genes and their expression pattern in wheat seeds. The Glo-3A gene shared 99% identity with the cDNA of WP5212 at the nucleotide and deduced amino acid level, indicating that we have identified the gene(s) encoding wheat protein WP5212. Southern analysis revealed the presence of multiple copies of Glo-3-like sequences in all wheat samples, including hexaploid, tetraploid and diploid species wheat seed. Aleurone and embryo tissue specificity of WP5212 gene expression, suggested by promoter region analysis, which demonstrated an absence of endosperm specific cis elements, was confirmed by immunofluorescence microscopy using anti-WP5212 antibodies. Conclusion Taken together, the results indicate that a diverse group of globulins exists in wheat, some of which could be associated with the pathogenesis of T1D in some susceptible individuals. These data expand our knowledge of specific wheat globulins and will enable further elucidation of their role in wheat biology and human health. PMID:19615078

Unexpected suppression of anti-Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin.

PubMed

Branch, Donald R; Scofield, Terry L; Moulds, John J; Swanson, Jane L

2011-04-01

Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti-D in D- mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG-induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316-22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β-1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ-1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis. Red blood cells and serum were analyzed using saline-tube indirect antiglobulin test methods. RhIG (RhoGAM) was administered after each amniocentesis performed at 28, 31, and 36 weeks' gestation. A group A, D-(cde), K+, Fy(a-b+), MNs, Jk(a+b+) mother with no detectable anti-D had an anti-Fy(a) titer of 4096 before RhIG but only 256 after RhIG. Mother gave birth to a group O, D-(cde), Fy(a+b+) healthy baby boy having a weak-positive direct antiglobulin test with anti-Fy(a) eluted from his cells and the titer in the cord serum was 4. This case demonstrates the potential immunosuppressive properties of RhIG for down regulation of a possible clinically significant alloantibody, not anti-D, where no D+ antigen is in the circulation of the mother. The case illustrates the potential utility for using RhIG to modulate antibody levels in situations other than for classical suppression of anti-D production. Although the mechanism in this case is unknown, TGFβ-1-mediated or antibody-mediated immunosuppression to soluble nonparticulate antigens are possible mechanisms. © 2010 American Association of Blood Banks.

Serum protein changes in immune and nonimmune pigeons infected with various strains of Trichomonas gallinae

USGS Publications Warehouse

Kocan, R.M.; Herman, C.M.

1970-01-01

Serum protein changes were studied in immune and nonimmune pigeons infected with three different strains of Trichomonas gallinae. Strain I (nonvirulent) produced no change in the relative concentration of serum components. Strains II (oral canker) and III (Jones' Barn) produced decreases in albumin and alpha globulins, and increases in beta and gamma globulins between the 7th and 20th days post infection. Birds infected with strain II began to return to normal by the 20th day, while all those infected with strain III were dead between 10 and 14 days post infection. Two serum protein patterns resulted from infection of immune birds with the Jones' Barn strain. One showed no change in relative protein concentrations and no tissue invasion by the parasite while the other was similar to that seen in nonimmune birds infected with a strain producing oral canker. These also showed evidence of tissue invasion by the parasite. It was concluded that tissue invasion was necessary to evoke a quantitative change in serum protein concentrations.

Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen

PubMed Central

Schaenman, Joanna M.; Shashidhar, Sumana; Rhee, Chanu; Wong, Jonathan; Navato, Shelly; Wong, Ruby M.; Ho, Dora Y.; Arai, Sally; Johnston, Laura; Brown, Janice M.

2017-01-01

The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naïve donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control. PMID:20736077

Sex-hormone-binding globulin.

PubMed

Anderson, D C

1974-01-01

A review was made to understand how plasma binding protein might influence sex-hormone action in target tissues. Steroids are predominately bound to plasma proteins and only unbound steroids enter the cells. Sex-hormone-binding globulin (SHBG) binds to both the main circulating steroid T and E2 but changes in SHBG concentrations exert significant results. Increased SHBG levels increase estrogen production and decreases T activity; whereas, increased androgens increase T action and inhibit SHBG production. These disturbances in hormone maintenance may lead to abnormal adult sex differentiation such as hirsutism and forms of hynaecomastia. By developing SHBG concentration measurement methods-responses of hirsutism to glucocorticoid or estrogem may be assessed. In addition, the effect of thyroid hormones on SHBG may also have therapeutic implications in endocrine disease.

RhD isoimmunization and current management modalities.

PubMed

Neal, J L

2001-01-01

To review the literature on current perspectives and treatment of RhD isoimmunization. A search was conducted on MEDLINE and CINAHL, and supplemental articles/ bulletins were obtained from cited references and the Web site of the American College of Obstetricians and Gynecologists. Recent texts also were reviewed. Key search words: isoimmunization, Rho (d) immune globulin, fetal erythroblastosis, intrauterine blood transfusions, alloimmunization. Articles and comprehensive works from indexed journals in the English language relevant to key words and published after 1995 were evaluated. Historically relevant periodicals and texts were also reviewed and selected. Data were extracted and organized under the following headings: testing of the antepartum patient, antepartum treatment of isoimmunization, testing of the postpartum patient, anti-D immune globulin, antepartum anti-D immune globulin prophylaxis, other antepartum and obstetric indications for anti-D immune globulin administration, postpartum anti-D immune globulin prophylaxis, nursing implications, and future possibilities. RhD isoimmunized pregnancies continue to contribute to worldwide perinatal and neonatal morbidity and mortality. This review describes the basic knowledge necessary to care for these pregnancies and the current management modalities. The management options for RhD compromised gestations continue to evolve almost as quickly as technological advances are made. Multiple areas of research in this field have surfaced, and nurses can become valuable members of these research teams. The literature also indicates that with the available knowledge and resources, the current rate of RhD isoimmunization can be further decreased with closer adherence to proposed management guidelines by all health care professionals.

Clinical Reactions and Serologic Changes After the Administration of Heterologous Antilymphocyte Globulin to Human Recipients of Renal Homografts

PubMed Central

Kashiwagi, Noboru; Brantigan, Charles O.; Brettschneider, Lawrence; Groth, Carl G.; Starzl, Thomas E.

2010-01-01

Summary Clinical reactions and serologic changes after intramuscular administration of horse anti-human lymphocyte globulin (ALG) were studied in 53 human recipients of renal homografts. The ALG was used as an adjuvant immunosuppressive drug. In the usual case 47 injections were given over a 4-month period. All patients had pain, tenderness, erythema, and swelling at the injection sites. Benign systemic side effects included fever in all cases, hives in eight cases, rash in five, pruritus in five, arthralgia in three, and periorbital edema in one. Anaphylactic reactions occurred in 11 cases. These were easily treated, and there was complete recovery in every instance within 90 min. In eight of these cases the ALG administration was discontinued. Subsequent injections were given in the other three. Four of 11 patients tested had positive skin tests to ALG before therapy. Antibodies against sheep red blood cells developed during therapy in 39 of 40 patients; 10 reached titers as high as 1:128 to 1:512. Precipitin antibodies as measured with an electroimmunodiffusion technique developed in 36 of 40 patients. All three immunologic tests were of value in predicting the probability of an anaphylactic reaction, but the discrimination was imperfect Immunoelectrophoretic studies of sera from 13 patients showed antibodies to horse beta globulins in all cases, to alpha globulins in 9 cases, and to gamma globulins in only 1. This finding indicates that a safer ALG could be made by removing the trace quantities of alpha and beta globulins from the immunologically more active gamma globulins. PMID:4181614

Correlation between serum total globulins and gamma globulins and their use to diagnose failure of passive transfer in foals.

PubMed

Fouché, Nathalie; Graubner, Claudia; Howard, Judith

2014-11-01

Various assays have been used as an aid to diagnose failure of passive transfer (FPT) of immunoglobulins in neonatal foals, but often lack sensitivity as screening tests, or are time consuming to perform and impractical as confirmatory tests. The aim of the present study was to evaluate whether measurement of serum total globulins (TG; i.e. total protein minus albumin) can be used to estimate the electrophoretic gamma globulin (EGG) fraction in hospitalised neonatal foals with suspected FPT. Sample data from 56 foals were evaluated retrospectively. The coefficient of rank correlation was 0.84. The area under the curve of ROC analysis was 0.887, 0.922 and 0.930 for EGG concentrations <2 g/L, < 4 g/L and <8 g/L, respectively. Cut-offs for TG achieved ≥90% sensitivity for detecting EGG <2 g/L, < 4 g/L and <8 g/L, with negative predictive values of >97% and >94%, using prevalence of 15% and 30%, respectively. These results suggest that measurement of TG can be used as a guide to predicting EGG, provided that appropriate cut-off values are selected, and this technique could be a useful initial screening test for FPT in foals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunity to Escherichia coli in pigs: Serum Gamma Globulin Levels, Indirect Hemagglutinating Antibody Titres and Bactericidal Activity Against E. coli in pigs up to five Weeks of Age

PubMed Central

Wilson, M. R.; Svendsen, J.

1972-01-01

Serum gamma globulin levels, indirect hemagglutinating antibody titres and bactericidal activity against the 0149:K91;K88ac:H10 Serotype of Escherichia coli were determined in pigs up to five weeks of age from vaccinated and non-vaccinated sows. Gamma globulin levels at two days of age were approximately twice adult levels, by three weeks of age they were one quarter of adult levels and remained so until five weeks of age. Indirect hemagglutinating antibody activity was highest at two days of age, fell until three weeks of age and then rose. Little or no indirect hemagglutinating antibody activity was detected in sera taken at two days of age from pigs from non-vaccinated sows. Only three of 26 two day old pigs had demonstrable bactericidal activity; by three weeks of age 16 of 26 had bactericidal activity. Serum from piglets of vaccinated sows had no more bactericidal activity than did sera from non-vaccinated sows. PMID:4110608

Comparison of cost of immune globulin intravenous therapy to conventional immunosuppressive therapy in treating patients with autoimmune mucocutaneous blistering diseases.

PubMed

Daoud, Yassine J; Amin, Ketan G

2006-04-01

Autoimmune mucocutaneous blistering diseases (AMBD) are a group of potentially fatal diseases that affect the skin and mucous membranes. AMBD have different target antigens as well as variable clinical presentation, course, and prognosis. The mainstay of conventional immunosuppressive therapy (CIST) for AMBD is long-term high-dose systemic corticosteroids and immunosuppressive agents. Such therapy has proven effective in many patients; however, in some patients, the disease continues to progress with significant sequelae such as blindness, loss of voice, anal, and vaginal stenosis which causes poor quality of life. Furthermore, the CIST may have some serious side effects including opportunistic infections which may cause death. Immune globulin intravenous (IGIV) therapy has been reportedly used in the management of patients with AMBD refractory to CIST. IGIV has shown to be more clinically beneficial than CIST by bringing about long-term clinical remission and less recurrence. The high cost of the IGIV is of concern to patients, physicians, and insurance companies. In this report, we compare the cost of IGIV to that of CIST in treating a cohort of 15 mucous membrane pemphigoid (MMP), 10 ocular cicatricial pemphigoid (OCP), 15 bullous pemphigoid (BP), and 32 pemphigus vulgaris (PV) patients. In each cohort of patients, CIST had significant side effects, many of which were hazardous and required prolonged and frequent hospitalizations. Some of these side effects were severe enough to require discontinuation of the treatment. We consider the total cost of CIST to be the actual cost of the drug, plus the cost of management of the side effects produced by CIST. In the same patient cohort, no significant side effects to IGIV were observed. None of the IGIV treated patients required physician visits, laboratory tests, or hospitalizations specifically related to IGIV therapy. Hence, the total cost of the IGIV therapy is the actual cost of the IGIV only. The mean total cost

The Effects of Environment and Physiological Cyclicity on the Immune System of Viperinae

PubMed Central

Kobolkuti, Lorand; Cadar, Daniel; Czirjak, Gabor; Niculae, Mihaela; Kiss, Timea; Sandru, Carmen; Spinu, Marina

2012-01-01

One of the important aspects of species' survival is connected with global climate changes, which also conditions the epidemiology of infectious diseases. Poikilotherms are exposed, as other species, to climatic influence, especially due to their physiological peculiarities such as important stages of their life cycle: hibernation, shedding, and active phase. The immune system serves as an accurate indicator of the health status and stress levels in these species. This study aimed to monitor the changes of innate (leukocyte subpopulations and total immune globulins) and adaptive immunity (in vitro leukocyte blast transformation) of two viper species, V. berus berus and V. ammodytes ammodytes, endemic in Europe and spread in different regions of Romania during their three major life cycles, hibernation, shedding, and active phase. The results indicated that seasonal variance and cycle rather than species and regional distribution influence the functionality of the immune system. PMID:22547989

Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: relationship to S-100B levels and blood-brain barrier function.

PubMed

Gressner, Olav A; Schifflers, Marie-Claire; Kim, Philipp; Heuts, Leo; Lahme, Birgit; Gressner, Axel M

2009-02-01

Preliminary studies report on significantly higher levels of the major cytoskeleton protein actin in CSF of patients with neurodegenerative conditions and that the dynamics of these levels obviously correlates with disease progression and clinical disability. One of the primary functions of actinfree Gc-Globulin is to bind and neutralize extracellular monomeric actin, released into the circulation by necrotic or ruptured cells, and thus ameliorating the clinical outcome in situations of severe organ damage. This is the first study to investigate actinfree Gc-Globulin and S100-B levels (as reliable marker of neurodegeneration) in paired CSF and serum samples of patients with multietiological CNS diseases. 42% of all patients with CNS disease displayed serum concentrations of actinfree Gc-Globulin above the established reference range. CSF concentrations of actinfree Gc-Globulin and S100-B were positively correlated with the severity of blood-brain barrier (BBB) dysfunction. Furthermore, patients with severe BBB dysfunction presented a higher percentage of intrathecal synthesis of actinfree Gc-Globulin compared to patients with mild to moderate dysfunction and to patients with normal BBB function. Representative longitudinal data from selected patients demonstrated an inverse behaviour of actinfree Gc-Globulin and S100-B CSF concentrations, suggesting a consumption of the actin scavenger capacity of Gc-Globulin in times of increased neuronal damage. This presumption was supported by the fact that those conditions associated with a severe neuronal damage, in particular CNS trauma, and highest S100-B concentrations simultaneously displayed lowest actinfree Gc-Globulin levels, and thus residual actin binding capacity of Gc-Globulin. In summary, our data propose a function of actinfree Gc-Globulin also in the clearance of actin filaments from CSF of patients with neuronal damage. However, active recruitment of hepatic derived actinfree Gc-Globulin to the site of CNS

Ammonia concentration and relative humidity in poultry houses affect the immune response of broilers.

PubMed

Wei, F X; Hu, X F; Xu, B; Zhang, M H; Li, S Y; Sun, Q Y; Lin, P

2015-04-10

To investigate the effect of ammonia (NH3) and humidity on the immune response of broilers, broilers were exposed to 30 or 70 mg/kg atmospheric NH3 for 21 days. Additionally, birds were exposed to 35, 60, and 85% relative humidity (RH). The relative weights of lymphoid organs, serum total protein, serum globulin, serum albumin, serum lysozyme, proliferation index of peripheral blood lymphocytes, and splenic cytokine gene expression were determined. Exposure to 70 mg/kg NH3 decreased the relative weight of the spleen during the experimental period, serum lysozyme concentration in the first and second weeks, and serum globulin concentration in the third week. The proliferation of peripheral blood lymphocytes was reduced. High levels of NH3 caused increase in IL-1β gene expression in the experimental period and IL-4 gene expression in the first week. Birds exposed to 85% RH had lower thymus and bursa of Fabricius weights in the third week and serum lysozyme concentration in the first week; IL-1β and IL-4 expressions were higher in the second and third weeks and first and second weeks, respectively, than in birds exposed to 60% RH. IL-4 expression was lower during the first week, and IL-1β expression was higher during the second week with 35% RH than with 60% RH. In conclusion, high NH3 level in the poultry house suppressed the immune response of broiler chickens. Neither high nor low RH benefited the immune response of broilers. Furthermore, there was an interactive effect between NH3 and RH on the immune response of broilers.

Tissue-specific and hormonally regulated expression of a rat alpha 2u globulin gene in transgenic mice.

PubMed Central

Soares, V da C; Gubits, R M; Feigelson, P; Costantini, F

1987-01-01

To investigate the tissue-specific and hormonal regulation of the rat alpha 2u globulin gene family, we introduced one cloned member of the gene family into the mouse germ line and studied its expression in the resulting transgenic mice. Alpha 2u globulingene 207 was microinjected on a 7-kilobase DNA fragment, and four transgenic lines were analyzed. The transgene was expressed at very high levels, specifically in the liver and the preputial gland of adult male mice. The expression in male liver was first detected at puberty, and no expression was detected in female transgenic mice. This pattern of expression is similar to the expression of endogenous alpha 2u globulin genes in the rat but differs from the expression of the homologous mouse major urinary protein (MUP) gene family in that MUPs are synthesized in female liver and not in the male preputial gland. We conclude that these differences between rat alpha 2u globulin and mouse MUP gene expression are due to evolutionary differences in cis-acting regulatory elements. The expression of the alpha 2u globulin transgene in the liver was abolished by castration and fully restored after testosterone replacement. The expression could also be induced in the livers of female mice by treatment with either testosterone or dexamethasone, following ovariectomy and adrenalectomy. Therefore, the cis-acting elements responsible for regulation by these two hormones, as well as those responsible for tissue-specific expression, are closely linked to the alpha 2u globulin gene. Images PMID:2446121

Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

PubMed

Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

1989-06-01

Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

Overestimation of Albumin Measured by Bromocresol Green vs Bromocresol Purple Method: Influence of Acute-Phase Globulins.

PubMed

Garcia Moreira, Vanessa; Beridze Vaktangova, Nana; Martinez Gago, Maria Dolores; Laborda Gonzalez, Belen; Garcia Alonso, Sara; Fernandez Rodriguez, Eloy

2018-05-22

Usually serum albumin is measured with dye-binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P < 0.05 as significant. Correlation of AlbBCG and AlbBCP was r = 0.948 (p < 0.0001), but mean difference was large. Bland-Altman plots showed greater bias at lower albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (< 1 g/L). The AlbBCG assay bias shows a good correlation with alpha-1-globulin concentrations (r = 0.758); moderate and weak correlations were observed with CRP (r = 0.729) and alpha-2-globulin (r = 0.585); we found no correlation with beta-globulin (r = 0.120) or gamma-globulin (r = -0.303). Mean aCa based on AlbBCG and AlbBCP methods were 2.34 ± 0.15 mmol/L and 2.46 ± 0.16 mmol/L (p < 0.01), with a mean BCG-BCP difference of -0.12. Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG.

Sensitization with 7S globulins from peanut, hazelnut, soy or pea induces IgE with different biological activities which are modified by soy tolerance.

PubMed

Kroghsbo, Stine; Bøgh, Katrine L; Rigby, Neil M; Mills, E N Clare; Rogers, Adrian; Madsen, Charlotte B

2011-01-01

It is not known why some foods sensitizing via the gastrointestinal tract are prevalent allergenic foods and others are not. Eating habits, processing, and the food matrix have been suggested to influence the allergenicity of a given food. Factors related to protein structure, such as stability to digestion, have also been suggested. 7S globulins from peanut, hazelnut, soy, and pea were studied to determine whether related proteins would induce a similar sensitization when removed from their 'normal' matrix. Brown Norway rats (soy tolerant or nontolerant) were immunized i.p. 3 times with 100 μg purified peanut, hazelnut, soy, or pea 7S without adjuvant. Sera were analyzed for specific antibodies by different ELISAs (IgG1, IgG2a, and IgE), inhibition ELISA, and rat basophilic leukemia cell assay. The 4 related 7S globulins induced a response with an almost identical level of specific antibodies, but peanut 7S induced IgE of higher avidity than hazelnut and pea 7S which, again, had a higher avidity than IgE induced by soy 7S. Soy tolerance reduced the functionality of IgE without influencing antibody titers. Although the 4 7S globulins are structurally related allergens, they induce antibodies with different antigen-binding characteristics. Peanut 7S induces IgE of a higher avidity than hazelnut and pea 7S which, again, has a higher avidity than IgE induced by soy 7S. We also show that soy tolerance influences the function of antibodies to peanut 7S. These findings may help explain how antibodies of different clinical significances can develop in different individuals sensitized to the same allergen. Copyright © 2011 S. Karger AG, Basel.

Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis.

PubMed

Ducloux, Didier; Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-09-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8 + T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8 + T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

Nutritional and physiological responses of young growing rats to diets containing raw cowpea seed meal, protein isolate (globulins), or starch.

PubMed

Olivera, Leticia; Canul, Rossana Rodriguez; Pereira-Pacheco, Fabiola; Cockburn, Joanna; Soldani, Florinda; McKenzie, Norma H; Duncan, Michelle; Olvera-Novoa, Miguel A; Grant, George

2003-01-01

The nutritional and physiological effects of raw cowpea (Vigna unguiculata (L) Walp.) seed meal, protein isolate (globulins), or starch on the metabolism of young growing rats have been evaluated in 14-day trials. Wet and dry weight gain, feed conversion efficiency, and lipid and protein accretion were significantly reduced as a result of inclusion of seed meal, globulins, or starch in the diet, with growth retardation being most marked with the seed meal. The proportional weights of the small intestine and pancreas were increased by meal diets, and serum cholesterol levels were slightly reduced. The globulins and raw starch also increased relative small intestine weights but had no effect on the pancreas or serum constituents. The effects of cowpeas on rats appeared to be due primarily to the combined actions of globulins, resistant starches, protease inhibitors, and possibly fiber and non-starch polysaccharides on intestinal and systemic metabolism.

Rapid changes in the serum total protein and globulin levels in complications caused by facultatively pathogenic Gram-negative bacteria.

PubMed

Petrás, G; Kiss, S; Juraszek, J; Merétey, K

1978-01-01

The changes in the levels of total protein and four globulin fractions were followed up throughout the entire course of complications caused by Gram-negative facultative pathogens in 37 acute cases of respiratory insufficiency accompanying different underlying illnesses and in 9 chronic, bedridden patients given artificial ventilation. At the onset of the infectious complications, in the first place in septic shock, the levels of various globulin fractions showed a decrease corresponding to a half-life of 2 to 4 days. Neither the increased catabolism, nor the protein losses by the urine and tracheal secretions offer a sufficient explanation for the escape of globulins of this extent from the plasma. It seems that this is a consequence of the increase in capillary permeability due to the effect of antigen-antibody reactions and that of endotoxin. As a result, in the critical phase of the infectious complications, at the point of culmination, e.g. in septic shock, diminished amount of different globulins is transported to the site of utilization, that is, to the inflammatory area.

Obtaining growth hormone from calf blood

NASA Technical Reports Server (NTRS)

Kalchev, L. A.; Ralchev, K. K.; Nikolov, I. T.

1979-01-01

The preparation of a growth hormone from human serum was used for the isolation of the hormone from calf serum. The preparation was biologically active - it increased the quantity of the free fatty acids released in rat plasma by 36.4 percent. Electrophoresis in Veronal buffer, ph 8.6, showed the presence of a single fraction having mobility intermediate between that of alpha and beta globulins. Gel filtration through Sephadex G 100 showed an elutriation curve identical to that obtained by the growth hormone prepared from pituitary glands.

Clinical mimics of infant botulism.

PubMed

Francisco, Ann Marie O; Arnon, Stephen S

2007-04-01

Since 1992, Human Botulism Immune Globulin has been provided by the California Department of Health Services to infants with probable infant botulism, the intestinal toxemia form of human botulism. Human Botulism Immune Globulin became available in California in 1992-1997 within a randomized, controlled, double-blinded, pivotal clinical trial and subsequently became available nationwide in 1998-2003 in an open-label study until its licensure in October 2003 as BabyBIG. Thereafter, Human Botulism Immune Globulin remained available nationwide as an approved orphan-drug product. To achieve prompt neutralization of circulating botulinum toxin, the decision to treat with Human Botulism Immune Globulin has been based on clinical criteria that include a consistent history and physical findings of bulbar palsies, hypotonia, and weakness. After licensure, the charts of patients who did not have laboratory-confirmed infant botulism were reviewed to identify their actual diagnoses. The approximately 5% of 681 patients treated with Human Botulism Immune Globulin who did not have infant botulism fell into 5 categories: spinal muscular atrophy, metabolic disorders, other infectious diseases, miscellaneous, and probable infant botulism lacking laboratory confirmation.

The Plasma Disappearance Time and Catabolic Half-Life of I 131-Labelled Normal Human Gamma Globulin in Amyloidosis and in Rheumatoid Arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mills, John A.; Calkins, Evan; Cohen, Alan S.

1961-10-01

The serum survival time and catabclic half-life of intravenously injected I 131-labeled pooled human gamma globulin - were studied in three patients with amyloidosis, four patients with rheumatoid arthritis, and three normal controls. The half-time of gamma globulin survival in the controsubjects ranged from 16.5 to 30 days. Two patients with amyloidosis, one primary and one secondary, both with the nephrotic syndrome, exhibited shortened serum half-times of 4.5 and 11 days, respectively. The serum half-time of the latter patient, before the appearance of clinical amyloidosis, was 14 days. One patient with primary amyloidosis but without nephrosis exhibited a half-time ofmore » serum gamma globulin disappearance of 21 days. The half-time of gamma globulin disappearance in four patients with chronic active rheumatoid arthritis varied between 19.5 and 8.5 days. The lower figure was found in a patient having a high titer of rheumatoid factor. If this subject is excepted, the average half- time in three rheumatoid subjects is 17 days. The catabolic half-life of the iodinated gamma globulin agreed in most instances with the serum half-time. The calculated distribution space of the injected gamma globulin showed no consistent alteration in either amyloidosis or rheumatoid arthritis as compared with the control subjects. Since the nephrotic syndrome from other causes may produce an accelerated catabolic half-life, a similar finding on these subjects cannot be ascribed to amyloidosis.« less

EVOLUTION OF THE IMMUNE RESPONSE

PubMed Central

Papermaster, Ben W.; Condie, Richard M.; Finstad, Joanne; Good, Robert A.

1964-01-01

the hagfish has no bands with mobilities of mammalian gamma globulins; that the lamprey has a single, relatively faint band of this type; and that multiple gamma bands are characteristic of the holostean, elasmobranchs, and teleosts studied. By this method of study, the bowfin appeared to have substantial amounts of gamma2 globulin. 7. We conclude that adaptive immunity and its cellular and humoral correlates developed in the lowest vertebrates, and that a rising level of immunologic reactivity and an increasingly differentiated and complex immunologic mechanism are observed going up the phylogenetic scale from the hagfish, to the lamprey, to the elasmobranchs, to the holosteans, and finally the teleosts. PMID:14113107

Clinical experience with thymoglobulin and antithymocyte globulin-Fresenius as induction therapy in renal transplant patients: a retrospective study.

PubMed

Cicora, Federico; Mos, Fernando; Paz, Marta; Roberti, Javier

2013-10-01

We describe our experiences with, and compare the outcomes of, 2 groups of renal transplant patients treated with thymoglobulin or antithymocyte globulin-Fresenius as induction therapy at transplant to reduce the incidence of acute rejection and prevent delayed allograft function. Twenty-four recipients of deceased-donor or living-donor kidney transplants received thymoglobulin, and 23 patients received antithymocyte globulin-Fresenius. Patient and graft survival and efficacy and safety were assessed at 3 months. The demographic characteristics of both groups were comparable, but the predominant donor type was significantly different. Incidence of complications, delayed graft function, and creatinine concentrations were comparable in both groups. At 3 months after the transplant, patient survival rate was 92% in the thymoglobulin group and 96% in the antithymocyte globulin-Fresenius group (P > .05), and death-censored graft survival rate for both groups was not significantly different. Average hematocrit and lymphocyte, neutrophil, and platelet counts were comparable in both groups at 3 months' follow-up. Average white blood count at 1 month was significantly different between the groups: at 5.62 ± 2.45 × 103 cells/mm³ in the thymoglobulin group and 7.85 ± 4.10 × 103 cells/mm³ in the ATG-F group (P < .05). Considering the study design limitations, we observed that our group of treated patients, safety, and efficacy of thymoglobulin and antithymocyte globulin-Fresenius were generally comparable.

Synthesis of Globulins in Maize Embryos 1

PubMed Central

Kriz, Alan L.; Schwartz, Drew

1986-01-01

The two major components of the globulin fraction in Zea mays embryos are specified by the Prot gene. Pulse-chase analysis of protein synthesis in cultured, immature embryos indicates that the smaller Prot-specific polypeptide, PROT, is derived from the larger polypeptide, PROT'. These experiments also demonstrate that PROT' is derived from a short-lived precursor polypeptide, prePROT'. The primary Prot-specific translation product, as detected by in vitro translation of immature embryo RNA, is of a lower apparent molecular weight than pre-PROT', suggesting the involvement of co- and/or post-translational modification in the production of prePROT'. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:16665136

Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study.

PubMed

Martín-Gandul, Cecilia; Pérez-Romero, Pilar; Mena-Romo, Damián; Molina-Ortega, Alejandro; González-Roncero, Francisco M; Suñer, Marta; Bernal, Gabriel; Cordero, Elisa

2018-03-23

Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8 + CD69 + INF-γ + T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8 + CD69 + INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

PubMed Central

Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

2012-01-01

Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

PubMed Central

Baron, Frédéric; Mohty, Mohamad; Blaise, Didier; Socié, Gérard; Labopin, Myriam; Esteve, Jordi; Ciceri, Fabio; Giebel, Sebastian; Gorin, Norbert Claude; Savani, Bipin N; Schmid, Christoph; Nagler, Arnon

2017-01-01

Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors. PMID:27927772

Treatment of aplastic anaemia with lower-dose anti-thymocyte globulin produces similar response rates and survival as per standard dose anti-thymocyte globulin schedules.

PubMed

Scott, A; Morris, K; Butler, J; Mills, A K; Kennedy, G A

2016-10-01

Aplastic anaemia (AA) is a rare acquired bone marrow failure syndrome resulting from the immune-mediated destruction of haemopoietic stem cells. For adults in whom first-line haemopoietic progenitor cell transplantation is not feasible, combination anti-thymocyte globulin (ATGAM) plus cyclosporine A is standard therapy; however, there are minimal data available regarding the optimal ATGAM dosage in terms of efficacy and survival. Our institutions have historically used different dosing protocols of ATGAM in the treatment of AA. We aimed to review the outcome of AA patients treated with these protocols and compare them to the published literature. We conducted a retrospective study of 31 adults who received first-line ATGAM for AA and compared response rates and survival between cohorts who received standard (40 mg/kg/day D1-4) versus lower-dose (15 mg/kg/day D1-5) ATGAM schedules. There were similar rates of response (64 vs 71%, P = 1.0), relapse (33 vs 33%, P = 1.0), transformation (14 vs 24%, P = 0.66) or infection (43 vs 47%, P = 1.0), respectively, between standard and lower-dose cohorts. At a median follow up of 24 months, there was no statistical difference between standard and lower-dose cohorts in either event-free (42.2 vs 64.7%, P = 0.91) or overall survival (73.1 vs 88.2%, P = 0.75). Our experience suggests that lower-dose ATGAM at 15 mg/kg/day D1-5 as treatment of AA produces similar responses and outcomes as per standard-dose ATGAM schedules. Prospective trials comparing ATGAM dose schedules in AA are warranted. © 2016 Royal Australasian College of Physicians.

d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.

1989-06-15

d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of (/sup 14/C)d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in femalemore » rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction.« less

Control of adhesion of human induced pluripotent stem cells to plasma-patterned polydimethylsiloxane coated with vitronectin and γ-globulin.

PubMed

Yamada, Ryotaro; Hattori, Koji; Tachikawa, Saoko; Tagaya, Motohiro; Sasaki, Toru; Sugiura, Shinji; Kanamori, Toshiyuki; Ohnuma, Kiyoshi

2014-09-01

Human induced pluripotent stem cells (hiPSCs) are a promising source of cells for medical applications. Recently, the development of polydimethylsiloxane (PDMS) microdevices to control the microenvironment of hiPSCs has been extensively studied. PDMS surfaces are often treated with low-pressure air plasma to facilitate protein adsorption and cell adhesion. However, undefined molecules present in the serum and extracellular matrix used to culture cells complicate the study of cell adhesion. Here, we studied the effects of vitronectin and γ-globulin on hiPSC adhesion to plasma-treated and untreated PDMS surfaces under defined culture conditions. We chose these proteins because they have opposite properties: vitronectin mediates hiPSC attachment to hydrophilic siliceous surfaces, whereas γ-globulin is adsorbed by hydrophobic surfaces and does not mediate cell adhesion. Immunostaining showed that, when applied separately, vitronectin and γ-globulin were adsorbed by both plasma-treated and untreated PDMS surfaces. In contrast, when PDMS surfaces were exposed to a mixture of the two proteins, vitronectin was preferentially adsorbed onto plasma-treated surfaces, whereas γ-globulin was adsorbed onto untreated surfaces. Human iPSCs adhered to the vitronectin-rich plasma-treated surfaces but not to the γ-globulin-rich untreated surfaces. On the basis of these results, we used perforated masks to prepare plasma-patterned PDMS substrates, which were then used to pattern hiPSCs. The patterned hiPSCs expressed undifferentiated-cell markers and did not escape from the patterned area for at least 7 days. The patterned PDMS could be stored for up to 6 days before hiPSCs were plated. We believe that our results will be useful for the development of hiPSC microdevices. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Serum albumin and globulin analysis for hepatocellular carcinoma detection avoiding false-negative results from alpha-fetoprotein test negative subjects

NASA Astrophysics Data System (ADS)

Wang, Jing; Feng, Shangyuan; Lin, Juqiang; Zeng, Yongyi; Li, Ling; Huang, Zufang; Li, Buhong; Zeng, Haishan; Chen, Rong

2013-11-01

Surface-enhanced Raman spectroscopy (SERS) of serum albumin and globulin were employed to detect hepatocellular carcinoma (HCC). Tentative assignments of SERS bands show specific biomolecular changes associated with cancer development. These changes include a decrease in relative amounts of tryptophan, glutamine, glycine, and serine, indicating excessive consumption of amino acids for protein duplication. Principal component analysis was also introduced to analyze the obtained spectra, resulting in both diagnostic sensitivity and specificity of 100%. More importantly, it reveals that this method can detect HCC patients with alpha-fetoprotein negative test results, suggesting its great potential as a new alternative to detect HCC.

Using Changes in Binding Globulins to Assess Oral Contraceptive Compliance

PubMed Central

Westhoff, Carolyn; Petrie, K.A.; Cremers, S.

2012-01-01

Background Validity of oral contraceptive pill (OCP) clinical trial results depends on participant compliance. Ethinyl estradiol (EE2) induces increases in hepatic binding globulin (BG) levels. Measuring these BG increases may provide an effective and convenient approach to distinguishing non-compliant from compliant OCP users in research settings. This analysis evaluated the usefulness of measuring increases in corticosteroid, sex hormone and thyroxine binding globulins (CBG, SHBG, TBG) as measures of OCP compliance. Methods We used frozen serum from a trial that compared ovarian suppression between normal weight and obese women randomized to one of two OCPs containing EE2 and levonorgestrel (LNG). Based on serial LNG measurements during the trial, 17% of participants were non-compliant. We matched non-compliant participants with compliant participants by age, BMI, ethnicity and OCP formulation. We measured CBG, SHBG and TBG levels, and compared change from baseline to 3-month follow-up between the non-compliant and compliant participants. Construction of receiver operator characteristic (ROC) curves allowed comparison of various BG measures. Results Changes in CBG and TBG distinguished OCP non-compliant users from compliant users (area under the ROC curve (AUROC), 0.86 and 0.89, p < 0.01). Changes in SHBG were less discriminating (AUROC 0.69) Conclusions EE2 induced increases in CBG and TBG provide a sensitive integrated marker of compliance with an LNG-containing OCP. PMID:22795088

Hericium caput-medusae (Bull.:Fr.) Pers. polysaccharide enhance innate immune response, immune-related genes expression and disease resistance against Aeromonas hydrophila in grass carp (Ctenopharyngodon idella).

PubMed

Gou, Changlong; Wang, Jiazhen; Wang, Yuqiong; Dong, Wenlong; Shan, Xiaofeng; Lou, Yujie; Gao, Yunhang

2018-01-01

The objective was to add 0, 400, 800 or 1200 mg/kg of Hericium caput-medusae polysaccharide (HCMP) to the basal diet of grass carp (Ctenopharyngodon idella) and determine effects on humoral innate immunity, expression of immune-related genes and disease resistance. Adding HCMP enhanced (P < 0.05) bactericidal activity at 1, 2 and 3 weeks and also lysozyme activity, complement C3, and SOD activity at 2 and 3 weeks. Supplementing 800 or 1200 mg/kg of HCMP for 2 or 3 weeks increased (P < 0.05) serum concentrations of total protein, albumin and globulin. Two immune-related genes (IL-1β and TNF-α) were up-regulated (P < 0.05) in HCMP supplemented groups given 800 or 1200 mg/kg HCMP after 2 and 3 weeks of feeding. Expression of anti-inflammatory cytokine IL-10 was down-regulated (P < 0.05) after receiving 800 or 1200 mg/kg HCMP for 2 or 3 weeks. Fish fed 800 mg/kg HCMP had maximal disease resistance against Aeromonas hydrophila (65.4%). In conclusion, HCMP enhanced immune response and expression of immune-related genes and increased disease resistance against Aeromonas hydrophila in grass carp, with greatest effects in fish given 800 mg/kg HCMP for 3 weeks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential representation of albumins and globulins during grain development in durum wheat and its possible functional consequences.

PubMed

Arena, Simona; D'Ambrosio, Chiara; Vitale, Monica; Mazzeo, Fiorella; Mamone, Gianfranco; Di Stasio, Luigia; Maccaferri, Marco; Curci, Pasquale Luca; Sonnante, Gabriella; Zambrano, Nicola; Scaloni, Andrea

2017-06-06

Durum wheat (Triticum turgidum ssp. durum (Desf.) Husn.) is an economically important crop used for the production of semolina, which is the basis of pasta and other food products. Its grains provide proteins and starch for human consumption. Grain development is a key process in wheat physiology; it is highly affected by a number of enzymes that control the metabolic processes governing accumulation of starch and storage proteins and ultimately grain weight. Most of these enzymes are present in the albumin/globulin grain fraction, which represents about a quarter of total seed proteins. With the aim to describe the dynamic profile of the albumin/globulin fraction during durum wheat grain development, we performed a proteomic analysis of this subproteome using a two-dimensional differential gel electrophoresis (2D-DIGE)-based approach and compared six developmental stages. A total of 285 differentially (237 over- and 48 under-) represented spots was identified by nanoLC-ESI-LIT-MS/MS, which were associated with 217 non-redundant Triticum sequence entries. Quantitative protein dynamics demonstrated that carbon metabolism, energy, protein destination/storage, disease/defense and cell growth/division functional categories were highly affected during grain development, concomitantly with progressive grain size increase and starch/protein reserve accumulation. Bioinformatic interaction prediction revealed a complex network of differentially represented proteins mainly centered at enzymes involved in carbon and protein metabolism. A description of 18 proteins associated with wheat flour human allergies was also obtained; these components showed augmented levels at the last developmental stages. By providing a comprehensive understanding of the molecular basis of durum wheat grain development, yield and quality formation, this study provides the foundation and reveals potential biomarkers for further investigations of durum wheat breeding and semolina quality. A 2D

The diagnostic value of a globulin/platelet model for evaluating liver fibrosis in chronic hepatitis B patients.

PubMed

Coskun, Banu Demet; Altinkaya, Engin; Sevinc, Eylem; Ozen, Mustafa; Karaman, Hatice; Karaman, Ahmet; Poyrazoglu, Orhan

2015-12-01

Liver biopsy, which is considered the best method for evaluating hepatic fibrosis, has important adverse events. Therefore, non-invasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis B. To verify the usefulness of a new fibrosis index the globulin/platelet model in patients with chronic hepatitis B and to compare it with other noninvasive tests for predicting significant fibrosis. This study was the second to evaluate the globulin/platelet model in HBV patients. We retrospectively investigated 228 patients with chronic hepatitis B who performed liver biopsy from 2013 to 2014. The globulin/platelet model, APGA [AST/Platelet/Gamma-glutamyl transpeptidase/Alfa-fetoprotein], FIB4, fibrosis index, cirrhosis discriminate score, and Fibro-quotient were calculated, and the diagnostic accuracies of all of the fibrosis indices were compared between the F0-2 (no-mild fibrosis) and F3-6 (significant fibrosis) groups. All of the noninvasive markers were significantly correlated with the stage of liver fibrosis (p < 0,001). To predict significant fibrosis (F ≥ 3), the area under the curve (95% CI) was found to be greatest for APGA (0.83 [0.74-0.86]), followed by FIB-4 (0.75[0.69-0.80]), the globulin/platelet model (0.74 [0.68-0.79]), fibrosis index (0.72 [0.6-0.78], cirrhosis discriminate score (0.71 [0.64-0.76]) and Fibro-quotient (0.62 [0.55-0.7]). The area under the receiver operating characteristic curves of APGA was significantly higher than that of the other noninvasive fibrosis markers (p < 0.05). While the APGA index was found to be the most valuable test for the prediction significant fibrosis in patients with chronic hepatitis B, GP model was the thirth valuable test. Therefore, we recommended that APGA could be used instead of the GP model for prediction liver fibrosis.

Small GTPase Sar1 is crucial for proglutelin and α-globulin export from the endoplasmic reticulum in rice endosperm.

PubMed

Tian, Lihong; Dai, Ling Ling; Yin, Zhi Jie; Fukuda, Masako; Kumamaru, Toshihiro; Dong, Xiang Bai; Xu, Xiu Ping; Qu, Le Qing

2013-07-01

Rice seed storage proteins glutelin and α-globulin are synthesized in the endoplasmic reticulum (ER) and deposited in protein storage vacuoles (PSVs). Sar1, a small GTPase, acts as a molecular switch to regulate the assembly of coat protein complex II, which exports secretory protein from the ER to the Golgi apparatus. To reveal the route by which glutelin and α-globulin exit the ER, four putative Sar1 genes (OsSar1a/b/c/d) were cloned from rice, and transgenic rice were generated with Sar1 overexpressed or suppressed by RNA interference (RNAi) specifically in the endosperm under the control of the rice glutelin promoter. Overexpression or suppression of any OsSar1 did not alter the phenotype. However, simultaneous knockdown of OsSar1a/b/c resulted in floury and shrunken seeds, with an increased level of glutelin precursor and decreased level of the mature α- and β-subunit. OsSar1abc RNAi endosperm generated numerous, spherical, novel protein bodies with highly electron-dense matrixes containing both glutelin and α-globulin. Notably, the novel protein bodies were surrounded by ribosomes, showing that they were derived from the ER. Some of the ER-derived dense protein bodies were attached to a blebbing structure containing prolamin. These results indicated that OsSar1a/b/c play a crucial role in storage proteins exiting from the ER, with functional redundancy in rice endosperm, and glutelin and α-globulin transported together from the ER to the Golgi apparatus by a pathway mediated by coat protein complex II.

Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).

PubMed

Schöttner, M; Gansser, D; Spiteller, G

1997-12-01

Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).

From glanders to globulins: A study in comparative medicine.

PubMed

Watkins, P E

2017-05-01

The anti-globulin test was described in 1945, and ever since has been synonymous with the lead author, Robin Coombs, a young veterinary surgeon, at that time embarking on a career in immunological research. This was marked by a number of important contributions in the field, including the description and categorisation of hypersensitivity reactions, co-authored with Philip Gell. Together they wrote the classical text, Clinical Aspects of Immunology, which has been updated and republished over the ensuing 50 years. Although Robin Coombs is best remembered for his contributions to medical immunology, he made a number of significant early advances in the field of veterinary immunology.

THE EMERGENCE OF ANTIBODIES WITH EITHER IDENTICAL OR UNRELATED INDIVIDUAL ANTIGENIC SPECIFICITY DURING REPEATED IMMUNIZATIONS WITH STREPTOCOCCAL VACCINES

PubMed Central

Eichmann, Klaus; Braun, Dietmar G.; Feizi, Ten; Krause, Richard M.

1970-01-01

Electrophoretically monodisperse antibody components in rabbit antisera to the carbohydrates of the Groups A and C streptococci have been examined for their individual antigenic specificity. In these antibody components which were isolated by preparative electrophoresis, individual antigenic specificity was confined to the specific antibody and was absent in the nonantibody γ-globulin. Radioprecipitation experiments and the use of immune absorbent columns constructed from goat anti-antisera, which had been absorbed with fraction II, revealed that all the specific antibody in an electrophoretically monodisperse component was reactive with the homologous anti-antibody. Antibodies with either identical or distinct individual antigenic specificities may occur in the same rabbit with repeated immunizations. Antibodies with identical antigenic specificity had identical electrophoretic mobility, whereas antibodies with unrelated antigenic specificities had distinct electrophoretic mobilities. In the interval between immunizations, if antibody to the carbohydrate antigen was absent, there was no detectable antibody with individual antigenic specificity. PMID:4192569

The effect of antilymphocytic antibody on the humoral immune response in different strains of mice

PubMed Central

Ghaffar, A.; James, K.

1973-01-01

The effect of a single batch of horse anti-mouse thymocyte globulin on the immune response to type III polysaccharide antigen has been investigated in 2–3-month-old male A/HeJ, C57B1, BALB/c, DBA/1, CBA and C3H mice. In almost all cases the intraperitoneal administration of 5 mg of this material on days –4 and –2 significantly suppressed the immune response to 0.1, 1.0 and 5.0 μg of antigen injected i.v. on day 0. Further studies undertaken in BALB/c mice indicated that effective suppression of the immune response to type III polysaccharide antigen could also be achieved by injecting 5 mg of this product (i.p.) some 15–30 minutes prior to antigenic challenge. Preliminary cell reconstitution studies in antilymphocytic antibody-treated CBA mice indicate that the ability to respond to type III polysaccharide can be partially restored by the injection of syngeneic thymocytes, bone marrow cells or spleen cells. PMID:4146227

Structure of γ-conglutin: insight into the quaternary structure of 7S basic globulins from legumes.

PubMed

Czubinski, Jaroslaw; Barciszewski, Jakub; Gilski, Miroslaw; Szpotkowski, Kamil; Debski, Janusz; Lampart-Szczapa, Eleonora; Jaskolski, Mariusz

2015-02-01

γ-Conglutin from lupin seeds is an unusual 7S basic globulin protein. It is capable of reducing glycaemia in mammals, but the structural basis of this activity is not known. γ-Conglutin shares a high level of structural homology with glycoside hydrolase inhibitor proteins, although it lacks any kind of inhibitory activity against plant cell-wall degradation enzymes. In addition, γ-conglutin displays a less pronounced structural similarity to pepsin-like aspartic proteases, but it is proteolytically dysfunctional. Only one structural study of a legume 7S basic globulin, that isolated from soybean, has been reported to date. The quaternary assembly of soybean 7S basic globulin (Bg7S) is arranged as a cruciform-shaped tetramer comprised of two superposed dimers. Here, the crystal structure of γ-conglutin isolated from Lupinus angustifolius seeds (LangC) is presented. The polypeptide chain of LangC is post-translationally cleaved into α and β subunits but retains its covalent integrity owing to a disulfide bridge. The protomers of LangC undergo an intricate quaternary assembly, resulting in a ring-like hexamer with noncrystallographic D3 symmetry. The twofold-related dimers are similar to those in Bg7S but their assembly is different as a consequence of mutations in a β-strand that is involved in intermolecular β-sheet formation in γ-conglutin. Structural elucidation of γ-conglutin will help to explain its physiological role, especially in the evolutionary context, and will guide further research into the hypoglycaemic activity of this protein in humans, with potential consequences for novel antidiabetic therapies.

Resolution of Mild Ganciclovir-Resistant Cytomegalovirus Disease with Reduced-Dose Cidofovir and CMV-Hyperimmune Globulin.

PubMed

Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Hong, Dana M; Gaber, A Osama

2014-01-01

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by "indirect" viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed "breakthrough" viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.

International reference reagents: antihuman globulin. An ISBT/ICSH joint working party report. International Society of Blood Transfusion. International Committee for Standardization in Haematology.

PubMed

Case, J; Ford, D S; Chung, A; Collins, R; Kochman, S; Mazda, T; Overbeeke, M; Perera, R; Sakuldamrongpanich, T; Scott, M; Voak, D; Zupańska, B

1999-01-01

An international working party has conducted a study designed to select a suitable reference reagent for antihuman globulin, to replace those first made available in 1987. The chosen preparation contains levels of anti-IgG and anti-C3 (anti-C3c and anti-C3d) potency that are considered suitable to serve for reference when evaluating either polyspecific antihuman globulin reagents or those containing their separate monospecific components. The reference material is available in 2-ml freeze-dried aliquots from seven assigned distribution centres.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

PubMed

Stranavova, L; Hruba, P; Girmanova, E; Tycova, I; Slavcev, A; Fronek, J; Slatinska, J; Reinke, P; Volk, H-D; Viklicky, O

2018-05-04

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.

[Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

PubMed

Zhou, Tong; Yang, Rupu; Li, Shihong; Zheng, Guoqing; Xi, Yu; Cheng, Xuemin; Hou, Jiaxiang; Cui, Liuxin; Ba, Yue

2013-03-01

To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

[Effect of specific antibodies on active immunity development in those inoculated with an antirabies vaccine].

PubMed

Kravchenko, A T; Latypova, R G; Morpgova, V M; Movsesiants, A A

1980-11-01

The study of the effect of gamma globulin introduced in different doses (0.5 and 0.25 ml/mg) in combination with Fermi rabies vaccine (observations on humans were made) and with cerebral rabies vaccine inactivated by UV irradiation (in animal experiments) demonstrated that the injection of the higher doses of gamma globulin resulted in lower geometrical mean of antibody titers. Therefore, in combined administration of rabies vaccine and gamma globulin for postexposure rabies prevention it is advisable to reduce the dose of gamma globulin by one-half.

Immune-directed therapy for type 1 diabetes at the clinical level: the Immune Tolerance Network (ITN) experience.

PubMed

Ehlers, Mario R; Nepom, Gerald T

2012-01-01

Reestablishing immune tolerance in type 1 diabetes (T1D), a chronic autoimmune disease, is a major goal. The Immune Tolerance Network (ITN) has initiated eight clinical trials of immunomodulatory therapies in recent-onset T1D over the past decade. Results have been mixed in terms of clinical efficacy, but the studies have provided valuable mechanistic insight that are enhancing our understanding of the disease and guiding the design of future trials. Trials of non-Fc-binding anti-CD3 mAbs have revealed that modulation of this target leads to partial responses, and ITN's AbATE trial led to identification of a robust responder group that could be distinguished from non-responders by baseline metabolic and immunologic features. A pilot study of the combination of IL-2 and rapamycin gave the first demonstration that frequency and function of regulatory T cells (Tregs) can be enhanced in T1D subjects, although the therapy triggered the activation of effectors with transient β-cell dysfunction. Similarly, therapy with anti-thymocyte globulin led to substantial lymphocyte depletion, but also to the activation of the acute-phase response with no clinical benefit during preliminary analyses. These and other results provide mechanistic tools that can be used as biomarkers for safety and efficacy in future trials. Furthermore, our results, together with those of other organizations, notably TrialNet, delineate the roles of the major components of the immune response in T1D. This information is setting the stage for future combination therapy trials. The development of disease-relevant biomarkers will also enable the implementation of innovative trial designs, notably adaptive trials, which will increase efficiencies in terms of study duration and sample size, and which will expedite the conduct of trials in which there are uncertainties about dose response and effect size.

Determining the time androgens and sex hormone-binding globulin take to return to baseline after discontinuation of oral contraceptives in women with polycystic ovary syndrome: a prospective study.

PubMed

Sánchez, Luis A; Pérez, Marilda; Centeno, Indira; David, Marisa; Kahi, Doris; Gutierrez, Elizabeth

2007-03-01

In this study, discontinuation of oral contraceptive pills in women with polycystic ovary syndrome was followed by the return of all measured androgens and sex hormone-binding globulin levels to basal values after 8 weeks. These observations are pertinent to the measurement of androgens and sex hormone-binding globulin levels in subjects who currently are taking oral contraceptive pills and have symptoms that are related to polycystic ovary syndrome.

Effect of maternal immunization with oral poliovirus vaccine on neonatal immunity.

PubMed

Linder, N; Handsher, R; Fruman, O; Shiff, E; Ohel, G; Reichman, B; Dagan, R

1994-11-01

During the summer of 1988, an outbreak of poliomyelitis caused by poliovirus 1 occurred in Israel, during which a national mass immunization campaign with oral poliovirus was undertaken. This prospective study was undertaken to assess the effect of maternal oral poliovirus immunization during the third trimester of pregnancy on neonatal immunity against poliovirus. Cord blood specimens of 88 neonates, born 2 to 7 weeks after maternal immunization, were examined for antipoliovirus antibodies and compared with 100 samples obtained from neonates 7 months before the outbreak. Blood samples were also obtained from the 62 mothers of neonates who had been immunized 2 to 5 weeks before delivery. Sera were tested for neutralizing antibodies to the 3 poliovirus types using a microneutralization technique. The geometric mean titer to poliovirus type 1 was significantly higher in neonates whose mothers were immunized during pregnancy (87.1) than in the offspring of the nonvaccinated group (53.0), P < 0.05. Two to 3 weeks after immunization, geometric mean titers against all 3 poliovirus types were higher in maternal blood than in cord blood whereas 4 to 5 weeks after vaccination a significant difference was found for type 3 only. Although oral poliovirus immunization during pregnancy resulted in higher neonatal antibody titers to poliovirus type 1, the proportion of newborns with titers of < 1:8 to the 3 poliovirus types did not change significantly.

Anthrax Vaccination and Self-reported Symptoms, Functional Status, and Medical Conditions in the National Health Survey of Gulf War Era Veterans and Their Families

DTIC Science & Technology

2003-04-01

botulism, immune globulin , plague, and meningncocu.s). Among the 11,441 Culf War veterans, a total of 4601 Gulf veterans (40.2%)) self-reported (S-R...administered (typhoid, borulinum toxoid, immune globulin , plague, and meningococus). This variable was coded as the sum of the number of vaccines...parametric Wilcoxon signecl- ranks test was used to assess whether the prc\\lalencc in S-R yes group was the same as the prevalcncc in the S-R n o

[FAB immunoglobulin fragments. I. The comparative characteristics of the serological and virus-neutralizing properties of a gamma globulin against tick-borne encephalitis and of the FAB fragments isolated from it].

PubMed

Barban, P S; Minaeva, V M; Pantiukhina, A N; Startseva, M G

1976-06-01

A comparative study was made of the serological properties and virus-neutralizing activity of antiencephalitis gamma-globulin and Fab-fragments isolated from it by gel-filtration. Horse immunoglobulins against the autumno-summer tick-borne encephalitis virus could be disintegrated with the aid of papaine to monovalent Fab-fragments which (according to the complement fixation reaction, the test of suppression of the complement fixation, and the HAIT) retained the serological activity whose level was compared with that of the serological activity of gamma-globulin. Fab-fragments possessed a marked virus-neutralizing activity. The mean value of a logarithm of the neutralization index was 2.65 +/- 0.2 for Fab-fragments and 3.74 +/- 0.38 for gamma-globulin (P less than 0.01).

Immunization in pregnancy.

PubMed

Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H; Boucher, Marc; Cormier, Beatrice; Ogilvie, Gina; Paquet, Caroline; Steenbeek, Audrey; Van Eyk, Nancy; van Schalkwyk, Julie; Wong, Thomas

2008-12-01

To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, and risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2007 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. Recommendations 1. All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A) 2. Health care providers should obtain an immunization history from all women accessing prenatal care. (III-A) 3. In general, live and/or live-attenuated virus vaccines are contraindicated during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3) 4. Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2) 5. Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III) 6. Inactivated viral vaccines, bacterial vaccines, and toxoids are considered safe in pregnancy. (II-1) 7. Women who are breastfeeding can still be immunized (passive-active immunization, live or killed vaccines). (II-1) 8. Pregnant women should be offered the influenza vaccine when pregnant during the influenza season. (II-1).

Response to phytohaemagglutinin of lymphocytes from mice treated with anti-lymphocyte globulin

PubMed Central

Tursi, A.; Greaves, M. F.; Torrigiani, G.; Playfair, J. H. L.; Roitt, I. M.

1969-01-01

Thymus, spleen, lymph node and peripheral blood lymphocytes taken from mice treated with anti-lymphocyte globulin (ALG) showed a greatly diminished response to PHA in vitro. Recovery of circulating lymphocyte levels preceded recovery of responsiveness to PHA. The latter could be prevented by reinjection of ALG or by thymectomy. Grafts were rejected within a period equal to the normal rejection time after PHA responsiveness had recovered to a value of approximately 20 per cent of the normal. Thus the effect of ALG on thymus dependent lymphocytes in mice can be monitored by assessing the PHA sensitivity of peripheral white blood cells. ImagesFIG. 1 PMID:4900922

The Immune Landscape of Non-Small Cell Lung Cancer: Utility of Cytologic and Histologic Samples Obtained Through Minimally Invasive Pulmonary Procedures.

PubMed

Beattie, Jason; Yarmus, Lonny; Wahidi, Momen M; Rivera, M Patricia; Gilbert, Christopher; Maldonado, Fabien; Czarnecka, Kasia; Argento, Angela; Chen, Alexander; Herth, Felix; Sterman, Daniel H

2018-05-14

The success of immune checkpoint inhibitors and the discovery of useful biomarkers to predict response to these agents is shifting much of the focus of personalized care for non-small cell lung cancer towards harnessing the immune response. With further advancement, more effective immunotherapy options will emerge along with more useful biomarkers. Paradoxically, minimally invasive small biopsy and cytology specimens have become the primary method for diagnosis of patients with advanced disease, as well for initial diagnosis and staging in earlier stage disease. For the benefit of these patients, we will continue to learn how to do more with less. In this perspective, we review aspects of immunobiology that underlie the current state of the art of existing and emerging immunologic biomarkers that hold potential to enhance the care of patients with non-small cell lung cancer. We address practical considerations for acquiring patient samples that accurately reflect disease immune status. We also propose a paradigm shift wherein the most important sample types that need to be proven in pioneering basic science and translation work and subsequent clinical trials are the specimens most often obtained clinically.

Isolation and purification of an early pregnancy factor-like molecule from culture supernatants obtained from lymphocytes of pregnant women: II. Identification of the molecule as a Fc-receptor-like molecule: a preliminary report.

PubMed

Aranha, C; Bordekar, A; Shahani, S

1998-11-01

Early pregnancy factor (EPF)-like activity from culture supernatants obtained from stimulated lymphocytes of pregnant women was characterized and identified. The enzyme-linked immunosorbent assay depending on the presence of "Fc" receptors on bovine spermatozoa was used to identify the EPF-like molecule purified by gel filtration and reverse-phase high-performance liquid chromatography. The results indicated that the crude lymphocyte culture supernatant, the EPF-positive G IV fraction obtained on gel filtration, and the EPF-positive reverse-phase high-performance liquid chromatography protein readily bound with the different concentrations of aggregated human gamma-globulin in a manner similar to that in which the standard control of aggregated human gamma-globulin binds to the bovine spermatozoa. EPF-like activity synthesized and secreted by lymphocytes during pregnancy may be a Fc-receptor-like molecule.

Combination of lamivudine and adefovir without hepatitis B immune globulin is safe and effective prophylaxis against hepatitis B virus recurrence in hepatitis B surface antigen-positive liver transplant candidates.

PubMed

Gane, Edward J; Patterson, Scott; Strasser, Simone I; McCaughan, Geoffrey W; Angus, Peter W

2013-03-01

Without effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. Combination prophylaxis with hepatitis B immune globulin (HBIG) and lamivudine (LAM) reduces long-term recurrence rates below 10%; however, HBIG is costly and inconvenient to administer. We, therefore, conducted a multicenter, prospective study of outcomes with an HBIG-sparing regimen of LAM plus adefovir dipivoxil (ADV) initiated at the time of listing for liver transplantation and continued after transplantation. Twenty-six patients were recruited into this study at the time of listing for transplantation, and 20 subsequently underwent transplantation. Twelve of the 26 patients had LAM exposure before the study baseline, but none had LAM resistance. The median HBV viral load before the institution of antiviral therapy was approximately 4.0 log(10) IU/mL (range=2.3-7.5 log(10) IU/mL). To the 20 patients who underwent transplantation, 800 IU of intramuscular HBIG was given immediately after transplantation and daily for 7 days only (total HBIG dose=6400 IU). All transplant patients remained alive without HBV recurrence (they were negative for hepatitis B surface antigen, and HBV DNA was undetectable) after a median follow-up of 57 months after transplantation (range=27-83 months). The median serum creatinine level in these patients rose from 81 to 119 μmol/L over the course of the study. No patient required dose reduction or cessation. After the completion of this prospective study, the regimen was modified so that no perioperative HBIG was administered if the pretransplant serum HBV DNA level was suppressed below 3 log(10) IU/mL. Another 28 patients with HBV-related liver disease underwent transplantation (18 without HBIG). All remained alive and well without HBV recurrence after a median follow-up of 22 months after transplantation (range=10-58 months). In conclusion, a combination of

Dissociation, aggregation of sesame alpha-globulin in nonionic detergent solution.

PubMed

Lakshmi, T S; Nandi, P K

1978-10-01

Nonionic detergents Triton X-100 and Brij 36T induce dissociation and aggregation of the protein sesame alpha-globulin above the critical micelle concentrations (cmc) of the detergents. Spectrophotometric titration in Triton shows no change in the pKInt value of the tyrosyl groups at 1x10-3 M detergent where both dissociation and aggregation of the protein are observed. Fluorescence measurement does not indicate any change in the environment of the tryptophan groups of the protein in Brij. Viscosity measurements show no major conformational change of the protein in the detergent solution. Binding measurements suggest that perhaps micelles of the detergent predominantly bind to the protein. The detergent micelles preferentially bind to the exposed hydrophobic surfaces of the protein subunits. The association of the protein detergent complex through electrostatic interaction is probably responsible for the formation of the aggregates.

Changes in the waking-sleeping behavior after albumin or $gamma$ globulin injection to lethally irradiated rats (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maigrot, J.C.; Cier, A.; Riotte, M.

1973-01-01

Studies were performed on chronically implanted rats. These rats were subjected to whole-body irradiations of 950 rads (LD 100% 6 days). The following reproducible changes were observed: serious nonreversible disturbances in the waking-sleeping behavior, manifested principally by an almost complete disappearance of paradoxical sleep 4 days after the exposure. The intraperitioneal administration, 4 to 5 days after irradiation of one or several 250mg doses of gamma -globulin enabled the rats to recover both quantitatively and qualitatively a paradoxical sleep identical to that observed with nonirradiated animals during 2 to 3 days. On the other hand when gamma globulins are injectedmore » into nonirradiated animals, the PS level does not alter in any significant way. In addition, injections of human albumin serum carried out under the same experimental conditions, appear to modify EEG parameters, which have been disturbed by irradiation as well as producing a significant improvement in the general state of the irradiated animal, this being confirmed by the prolonged survival time observed. (FR)« less

RhIG for the treatment of immune thrombocytopenia: consensus and controversy

PubMed Central

Despotovic, Jenny M.; Lambert, Michele P.; Herman, Jay H.; Gernsheimer, Terry B.; McCrae, Keith R.; Tarantino, Michael D.; Bussel, James B.

2012-01-01

Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection. PMID:21981825

Measuring polio immunity to plan immunization activities.

PubMed

Voorman, Arend; Lyons, Hil M

2016-11-21

The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Purification and properties of squirrel monkey (Saimiri sciureus) corticosteroid binding globulins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhn, R.W.; Weber, C.V.; Siiteri, P.K.

1988-04-05

Corticosteroid binding globulin (CBG), a serum glycoprotein which binds glucocorticoids and progestins with high affinity, is widely distributed throughout the animal world. Although its charge and size characteristics have largely been conserved across species, the authors found the behavior of CBG in squirrel monkey (Saimiri sciureus) serum during fractionation by polyacrylamide gel electrophoresis or Sephadex chromatography was consistent with a molecule about twice the size of that found in most species. To more fully understand the basis for this difference, they purified the protein by sequential affinity and DEAE-Sepharose chromatographies. The final product was obtained in greater than 60% yieldmore » and was found to migrate as a single homogeneous band when examined by electrophoresis. The steroid binding specificity of the purified protein was identical with that of the protein in the starting serum. In contrast to the single protein band observed following electrophoresis under normal conditions, separations in the presence of sodium dodecyl sulfate (SDS) resolved the pure protein into two bands: one at 54,000 daltons and one at 57,000 daltons. Unlike other species, squirrel monkey CBG exists as a dimer in its native state. Antibodies were generated against the purified material and tested for cross-reactivity against the sera from other species by both radioimmunodiffusion and radioimmunoassay techniques. Only serum from titi monkeys was observed to cross-react when examined by radioimmunoassay. Taken together, the results suggest that New World monkey CBG's are distinct from those of other species in both size and immunologic characteristics.« less

COMPLEMENT FIXATION IN DISEASED TISSUES

PubMed Central

Burkholder, Peter M.

1961-01-01

An immunohistologic complement fixation test has been used in an effort to detect immune complexes in sections of kidney from rats injected with rabbit anti-rat kidney serum and in sections of biopsied kidneys from four humans with membranous glomerulonephritis. Sections of the rat and human kidneys were treated with fluorescein-conjugated anti-rabbit globulin or antihuman globulin respectively. Adjacent sections in each case were incubated first with fresh guinea pig serum and then in a second step were treated with fluorescein-conjugated antibodies against fixed guinea pig complement to detect sites of fixation of the complement. It was demonstrated that the sites of rabbit globulin in glomerular capillary walls of the rat kidneys and the sites of localized human globulin in thickened glomerular capillary walls and swollen glomerular endothelial cells of the human kidneys were the same sites in which guinea pig complement was fixed in vitro. It was concluded from these studies that rabbit nephrotoxic antibodies localize in rat glomeruli in complement-fixing antigen-antibody complexes. Furthermore, it was concluded that the deposits of human globulin in the glomeruli of the human kidneys behaved like antibody globulin in complement-fixing antigen-antibody complexes. The significance of demonstrating complement-fixing immune complexes in certain diseased tissues is discussed in regard to determination of the causative role of allergic reactions in disease. PMID:19867205

CELLS INVOLVED IN THE IMMUNE RESPONSE

PubMed Central

Abdou, Nabih I.; Richter, Maxwell

1969-01-01

Rabbits were made immunologically tolerant to either human serum albumin or bovine gamma globulin by the neonatal administration of antigen. At 10 wk of age, they were challenged with the tolerogenic antigen and found to be non-responsive. However, these tolerant rabbits could respond with humoral antibody formation directed toward the tolerogenic antigen if they were treated with normal, allogeneic bone marrow or bone marrow obtained from a rabbit made tolerant toward a different antigen. They were incapable of responding if they were given bone marrow obtained from a rabbit previously made tolerant to the tolerogenic antigen. Irradiated rabbits were unable to respond if treated with tolerant bone marrow, but could respond well if given normal bone marrow. Since it has previously been demonstrated that the antibody-forming cell, in an irradiated recipient of allogeneic bone marrow, is of recipient and not donor origin, the data presented strongly indicate that the unresponsive cell in the immunologically tolerant rabbit is the antigen-reactive cell. PMID:4183777

Immunization in pregnancy.

PubMed

Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

2009-11-01

To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed

Immunohistochemical analysis of human milk fat globulin expression in extramammary Paget's disease.

PubMed

Ohnishi, T; Watanabe, S

2001-03-01

Primary extramammary Paget's disease is thought to be an intraepidermal carcinoma indicating apocrine secretory differentiation. In addition to expression in breast tissue, human milk fat globulin (HMFG) is expressed in the normal apocrine glands and tumours with apocrine differentiation. In this study HMFG expression in extramammary Paget's disease was analysed immunohistochemically in 18 cases of primary extramammary Paget's disease and two cases of secondary extramammary Paget's disease. The proportion and staining pattern of positive tumour cells with the anti-HMFG antibody was variable in each case. Cytoplasmic staining was observed frequently in dermal invasion and metastasis of Paget cells. The variabilities were thought to be due to modulation of the cellular localization of the cell surface component, HMFG, according to changes in cellular differentiation or malignant potency.

Treatment of US crotalidae bites: comparisons of serum and globulin-based polyvalent and antigen-binding fragment antivenins.

PubMed

Seger, Donna; Kahn, Stephen; Krenzelok, Edward P

2005-01-01

In the US, two antivenins are marketed for the treatment of snake envenomation. The horse-derived serum-globulin-based Antivenin (Crotalidae) Polyvalent (ACP) has been available since 1954. There are few data on the efficacy and incidence of adverse events that occur following the administration of ACP. Most of the data are retrospective, anecdotal, or case reports. In 2000, ovine-derived serum-globulin-based ACP (Crofab) became available. Crofab is said to cause fewer reactions than ACP, but there are few comparative data to substantiate this claim. Although both antivenins ameliorate the systemic symptoms following snake envenomation, the efficacy of either antivenin in decreasing oedema and swelling is unknown for a number of reasons. Clinical trials are small and have not included control arms. The degree of oedema, as well as the efficacy of the antivenin in decreasing oedema, may depend on the genera of the snake (usually unknown) that envenomated the patient. This article compares available data on clinical aspects of the two antivenins. More prospective data are needed to determine the comparative efficacy of the two antivenins, or the efficacy of Crofab in preventing tissue oedema. There are still unanswered questions regarding the optimal dosing regimen of Crofab.

Modified immunosuppressive therapy with porcine antilymphocyte globulin plus delayed cyclosporine A in children with severe aplastic anemia.

PubMed

Cui, Qingya; Sha, Pingping; Chen, Haifei; Shen, Hongshi; Qin, Longmei; Li, Zhengyang; Wu, Tianqin; Wang, Zhaoyue

2018-01-01

Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) is the standard treatment for children with severe aplastic anemia (SAA) with no human leukocyte antigen-matched siblings. Due to the unavailability of horse ATG in China, porcine antilymphocyte globulin (p-ALG), which is less expensive and more effective than rabbit ATG, is widely used. We sought to evaluate the efficacy and safety profile of modified IST with p-ALG plus delayed CsA at day 21 in 50 SAA children. Eighteen SAA patients who progressed from nonsevere aplastic anemia (NSAA) were classified as SAA-II; the other 32 patients were classified as SAA-I. Overall response (OR) rates at 3, 6 and 12 months were 56, 64 and 62%, respectively. The 10-year overall survival (OS) rate and disease-free survival (DFS) rate were 80 and 56%. The OR, OS and DFS rates in the SAA-I group were clearly better than those in the SAA-II group. Death rate from infection within 30 days was 4%. Modified IST with p-ALG plus delayed CsA is a reliable and well-tolerated treatment for children with SAA, and reduces early death due to infection. Modified IST is more suitable for children with SAA-I.

Studies of the antibody nature of the rheumatoid factor

PubMed Central

Aho, K.; Harboe, M.; Leikola, J.

1964-01-01

The reaction of the rheumatoid factor (RF) with 7S γ-globulin antibodies of nine persons immunized with sheep erythrocytes was studied. All of a panel of rheumatoid sera with high Waaler-Rose titres agglutinated sheep cells sensitized with the human anti-sheep cell antibodies and O Rh positive cells sensitized with the `diagnostic' anti-CD serum Ripley. The RF measurable with these systems could be absorbed to diphtheria toxoid—human antitoxin precipitate, whereas the absorption with egg albumin—rabbit anti-egg albumin precipitate did not result in any appreciable titre reduction. However, the eluate from the rabbit precipitate was highly active in these systems, whereas Rh positive cells sensitized with anti-Rh sera suitable for Gm(a) typing were not regularly agglutinated. A markedly greater concentration of native than of heat-aggregated γ-globulin was needed for inhibition of the agglutination by the RF of cells heavily sensitized with the human anti-sheep cell antibodies. No appreciable difference in this respect was seen when using lightly sensitized cells. Only the heavily sensitized cells fixed complement. The `natural' 7S γ-globulin antibodies against sheep cells were neither suited for demonstration of RF nor did they fix complement. Sheep cells coated with 7S γ-globulin antibodies of a Gm(a+) person were agglutinated by a non-rheumatoid anti-Gm(a) serum, and this system was well suited for Gm(a) typing, whereas cells coated with antibodies of a Gm(a-) person were not agglutinated. Rheumatoid anti-Gm(a) sera agglutinated cells sensitized with antibodies of both Gm(a+) and Gm(a-) persons. Using cells coated with Gm(a+) antibodies, some distinction between Gm(a+) and Gm(a-) sera could be obtained under carefully controlled conditions. The use of a Gm(a-) coat resulted in a slight difference in the inhibiting capacity, which had no relation to the serum's Gm(a) type. The results suggest that the reaction of the RF with sheep cells heavily sensitized

Influence of antigen on immune complex behavior in mice.

PubMed

Finbloom, D S; Magilavy, D B; Harford, J B; Rifai, A; Plotz, P H

1981-07-01

To explore the possibility that the behavior of immune complexes can, under some circumstances, be directed by the antigen, we have studied the behavior of complexes of identical size made with the glycoproteins, orosomucoid (OR), and ceruloplasmin: or with their desialylated derivatives, asialo-orosomucoid (ASOR) and asialo-ceruloplasmin. Such desialylated proteins are rapidly removed from the circulation by a hepatic cell receptor for galactose, the sugar exposed upon removal of sialic acid. Mixtures of 125I-goat anti-ASOR with either ASOR or OR and mixtures of 125I-rabbit anti-OR with either ASOR or OR form complexes identically. The complexes were separated by density gradient centrifugation and injected intravenously into C3H mice. Blood clearance and hepatic uptake of the OR complexes and ASOR complexes were markedly different. T 1/2 for the goat OR complexes exceeded 300 min, whereas that for the ASOR complexes was 15 min. More detailed studies using rabbit complexes of various sizes revealed that light rabbit complexes behaved similarly to the goat complexes. The light rabbit OR complexes were cleared slowly, with only 18% found in the liver at 60 min, whereas the light rabbit ASOR complexes were cleared much more rapidly, with 62% found within the liver by 30 min. This rapid clearance was completely suppressed by a prior injection of a blocking dose of ASOR, which implies uptake by a galactose-mediated mechanism on hepatocytes. As the size of the rabbit complexes increased, so did the rate of Fc receptor-mediated clearance. Heavy rabbit OR complexes were cleared more rapidly than light OR complexes but not so rapidly as heavy ASOR complexes. The clearance and hepatic uptake of the heavy OR complexes were markedly suppressed by a prior injection of heat-aggregated gamma globulin, a known Fc receptor-blocking agent (45% hepatic uptake without and 6% with aggregated gamma globulin). The heavy rabbit ASOR complexes exhibited inhibition of blood clearance and

Shared decision making in the management of children with newly diagnosed immune thrombocytopenia.

PubMed

Beck, Carolyn E; Boydell, Katherine M; Stasiulis, Elaine; Blanchette, Victor S; Llewellyn-Thomas, Hilary; Birken, Catherine S; Breakey, Vicky R; Parkin, Patricia C

2014-10-01

This study aimed to examine the treatment decision-making process for children hospitalized with newly diagnosed immune thrombocytopenia (ITP). Using focus groups, we studied children with ITP, parents of children with ITP, and health care professionals, inquiring about participants' experience with decision support and decision making in newly diagnosed ITP. Data were examined using thematic analysis. Themes that emerged from children were feelings of "anxiety, fear, and confusion"; the need to "understand information"; and "treatment choice," the experience of which was age dependent. For parents, "anxiety, fear, and confusion" was a dominant theme; "treatment choice" revealed that participants felt directed toward intravenous immune globulin (IVIG) for initial treatment. For health care professionals, "comfort level" highlighted factors contributing to professionals' comfort with offering options; "assumptions" were made about parental desire for participation in shared decision making (SDM) and parental acceptance of treatment options; "providing information" was informative regarding modes of facilitating SDM; and "treatment choice" revealed a discrepancy between current practice (directed toward IVIG) and the ideal of SDM. At our center, families of children with newly diagnosed ITP are not experiencing SDM. Our findings support the implementation of SDM to facilitate patient-centered care for the management of pediatric ITP.

A portion of heifers attaining “early puberty” do not display estrus, are anovulatory and have altered sex hormone binding globulin concentrations

USDA-ARS?s Scientific Manuscript database

Cows with excess androstenedione (High A4) in the follicular fluid of dominant follicles attain puberty earlier than their low androstenedione counterparts. Furthermore, High A4 cows are anovulatory (chronic or sporadic) and have lower Sex Hormone Binding Globulin (SHBG) compared to Low A4 ovulator...

STUDIES ON THE ANTIGENIC PROPERTIES OF COMPLEMENT

PubMed Central

Klein, Paul G.; Burkholder, Peter M.

1960-01-01

Sheep erythrocytes sensitized with amboceptor and persensitized thereafter with guinea pig complement are agglutinated by rabbit anti-guinea pig globulin and by immune sera obtained by injection of rabbits with fixed complement. In this agglutination neither C'1 nor C'2 takes part. Fixed C'4 acts as an agglutinogen. An additional agglutinogen, distinct from C'4, was found on persensitized cells. This additional agglutinogen appears to be distinct from hemolytically active C'3. PMID:14409703

Immune complex orchitis in vasectomized rabbits

PubMed Central

1976-01-01

The results of the present study show that bilaterally vasectomized rabbits with high levels of antibodies to sperm antigens frequently develop an orchitis associated with granular deposits of rabbit IgG and C3 in the basement membranes of seminiferous tubules. The immune deposits correspond in location to electron-opaque deposits seen by electron microscopy. The "membranous orchitis" is characterized by thickening of tubular basement membranes, acc-mulation of macrophages and a few polymorphonuclear leukocytes, and destruction of the basal lamina, of the Sertoli and spermatogenetic cells. The pathogenetic role of the immune deposits and the possibility that they contain antigen- antibody complexes is indicated by: (a) selective accumulation of IgG and C3 granular deposits along the basement membranes of seminiferous tubules in rabbits producing high and persistent levels of antibodies to sperm antigens; (b) the elution of immunoglobulins from tissues with chaotropic ion-containing buffers, acid buffers, or heat; (c) the observation that the immuno-globulins accumulated in the testis contain antibody to sperm antigens; and (d) the demonstration of sperm antigens in a location similar to that of IgG and C3. It is postulated that sperm antigen-antibody complexes are formed in the basement membranes of seminiferous tubules when antigens leaking out of the tubules react with specific antibody coming from the circulation. In two rabbits with higher levels of circulating antisperm antibodies and severe orchitis, granular deposits of IgG and C3 were also present in renal glomeruli. Immunoglobulins eluted from the kidneys contained antibody with antisperm activity. These findings are consistent with the hypothesis that in some vasectomized rabbits extratesticular lesions may develop by a mechanism comparable to that of chronic serum sickness. PMID:129498

State-Level Immunization Information Systems: Potential for Childhood Immunization Data Linkages.

PubMed

Fuller, Jill E; Walter, Emmanuel B; Dole, Nancy; O'Hara, Richard; Herring, Amy H; Durkin, Maureen S; Specker, Bonny; Wey, Betty

2017-01-01

Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research and gather information about data formats. We evaluated quality of data from IIS, medical records, and reports from parents of 119 National Children's Study participants at three locations. Results IIS data were comparable to MRA data and both were more complete than parental report. Agreement between IIS and MRA data was greater than between parental report and MRA, suggesting IIS and MRA are better sources than parental report. Obtaining IIS data took less staff time than chart review, making IIS data linkage for research a preferred choice. Conclusions IIS survey results indicate data can be obtained by researchers using data linkages. IIS are an accessible and feasible child immunization information source and these registries reduce reliance on parental report or medical record abstraction. Researchers seeking to link IIS data with large multi-site studies should consider acquiring IIS data, but may need strategies to overcome barriers to data completeness and linkage.

Role of the eosinophil in serum-mediated adherence of equine leukocytes to infective larvae of Strongylus vulgaris.

PubMed

Klei, T R; Chapman, M R; Dennis, V A

1992-06-01

The adherence of equine leukocytes to Strongylus vulgaris infective larvae (L3) in the presence of normal and immune sera was examined in vitro. Immune sera promoted adherence of buffy coat cells from ponies with S. vulgaris-induced eosinophilia (eosinophilic ponies) to S. vulgaris L3. However, eosinophils in the buffy coat cells were the predominant adherent cell type. Studies using leukocyte populations enriched for eosinophils, neutrophils, and mononuclear cells from eosinophilic ponies support the observations using buffy coat cells that eosinophils were the main effector cells. Adherent eosinophils from eosinophilic ponies immobilized L3. Neutrophils were less adherent and did not immobilize L3. Mononuclear cells failed to adhere. Normal eosinophils from strongly-naive ponies did not immobilize S. vulgaris L3 in the presence of immune serum, suggesting the in vivo activation of eosinophils in eosinophilic animals. Immune serum promoted less adherence of buffy coat cells to Strongylus edentatus or mixed species of Cyathostominae L3, suggesting that the serum-mediated cellular adherence phenomenon was species-specific. Normal serum promoted less cellular adherence to S. vulgaris L3 than immune serum. The adherence mediated by normal serum was removed by heat inactivation, suggesting that this nonspecific phenomenon was a complement-mediated reaction. Immune globulins promoted reactions similar to that seen using heat-inactivated immune serum, whereas normal globulins did not promote adherence. Immune globulins absorbed with pieces of S. vulgaris adult worms did not promote the adherence of buffy coat cells to S. vulgaris L3, suggesting that adult and L3 stages share antigens important in this phenomenon that resulted in the removal of specific adherence antibody during absorption.

General and Virus-Specific Immune Cell Reconstitution Following Double Cord Blood Transplantation

PubMed Central

Saliba, Rima M.; Rezvani, Katayoun; Leen, Ann; Jorgensen, Jeffrey; Shah, Nina; Hosing, Chitra; Parmar, Simrit; Oran, Betul; Olson, Amanda; Mehta, Rohtesh S.; Chemaly, Roy F.; Saunders, Ila M.; Bollard, Catherine M.; Shpall, Elizabeth J.

2015-01-01

Cord blood transplantation (CBT) is curative for many patients with hematologic malignancies but is associated with delayed immune recovery and an increased risk of viral infections compared to human leukocyte antigen (HLA) matched bone marrow or peripheral blood progenitor cell transplantation. In this study we evaluated the significance of lymphocyte recovery in 125 consecutive patients with hematologic malignancies who underwent double-unit CBT (DUCBT) with an anti-thymocyte globulin-containing regimen at our institution. A subset of 65 patients were prospectively evaluated for recovery of T, natural killer (NK) and B cells and in 46 patients we also examined viral-specific T cell recovery against Adenovirus, Epstein-Barr virus, cytomegalovirus, BK virus, respiratory syncytial virus and Influenza antigen. Our results indicate that in recipients of DUCBT, the day 30 absolute lymphocyte count is highly predictive of non-relapse mortality (NRM) and overall survival (OS). Immune recovery post-DUCBT was characterized by prolonged CD8+ and CD4+ T lymphopenia associated with preferential expansion of B and NK cells. We also observed profound delays in quantitative and functional recovery of viral-specific CD4+ and CD8+ T-cell responses for the first year post-CBT. Taken together, our data support efforts aimed at optimizing viral-specific T cell recovery to improve outcomes post-CBT. PMID:25708219

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

PubMed Central

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Plasma fractionation issues.

PubMed

Farrugia, Albert; Evers, Theo; Falcou, Pierre-Francois; Burnouf, Thierry; Amorim, Luiz; Thomas, Sylvia

2009-04-01

Procurement and processing of human plasma for fractionation of therapeutic proteins or biological medicines used in clinical practice is a multi-billion dollar international trade. Together the private sector and public sector (non-profit) provide large amounts of safe and effective therapeutic plasma proteins needed worldwide. The principal therapeutic proteins produced by the dichotomous industry include gamma globulins or immunoglobulins (including pathogen-specific hyperimmune globulins, such as hepatitis B immune globulins) albumin, factor VIII and Factor IX concentrates. Viral inactivation, principally by solvent detergent and other processes, has proven highly effective in preventing transmission of enveloped viruses, viz. HBV, HIV, and HCV.

Construction of an Ostrea edulis database from genomic and expressed sequence tags (ESTs) obtained from Bonamia ostreae infected haemocytes: Development of an immune-enriched oligo-microarray.

PubMed

Pardo, Belén G; Álvarez-Dios, José Antonio; Cao, Asunción; Ramilo, Andrea; Gómez-Tato, Antonio; Planas, Josep V; Villalba, Antonio; Martínez, Paulino

2016-12-01

The flat oyster, Ostrea edulis, is one of the main farmed oysters, not only in Europe but also in the United States and Canada. Bonamiosis due to the parasite Bonamia ostreae has been associated with high mortality episodes in this species. This parasite is an intracellular protozoan that infects haemocytes, the main cells involved in oyster defence. Due to the economical and ecological importance of flat oyster, genomic data are badly needed for genetic improvement of the species, but they are still very scarce. The objective of this study is to develop a sequence database, OedulisDB, with new genomic and transcriptomic resources, providing new data and convenient tools to improve our knowledge of the oyster's immune mechanisms. Transcriptomic and genomic sequences were obtained using 454 pyrosequencing and compiled into an O. edulis database, OedulisDB, consisting of two sets of 10,318 and 7159 unique sequences that represent the oyster's genome (WG) and de novo haemocyte transcriptome (HT), respectively. The flat oyster transcriptome was obtained from two strains (naïve and tolerant) challenged with B. ostreae, and from their corresponding non-challenged controls. Approximately 78.5% of 5619 HT unique sequences were successfully annotated by Blast search using public databases. A total of 984 sequences were identified as being related to immune response and several key immune genes were identified for the first time in flat oyster. Additionally, transcriptome information was used to design and validate the first oligo-microarray in flat oyster enriched with immune sequences from haemocytes. Our transcriptomic and genomic sequencing and subsequent annotation have largely increased the scarce resources available for this economically important species and have enabled us to develop an OedulisDB database and accompanying tools for gene expression analysis. This study represents the first attempt to characterize in depth the O. edulis haemocyte transcriptome in

Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol-binding globulin concentrations.

PubMed

Chung, T T; Gunganah, K; Monson, J P; Drake, W M

2016-04-01

Patients taking hydrocortisone (HC) replacement for primary or secondary adrenal failure require individual adjustment of their dose. In addition to modifying the administered doses of HC for each patient, physicians are increasingly interested in variations in the bioavailability of glucocorticoid replacement. One potential determinant of the bioavailability of replaced HC is a variation in serum cortisol-binding globulin (CBG) concentration, which may, in turn, affect interpretation of cortisol profiles and individual dose selection for patients on hydrocortisone replacement therapy. To investigate the hypothesis that there is a circadian variation in CBG levels. A total of 34 male patients divided into 3 groups (10 patients with non-somatotroph structural pituitary disease on HC replacement, 11 patients with treated acromegaly on HC replacement and 13 patients with treated acromegaly not on HC replacement) and 10 healthy volunteers were included. Cortisol and CBG levels were measured at 6 time points (0800, 1100, 1300, 1500, 1700 and 1900). No significant circadian variation in CBG concentration was found in any of the 4 groups. Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol-binding globulin concentration. Changes in serum cortisol levels may thus be explained by other factors including 11 β-hydroxysteroid dehydrogenase type 1 activity or circadian changes in the binding properties of CBG. © 2015 John Wiley & Sons Ltd.

Cholestatic Liver Disease after Rituximab and Adalimumab and the Possible Role of Cross-Reacting Antibodies to Fab 2 Fragments

PubMed Central

Koetter, Ina; Schwab, Matthias; Fritz, Peter; Kimmel, Martin; Alscher, M. Dominik; Braun, Niko

2013-01-01

Background Millions of patients are treated with therapeutic monoclonal antibodies (Tmabs) for miscellaneous diseases. We investigated sera from six patients who received immune globulin, from one patient with refractory anti-neutrophil-cytoplasmic antibody (ANCA)-associated granulomatosis with polyangiitis (GPA) who developed two episodes of acute cholestatic liver disease, one after treatment with rituximab and a second after adalimumab and a healthy control group. Methods Three sera from the patient and six sera from patients who received immune globulin were analyzed for antibodies to rituximab and adalimumab by ELISA. Additionally, sera from the patients and from nine healthy blood donors were coated with the Fab fragment of an unrelated humanized monoclonal antibody, with human Fc proteins as well as a mouse IgG globulin. Results Viral serology for hepatitis A, B, C and autoantibodies specific for autoimmune liver disorders were negative. In all three sera from the patient antibodies to rituximab could be detected, but also antibodies to adalimumab were present even at time points when the patient had not yet received adalimumab, indicating cross reactivity between both substances. Testing against an unrelated human Fab fragment revealed positive results, indicating that the patient had antibodies against human Fab fragments in general. The Fc proteins were negative, and patients’ sera did also not react with mouse IgG globulins. Remarkably, 2 out of 5 patients which were treated with immune globulin had antibodies against human Fab fragments in general whereas in none of the samples from healthy controls antibodies to Fab fragment could be detected. Conclusion This is the first study demonstrating cholestatic liver disease induced by two different Tmabs. Cross - reacting antibodies to Fab2 fragments in general are probably involved. Further studies must show if these Fab2 antibodies in general are related with drug-induced side effects and accelerated drug

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

PubMed Central

Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

2015-01-01

In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. PMID:25902927

Immunizations for foreign travel.

PubMed Central

Hill, D. R.

1992-01-01

One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations. Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications. There are three categories of immunizations for foreign travel. The first category includes immunizations which are routinely recommended whether or not the individual is traveling. Many travelers are due for primary vaccination or boosting against tetanus-diphtheria, measles-mumps-rubella, pneumococcal pneumonia, and influenza, for example, and the pre-travel visit is an ideal time to administer these. The second category are immunizations which might be required by a country as a condition for entry; these are yellow fever and cholera. The final category contains immunizations which are recommended because there is a risk of acquiring a particular disease during travel. Typhoid fever, meningococcal disease, rabies, and hepatitis are some examples. Travelers who are pregnant or who are infected with the human immunodeficiency virus require special consideration. Provision of appropriate immunizations for foreign travel is an important aspect of preventing illness in travelers. PMID:1337807

Construction of Rabbit Immune Antibody Libraries.

PubMed

Nguyen, Thi Thu Ha; Lee, Jong Seo; Shim, Hyunbo

2018-01-01

Rabbits have distinct advantages over mice as a source of target-specific antibodies. They produce higher affinity antibodies than mice, and may elicit strong immune response against antigens or epitopes that are poorly immunogenic or tolerated in mice. However, a great majority of currently available monoclonal antibodies are of murine origin because of the wider availability of murine fusion partner cell lines and well-established tools and protocols for fusion and cloning of mouse hybridoma. Phage-display selection of antibody libraries is an alternative method to hybridoma technology for the generation of target-specific monoclonal antibodies. High-affinity monoclonal antibodies from nonmurine species can readily be obtained by constructing immune antibody libraries from B cells of the immunized animal and screening the library by phage display. In this article, we describe the construction of a rabbit immune Fab library for the facile isolation of rabbit monoclonal antibodies. After immunization, B-cell cDNA is obtained from the spleen of the animal, from which antibody variable domain repertoires are amplified and assembled into a Fab repertoire by PCR. The Fab genes are then cloned into a phagemid vector and transformed to E. coli, from which a phage-displayed immune Fab library is rescued. Such a library can be biopanned against the immunization antigen for rapid identification of high-affinity, target-specific rabbit monoclonal antibodies.

Immune status of free-ranging green turtles with fibropapillomatosis from Hawaii

USGS Publications Warehouse

Work, Thierry M.; Rameyer, Robert; Balazs, George H.; Cray, Carolyn; Chang, Sandra P.

2001-01-01

Cell-mediated and humoral immune status of free-ranging green turtles (Chelonia mydas) in Hawaii (USA) with and without fibropapillornatosis (FP) were assessed. Tumored and non-tumored turtles from Kaneohe Bay (KB) on the island of Oahu and from FP-free areas on the west (Kona/Kohala) coast of the island of Hawaii were sampled from April 1998 through February 1999. Turtles on Oahu were grouped (0-3) for severity of tumors with 0 for absence of tumors, 1 for light, 2 for moderate, and 3 for most severe. Turtles were weighed, straight carapace length measured and the regression slope of weight to straight carapace length compared between groups (KB0, KB1, KB2, KB3, Kona). Blood was assayed for differential white blood cell count, hematocrit, in vitro peripheral blood mononuclear cell (PBMC) proliferation in the presence of concanavalin A (ConA) and phytohaemagglutinin (PHA), and protein electrophoresis. On Oahu, heterophil/lymphocyte ratio increased while eosinophil/monocyte ratio decreased with increasing tumors score. Peripheral blood mononuclear cell proliferation indices for ConA and PHA were significantly lower for turtles with tumor scores 2 and 3. Tumor score 3 turtles (KB3) had significantly lower hematocrit, total protein, alpha 1, alpha 2, and gamma globulins than the other four groups. No significant differences in immune status were seen between non-tumored (or KB1) turtles from Oahu and Hawaii. There was no significant difference between groups in regression slopes of body condition to carapace length. We conclude that turtles with severe FP are imunosuppressed. Furthermore, the lack of significant difference in immune status between non-tumored (and KB1) turtles from Oahu and Kona/Kohala indicates that immunosuppression may not be a prerequisite for development of FP.

BINDING OF SOLUBLE IMMUNE COMPLEXES TO HUMAN LYMPHOBLASTOID CELLS

PubMed Central

Theofilopoulos, Argyrios N.; Dixon, Frank J.; Bokisch, Viktor A.

1974-01-01

In the present work we studied the expression of membrane-bound Ig (MBIg) as well as receptors for IgG Fc and complement on nine human lymphoblastoid cell lines. When MBIg and receptors for IgG Fc were compared, four categories of cell lines could be distinguished: (a) cell lines having both MBIg and receptors for IgG Fc, (b) cell lines having MBIg but lacking receptors for IgG Fc, (c) cell lines lacking MBIg but having receptors for IgG Fc, and (d) cell lines lacking both MBIg and receptors for IgG Fc. Two types of receptors for complement could be detected on the cell lines studied, one for C3-C3b and one for C3d. When sensitized red cells carrying C3b or C3d were used for rosette tests, three categories of cell lines could be distinguished: (a) cell lines having receptors for C3b and C3d, (b) cell lines having receptors only for C3d and (c) cell lines lacking both receptors. However, when a more sensitive immunofluorescent method was used instead of the rosette technique, it was found that cell lines unable to form rosettes with EAC1423bhu were able to bind soluble C3 or C3b which indicated the presence of these receptors on the cell surface. Inhibition experiments showed that receptors for C3-C3b and receptors for C3d are distinct and that receptors for C3-C3b and C3d are different from receptors for IgG Fc. A cell line (Raji) without MBIg but with receptors for IgG Fc, C3-C3b, and C3d was selected for use in studying the binding mechanism of soluble immune complexes to cell surface membrane. Aggregated human gamma globulin was used in place of immune complexes. Immune complexes containing complement bind to Raji cells only via receptors for complement, namely receptors for C3-C3b and C3d. Binding of immune complexes containing complement to cells is much greater than that of complexes without complement. Immune complexes bound to cells via receptors for complement can be partially released from the cell surface by addition of normal human serum as well as

78 FR 12763 - Pediatric Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-25

... [Immune Globulin Subcutaneous (Human), 20% Liquid], INOMAX (nitric oxide), INVEGA (paliperidone), KEDBUMIN... (moxifloxacin ophthalmic solution 0.5%), NATROBA (spinosad), NEXIUM (esomeprazole magnesium), NEXIUM IV...

No. 357-Immunization in Pregnancy.

PubMed

Castillo, Eliana; Poliquin, Vanessa

2018-04-01

To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization and risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to January 2017 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the SOGC under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

PubMed Central

Roider, Tobias; Katzfuß, Michael; Matos, Carina; Singer, Katrin; Renner, Kathrin; Oefner, Peter J.; Dettmer-Wilde, Katja; Herr, Wolfgang; Holler, Ernst; Kreutz, Marina; Peter, Katrin

2016-01-01

Antithymocyte globulin (ATG) is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon®) on human monocyte-derived dendritic cells (DC). ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo. PMID:27973435

Immune changes during short-duration missions

NASA Technical Reports Server (NTRS)

Taylor, G. R.

1993-01-01

Spaceflight materially influences the immune mechanism of humans and animals. Effects resulting from missions of less than 1 month are examined. Effects from longer missions are discussed in the companion paper by Konstantinova et al. Most immunology studies have involved analyses of subjects and samples from subjects obtained after flight, with the data being compared with similar data obtained before flight. These studies have demonstrated that short-duration missions can result in a postflight depression in blast cell transformation, major changes in cytokine function, and alterations in the relative numbers of immune cell populations. In addition to these post- vs. preflight studies, some data have been produced in flight. However, these in vitro analyses have been less than satisfactory because of differences between in-flight and ground-control conditions. Recently, both the U.S. and Russian space programs have started collecting in-flight, in vivo, cell-mediated immunity data. These studies have confirmed that the human cell-mediated immune system is blunted during spaceflight.

Immune changes during short-duration missions.

PubMed

Taylor, G R

1993-09-01

Spaceflight materially influences the immune mechanism of humans and animals. Effects resulting from missions of less than 1 month are examined. Effects from longer missions are discussed in the companion paper by Konstantinova et al. Most immunology studies have involved analyses of subjects and samples from subjects obtained after flight, with the data being compared with similar data obtained before flight. These studies have demonstrated that short-duration missions can result in a postflight depression in blast cell transformation, major changes in cytokine function, and alterations in the relative numbers of immune cell populations. In addition to these post- vs. preflight studies, some data have been produced in flight. However, these in vitro analyses have been less than satisfactory because of differences between in-flight and ground-control conditions. Recently, both the U.S. and Russian space programs have started collecting in-flight, in vivo, cell-mediated immunity data. These studies have confirmed that the human cell-mediated immune system is blunted during spaceflight.

Humoral immune responses against gonadotropin releasing hormone elicited by immunization with phage-peptide constructs obtained via phage display.

PubMed

Samoylov, Alexandre; Cochran, Anna; Schemera, Bettina; Kutzler, Michelle; Donovan, Caitlin; Petrenko, Valery; Bartol, Frank; Samoylova, Tatiana

2015-12-20

Phage display is based on genetic engineering of phage coat proteins resulting in fusion peptides displayed on the surface of phage particles. The technology is widely used for generation of phages with novel characteristics for numerous applications in biomedicine and far beyond. The focus of this study was on development of phage-peptide constructs that stimulate production of antibodies against gonadotropin releasing hormone (GnRH). Phage-peptide constructs that elicit production of neutralizing GnRH antibodies can be used for anti-fertility and anti-cancer applications. Phage-GnRH constructs were generated via selection from a phage display library using several types of GnRH antibodies as selection targets. Such phage constructs were characterized for sequence similarities to GnRH peptide and frequency of their occurrence in the selection rounds. Five of the constructs with suitable characteristics were tested in mice as a single dose 5×10(11) virions (vir) vaccine and were found to be able to stimulate production of GnRH-specific antibodies, but not to suppress testosterone (indirect indicator of GnRH antibody neutralizing properties). Next, one of the constructs was tested at a higher dose of 2×10(12) vir per mouse in combination with a poly(lactide-co-glycolide) (PLGA)-based adjuvant. This resulted in multifold increase in GnRH antibody production and significant reduction of serum testosterone, indicating that antibodies produced in response to the phage-GnRH immunization possess neutralizing properties. To achieve optimal immune responses for desired applications, phage-GnRH constructs can be modified with respect to flanking sequences of GnRH-like peptides displayed on phage. Anticipated therapeutic effects also might be attained using optimized phage doses, a combination of several constructs in a single treatment, or application of adjuvants and advanced phage delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Heat-Induced Soluble Protein Aggregates from Mixed Pea Globulins and β-Lactoglobulin.

PubMed

Chihi, Mohamed-Lazhar; Mession, Jean-luc; Sok, Nicolas; Saurel, Rémi

2016-04-06

The present work investigates the formation of protein aggregates (85 °C, 60 min incubation) upon heat treatment of β-lactoglobulin (βlg)-pea globulins (Glob) mixtures at pH 7.2 and 5 mM NaCl from laboratory-prepared protein isolates. Various βlg/Glob weight ratios were applied, for a total protein concentration of 2 wt % in admixture. Different analytical methods were used to determine the aggregation behavior of "mixed" aggregates, that is, surface hydrophobicity and also sulfhydryl content, protein interactions by means of SDS-PAGE electrophoresis, and molecule size distribution by DLS and gel filtration. The production of "mixed" thermal aggregates would involve both the formation of new disulfide bonds and noncovalent interactions between the denatured βlg and Glob subunits. The majority of "mixed" soluble aggregates displayed higher molecular weight and smaller diameter than those for Glob heated in isolation. The development of pea-whey protein "mixed" aggregates may help to design new ingredients for the control of innovative food textures.

Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

Watson, J C; Hadler, S C; Dykewicz, C A; Reef, S; Phillips, L

1998-05-22

These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.

Inborn Errors in Immunity

PubMed Central

Lionakis, M.S.; Hajishengallis, G.

2015-01-01

In recent years, the study of genetic defects arising from inborn errors in immunity has resulted in the discovery of new genes involved in the function of the immune system and in the elucidation of the roles of known genes whose importance was previously unappreciated. With the recent explosion in the field of genomics and the increasing number of genetic defects identified, the study of naturally occurring mutations has become a powerful tool for gaining mechanistic insight into the functions of the human immune system. In this concise perspective, we discuss emerging evidence that inborn errors in immunity constitute real-life models that are indispensable both for the in-depth understanding of human biology and for obtaining critical insights into common diseases, such as those affecting oral health. In the field of oral mucosal immunity, through the study of patients with select gene disruptions, the interleukin-17 (IL-17) pathway has emerged as a critical element in oral immune surveillance and susceptibility to inflammatory disease, with disruptions in the IL-17 axis now strongly linked to mucosal fungal susceptibility, whereas overactivation of the same pathways is linked to inflammatory periodontitis. PMID:25900229

Infant botulism type Ba: first culture-confirmed case in the United Arab Emirates.

PubMed

Fathalla, Waseem M; Mohammed, Khalid A; Ahmed, Elamin

2008-09-01

We report on a 3-month-old girl with culture-confirmed infant botulism caused by a rare double toxin-producing Clostridium botulinum type Ba. This case was not related to honey-feeding. The clinical course was prolonged, with minimal spontaneous improvement at onset, and a period of fluctuating motor weakness and nasogastric feeding dependence afterward. Neurophysiologic studies produced normal results. Human botulism immune globulin was administered empirically on day 23 of presentation, with rapid full recovery. This case highlights the importance of pursuing diagnoses of infant botulism despite normal results of neurophysiologic testing and no history of honey-feeding. Our case also demonstrates a favorable response to human botulism immune globulin, despite the relatively late treatment.

Late Pregnancy Thyroid-Binding Globulin Predicts Perinatal Depression

PubMed Central

Pedersen, Cort; Leserman, Jane; Garcia, Nacire; Stansbury, Melissa; Meltzer-Brody, Samantha; Johnson, Jacqueline

2016-01-01

Previously we found that late pregnancy total and free thyroxine (TT4, FT4) concentrations were negatively related to greater pre and/or postpartum depressive symptoms. In a much larger cohort, the current study examined whether these thyroid indices measured earlier in the third trimester (31-33 weeks) predict subsequent perinatal depression and anxiety ratings as well as syndromal depression. Thyroid-binding globulin (TBG) concentrations increase markedly during pregnancy and may be an index of sensitivity to elevated estrogen levels. TBG was examined in this study because prior findings suggest that postpartum depression is related to sensitivity to mood destabilization by elevated sex hormone concentrations during pregnancy. Our cohort was 199 euthyroid women recruited from a public health obstetrics clinic (63.8% Hispanic, 21.6% Black). After screening and blood draws for hormone measures at pregnancy weeks 31-33, subjects were evaluated during home visits at pregnancy weeks 35-36 as well as postpartum weeks 6 and 12. Evaluations included psychiatric interviews for current and life-time DSM-IV psychiatric history (M.I.N.I.-Plus), subject self-ratings and interviewer ratings for depression and anxiety (Edinburgh Postnatal Depression Scale, Montgomery-Ǻsberg Depression Rating Scale; Spielberger State-Trait Anxiety Inventory, Hamilton Anxiety Inventory), as well as a standardized interview to obtain life-time trauma history. Numerous covariates were included in all regression analyses. Trauma and major depression history were robustly significant predictors of depression and anxiety ratings over the study period when these variables were analyzed individually or in a combined model including FT4 or TBG (p<.001). When analyzed alone, FT4 levels were a less strong but still significant predictor of all depression and anxiety ratings (p<.05) while TBG levels was a significant or nearly significant predictor of most ratings. FT4, TBG and trauma history, but not

Influence of health providers on pediatrics' immunization rate.

PubMed

Al-lela, Omer Q B; Baidi Bahari, Mohd; Al-abbassi, Mustafa G; Salih, Muhannad R M; Basher, Amena Y

2012-12-01

To identify the immunization providers' characteristics associated with immunization rate in children younger than 2 years. A cohort and a cluster sampling design were implemented; 528 children between 18 and 70 months of age were sampled in five public health clinics in Mosul-Iraq. Providers' characterizations were obtained. Immunization rate for the children was assessed. Risk factors for partial immunization were explored using both bivariate analyses and multi-level logistic regression models. Less than half of the children had one or more than one missed dose, considered as partial immunization cases. The study found significant association of immunization rate with provider's type. Two factors were found that strongly impacted on immunization rate in the presence of other factors: birthplace and immunization providers' type.

Specific labeling of the thyroxine binding site in thyroxine-binding globulin: determination of the amino acid composition of a labeled peptide fragment isolated from a proteolytic digest of the derivatized protein.

PubMed

Tabachnick, M; Perret, V

1987-08-01

[125I] Thyroxine has been covalently bound to the thyroxine binding site in thyroxine-binding globulin by reaction with the bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. An average of 0.47 mol of [125I] thyroxine was incorporated per mol protein; nonspecific binding amounted to 8%. A labeled peptide fragment was isolated from a proteolytic digest of the derivatized protein by HPLC and its amino acid composition was determined. Comparison with the amino acid sequence of thyroxine-binding globulin indicated partial correspondence of the labeled peptide with two possible regions in the protein. These regions also coincide with part of the barrel structure present in the closely homologous protein, alpha 1-antitrypsin.

Expression of corticosteroid binding globulin in the rat olfactory system.

PubMed

Dölz, Wilfried; Eitner, Annett; Caldwell, Jack D; Jirikowski, Gustav F

2013-05-01

Glucocorticoids are known to act on the olfactory system although their mode of action is still unclear since nuclear glucocorticoid receptors are mostly absent in the olfactory mucosa. In this study we used immunocytochemistry, in situ hybridization, and RT-PCR to study the expression and distribution of corticosteroid binding globulin (CBG) in the rat olfactory system. Mucosal goblet cells could be immunostained for CBG. Nasal secretion contained measurable amounts of CBG suggesting that CBG is liberated. CBG immunoreactivity was localized in many of the basal cells of the olfactory mucosa, while mature sensory cells contained CBG only in processes as determined by double immunostaining with the olfactory marker protein OMP. This staining was most pronounced in the vomeronasal organ (VNO). The appearance of CBG in the non-sensory and sensory parts of the VNO and in nerve terminals in the accessory bulb indicated axonal transport. Portions of the periglomerular cells, the mitral cells and the tufted cells were also CBG positive. CBG encoding transcripts were confirmed by RT-PCR in homogenates of the olfactory mucosa and VNO. Olfactory CBG may be significant for uptake, accumulation and transport of glucocorticoids, including aerosolic cortisol. Copyright © 2012 Elsevier GmbH. All rights reserved.

[Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction].

PubMed

Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Cumsille, Miguel Angel

2012-05-01

Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis.

PubMed

Deswal, Ritu; Yadav, Arun; Dang, Amita Suneja

2018-02-01

Sex hormone-binding globulin (SHBG) is a glycoprotein which regulates bioavailability of sex steroid hormones. Interest in SHBG has escalated in recent years because of its inverse association with polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II. This meta-analysis was performed to examine the associations of SHBG with PCOS and to correlate serum SHBG levels with various PCOS associated endocrine and metabolic dysregulation as well as to determine the effects of various therapeutic agents on serum SHBG levels in PCOS patients in order to assess the true accuracy of SHBG in the prediction of PCOS. A literature search was performed using Pub-Med, Science direct, google scholar, EMBASE, and Cochrane library. A total of 675 relevant records were identified, of which 62 articles were included. Meta-analysis using a random-effects model was performed using STATA version 13 to calculate standardized mean difference (SMD) with 95% confidence intervals (95 % CIs). SHBG levels in controls were significantly higher than that of PCOS patients (SMD= -0.83, 95%CI = -1.01, -0.64), with significant heterogeneity across studies (I 2 = 93.9% and p=0.000). Our results suggest that the lower serum SHBG levels are associated with the risk of PCOS. SHBG may also play an important role in various metabolic disturbances in PCOS patients. Therapeutic interventions improved SHBG levels in PCOS women which further reduced PCOS associated complications. Therefore, SHBG levels may prove to be a useful biomarker for the diagnosis and treatment of PCOS. Systematic review registration: PROSPERO CRD42017057972 Abbreviations: PCOS: polycystic ovary syndrome; SHBG: sex hormone-binding globulin.

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

21 CFR 610.21 - Limits of potency.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Diphtheria Antitoxin, 500 units per milliliter. Tetanus Antitoxin, 400 units per milliliter. Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container. Antigens Cholera Vaccine, 8 units each of...

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

PubMed Central

Vora, Kalpit A; Porter, Gene; Peng, Roche; Cui, Yan; Pryor, Kellyann; Eiermann, George; Zaller, Dennis M

2009-01-01

Background Current literature suggests that dipeptidyl peptidase IV (DPP-IV; CD26) plays an essential role in T-dependent immune responses, a role that could have important clinical consequences. To rigorously define the role of DPP-IV in the immune system, we evaluated genetic and pharmacological inhibition of the enzyme on T-dependent immune responses in vivo. Results The DPP-IV null animals mounted robust primary and secondary antibody responses to the T dependent antigens, 4-hydroxy-3-nitrophenylacetyl-ovalbumin (NP-Ova) and 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin (NP-CGG), which were comparable to wild type mice. Serum levels of antigen specific IgM, IgG1, IgG2a, IgG2b and IgG3 were similar between the two groups of animals. DPP-IV null animals mounted an efficient germinal center reaction by day 10 after antigen stimulation that was comparable to wild type mice. Moreover, the antibodies produced by DPP-IV null animals after repeated antigenic challenge were affinity matured. Similar observations were made using wild type animals treated with a highly selective DPP-IV inhibitor during the entire course of the experiments. T cell recall responses to ovalbumin and MOG peptide, evaluated by measuring proliferation and IL-2 release from cells isolated from draining lymph nodes, were equivalent in DPP-IV null and wild type animals. Furthermore, mice treated with DPP-IV inhibitor had intact T-cell recall responses to MOG peptide. In addition, female DPP-IV null and wild type mice treated with DPP-IV inhibitor exhibited normal and robust in vivo cytotoxic T cell responses after challenge with cells expressing the male H-Y minor histocompatibility antigen. Conclusion These data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge. PMID:19358731

Proteomic Analysis of Synovial Fluid Obtained From a Dog Diagnosed With Idiopathic Immune-Mediated Polyarthritis.

PubMed

Tan, Wei Miao; Lau, Seng Fong; Ajat, Mokrish; Mansor, Rozaihan; Abd Rani, Puteri Azaziah Megat; Rahmad, Norasfaliza Binti

2017-03-01

This case study is to report the proteins detected by proteomic analysis of synovial fluid from a dog diagnosed with idiopathic immune-mediated polyarthritis, and to compare it with healthy dogs. Synovial fluid was collected via arthrocentesis from a dog diagnosed with immune-mediated polyarthritis. Protein precipitation was performed on the synovial fluid, followed by isoelectric focusing and 2-dimensional gel electrophoresis. The spots on the 2-dimensional gels were analyzed using MALDI-TOF/MS. The results were then analyzed against the MASCOT database. The results from the proteomic analysis revealed an abundance of several types of immunoglobulins together with the presence of complement C4b-binding protein alpha chain. Actin and keratin were also among the proteins detected. Proteomic studies, facilitate a better understanding of the different levels of proteins expressed during disease activity. Potential disease biomarkers can aid in the diagnosis of disease, as well as help in monitoring treatment efficacy and providing prognosis for the patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Corticosteroid-Binding Globulin: Structure-Function Implications from Species Differences

PubMed Central

Gardill, Bernd R.; Vogl, Michael R.; Lin, Hai-Yan; Hammond, Geoffrey L.; Muller, Yves A.

2012-01-01

Corticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 Å crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of β-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species. PMID:23300763

Effect of Dietary Combination of Methionine and Fish Oil on Cellular Immunity and Plasma Fatty Acids in Infectious Bursal Disease Challenged Chickens

PubMed Central

Kasim, Azhar; Yong Meng, Goh; Teck Chwen, Loh; Kamalidehghan, Behnam; Soleimani Farjam, Abdoreza

2013-01-01

This study was carried out to investigate the modulatory effects of dietary methionine and fish oil on immune response, plasma fatty acid profile, and blood parameters of infectious bursal disease (IBD) challenged broiler chickens. A total of 300 one-day-old male broiler chicks were assigned to one of six dietary treatment groups in a 3 × 2 factorial arrangement. There were three levels of fish oil (0, 2.5 and 5.5%), and two levels of methionine (NRC recommendation and twice NRC recommendation). The results showed that the birds fed with 5.5% fish oil had higher total protein, white blood cell count, and IL-2 concentration than those of other groups at 7 days after IBD challenge. Inclusion of fish oil in diet had no effect on IFN-γ concentration. However, supplementation of methionine twice the recommendation enhanced the serum IFN-γ and globulin concentration. Neither of fish oil nor methionine supplementation affected the liver enzymes concentration. It can be suggested that a balance of moderate level of fish oil (2.5%) and methionine level (twice NRC recommendation) might enhance immune response in IBD challenged broiler chickens. PMID:24198724

Pharmaceutical approval update.

PubMed

Gohil, Kunj

2014-11-01

Naltrexone/bupropion (Contrave) for weight management; pembrolizumab (Keytruda) for melanoma; dolutegravir/abacavir/lamivudine (Triumeq) for HIV-1; and immune globulin infusion 10% (human) with recombinant human hyaluronidase (Hyqvia) for primary immunodeficiency.

Respiratory syncytial virus (RSV)

MedlinePlus

RSV; Palivizumab; Respiratory syncytial virus immune globulin; Bronchiolitis - RSV ... Crowe JE. Respiratory syncytial virus. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ...

Factors associated with maternal influenza immunization decision-making. Evidence of immunization history and message framing effects.

PubMed

Frew, Paula M; Owens, Lauren E; Saint-Victor, Diane S; Benedict, Samantha; Zhang, Siyu; Omer, Saad B

2014-01-01

We examined pregnant women's intention to obtain the seasonal influenza vaccine via a randomized controlled study examining the effects of immunization history, message exposure, and sociodemographic correlates. Pregnant women ages 18-50 participated in a randomized message framing study from September 2011 through May 2012. Venue-based sampling was used to recruit racial and ethnic minority women throughout Atlanta, Georgia. Key outcomes were evaluated using bivariate and multivariate analyses. History of influenza immunization was positively associated with intent to immunize during pregnancy [OR=2.31, 90%CI: (1.06, 5.00)]. Significant correlates of intention to immunize included perceived susceptibility to influenza during pregnancy [OR=3.8, 90% CI: (1.75, 8.36)] and vaccine efficacy [OR=10.53, 90% CI: (4.34, 25.50)]. Single message exposure did not influence a woman's intent to vaccinate. Prior immunization, perceived flu susceptibility and perceived vaccine effectiveness promoted immunization intent among this population of pregnant minority women. Vaccine efficacy and disease susceptibility are critical to promoting immunization among women with no history of seasonal influenza immunization, while those who received the vaccine are likely to do so again. These findings provide evidence for the promotion of repeated exposure to vaccine messages emphasizing vaccine efficacy, normative support, and susceptibility to influenza.

Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats.

PubMed

Sadek, Km; Saleh, Ea

2014-12-01

Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase (p < 0.05) in total protein, globulin, immunoglobulin M (IgM) and IgG levels, and total antioxidant capacity. In contrast, significant decrease (p < 0.05) in blood glucose, total cholesterol, low-density lipoprotein-cholesterol, alanine aminotransferase, C-reactive protein, and malondialdehyde levels were observed. Compared with CCl4-intoxicated rats, significant differences in the albumin, triacylglycerol, high-density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, cardiovascular risk factor, calcium and magnesium levels were not detected. The results of the present study showed that fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said "Keep the fast, keep your health". © The Author(s) 2014.

United States Army Medical Materiel Development Activity - 1989

DTIC Science & Technology

1990-01-31

physicians to treat diseases such as Korean Hemorrhagic Fever and Lassa Fever. * J-5 Human Monoclonal Antibody is secreted by cultured hybridomas that were...volunteer studies involving a collaborative effort between WRAIR and the Swiss Serum and Vaccine Institute (SSVI). s Lassa Fever Immune Plasma is an...immune globulin used to treat Lassa fever infections. The collection of human immune plasma in Africa is an ongoing contract effort. USANRIID performs

Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

PubMed Central

Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2013-01-01

Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

Preparation of a Homologous (Human) Intravenous Botulinal Immune Globulin.

DTIC Science & Technology

1983-05-01

lipoprotein ( HDL ) per ml of plasma to ŗ.06 mg/ml for beta- lipoprotein (LDL). Triglyceride and cholesterol levels were intermediate within this...OF LIPOPROTEIN DURING FRACTIONATION "( HDL ) (LDL) Triglyceride Cholesterol cxLipoprotein 8 LipoproteinSample mg/ml mg/ml mg/mi m/ml IVBG-l.A:"Plasma...plasminogen, prekallikrein, triglycerides , cholesterol , alpha- lipoprotein , beta- lipoprotein , clotting factors, fibrinogen and complement

Spaceflight and immune responses of Rhesus monkeys

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

1994-01-01

Evidence from both human and rodent studies indicates that alterations in immunological parameters occur after space flight. The objective of this project is to determine the effects of space flight on immune responses of Rhesus monkeys. The expected significance of the work is a determination of the range of immunological functions of the Rhesus monkey, a primate similar in many ways to man, affected by space flight. Changes in immune responses that could yield alterations in resistance to infection may be determined as well as the duration of alterations in immune responses. Additional information on the nature of cellular interactions for the generation of immune responses may also be obtained.

Immune checkpoint failures in inflammatory myopathies: An overview.

PubMed

Herbelet, Sandrine; De Bleecker, Jan L

2018-06-06

Dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), immune mediated necrotizing myopathy (IMNM) and overlap myositis (OM) are classified as inflammatory myopathies (IM) with involvement of autoimmune features such as autoreactive lymphocytes and autoantibodies. Autoimmunity can be defined as a loss in self-tolerance and attack of autoantigens by the immune system. Self-tolerance is achieved by a group of immune mechanisms occurring in central and periphal lymphoid organs and tissues, called immune checkpoints, that work in synergy to protect the body from harmful immune reactions. Autoimmune disorders appear when immune checkpoints fail. In this review, the different immune checkpoint failures are discussed in DM, PM, IBM and IMNM. Exploring research contribution in each of these immune checkpoints might help to highlight research perspectives in the field and obtain a more complete picture of IM disease pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Bed rest and immunity

NASA Astrophysics Data System (ADS)

Sonnenfeld, Gerald; Aviles, Hernan; Butel, Janet S.; Shearer, William T.; Niesel, David; Pandya, Utpal; Allen, Christopher; Ochs, Hans D.; Blancher, Antoine; Abbal, Michel

2007-02-01

Space flight has been shown to result in altered immune responses. The current study was designed to investigate this possibility by using the bed rest model of some space flight conditions. A large number of women are included as subjects in the study. The hypothesis being tested is: 60 days head-down tilt bed rest of humans will affect the immune system and resistance to infection. Blood, urine and saliva samples will be obtained from bed rest subjects prior to, at intervals during, and after completion of 60 days of head-down tilt bed rest. Leukocyte blastogenesis, cytokine production and virus reactivation will be assessed. The ability of the subjects to respond appropriately to immunization with the neoantigen bacteriophage φX-174 will also be determined. Bed rest is being carried out at MEDES, Toulouse France, and the University of Texas Medical Branch, Galveston, TX. The studies to be carried out in France will also allow assessment of the effects of muscle/bone exercise and nutritional countermeasures on the immune system in addition to the effects of bed rest.

Opsonic and protective activity of immunoglobulin, modified immunoglobulin, and serum against neonatal Escherichia coli K1 infection.

PubMed

Bortolussi, R; Fischer, G W

1986-02-01

Because modified immune serum globulin (M-ISG) has been proposed for therapy in neonatal bacterial sepsis, we evaluated it in a suckling rat model of Escherichia coli K1 sepsis. We compared a M-ISG preparation (lot 2581), which was protective against group B streptococcal (GBS) sepsis, with other M-ISG, standard ISG preparations and with adult and cord serum. All immune serum preparations and sera demonstrated opsonic activity against E. coli K1 and were superior to saline in protecting against death due to E. coli K1 sepsis. Survival rates were higher for one M-ISG preparation (lot 2581) than for randomly selected standard immune serum globulin and cord sera but were similar to adult sera in these protection studies. Therapeutic and opsonic activity of standard immune serum globulin and M-ISG prepared from the same donors were similar, suggesting that the different processes used for their manufacture did not affect these activities. Because the M-ISG preparation studied showed protective activity to both GBS and E. coli K1, we studied it further by adsorbing the preparation with GBS and E. coli K1. Opsonic activity to E. coli K1 was removed by E. coli adsorption but not by adsorption with GBS, indicating that this activity was not due to a single cross-reacting antibody. Empirical therapy with M-ISG prescreened for opsonic activity to both E. coli K1 and GBS may be of clinical value. Trials appear warranted to study the pharmacology and efficacy of M-ISG in septic newborns.

Accuracy of a state immunization registry in the pediatric emergency department.

PubMed

Stecher, Dawn S; Adelman, Raymond; Brinkman, Traci; Bulloch, Blake

2008-02-01

The purpose of this study was to ascertain whether either parental recall or a state immunization registry was as accurate as the medical record in determining immunization status in the emergency department (ED). A convenience sample of children younger than 5 years who presented to the ED between July 2004 and May 2005 were enrolled prospectively. After obtaining informed consent, parents were asked about their child's immunization status. All children then had their immunization data accessed in the Arizona State Immunization Information System. The information obtained from the state registry, as well as the information from the parental interview, was then compared with the information on the medical record obtained from the primary care physician (PCP). Data were analyzed using simple descriptive statistics. A total of 332 children were enrolled in the study. A total of 302 (91%) children enrolled were found in the state database, and 222 (74%) of these had a medical record available for comparison. The database agreed with the PCP record in 130 (59%) cases; parental report agreed with the PCP record in 149 (62%) cases. Although most children can be found in the state immunization registry, it seems to be similar in accuracy to parental recall of immunization status when each is compared with the medical record. This may have been due to either underreporting of immunizations from the community or a delay in updating the state database. At this time, neither parental recall nor the database would accurately determine a child's immunization status during an ED visit.

Microbiota and Mucosal Immunity in Amphibians

PubMed Central

Colombo, Bruno M.; Scalvenzi, Thibault; Benlamara, Sarah; Pollet, Nicolas

2015-01-01

We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota. PMID:25821449

Blood Transfusion

MedlinePlus

... cells) Plasma and cryoprecipitate Gamma globulin Albumin Blood Irradiation A rare but potentially life-threatening complication of ... who are considered to have impaired immune system. Irradiation prevents white cells from attacking. Red Cell Transfusion ...

Sex hormone-binding globulin and the risk for metabolic syndrome in children of South Asian Indian origin.

PubMed

Krishnasamy, Sathya S; Chang, Chih; Wang, Chenxi; Chandiramani, Raina; Winters, Stephen J

2012-01-01

To determine whether the plasma level of sex hormone-binding globulin (SHBG) identifies South Asian Indian children at risk for metabolic syndrome. Adults and their children aged 5 to 9 years were recruited at the annual health fair at the Hindu temple serving the South Asian Indian community in Louisville, Kentucky. Anthropometric data were collected in adults and children, and blood pressure, lipid, and glucose levels were measured in adults. SHBG levels were measured in children using a fingerstick blood sample. In adults, metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. Twelve months later, follow-up anthropometric data were obtained for a portion of the children. The study included 30 sets of parents and 30 children. The prevalence of metabolic syndrome among 310 adults attending the health fair was 42% in men and 39% in women. Children with 1 parent with metabolic syndrome had 24% lower SHBG levels that increased to 55% if both parents had metabolic syndrome. SHBG levels were inversely related to waist circumference and to body mass index percentile. Both SHBG and waist circumference predicted weight gain over 1 year in children. CONCLUSIONS Low SHBG levels were found in South Asian Indian children whose parents had attributes of metabolic syndrome. The dose dependency of SHBG is consistent with inheritance of a genetic trait, and if the results are applicable to other racial/ethnic groups, SHBG may be a useful marker to identify at-risk children for early intervention.

Vaccine-derived poliomyelitis 12 years after infection in Minnesota.

PubMed

DeVries, Aaron S; Harper, Jane; Murray, Andrew; Lexau, Catherine; Bahta, Lynn; Christensen, Jaime; Cebelinski, Elizabeth; Fuller, Susan; Kline, Susan; Wallace, Gregory S; Shaw, Jing H; Burns, Cara C; Lynfield, Ruth

2011-06-16

A 44-year-old woman with long-standing common variable immunodeficiency who was receiving intravenous immune globulin suddenly had paralysis of all four limbs and the respiratory muscles, resulting in death. Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval [CI], 10.9 to 13.2), when her child received the oral poliovirus vaccine. No secondary cases were identified among close contacts or 2038 screened health care workers. Patients with common variable immunodeficiency can be chronically infected with poliovirus, and poliomyelitis can develop despite treatment with intravenous immune globulin.

Immunization history of children with inflammatory bowel disease.

PubMed

Soon, Ing Shian; deBruyn, Jennifer C C; Wrobel, Iwona

2013-04-01

Protection against vaccine-preventable diseases is important in children with inflammatory bowel disease (IBD) due to frequent immunosuppressive therapy use. The chronic relapsing nature and treatment regimen of IBD may necessitate modified timing of immunizations. To evaluate the completeness of immunizations in children with IBD. Immunization records of all children with IBD followed at the Alberta Children's Hospital (Calgary, Alberta) were reviewed. For children with incomplete immunization according to the province of Alberta schedule, the reasons for such were clarified. Demographic data and age at diagnosis were also collected. Immunization records were obtained from 145 (79%) children with IBD. Fifteen children had incomplete routine childhood immunizations, including two with no previous immunizations. The most common incomplete immunizations included hepatitis B (n=9), diphtheria, tetanus, acellular pertussis at 14 to 16 years of age (n=7), and diphtheria, tetanus, acellular pertussis, inactivated polio at four to six years of age (n=6). The reasons for incomplete immunization included use of immunosuppressive therapy at time of scheduled immunization; IBD-related symptoms at time of scheduled immunization; parental refusal; recent move from elsewhere with different immunization schedule; unawareness of routine immunization; and needle phobia. Although the majority of children with IBD had complete childhood immunizations, suboptimal immunizations were present in 10%. With increasing use of immunosuppressive therapy in IBD, physicians caring for children with IBD must periodically evaluate immunization status and ensure the completeness of childhood immunizations.

21 CFR 610.41 - Donor deferral.

Code of Federal Regulations, 2010 CFR

2010-04-01

... infection due to hepatitis B surface antigen (HBsAg) when previously tested under § 610.40(a), (b), and (e) subsequently may donate Source Plasma for use in the preparation of Hepatitis B Immune Globulin (Human...

Mucosal immunity to poliovirus.

PubMed

Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

2011-10-01

The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

Quercetin, Inflammation and Immunity

PubMed Central

Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

2016-01-01

In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

Valganciclovir (VGCV) followed by cytomegalovirus (CMV) hyperimmune globulin compared to VGCV for 200 days in abdominal organ transplant recipients at high risk for CMV infection: A prospective, randomized pilot study.

PubMed

Fleming, James N; Taber, David J; Weimert, Nicole A; Nadig, Satish; McGillicuddy, John W; Bratton, Charles F; Baliga, Prabhakar K; Chavin, Kenneth D

2017-12-01

With the advent of effective antivirals against cytomegalovirus (CMV), use of CMV hyperimmune globulin (HIG) has decreased. Although antiviral prophylaxis in patients at high risk for CMV is effective, many patients still have late infection, never developing antibodies sufficient to achieve immunity. Utilizing a combination of antiviral and CMV HIG may allow patients to achieve immunity and decrease late CMV infections. This was a prospective randomized, open-label, pilot study comparing valganciclovir (VGCV) prophylaxis for 200 days vs VGCV for 100 days followed by CMV HIG in abdominal transplant recipients at high risk for CMV. The primary outcome was a comparison of late CMV disease. Forty patients were randomized to VGCV for 200 days (n = 20) or VGCV for 100 days followed by 3 doses of monthly CMV HIG (n = 20). Numerically, more overall CMV infections occurred in the CMV HIG group (45 vs 20%, P = .09). No differences in overall CMV infections or late CMV disease were seen between groups (20% vs 15%, P = 1.00 and 0 vs 0, P = 1.00). All CMV disease occurred within 200 days, with 63% occurring while patients were on VGCV. No differences were found in toxicities, graft function, or rejection between groups. Patients with CMV infection at any time had a higher body weight than those who did not have an infection (82 vs 95 kg, P = .049). Use of CMV HIG sequentially with prophylaxis may be an effective and affordable prophylactic regimen in abdominal transplant recipients at high risk for CMV, and warrants larger prospective study. Increased monitoring for patients with obesity may be warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Thymic function, anti-thymocytes globulins, and cancer after renal transplantation.

PubMed

Ducloux, Didier; Bamoulid, Jamal; Courivaud, Cécile; Gaugler, Béatrice; Rebibou, Jean-Michel; Ferrand, Christophe; Chalopin, Jean-Marc; Borg, Christophe; Tiberghien, Pierre; Saas, Philippe

2011-07-01

Prolonged CD4 T cell lymphopenia after polyclonal antithymocyte globulins (ATG) is associated with an increased rate of cancers. Here, we examined whether pre-transplant thymic function estimated by TREC levels is predictive of cancer occurrence following ATG treatment. The impact of TREC on cancer occurrence was analyzed in 115 consecutive incident renal transplant recipients having received ATG. Mean follow-up was 7.5±2.6years. After ATG induction, patients with the lowest pre-transplant TREC values had lower post-transplant CD4(+) and CD4(+) CD45RA(+) CD45RO(-) T cell counts, and a higher frequency of T cells with a regulatory phenotype (CD127(+)CD4(+)CD25(+)Foxp3(+)). Log-transformed pre-transplant TREC values were significantly lower in patients who developed cancer after transplantation (p<0.0001). The cumulative incidence of cancer was higher in patients having the lowest pre-transplant TREC values (T1 [low]: 47.4%, T2 [medium]: 12.5%, and T3 [high]: 2.7%; p<0.0001). In multivariate analysis, pre-transplant TREC value was the only predictive factor of cancer (HR, 0.39; 95% CI, 0.16 to 0.97, for one log (TREC/10(6) PBMC); p=0.046). Pre-transplant thymic function is associated with an increased rate of post-transplant cancer in patients having received ATG. Omitting ATG in recipients with low pre-transplant TREC values should be considered. Copyright © 2011 Elsevier B.V. All rights reserved.

[The protective role of postvaccinal immunity in mumps in children].

PubMed

Zheleznikova, G F; Ivanova, V V; Bekhtereva, M K; Gnilevskaia, Z U; Monakhova, N E; Novozhilova, E V; Goleva, O V; Sizemov, A N

2000-01-01

The immunological study of children with infectious parotitis (IP) without complications and with such complications as pancreatitis, meningitis or orchitis in the glandular form was carried out. In accordance with the previously proposed principle, 4 types of immune response (IR) were established on the basis of differences in initial resistance and the IR profile: cell-mediated immunity (types I and III) and humoral immunity (types II and IV). The patients included nonvaccinated children, as well as children vaccinated on epidemic indications, 3-6, 7-9, 10 and more years before infection. The comparative analysis of the number of IP cases with and without complications in the groups of children, divided according to their immunization history and the type of IR, revealed that postvaccinal immunity in children vaccinated on epidemic indications (less than a month ago) or 3-6 years before infection had protective potential, sufficient for the prevention of complicated forms of IP. Immunity obtained 7-9 years ago was effective for the protection from IP complications only in cell-mediated, but not humoral IR. Postvaccinal immunity obtained more than 10 years ago did not ensure the decrease in the occurrence of complicated forms of IP (in comparison with that in nonvaccinated patients) in children with any type of IR.

Immune response

MedlinePlus

Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... normal and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense ...

T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT.

PubMed

Luo, Yi; Xiao, Haowen; Lai, Xiaoyu; Shi, Jimin; Tan, Yamin; He, Jingsong; Xie, Wanzhuo; Zheng, Weiyan; Zhu, Yuanyuan; Ye, Xiujin; Yu, Xiaohong; Cai, Zhen; Lin, Maofang; Huang, He

2014-10-23

We developed an approach of T-cell-replete haploidentical hematopoietic stem cell transplantation (HSCT) with low-dose anti-T-lymphocyte globulin and prospectively compared outcomes of all contemporaneous T-cell-replete HSCT performed at our center using matched sibling donors (MSDs), unrelated donors (URDs), and haploidentical related donors (HRDs). From 2008 to 2013, 90 patients underwent MSD-HSCT, 116 underwent URD-HSCT, and 99 underwent HRD-HSCT. HRDs were associated with higher incidences of grades 2 to 4 (42.4%) and severe acute graft-versus-host disease (17.2%) and nonrelapse mortality (30.5%), compared with MSDs (15.6%, 5.6%, and 4.7%, respectively; P < .05), but were similar to URDs, even fully 10/10 HLA-matched URDs. For high-risk patients, a superior graft-versus-leukemia effect was observed in HRD-HSCT, with 5-year relapse rates of 15.4% in HRD-HSCT, 28.2% in URD-HSCT (P = .07), and 49.9% in MSD-HSCT (P = .002). Furthermore, 5-year disease-free survival rates were not significantly different for patients undergoing transplantation using 3 types of donors, with 63.6%, 58.4%, and 58.3% for MSD, URD, and HRD transplantation, respectively (P = .574). Our data indicate that outcomes after HSCT from suitably matched URDs and HRDs with low-dose anti-T-lymphocyte globulin are similar and that HRD improves outcomes of patients with high-risk leukemia. This trial was registered at www.chictr.org (Chinese Clinical Trial Registry) as #ChiCTR-OCH-12002490. © 2014 by The American Society of Hematology.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

Testicular defense systems: immune privilege and innate immunity

PubMed Central

Zhao, Shutao; Zhu, Weiwei; Xue, Shepu; Han, Daishu

2014-01-01

The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation. PMID:24954222

A peptide derived from enzymatic digestion of globulins from amaranth shows strong affinity binding to the replication origin of Tomato yellow leaf curl virus reducing viral replication in Nicotiana benthamiana.

PubMed

Mendoza-Figueroa, J S; Kvarnheden, A; Méndez-Lozano, J; Rodríguez-Negrete, E-A; Arreguín-Espinosa de Los Monteros, R; Soriano-García, M

2018-02-01

Tomato yellow leaf curl virus (TYLCV; genus Begomovirus; family Geminiviridae) infects mainly plants of the family Solanaceae, and the infection induces curling and chlorosis of leaves, dwarfing of the whole plant, and reduced fruit production. Alternatives for direct control of TYLCV and other geminiviruses have been reported, for example, the use of esterified whey proteins, peptide aptamer libraries or artificial zinc finger proteins. The two latter alternatives affect directly the replication of TYLCV as well as of other geminiviruses because the replication structures and sequences are highly conserved within this virus family. Because peptides and proteins offer a potential solution for virus replication control, in this study we show the isolation, biochemical characterization and antiviral activity of a peptide derived from globulins of amaranth seeds (Amaranthus hypochondriacus) that binds to the replication origin sequence (OriRep) of TYLCV and affects viral replication with a consequent reduction of disease symptoms in Nicotiana benthamiana. Aromatic peptides obtained from papain digests of extracted globulins and albumins of amaranth were tested by intrinsic fluorescent titration and localized surface resonance plasmon to analyze their binding affinity to OriRep of TYLCV. The peptide AmPep1 (molecular weight 2.076 KDa) showed the highest affinity value (Kd = 1.8 nM) for OriRep. This peptide shares a high amino acid similarity with a part of an amaranth 11S globulin, and the strong affinity of AmPep1 could be explained by the presence of tryptophan and lysine facilitating interaction with the secondary structure of OriRep. In order to evaluate the effect of the peptide on in vitro DNA synthesis, rolling circle amplification (RCA) was performed using as template DNA from plants infected with TYLCV or another begomovirus, pepper huasteco yellow vein virus (PHYVV), and adding AmPep1 peptide at different concentrations. The results showed a decrease in

Canine cancer screening via ultraviolet absorbance and fluorescence spectroscopy of serum proteins

NASA Astrophysics Data System (ADS)

Dickerson, Bryan D.; Geist, Brian L.; Spillman, William B., Jr.; Robertson, John L.

2007-11-01

A cost-effective optical cancer screening and monitoring technique was demonstrated in a pilot study of canine serum samples and was patented for commercialization. Compared to conventional blood chemistry analysis methods, more accurate estimations of the concentrations of albumin, globulins, and hemoglobin in serum were obtained by fitting the near UV absorbance and photoluminescence spectra of diluted serum as a linear combination of component reference spectra. Tracking these serum proteins over the course of treatment helped to monitor patient immune response to carcinoma and therapy. For cancer screening, 70% of dogs with clinical presentation of cancer displayed suppressed serum hemoglobin levels (below 20 mg/dL) in combination with atypical serum protein compositions, that is, albumin levels outside of a safe range (from 4 to 8 g/dL) and globulin levels above or below a more normal range (from 1.7 to 3.7 g/dL). Of the dogs that met these criteria, only 20% were given a false positive label by this cancer screening test.

[Rational method of obtaining sera with a high titre of virus-neutralizing antibodies. Report 2].

PubMed

Kravchenko, A T; Omel'chenko, T N; Tsetlin, E M

1978-02-01

In addition to report I (ZHMEI, 1977, No. 1) a study was made of 9 more schemes of rabbit immunization with the poliomyelitis virus, type I, for the purpose of obtaining the neutralizing sera of high titre. Vitamins A and C were used in the experiments in the capacity of the activators of the organism reaction; Freund's adjuvant of different make was tested; different reimmunization periods and different amounts of the adjuvant were administered. Titration of rabbit sera in the process of immunization and reimmunization showed immunization into the lymph nodes with the subsequent single reimmunization in one month to be the most effective and economical method of obtaining high effective sera.

Influence of extremely low frequency electromagnetic fields on growth performance, innate immune response, biochemical parameters and disease resistance in rainbow trout, Oncorhynchus mykiss.

PubMed

Nofouzi, Katayoon; Sheikhzadeh, Najmeh; Mohamad-Zadeh Jassur, Davood; Ashrafi-Helan, Javad

2015-06-01

The effects of extremely low frequency electromagnetic fields on rainbow trout growth performance, innate immunity and biochemical parameters were studied. Rainbow trout (17-18 g) were exposed to electromagnetic fields (15 Hz) at 0.01, 0.1, 0.5, 5 and 50 µT, for 1 h daily over period of 60 days. Growth performance of fish improved in different treatment groups, especially at 0.1, 0.5, 5 and 50 µT. Immunological parameters, specifically hemagglutinating titer, total antiprotease and α1-antiprotease levels in treatment groups, were also enhanced. Total protein and globulin contents in the serum of fish exposed to 0.1, 0.5, 5 and 50 µT were significantly higher than those in the control group. No significant differences were found in serum enzyme activities, namely aspartate aminotransferase and alanine aminotransferase of fish in all treatment groups. Conversely, alkaline phosphatase level decreased in fish exposed to 0.01 and 50 µT electromagnetic fields. Meanwhile, electromagnetic induction at 0.1, 0.5, 5 and 50 µT enhanced fish protection against Yersinia ruckeri. These results indicated that these specific electromagnetic fields had possible effects on growth performance, nonspecific immunity and disease resistance of rainbow trout.

Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types

PubMed Central

Ferreira, Lauren; Macaulay, Iain C.; Stubbington, Michael J.T.

2017-01-01

The immune system of vertebrate species consists of many different cell types that have distinct functional roles and are subject to different evolutionary pressures. Here, we first analyzed conservation of genes specific for all major immune cell types in human and mouse. Our results revealed higher gene turnover and faster evolution of trans-membrane proteins in NK cells compared with other immune cell types, and especially T cells, but similar conservation of nuclear and cytoplasmic protein coding genes. To validate these findings in a distant vertebrate species, we used single-cell RNA sequencing of lck:GFP cells in zebrafish and obtained the first transcriptome of specific immune cell types in a nonmammalian species. Unsupervised clustering and single-cell TCR locus reconstruction identified three cell populations, T cells, a novel type of NK-like cells, and a smaller population of myeloid-like cells. Differential expression analysis uncovered new immune-cell–specific genes, including novel immunoglobulin-like receptors, and neofunctionalization of recently duplicated paralogs. Evolutionary analyses confirmed the higher gene turnover of trans-membrane proteins in NK cells compared with T cells in fish species, suggesting that this is a general property of immune cell types across all vertebrates. PMID:28087841

Lasting monitoring of immune state in patients with coronary atherosclerosis

NASA Astrophysics Data System (ADS)

Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.

2007-02-01

Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.

APRIL:TACI axis is dispensable for the immune response to rabies vaccination.

PubMed

Haley, Shannon L; Tzvetkov, Evgeni P; Lytle, Andrew G; Alugupalli, Kishore R; Plummer, Joseph R; McGettigan, James P

2017-08-01

There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)-expressed by B cells in various stages of maturation-with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent

Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores.

PubMed

Key, T J; Roe, L; Thorogood, M; Moore, J W; Clark, G M; Wang, D Y

1990-07-01

Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

TERMINATION OF TOLERANCE TO HUMAN GAMMA GLOBULIN IN MICE BY ANTIGEN AND BACTERIAL LIPOPOLYSACCHARIDE (ENDOTOXIN)

PubMed Central

Chiller, Jacques M.; Weigle, William O.

1973-01-01

Bacterial lipopolysaccharides (endotoxin) allowed the circumvention of the thymus-derived (T) cell helper function otherwise required for the antibody response in mice to human gamma globulin (HGG). In an analogous fashion, the state of tolerance to HGG, existing at a time when bone marrow-derived (B) cells had lost their unresponsiveness, could be terminated by the injection of both immunogenic HGG and endotoxin, but by neither given alone. However, no effect on tolerance to HGG could be observed when this regimen was followed at a time when B cells were tolerant. After the spontaneous recovery from tolerance in B cells, it seemed that specific priming was occurring in that population. This phenomenon was observed either by the injection of endotoxin and HGG or by the adoptive transfer of cells into irradiated hosts. These data have been discussed in the light of potential autoimmune manifestations that could theoretically follow a simultaneous gram-negative bacterial infection along with a release of self-antigen. PMID:4120288

Fast-track surgery improves postoperative clinical recovery and cellular and humoral immunity after esophagectomy for esophageal cancer.

PubMed

Chen, Lantao; Sun, Lixin; Lang, Yaoguo; Wu, Jun; Yao, Lei; Ning, Jinfeng; Zhang, Jinfeng; Xu, Shidong

2016-07-11

Our aim was to investigate the influence of FTS on human cellular and humoral immunity using a randomized controlled clinical study in esophageal cancer patients. Between October 2013 and December 2014, 276 patients with esophageal cancer in our department were enrolled in the study. The patients were randomized into two groups: FTS pathway group and conventional pathway group. The postoperative hospital stay, hospitalization expenditure, and postoperative complications were recorded. The markers of inflammatory and immune function were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (POD), including serum level of interleukin-6 (IL-6), C-reactive protein (CRP), serum globulin, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA) and lymphocyte subpopulations (CD3 lymphocytes, CD4 lymphocytes, CD8 lymphocytes and the CD4/CD8 ratio) in the patients between the two groups. In all, 260 patients completed the study: 128 in the FTS group and 132 in the conventional group. We found implementation of FTS pathway decreases postoperative length of stay and hospital charges (P < 0.05). In addition, inflammatory reactions, based on IL-6 and CRP levels, were less intense following FTS pathway compared to conventional pathway on POD1 and POD3 (P < 0.05). On POD1 and POD3, the levels of IgG, IgA, CD3 lymphocytes, CD4 lymphocytes and the CD4/CD8 ratio in FTS group were significantly higher than those in control group (All P < 0.05). However, there were no differences in the level of IgM and CD8 lymphocytes between the two groups. FTS improves postoperative clinical recovery and effectively inhibited release of inflammatory factors via the immune system after esophagectomy for esophageal cancer. ChiCTR-TRC-13003562 , the date of registration: August 29, 2013.

Grizzly bear corticosteroid binding globulin: Cloning and serum protein expression.

PubMed

Chow, Brian A; Hamilton, Jason; Alsop, Derek; Cattet, Marc R L; Stenhouse, Gordon; Vijayan, Mathilakath M

2010-06-01

Serum corticosteroid levels are routinely measured as markers of stress in wild animals. However, corticosteroid levels rise rapidly in response to the acute stress of capture and restraint for sampling, limiting its use as an indicator of chronic stress. We hypothesized that serum corticosteroid binding globulin (CBG), the primary transport protein for corticosteroids in circulation, may be a better marker of the stress status prior to capture in grizzly bears (Ursus arctos). To test this, a full-length CBG cDNA was cloned and sequenced from grizzly bear testis and polyclonal antibodies were generated for detection of this protein in bear sera. The deduced nucleotide and protein sequences were 1218 bp and 405 amino acids, respectively. Multiple sequence alignments showed that grizzly bear CBG (gbCBG) was 90% and 83% identical to the dog CBG nucleotide and amino acid sequences, respectively. The affinity purified rabbit gbCBG antiserum detected grizzly bear but not human CBG. There were no sex differences in serum total cortisol concentration, while CBG expression was significantly higher in adult females compared to males. Serum cortisol levels were significantly higher in bears captured by leg-hold snare compared to those captured by remote drug delivery from helicopter. However, serum CBG expression between these two groups did not differ significantly. Overall, serum CBG levels may be a better marker of chronic stress, especially because this protein is not modulated by the stress of capture and restraint in grizzly bears. Copyright 2010 Elsevier Inc. All rights reserved.

Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts.

PubMed

Gansser, D; Spiteller, G

1995-01-01

A test system is described, which allows the search for compounds interfering with human sex hormone-binding globulin (SHBG) even in complex plant extracts. The method has been evaluated and applied to Urtica dioica root extracts. The lignan secoisolariciresinol (5) as well as a mixture of isomeric (11 E)-9,10,13-trihydroxy-11-octadecenoic and (10 E)-9,12,13-trihydroxy-10-octadecenoic acids (3 and 4, resp.) were demonstrated to reduce binding activity of human SHBG. Methylation of the mixture of 3 and 4 increased its activity about 10-fold.

Intravital imaging of cutaneous immune responses.

PubMed

Nakamizo, Satoshi; Egawa, Gyohei; Bing, Jasmine Tan Kah; Kabashima, Kenji

2018-05-25

Various immune cells are present in the skin and modulate the cutaneous immune response. In order to capture such dynamic phenomena, intravital imaging is an important technique and there is a possibility to provide substantial information that is not available using conventional histological analysis. Multiphoton microscope enable direct, three-dimensional, minimally invasive imaging of biological samples with high spatiotemporal resolution, and now become the main method for intravital imaging studies. Here, we will introduce the latest knowledge obtained by intravital imaging of the skin. Copyright © 2018 Elsevier Inc. All rights reserved.

Immunological unresponsiveness in mice. II. Cellular basis of immunological unresponsiveness induced in foetal and neonatal mice by transfer of human gamma-globulin by the maternal route.

PubMed Central

Shinka, S; Komatsu, T; Dohi, Y; Amano, T

1979-01-01

The cellular basis of the mechanism of immunological tolerance to human gamma-globulin (H gamma G) induced in foetal and neonatal mice by materno-foetal or materno-neonatal transfer after a single injection of tolerogen (deaggregated H gamma G) into the mothers was investigated using a cell transfer system and assays of passive haemagglutinating antibodies and plaque-forming cells to H gamma G. The results demonstrated that B cells are mainly involved in the tolerance induced on the fourteenth day of gestation, whereas inactivation of T cells may account for the tolerance induced on the eighteenth day of gestation and in the neonatal stage. Treatment of the mothers with tolerogen and then anti-H gamma G serum reduced the tolerance induced on the fourteenth day of gestation, but did not affect that induced on the eighteenth day of gestation and in the neonatal stage. Cell transfer experiments showed that B-cell tolerance induced on the fourteenth day of gestation was prevented by passive antibody, while T-cell tolerance induced on the eighteenth day of gestation and in the neonatal stage was not affected by passive antibody. Assay of the anti-DNP antibody response after immunization with DNP10-H gamma G showed that treatment of mice with the tolerogen on the eighteenth day of gestation, but not the fourteenth day of gestation, inactivated H gamma G-reactive helper cells. The significance of these results is discussed in relation to the results of the cell transfer experiments described as above. PMID:89080

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

PubMed Central

Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

2016-01-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices

PubMed Central

Vellozzi, Claudia; Reingold, Arthur; Harris, Aaron; Haber, Penina; Ward, John W.; Nelson, Noele P.

2018-01-01

Summary Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged <19 years who have not been vaccinated previously. ACIP recommends vaccination of adults at risk for HBV infection, including universal vaccination of adults in settings in which a high proportion have risk factors for HBV infection and vaccination of adults requesting protection from HBV without acknowledgment of a specific risk factor. These recommendations also provide CDC guidance for postexposure prophylaxis following occupational and other exposures. This report also briefly summarizes previously published American Association for the Study of Liver Diseasest guidelines for maternal antiviral therapy to reduce perinatal HBV transmission. PMID:29939980

Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.

PubMed

Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

2018-03-01

Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage. © 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Differential expression and elution behavior of basic 7S globulin among cultivars under hot water treatment of soybean seeds.

PubMed

Fujiwara, Keigo; Cabanos, Cerrone; Toyota, Kenji; Kobayashi, Yasunori; Maruyama, Nobuyuki

2014-06-01

Basic 7S globulin (Bg7S), which accumulates in mature soybean (Glycine max) seeds, is an extracellular matrix protein. A large amount of Bg7S is synthesized de novo and is eluted from soybean seeds when immersed in 50-60°C water (hot water treatment, HWT). However, the Bg7S elution mechanism remains unclear. Under HWT, the seeds probably undergo heat stress and flooding stress. To obtain fundamental knowledge related to how Bg7S is eluted from hot-water-treated seeds, this study compared Bg7S elution among soybean cultivars having different flooding tolerance during pre-germination. The amounts of Bg7S eluted from seeds varied significantly among cultivars. Elution was suppressed by seed coats regarded as preventing the leakage of seed contents by rapid water imbibition. Furthermore, Bg7S expression levels differed among cultivars, although the difference did not result from any variation in Bg7S promoter sequences. However, the expression levels of Bg7S under HWT were not associated with the flooding tolerance level. Immunoelectron microscopy revealed that the Bg7S accumulated in the intercellular space of hot-water-treated seeds. Plasma membrane shrinkage was observed. The main proteins eluted from seeds under HWT were located in the extracellular space. This study clarified the mechanism of Bg7S elution from seeds under HWT. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types.

PubMed

Carmona, Santiago J; Teichmann, Sarah A; Ferreira, Lauren; Macaulay, Iain C; Stubbington, Michael J T; Cvejic, Ana; Gfeller, David

2017-03-01

The immune system of vertebrate species consists of many different cell types that have distinct functional roles and are subject to different evolutionary pressures. Here, we first analyzed conservation of genes specific for all major immune cell types in human and mouse. Our results revealed higher gene turnover and faster evolution of trans -membrane proteins in NK cells compared with other immune cell types, and especially T cells, but similar conservation of nuclear and cytoplasmic protein coding genes. To validate these findings in a distant vertebrate species, we used single-cell RNA sequencing of lck:GFP cells in zebrafish and obtained the first transcriptome of specific immune cell types in a nonmammalian species. Unsupervised clustering and single-cell TCR locus reconstruction identified three cell populations, T cells, a novel type of NK-like cells, and a smaller population of myeloid-like cells. Differential expression analysis uncovered new immune-cell-specific genes, including novel immunoglobulin-like receptors, and neofunctionalization of recently duplicated paralogs. Evolutionary analyses confirmed the higher gene turnover of trans -membrane proteins in NK cells compared with T cells in fish species, suggesting that this is a general property of immune cell types across all vertebrates. © 2017 Carmona et al.; Published by Cold Spring Harbor Laboratory Press.

Hepatitis A Test

MedlinePlus

... of immune globulin instead of the vaccine for post-exposure protection. Although hepatitis A IgM antibodies are considered diagnostic for acute infection with hepatitis A, there has been increasing use of the test in people who do not have signs and ...

Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens

PubMed Central

Uddowla, Sabena; Freytag, Lucy C.; Clements, John D.

2007-01-01

In this study, we compare four different adjuvants, LT(R192G), CpG ODN, MPL®TDM and alum, for their ability to affect the magnitude, distribution, and duration of antibody responses against F1-V, the lead-candidate antigen for the next generation vaccine against plague, in a murine model. In addition, three different routes of immunization – intranasal (IN), transcutaneous (TC), and subcutaneous (SC), were compared with each adjuvant. Since aerosol exposure to biological warfare agents is of primary concern, both serum and bronchioalveolar lavage (BAL) were analyzed for antigen-specific antibody responses. The most significant findings of the study reported here are that 1) the adjuvant influences the Type 1/Type 2 balance of the antibody response in both the serum and BAL, 2) mucosal immunization is not necessary to obtain F1-V-specific BAL responses, 3) non-traditional adjuvants such as LT(R192G) work when delivered SC, 4) the route of immunization affects the magnitude of the immune response, and 5) F1-V is highly immunogenic by some routes even in the absence of an exogenously applied adjuvant. These studies provide important insights into the influence of different classes of adjuvants on the immune outcome in biodefense vaccines and for development of new generation vaccines against other pathogens as well. PMID:17933440

Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

PubMed

Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

2015-06-23

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

U.S. Immunization program adult immunization activities and resources.

PubMed

Woods, LaDora O; Bridges, Carolyn B; Graitcer, Samuel B; Lamont, Brock

2016-04-02

Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve vaccination of

U.S. Immunization program adult immunization activities and resources

PubMed Central

Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

2016-01-01

ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve

Seasonal trends in nesting leatherback turtle (Dermochelys coriacea) serum proteins further verify capital breeding hypothesis

PubMed Central

Perrault, Justin R.; Wyneken, Jeanette; Page-Karjian, Annie; Merrill, Anita; Miller, Debra L.

2014-01-01

Serum protein concentrations provide insight into the nutritional and immune status of organisms. It has been suggested that some marine turtles are capital breeders that fast during the nesting season. In this study, we documented serum proteins in neophyte and remigrant nesting leatherback sea turtles (Dermochelys coriacea). This allowed us to establish trends across the nesting season to determine whether these physiological parameters indicate if leatherbacks forage or fast while on nesting grounds. Using the biuret method and agarose gel electrophoresis, total serum protein (median = 5.0 g/dl) and protein fractions were quantified and include pre-albumin (median = 0.0 g/dl), albumin (median = 1.81 g/dl), α1-globulin (median = 0.90 g/dl), α2-globulin (median = 0.74 g/dl), total α-globulin (median = 1.64 g/dl), β-globulin (median = 0.56 g/dl), γ-globulin (median = 0.81 g/dl) and total globulin (median = 3.12 g/dl). The albumin:globulin ratio (median = 0.59) was also calculated. Confidence intervals (90%) were used to establish reference intervals. Total protein, albumin and total globulin concentrations declined in successive nesting events. Protein fractions declined at less significant rates or remained relatively constant during the nesting season. Here, we show that leatherbacks are most likely fasting during the nesting season. A minimal threshold of total serum protein concentrations of around 3.5–4.5 g/dl may physiologically signal the end of the season's nesting for individual leatherbacks. The results presented here lend further insight into the interaction between reproduction, fasting and energy reserves and will potentially improve the conservation and management of this imperiled species. PMID:27293623

A minimal model for multiple epidemics and immunity spreading.

PubMed

Sneppen, Kim; Trusina, Ala; Jensen, Mogens H; Bornholdt, Stefan

2010-10-18

Pathogens and parasites are ubiquitous in the living world, being limited only by availability of suitable hosts. The ability to transmit a particular disease depends on competing infections as well as on the status of host immunity. Multiple diseases compete for the same resource and their fate is coupled to each other. Such couplings have many facets, for example cross-immunization between related influenza strains, mutual inhibition by killing the host, or possible even a mutual catalytic effect if host immunity is impaired. We here introduce a minimal model for an unlimited number of unrelated pathogens whose interaction is simplified to simple mutual exclusion. The model incorporates an ongoing development of host immunity to past diseases, while leaving the system open for emergence of new diseases. The model exhibits a rich dynamical behavior with interacting infection waves, leaving broad trails of immunization in the host population. This obtained immunization pattern depends only on the system size and on the mutation rate that initiates new diseases.

[Experimental xenogenic immune pancreatitis. --Immunohistological, enzyme histochemical and ultrastructural studies (author's transl)].

PubMed

Nizze, H

1975-01-01

Repeated intraperitoneal injections of anti-mouse pancreas rabbit serum or of anti-mouse pancreas guinea pig serum produce a chronical sclerotizing pancreatitis. This study has the aim to contribute to the further elucidation of the changes which occur in the acinar cells, as well as to the etiology and pathogenesis of immune pancreatitis, by means of immunohistological, enzyme histochemical and electron microscopic studies. Anti-mouse pancreas rabbit serum was obtained by sensitization of rabbits with an admixture of AB-mouse pancreas extract (100,000 g - supernatant) and complete Freund's adjuvant [details see NIZZE, Exp. Path. (1975a)]. The presence of precipitating mouse pancreas antibodies in the rabbit serum was ascertained by the agargel diffusion test according to Duchterlony (1958). The experiments were performed with 54 adult male white mice (AB colony strain) of 22 to 30 g.b.s. (averagely 26 g). The animals were divided into 4 groups which were treated as follows: 1. 24 mice with anti-mouse pancreas rabbit serum, 2. 12 mice with rabbit normal serum, 3. 12 mice with physiological saline, 4. 6 mice remained untreated (controls) Always 4 animals of the group 1 as well as each 2 of the groups 2 and 3 were administered in total 1, 3, 5, 9, 17 or 33 intraperitoneal injections of 0.3 ml of the correspondent serum or with physiological saline within 3 hours, 1, 2, 4, 8 or 16 days. The last injection was regularly applied 3 hours before sacrification by decapitation. The time of sacrification was always at 11.00 o'clock a.m. For immunohistological and enzyme histochemical investigations 10 mum thick cryostat sections were prepared consisting of pancreatic specimens piled up to a bloc. In each case the tissue samples were taken from the experimental animals and from one control animal sacrificed at the same day. The sections were incubated in FITC-labelled anti-rabbit globulin goat serum at room temperature for 30 min in a moist chamber. For control of specificity

Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

PubMed

Muscoplat, Miriam Halstead; Rajamani, Sripriya

2017-01-01

The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

How do plants achieve immunity? Defence without specialized immune cells.

PubMed

Spoel, Steven H; Dong, Xinnian

2012-01-25

Vertebrates have evolved a sophisticated adaptive immune system that relies on an almost infinite diversity of antigen receptors that are clonally expressed by specialized immune cells that roam the circulatory system. These immune cells provide vertebrates with extraordinary antigen-specific immune capacity and memory, while minimizing self-reactivity. Plants, however, lack specialized mobile immune cells. Instead, every plant cell is thought to be capable of launching an effective immune response. So how do plants achieve specific, self-tolerant immunity and establish immune memory? Recent developments point towards a multilayered plant innate immune system comprised of self-surveillance, systemic signalling and chromosomal changes that together establish effective immunity.

[Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

PubMed

Wang, Jun-Ye; Ma, Guo-Wei; Dai, Shu-Qin; Rong, Tie-Hua; Wang, Xin; Lin, Peng; Ye, Wen-Feng; Zhang, Lan-Jun; Li, Xiao-Dong; Zhang, Xu; Yao, Guang-Yu

2007-07-01

Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.

Voluntarily Reported Immunization Registry Data: Reliability and Feasibility to Predict Immunization Rates, San Diego, California, 2013.

PubMed

Madewell, Zachary J; Wester, Robert B; Wang, Wendy W; Smith, Tyler C; Peddecord, K Michael; Morris, Jessica; DeGuzman, Heidi; Sawyer, Mark H; McDonald, Eric C

Accurate data on immunization coverage levels are essential to public health program planning. Reliability of coverage estimates derived from immunization information systems (IISs) in states where immunization reporting by medical providers is not mandated by the state may be compromised by low rates of participation. To overcome this problem, data on coverage rates are often acquired through random-digit-dial telephone surveys, which require substantial time and resources. This project tested both the reliability of voluntarily reported IIS data and the feasibility of using these data to estimate regional immunization rates. We matched telephone survey records for 553 patients aged 19-35 months obtained in 2013 to 430 records in the San Diego County IIS. We assessed concordance between survey data and IIS data using κ to measure the degree of nonrandom agreement. We used multivariable logistic regression models to investigate differences among demographic variables between the 2 data sets. These models were used to construct weights that enabled us to predict immunization rates in areas where reporting is not mandated. We found moderate agreement between the telephone survey and the IIS for the diphtheria, tetanus, and acellular pertussis (κ = 0.49), pneumococcal conjugate (κ = 0.49), and Haemophilus influenzae type b (κ = 0.46) vaccines; fair agreement for the varicella (κ = 0.39), polio (κ = 0.39), and measles, mumps, and rubella (κ = 0.35) vaccines; and slight agreement for the hepatitis B vaccine (κ = 0.17). Consistency in factors predicting immunization coverage levels in a telephone survey and IIS data confirmed the feasibility of using voluntarily reported IIS data to assess immunization rates in children aged 19-35 months.

Voluntarily Reported Immunization Registry Data: Reliability and Feasibility to Predict Immunization Rates, San Diego, California, 2013

PubMed Central

Wester, Robert B.; Wang, Wendy W.; Smith, Tyler C.; Peddecord, K. Michael; Morris, Jessica; DeGuzman, Heidi; Sawyer, Mark H.; McDonald, Eric C.

2017-01-01

Objectives: Accurate data on immunization coverage levels are essential to public health program planning. Reliability of coverage estimates derived from immunization information systems (IISs) in states where immunization reporting by medical providers is not mandated by the state may be compromised by low rates of participation. To overcome this problem, data on coverage rates are often acquired through random-digit-dial telephone surveys, which require substantial time and resources. This project tested both the reliability of voluntarily reported IIS data and the feasibility of using these data to estimate regional immunization rates. Methods: We matched telephone survey records for 553 patients aged 19-35 months obtained in 2013 to 430 records in the San Diego County IIS. We assessed concordance between survey data and IIS data using κ to measure the degree of nonrandom agreement. We used multivariable logistic regression models to investigate differences among demographic variables between the 2 data sets. These models were used to construct weights that enabled us to predict immunization rates in areas where reporting is not mandated. Results: We found moderate agreement between the telephone survey and the IIS for the diphtheria, tetanus, and acellular pertussis (κ = 0.49), pneumococcal conjugate (κ = 0.49), and Haemophilus influenzae type b (κ = 0.46) vaccines; fair agreement for the varicella (κ = 0.39), polio (κ = 0.39), and measles, mumps, and rubella (κ = 0.35) vaccines; and slight agreement for the hepatitis B vaccine (κ = 0.17). Conclusions: Consistency in factors predicting immunization coverage levels in a telephone survey and IIS data confirmed the feasibility of using voluntarily reported IIS data to assess immunization rates in children aged 19-35 months. PMID:28379785

Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis. [X radiation, mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.

1978-12-01

The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log/sub 10/PD/sub 50/ values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplantedmore » Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain.« less

How safe is the use of chlorpyrifos: Revelations through its effect on layer birds.

PubMed

Singh, P P; Kumar, Ashok; Chauhan, R S; Pankaj, P K

2016-07-01

The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF) insecticide after oral administration in layer chickens. A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose) for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

A new immunization procedure for the obtention of anti-leucine enkephalin antibodies. Part I. Immunization procedure and physicochemical characteristics of antibodies.

PubMed

Cupo, A; Vion-Dury, J; Jarry, T

1986-10-01

We described here a new immunization procedure to obtain high titre and high specific antibodies against Leu-enkephalin (LE). The immunogen form is composed of one part of LE conjugate and one part of LE-Arg6 conjugate. We have observed an increase of titre, affinity and specificity of the antibodies in the coimmunization procedure compared to those obtained by conventional immunization involving only the LE conjugate. The Leu-enkephalin antibodies exhibit a high affinity (KD 8 X 10(-12) M) and we are able to detect the Leu-enkephalin at the 10(-15) mole level. These LE antibodies are highly specific of the C part of LE peptide and cross-react weakly with Met-enkephalin (1%).

Tetanus: Diagnosis and Treatment

MedlinePlus

... is a medical emergency requiring: Care in the hospital Immediate treatment with medicine called human tetanus immune globulin (TIG) Aggressive wound care Drugs to control muscle spasms Antibiotics Tetanus vaccination Depending on how serious the infection is, a machine to help you breathe may ...

Management of immunization solid wastes in Kano State, Nigeria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oke, I.A.

Inadequate management of waste generated from injection activities can have a negative impact on the community and environment. In this paper, a report on immunization wastes management in Kano State (Nigeria) is presented. Eight local governments were selected randomly and surveyed by the author. Solid wastes generated during the Expanded Programme on Immunization were characterised using two different methods: one by weighing the waste and the other by estimating the volume. Empirical data was obtained on immunization waste generation, segregation, storage, collection, transportation, and disposal; and waste management practices were assessed. The study revealed that immunization offices were accommodated inmore » either in local government buildings, primary health centres or community health care centres. All of the stations demonstrated a high priority for segregation of the infectious wastes. It can be deduced from the data obtained that infectious waste ranged from 67.6% to 76.7% with an average of 70.1% by weight, and 36.0% to 46.1% with an average of 40.1% by volume. Non-infectious waste generated ranged from 23.3% to 32.5% with an average of 29.9% by weight and 53.9% to 64.0% with an average of 59.9% by volume. Out of non-infectious waste (NIFW) and infectious waste (IFW), 66.3% and 62.4% by weight were combustible and 33.7% and 37.6% were non-combustible respectively. An assessment of the treatment revealed that open pit burning and burial and small scale incineration were the common methods of disposal for immunization waste, and some immunization centres employed the services of the state or local government owned solid waste disposal board for final collection and disposal of their immunization waste at government approved sites.« less

Supplementary polio immunization activities and prior use of routine immunization services in non-polio-endemic sub-Saharan Africa.

PubMed

Helleringer, Stephane; Frimpong, Jemima A; Abdelwahab, Jalaa; Asuming, Patrick; Touré, Hamadassalia; Awoonor-Williams, John Koku; Abachie, Thomas; Guidetti, Flavia

2012-07-01

To determine participation in polio supplementary immunization activities (SIAs) in sub-Saharan Africa among users and non-users of routine immunization services and among users who were compliant or non-compliant with the routine oral poliovirus vaccine (OPV) immunization schedule. Data were obtained from household-based surveys in non-polio-endemic sub-Saharan African countries. Routine immunization service users were children (aged < 5 years) who had ever had a health card containing their vaccination history; non-users were children who had never had a health card. Users were considered compliant with the OPV routine immunization schedule if, by the SIA date, their health card reflected receipt of required OPV doses. Logistic regression measured associations between SIA participation and use of both routine immunization services and compliance with routine OPV among users. Data from 21 SIAs conducted between 1999 and 2010 in 15 different countries met inclusion criteria. Overall SIA participation ranged from 70.2% to 96.1%. It was consistently lower among infants than among children aged 1-4 years. In adjusted analyses, participation among routine immunization services users was > 85% in 12 SIAs but non-user participation was >85% in only 5 SIAs. In 18 SIAs, participation was greater among users (P < 0.01 in 16, 0.05 in 1 and < 0.10 in 1) than non-users. In 14 SIAs, adjusted analyses revealed lower participation among non-compliant users than among compliant users (P < 0.01 in 10, < 0.05 in 2 and < 0.10 in 2). Large percentages of children participated in SIAs. Prior use of routine immunization services and compliance with the routine OPV schedule showed a strong positive association with SIA participation.

Eosinophilic fasciitis

MedlinePlus

... include: CBC with differential Gamma globulins (a type of immune system protein) Erythrocyte sedimentation rate ( ESR ) MRI Muscle biopsy ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is ...

Emerging Role of Corticosteroid-Binding Globulin in Glucocorticoid-Driven Metabolic Disorders.

PubMed

Moisan, Marie-Pierre; Castanon, Nathalie

2016-01-01

Glucocorticoid hormones (GCs) are critical for survival since they ensure the energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism, and storage. However, to be beneficial to the body, GC levels should be maintained in an optimal window of concentrations. Not surprisingly, conditions of GC excess or deficiency, e.g., Cushing's syndrome or Addison's disease, are associated with severe alterations of energy metabolism. Corticosteroid-binding globulin (CBG), through its high specific affinity for GCs, plays a critical role in regulating plasma GC levels and their access to target cells. Genetic studies in various species including humans have revealed that CBG is the major factor influencing interindividual genetic variability of plasma GC levels, both in basal and stress conditions. Some, but not all, of these genetic studies have also provided data linking CBG levels to body composition and insulin levels. The examination of CBG-deficient mice submitted to hyperlipidic diets unveiled specific roles for CBG in lipid storage and metabolism. An influence of CBG on appetite has not been reported but remains to be more finely analyzed. Finally, only male mice have been examined under high-fat diet, while obesity is affecting women even more than men. Overall, a role of CBG in GC-driven metabolic disorders is emerging in recent studies. Although subtle, the influence of CBG in these diseases could open the way to new therapeutic interventions since CBG is easily accessible in the blood.

Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells.

PubMed

Cao, Qi; Wang, Li; Du, Fang; Sheng, Huiming; Zhang, Yan; Wu, Juanjuan; Shen, Baihua; Shen, Tianwei; Zhang, Jingwu; Li, Dangsheng; Li, Ningli

2007-07-01

Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Th1 responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice. Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naïve mice. Further analysis showed that the serum of immunized mice contains a high level of anti-CD25 antibody (about 30 ng/ml, p<0.01 vs controls). Consistent with a role of anti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naïve mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Th1 response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.

Comparison of Serum Protein Electrophoresis Values in Wild and Captive Whooping Cranes ( Grus americana ).

PubMed

Hausmann, Jennifer C; Cray, Carolyn; Hartup, Barry K

2015-09-01

Protein electrophoresis of serum samples from endangered, wild whooping cranes ( Grus americana ) was performed to help assess the health of the only self-sustaining, migratory population in North America. Serum samples from wild adult cranes (n = 22) were taken at Aransas National Wildlife Refuge, Texas, USA during winter. Wild juvenile cranes (n = 26) were sampled at Wood Buffalo National Park, Northwest Territories, Canada, in midsummer. All captive crane samples were acquired from the International Crane Foundation, Baraboo, WI, USA. Captive adult cranes (n = 30) were sampled during annual examinations, and archived serum samples from captive juvenile cranes (n = 19) were selected to match the estimated age of wild juveniles. Wild juveniles had significantly lower concentrations of all protein fractions than wild adults, except for prealbumin and γ globulins. All protein fraction concentrations for wild juveniles were significantly lower compared with captive juveniles, except for prealbumin and γ globulins, which were higher. Wild adults had significantly greater γ globulin concentrations than captive adults. Captive juveniles had significantly lower prealbumin and albumin concentrations and albumin : globulin ratios than captive adults. The higher γ globulin concentrations in wild versus captive cranes are likely because of increased antigenic exposure and immune stimulation. Protein fraction concentrations vary significantly with age and natural history in this species. Reference intervals for serum protein electrophoresis results from captive adult whooping cranes are provided in this study.

Hepatitis A, B and nAnB: The Viruses and their Prevention

PubMed Central

Minuk, G. Y.

1985-01-01

Three viruses commonly infect the liver: hepatitis A virus (HAV), hepatitis B virus (HBV) and the virus(es) responsible for non A non B hepatitis (nAnB). HAV infection occurs predominantly by the fecal-oral route and thus is more common in areas where living conditions are poor and personal hygiene suboptimal. Immune serum globulin (ISG) prevents this form of hepatitis. HBV infection can be spread by either parenteral (e.g. drug abuse) or non-parenteral (e.g. intimate contact) routes. High risk, susceptible individuals should be vaccinated with the HBV vaccine for longterm protection. Hepatitis B immune globulin (HBIG) remains the treatment of choice after exposure, but its protective effect does not exceed three to four months. The nAnB agent is spread by the same routes as HBV infection. At present there is no convincing evidence that any form of active or passive prophylaxis is beneficial for this form of hepatitis. PMID:21279152

Improved serological response to human diploid cell rabies vaccine when given simultaneously with antirabies hyperimmune globulin.

PubMed

Navarrete-Navarro, S; Aguilar-Setién, A; Avila-Figueroa, C; Hernández-Sierra, F; Santos-Preciado, J I

1999-01-01

The prevention of rabies in Mexico continues to be an important goal for the health sector. Although the prevalence of this disease continues to fall, between 1990 and 1995 a total of 238 cases were registered (an average of 40 cases annually), with a mean annual incidence of 0.04 cases per 100,000 inhabitants and a mortality of almost 100%, so that it is important to rely on highly effective vaccines with few side effects. The objective of this work was to evaluate seroconversion and tolerance to the human diploid cell antirabies vaccine administered to individuals with a history of exposure to rabies, to compare these results with those reported in the literature for the Fuenzalida vaccine, a rabies vaccine produced in the brain tissue of suckling mice, and to find the role antirabies hyperimmune gamma globulin plays in the concentration of post-vaccination antibody concentrations. An analytical transverse study was carried out in 40 children and adults with a history of rabies exposure who were given a complete, five-dose intramuscular schedule of the human diploid cell rabies vaccine. Subjects were followed daily, and local and systemic signs and symptoms were recorded. Two blood samples (at baseline and at the end of the vaccination schedule) were taken and antibody titers against rabies glycoprotein, using the ELISA technique, were measured. Adverse side effects produced by the human diploid cell antirabies vaccine, such as frequency of pain, erythema, itching, and regional adenopathy were fewer than those reported in the literature for the Fuenzalida vaccine (p < 0.05), and of induration and local pain (p < 0.05) in relation to the latter vaccine. All patients seroconverted, producing geometric mean antibody titers of 6.22 IU/mL, an arithmetic mean titer of 9.66 IU/mL with a SD of 9.1 IU/mL. The level of tolerance to the diploid cell vaccine was good and its adverse effects were minimal and fewer than those reported for the Fuenzalida rabies vaccine

Impact of pharmacists providing immunizations on adolescent influenza immunization.

PubMed

Robison, Steve G

2016-01-01

To determine if the Oregon law change in 2011 to allow pharmacists to immunize adolescents 11 to 17 years of age increased influenza immunizations or changed existing immunization venues. With the use of Oregon's ALERT Immunization Information System (IIS), 2 measures of impact were developed. First, the change in adolescent age 11-17 influenza immunizations before (2007-2010) and after (2011-2014) the pharmacy law change was evaluated against a reference cohort (aged 7-10) not affected by the law. Community pharmacies were also compared with other types of influenza immunization sites within one of the study influenza seasons (2013-2014). From 2007 to 2014, adolescent influenza immunizations at community pharmacies increased from 36 to 6372 per year. After the 2011 pharmacy law change, adolescents aged 11 to 17 were more likely to receive an influenza immunization compared with the reference population (odds ratio, 1.21; 95% CI, 1.19-1.22). Analysis of the 2013-2014 influenza season suggests that community pharmacies immunized a different population of adolescents than other providers. The 2011 change in Oregon law allowed pharmacists to increase the total of influenza immunizations given to adolescents. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Potential effects of brevetoxins and toxic elements on various health variables in Kemp's ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles after a red tide bloom event.

PubMed

Perrault, Justin R; Stacy, Nicole I; Lehner, Andreas F; Mott, Cody R; Hirsch, Sarah; Gorham, Jonathan C; Buchweitz, John P; Bresette, Michael J; Walsh, Catherine J

2017-12-15

Natural biotoxins and anthropogenic toxicants pose a significant risk to sea turtle health. Documented effects of contaminants include potential disease progression and adverse impacts on development, immune function, and survival in these imperiled species. The shallow seagrass habitats of Florida's northwest coast (Big Bend) serve as an important developmental habitat for Kemp's ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles; however, few studies have been conducted in this area. Our objectives were (1) to evaluate plasma analytes (mass, minimum straight carapace length, body condition index [BCI], fibropapilloma tumor score, lysozyme, superoxide dismutase, reactive oxygen/nitrogen species, plasma protein electrophoresis, cholesterol, and total solids) in Kemp's ridleys and green turtles and their correlation to brevetoxins that were released from a red tide bloom event from July-October 2014 in the Gulf of Mexico near Florida's Big Bend, and (2) to analyze red blood cells in Kemp's ridleys and green turtles for toxic elements (arsenic, cadmium, lead, mercury, selenium, thallium) with correlation to the measured plasma analytes. Positive correlations were observed between brevetoxins and α 2 -globulins in Kemp's ridleys and α 2 - and γ-globulins in green turtles, indicating potential immunostimulation. Arsenic, cadmium, and lead positively correlated with superoxide dismutase in Kemp's ridleys, suggesting oxidative stress. Lead and mercury in green turtles negatively correlated with BCI, while mercury positively correlated with total tumor score of green turtles afflicted with fibropapillomatosis, suggesting a possible association with mercury and increased tumor growth. The total tumor score of green turtles positively correlated with total protein, total globulins, α 2 -globulins, and γ-globulins, further suggesting inflammation and immunomodulation as a result of fibropapillomatosis. Lastly, brevetoxin concentrations were positively

Integrated Immune

NASA Technical Reports Server (NTRS)

Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

2010-01-01

This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

N-Glycans Modulate the Function of Human Corticosteroid-Binding Globulin*

PubMed Central

Sumer-Bayraktar, Zeynep; Kolarich, Daniel; Campbell, Matthew P.; Ali, Sinan; Packer, Nicolle H.; Thaysen-Andersen, Morten

2011-01-01

Human corticosteroid-binding globulin (CBG), a heavily glycosylated protein containing six N-linked glycosylation sites, transports cortisol and other corticosteroids in blood circulation. Here, we investigate the biological importance of the N-glycans of CBG derived from human serum by performing a structural and functional characterization of CBG N-glycosylation. Liquid chromatography-tandem MS-based glycoproteomics and glycomics combined with exoglycosidase treatment revealed 26 complex type N-glycoforms, all of which were terminated with α2,3-linked neuraminic acid (NeuAc) residues. The CBG N-glycans showed predominantly bi- and tri-antennary branching, but higher branching was also observed. N-glycans from all six N-glycosylation sites were identified with high site occupancies (70.5–99.5%) and glycoforms from all sites contained a relatively low degree of core-fucosylation (0–34.9%). CBG showed site-specific glycosylation and the site-to-site differences in core-fucosylation and branching could be in silico correlated with the accessibility to the individual glycosylation sites on the maturely folded protein. Deglycosylated and desialylated CBG analogs were generated to investigate the biological importance of CBG N-glycans. As a functional assay, MCF-7 cells were challenged with native and glycan-modified CBG and the amount of cAMP, which is produced as a quantitative response upon CBG binding to its cell surface receptor, was used to evaluate the CBG:receptor interaction. The removal of both CBG N-glycans and NeuAc residues increased the production of cAMP significantly. This confirms that N-glycans are involved in the CBG:receptor interaction and indicates that the modulation is performed by steric and/or electrostatic means through the terminal NeuAc residues. PMID:21558494

Attitudes of Swiss Health Care Providers Toward Childhood Immunizations.

PubMed

Schuler, Marianne; Schaedelin, Sabine; Aebi, Christoph; Berger, Christoph; Crisinel, Pierre-Alex; Diana, Alessandro; Niederer-Loher, Anita; Siegrist, Claire-Anne; Vaudaux, Bernard; Heininger, Ulrich

2017-06-01

INFOVAC is a network providing information about immunization issues to health professionals. The aim of this study was to assess the attitude of INFOVAC subscribers toward the current Swiss immunization schedule, potential modifications, and current and hypothetical immunization practices regarding their own children. In March 2015, a Web-based survey was sent to 4260 physicians and pharmacists subscribed to INFOVAC. Participation was anonymous and voluntary. The following information was obtained: (1) current immunization status of own children; (2) which immunizations would currently be accepted for a hypothetical own child and (3) attitudes toward potential modifications of the Swiss immunization schedule. Descriptive methods and multivariate models to correct for covariables were used for data analysis. Nine hundred and fifty-five valid questionnaires were received: 886/3704 (23.9%) from physicians and 69/556 (12.4%) from pharmacists. Current (>95%) and hypothetical (>99%) immunization rates were high for diphtheria, tetanus, pertussis, poliomyelitis and measles-mumps-rubella. Most pediatricians (61%) would support more vaccines for their children than currently recommended by the Swiss immunization advisory committee, whereas about 50% of other physicians and pharmacists would decline at least one of the recommended immunizations, most frequently varicella, pneumococcal or meningococcal C conjugate vaccines. Strong general support was expressed for the expansion of human papillomavirus immunization to males, acceleration of the measles-mumps-rubella schedule and a 2 + 1 instead of 3 + 1 diphtheria-tetanus-pertussis, acellular-inactivated poliomyelitis vaccine (DTPa-IPV)/Haemophilus influenzae type b ± hepatitis B virus (HBV) schedule. Survey participants generally demonstrated a positive attitude toward immunization, with pediatricians being the most progressive subgroup with the largest percentage of participants (63.1%) neither declining nor postponing any

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

PubMed

Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

2015-07-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Supplementary polio immunization activities and prior use of routine immunization services in non-polio-endemic sub-Saharan Africa

PubMed Central

Frimpong, Jemima A; Abdelwahab, Jalaa; Asuming, Patrick; Touré, Hamadassalia; Awoonor-Williams, John Koku; Abachie, Thomas; Guidetti, Flavia

2012-01-01

Abstract Objective To determine participation in polio supplementary immunization activities (SIAs) in sub-Saharan Africa among users and non-users of routine immunization services and among users who were compliant or non-compliant with the routine oral poliovirus vaccine (OPV) immunization schedule. Methods Data were obtained from household-based surveys in non-polio-endemic sub-Saharan African countries. Routine immunization service users were children (aged < 5 years) who had ever had a health card containing their vaccination history; non-users were children who had never had a health card. Users were considered compliant with the OPV routine immunization schedule if, by the SIA date, their health card reflected receipt of required OPV doses. Logistic regression measured associations between SIA participation and use of both routine immunization services and compliance with routine OPV among users. Findings Data from 21 SIAs conducted between 1999 and 2010 in 15 different countries met inclusion criteria. Overall SIA participation ranged from 70.2% to 96.1%. It was consistently lower among infants than among children aged 1–4 years. In adjusted analyses, participation among routine immunization services users was > 85% in 12 SIAs but non-user participation was > 85% in only 5 SIAs. In 18 SIAs, participation was greater among users (P < 0.01 in 16, 0.05 in 1 and < 0.10 in 1) than non-users. In 14 SIAs, adjusted analyses revealed lower participation among non-compliant users than among compliant users (P < 0.01 in 10, < 0.05 in 2 and < 0.10 in 2). Conclusion Large percentages of children participated in SIAs. Prior use of routine immunization services and compliance with the routine OPV schedule showed a strong positive association with SIA participation. PMID:22807595

Assessing immune competence in pigs by immunization with tetanus toxoid.

PubMed

Gimsa, U; Tuchscherer, A; Gimsa, J; Tuchscherer, M

2018-01-01

Immune competence can be tested by challenging organisms with a set of infectious agents. However, disease control requirements impose restrictions on the infliction of infections upon domestic pigs. Alternatively, vaccinations induce detectable immune responses that reflect immune competence. Here, we tested this approach with tetanus toxoid (TT) in young domestic pigs. To optimize the vaccination protocol, we immunized the pigs with a commercial TT vaccine at the age of 21 or 35 days. Booster immunizations were performed either 14 or 21 days later. TT-specific antibodies in plasma as well as lymphoproliferative responses were determined both 7 and 14 days after booster immunization using ELISA and lymphocyte transformation tests, respectively. In addition, general IgG and IgM plasma concentrations and mitogen-induced proliferation were measured. The highest TT-specific antibody responses were detected when blood samples were collected 1 week after a booster immunization conducted 21 days after primary immunization. The pigs' age at primary immunization did not have a significant influence on TT-specific antibody responses. Similarly, the TT-specific proliferative responses were highest when blood samples were collected 1 week after booster immunization, while age and time of primary and booster immunization were irrelevant in our setup. While general IgG and IgM plasma levels were highly age dependent, there were no significant age effects for TT-specific immune responses. In addition, mitogen-induced proliferation was independent of immunization as well as blood sampling protocols. In summary, our model of TT vaccination provides an interesting approach for the assessment of immune competence in young pigs. The detected vaccination effects were not biased by age, even though our data were acquired from immune systems that were under development during our tests.

Integrated Circuit Immunity

NASA Technical Reports Server (NTRS)

Sketoe, J. G.; Clark, Anthony

2000-01-01

This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

Validation of Procedures for Monitoring Crewmember Immune Function

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

2008-01-01

(activation, deficiency, dysregulation) and the response of the immune system to specific latent virus reactivation (known to occur during space flight) will be thoroughly assessed. The first in-flight activity for integrated immunity very recently occurred during the STS-120 Space Shuttle mission. The protocols functioned well from a technical perspective, and accurate in-flight data was obtained from 1 Shuttle and 2 ISS crewmembers. Crew participation rates for the study continue to be robust.

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diphtheria, measles, and for at least one type of poliomyelitis. In the event the final bulk solution is... less than 2 units of diphtheria antitoxin per ml. (2) A measles neutralizing antibody level that, when... Biologics Evaluation and Research: (1) Reference Immune Globulin for correlation of measles antibody titers...

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diphtheria, measles, and for at least one type of poliomyelitis. In the event the final bulk solution is... less than 2 units of diphtheria antitoxin per ml. (2) A measles neutralizing antibody level that, when... Biologics Evaluation and Research: (1) Reference Immune Globulin for correlation of measles antibody titers...

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diphtheria, measles, and for at least one type of poliomyelitis. In the event the final bulk solution is... less than 2 units of diphtheria antitoxin per ml. (2) A measles neutralizing antibody level that, when... Biologics Evaluation and Research: (1) Reference Immune Globulin for correlation of measles antibody titers...

Immunization Program

Science.gov Websites

Department home page Immunizations Search: Search Toggle navigation Medical Services Disease Control Facebook Contacts CoverageRates Diseases Immunization Homepage Immunization Honor Roll HPV NDIIS Medical Providers

[Adoptive Cell Therapy with Immune Checkpoint Blockade].

PubMed

Aruga, Atsushi

2017-09-01

Cancer immunotherapy are taking a leading role of cancer therapy due to the development of the immune checkpoint blockade. To date, however, only about 20% of patients have clinical responses and the cancer-specific T cells in cancer site are required to obtain beneficial effects. There has been an innovative development in the field of adoptive cell therapy, especially receptor gene-modified T cells in recent years. The effector cells mostly express PD-1, therefore the cytotoxic reactivity of the effector cells are inhibited by PD-L1. The combination of the adoptive cell therapy and the immune checkpoint blockade is expected to enhance efficacy. On the other hand, the immune-related adverse events may also be enhanced, therefore, it is needed to develop the combination therapy carefully, improving the cancer antigen-specificity or dealing with the cytokine release syndrome.

Immunogenic Activity of a Ribosomal Fraction Obtained from Mycobacterium tuberculosis

PubMed Central

Youmans, Anne S.; Youmans, Guy P.

1965-01-01

Youmans, Anne S. (Northwestern University Medical School, Chicago, Ill.), and Guy P. Youmans. Immunogenic activity of a ribosomal fraction obtained from Mycobacterium tuberculosis. J. Bacteriol. 89:1291–1298. 1965.—The highly immunogenic particulate fraction obtained from mechanically ruptured cells of the H37Ra strain of Mycobacterium tuberculosis was suspended and centrifuged at 20,360 × g. The supernatant liquid from this centrifugation was centrifuged at 56,550 × g to remove the larger particles, and the supernatant liquid from this was centrifuged at 144,000 × g to obtain a ribosomal fraction. The sediments from the first two centrifugations were highly immunogenic, but the ribosomal fraction showed only slight capacity to immunize mice. However, when the ribosomal fraction was mixed with Freund's incomplete adjuvant, the immunogenic activity was equivalent to the particulate fraction from which it was prepared. To test the hypothesis that some membranous substance in the particulate fraction was acting as an adjuvant for the smaller particles in the ribosomal fraction, portions of the particulate fraction were treated separately with each of the membrane-disrupting agents, sodium deoxycholate, sodium lauryl sulfate, and 1 m sodium chloride. The treated materials were then centrifuged at 144,000 × g, and the sediments were tested for immunogenicity both with and without the addition of Freund's incomplete adjuvant. Without the adjuvant, the immunizing activities were very weak or absent; with the adjuvant, they were equivalent to that of the particulate fraction from which they were prepared. Other factors which have been found to damage or destroy membranes, such as freezing and thawing, and heat, also significantly decreased the immunogenic activity of the particulate fraction unless it was incorporated into Freund's incomplete adjuvant. The larger particles which sedimented at 56,550 × g were also treated with sodium lauryl sulfate and sodium

Integrated Immune Experiment

NASA Technical Reports Server (NTRS)

Crucian, Brian

2009-01-01

This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

Addressing immunization registry population inflation in adolescent immunization rates.

PubMed

Robison, Steve G

2015-01-01

While U.S. adolescent immunization rates are available annually at national and state levels, finding pockets of need may require county or sub-county information. Immunization information systems (IISs) are one tool for assessing local immunization rates. However, the presence of IIS records dating back to early childhood and challenges in capturing mobility out of IIS areas typically leads to denominator inflation. We examined the feasibility of weighting adolescent immunization records by length of time since last report to produce more accurate county adolescent counts and immunization rates. We compared weighted and unweighted adolescent denominators from the Oregon ALERT IIS, along with county-level Census Bureau estimates, with school enrollment counts from Oregon's annual review of seventh-grade school immunization compliance for public and private schools. Adolescent immunization rates calculated using weighted data, for the state as a whole, were also checked against comparable National Immunization Survey (NIS) rates. Weighting individual records by the length of time since last activity substantially improved the fit of IIS data to county populations for adolescents. A nonlinear logarithmic (ogive) weight produced the best fit to the school count data of all examined estimates. Overall, the ogive weighted results matched NIS adolescent rates for Oregon. The problem of mobility-inflated counts of teenagers can be addressed by weighting individual records based on time since last immunization. Well-populated IISs can rely on their own data to produce adolescent immunization rates and find pockets of need.

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

PubMed Central

Almeida, Freya M Freyre; Blanco, Aracelys; Trujillo, Heidy; Hernández, Dunia; García, Daymir; Alba, José S; Abad, Matilde López; Merino, Nelson; Lobaina, Yadira

2016-01-01

ABSTRACT The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel

Immunization against lysozyme-like proteins affect sperm function and fertility in the rat.

PubMed

Narmadha, Ganapathy; Yenugu, Suresh

2016-11-01

Proteins of the epididymal and testicular mileu contribute to sperm maturation and a vast majority of them remain uncharacterised. In this study, the role of three Lysozyme-like (LYZL) proteins, namely LYZL1, LYZL4 and LYZL6 in sperm function was assessed using in vitro neutralization and auto antibodies generation model. Rats immunized with LYZL1, LYZL4 and LYZL6 proteins had a litter size of 5.93, 8.47 and 2.10 respectively compared to 9.96 in the control rats. The litter size was further reduced to 4.53, 7.67 and 1.23 for the corresponding proteins in the second mating conducted 14 weeks after immunization. Epididymal and testicular fluids obtained from the immunized rats displayed a very high antibody titre against all the three proteins. Sperm count was significantly reduced in rats immunized with LYZL1 or LYZL6 and to a lower extent in LYZL4 group. Acrosome reaction associated calcium release was inhibited in spermatozoa obtained from LYZL1 or LYZL4 or LYZL6 immunized rats as well as in spermatozoa incubated with antiserum against the three proteins. Impairment in path velocity, progressive velocity and track speed were observed in spermatozoa obtained from LYZL6 immunized rats. Treatment of spermatozoa with LYZL6 recombinant protein did not potentiate calcium release and acrosome reaction. Results of this study indicate a role for LYZL proteins in sperm function and further studies are warranted to explore them as potential contraceptive agents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of a Cordia-IC enzyme-linked immunosorbent assay kit for the detection of circulating immune complexes.

PubMed Central

Landoy, Z; West, T E; Vladutiu, A O; Fitzpatrick, J E

1985-01-01

A commercial kit (Cordia-IC) from Cordis Laboratory, Miami, Fla., was compared with the Raji cell radioimmunoassay for its ability to detect circulating immune complexes (CIC) in sera from 30 control subjects and 118 patients with infectious diseases. The 118 patients were categorized into the following groups: (i) 23 patients with bacterial endocarditis, (ii) 41 patients with bacteremia from an infected intravascular catheter or access device, and (iii) 54 patients with Staphylococcus aureus bacteremia related to a deep tissue infection. The Cordia-IC was comparable to the Raji cell radioimmunoassay in intraassay variability (4.0 versus 8.0%) and interassay reproducibility (8.7 versus 20.0%). Neither assay found CIC amounts above 12.5 micrograms equivalents (eq) of aggregated human gamma globulin (AHG) per ml in any of the 30 control individuals. In group 1, Cordia-IC detected 19 of 23 positives (mean, 73.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 23 positives (mean, 54.8 micrograms eq of AHG per ml). In group 2, Cordia-IC detected 19 of 41 positives (mean, 20.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 41 positives (mean, 15.1 micrograms eq of AHG per ml). In group 3, Cordia-IC found 38 of 54 positives (mean, 28.0 micrograms eq of AHG per ml), whereas the Raji cell found 32 of 54 positives (mean, 23.9 micrograms eq of AHG per ml). Statistically, these findings were not significantly different in any of the three patient groups (P> 0.15), and there was an overall good correlation between the results obtained by the two assays (r+0.64, P<0.001). The Cordia-IC provided a suitable assay for the detection of CIC and might find application in routine clinical laboratories. PMID:3897269

Correlation between urinary GAG and anti-idursulfase ERT neutralizing antibodies during treatment with NICIT immune tolerance regimen: A case report☆,☆☆

PubMed Central

Kim, Sarah; Whitley, Chester B.; Jarnes Utz, Jeanine R.

2018-01-01

Introduction Antibodies to intravenous idursulfase enzyme replacement therapy (ERT) for patients with Hunter syndrome (mucopolysaccharidosis type II, MPS II) can have a harmful clinical impact, including both increasing risk of infusion reactions and inhibiting therapeutic activity. Thus, failure to monitor anti-idursulfase antibodies and neutralizing antibodies, and delays in reporting results, may postpone critical clinical decisions. Hypothesis Urinary glycosaminoglycan (GAG) levels may be used as a biomarker for anti-idursulfase antibodies and neutralizing antibodies to improve timeliness in monitoring and managing ERT. Methods This is a case report describing a patient with MPS II with high levels of neutralizing antibodies and worsened clinical status who was treated for five years with a non-immunosuppressive and non-cytotoxic immune tolerance (NICIT) regimen, consisting of intravenous immune globulin and frequent infusions of idursulfase. Neutralizing antibodies and total anti-idursulfase antibodies were measured by two different methods, the direct 1,9-dimethylmethylene blue (DMB) assay and cetylpyridinium chloride carbazole-borate (CPC) assay. Results Neutralizing antibodies, measured as percent inhibition of enzyme activity and also by total neutralizing antibody titer, were correlated with quantitative urinary GAG measured by DMB assay (p = 0.026, p = 0.0067), and quantitative urinary GAG by CPC assay with percent inhibition of enzyme activity by neutralizing antibodies (p = 0.0475). The NICIT regimen showed a sustained immune tolerance after five years and was well-tolerated. Conclusions Urinary GAG, measured by DMB assay, may be a biomarker for anti-idursulfase neutralizing antibodies and is useful for managing immune tolerance regimens for patients with MPS II who have high levels of anti-idursulfase neutralizing antibodies. This study highlights the importance of regular and frequent monitoring of urinary GAG in patients with MPS II who are

Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis

PubMed Central

Laurent, Michaël R.; Hammond, Geoffrey L.; Blokland, Marco; Jardí, Ferran; Antonio, Leen; Dubois, Vanessa; Khalil, Rougin; Sterk, Saskia S.; Gielen, Evelien; Decallonne, Brigitte; Carmeliet, Geert; Kaufman, Jean-Marc; Fiers, Tom; Huhtaniemi, Ilpo T.; Vanderschueren, Dirk; Claessens, Frank

2016-01-01

Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology. PMID:27748448

Natural Immunity to HIV: a delicate balance between strength and control.

PubMed

Poudrier, Johanne; Thibodeau, Valérie; Roger, Michel

2012-01-01

Understanding how the mucosal immune system in the human female reproductive tract might prevent or facilitate HIV infection has important implications for the design of effective interventions. We and others have established cohorts of highly-exposed, HIV-seronegative individuals, such as HIV-uninfected commercial sex workers, who have remained HIV-negative after more than 5 years of active prostitution. Observations obtained in studies of such individuals, who represent a model of natural immunity to HIV, indicate that HIV resistance may be associated with the host's capacity to preserve systemic integrity by constraining immune activity and controlling inflammatory conditions at the mucosal point of entry. This likely necessitates the orchestration of balanced, first-line and adaptive immune responses.

Comparison of the efficiency control of mycotoxins by some optical immune biosensors

NASA Astrophysics Data System (ADS)

Slyshyk, N. F.; Starodub, N. F.

2013-11-01

It was compared the efficiency of patulin control at the application of such optical biosensors which were based on the surface plasmon resonance (SPR) and nano-porous silicon (sNPS). In last case the intensity of the immune reaction was registered by measuring level of chemiluminescence (ChL) or photocurrent of nPS. The sensitivity of this mycotoxin determination by first type of immune biosensor was 0.05-10 mg/L Approximately the same sensitivity as well as the overall time analysis were demonstrated by the immune biosensor based on the nPS too. Nevertheless, the last type of biosensor was simpler in technical aspect and the cost of analysis was cheapest. That is why, it was recommend the nPS based immune biosensor for wide screening application and SPR one for some additional control or verification of preliminary obtained results. In this article a special attention was given to condition of sample preparation for analysis, in particular, micotoxin extraction from potao and some juices. Moreover, it was compared the efficiency of the above mentioned immune biosensors with such traditional approach of mycotoxin determination as the ELISA-method. In the result of investigation and discussion of obtained data it was concluded that both type of the immune biosensors are able to fulfill modern practice demand in respect sensitivity, rapidity, simplicity and cheapness of analysis.

Bibliography of Germfree Research 1885-1963. 1979 Supplement,

DTIC Science & Technology

1979-01-01

1):244-249, 1979. (Ja) -6- J_1 102. Jaroskova, L., Trebichavsky, I., Kovaru, F. and Prokesova, L. Membrane immuno- globulins in pig foetuses and... foetus as a germ- free model in the study of development of cellular and humoral immunity. Folia Microbiologica. 24(1) :78-79, 1979. 190. Pozharisskii

Effect of endosulfan on immunological competence of layer birds.

PubMed

Singh, P P; Kumar, Ashok; Chauhan, R S; Pankaj, P K

2016-07-01

The present study was aimed to investigate the immunological competence of endosulfan insecticide after limited oral administration in White Leghorn layer chickens. A total of 20 White Leghorn birds were given endosulfan in drinking water at 30 ppm/bird/day (no observable effect level dose) for a period of 3-months. Immune competence status of layer birds and chicks hatched from endosulfan offered birds were estimated at 15-day interval in layer birds and at monthly interval in chicks using immunological, biochemical parameters, and teratological estimates. There was a significant decrease in levels of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds fed with endosulfan as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with endosulfan as compared to control. Subsequently, chicks produced from endosulfan-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. The exposure to endosulfan in limited oral dosage was able to exhibit hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting cautious usage of endosulfan insecticide in poultry sheds.

Rabbit antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients.

PubMed

Hardinger, Karen L; Brennan, Daniel C; Schnitzler, Mark A

2009-05-15

In a randomized, international study comparing rabbit antithymocyte globulin (TMG) and basiliximab (BAS) induction in renal transplant recipients at risk for delayed graft function or acute rejection (n=278), TMG was associated with less acute rejection at 1 year. This study analyzed outcomes stratified by standard criteria donor (SCD), extended criteria donor (ECD), and hypertensive donor. Data-capture limitations necessitated defining ECD as donor age more than 60 years or 50 to 60 years with hypertension and renal insufficiency. Seventy-five recipients received ECD-kidneys (28.4% TMG vs. 25.6% BAS, P=NS) and 203 recipients received SCD-kidneys (72.6% TMG vs. 74.4% BAS, P=NS). Recipients of an ECD or hypertensive donor-kidney had similar outcomes between treatment groups. Recipients of an SCD-kidney treated with TMG had less rejection (odds ratio [OR] 0.48). Recipients of a normotensive donor-kidney treated with TMG had less rejection (OR 0.56). Recipients of a normotensive, SCD-kidney treated with TMG had less rejection (OR 0.47) and death (OR 0.17) than their counterparts treated with BAS. Contrary to its perceived niche in recipients of ECD-kidneys, TMG was most beneficial in patients who received a normotensive, deceased SCD kidney.

Transcriptomic immune response of Tenebrio molitor pupae to parasitization by Scleroderma guani.

PubMed

Zhu, Jia-Ying; Yang, Pu; Zhang, Zhong; Wu, Guo-Xing; Yang, Bin

2013-01-01

Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE) analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26%) showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular understanding of the host-parasitoid interaction.

Transcriptomic Immune Response of Tenebrio molitor Pupae to Parasitization by Scleroderma guani

PubMed Central

Zhu, Jia-Ying; Yang, Pu; Zhang, Zhong; Wu, Guo-Xing; Yang, Bin

2013-01-01

Background Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE) analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. Methodology/Principal Findings In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26%) showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. Conclusions/Significance obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular understanding of the host

The flip side of immune surveillance: immune dependency.

PubMed

Prehn, Richmond T; Prehn, Liisa M

2008-04-01

The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.

Skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria

PubMed Central

Obeid, Michel; Franetich, Jean-François; Lorthiois, Audrey; Gego, Audrey; Grüner, Anne Charlotte; Tefit, Maurel; Boucheix, Claude; Snounou, Georges; Mazier, Dominique

2013-01-01

The Plasmodium-infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. However, it has recently been demonstrated that priming also occurs in the skin. We wished to establish if sterile protection could be obtained in the absence of priming by infected hepatocytes. To this end, we developed a subcutaneous (s.c.) immunization protocol where few, possibly none, of the immunizing irradiated Plasmodium yoelii sporozoites infect hepatocytes, and also used CD81-deficient mice non-permissive to productive hepatocyte infections. We then compared and contrasted the patterns of priming with those obtained by intradermal immunization, where priming occurs in the liver. Using sterile immunity as a primary read-out, we exploited an inhibitor of T-cell migration, transgenic mice with conditional depletion of dendritic cells and adoptive transfers of draining lymph node-derived T cells, to provide evidence that responses leading to sterile immunity can be primed in the skin-draining lymph nodes with little, if any, contribution from the infected hepatocyte. PMID:23255300

Validation of Procedures for Monitoring Crewmember Immune Function

NASA Technical Reports Server (NTRS)

Pierson, Duane; Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Sams, Clarence

2010-01-01

The objective of this Supplemental Medical Objective (SMO) is to determine the status of the immune system, physiological stress and latent viral reactivation (a clinical outcome that can be measured) during both short and long-duration spaceflight. In addition, this study will develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. Pre-mission, in-flight and post-flight blood and saliva samples will be obtained from participating crewmembers. Assays included peripheral immunophenotype, T cell function, cytokine profiles, viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. To date, 18 short duration (now completed) and 8 long-duration crewmembers have completed the study. The long-duration phase of this study is ongoing. For this presentation, the final data set for the short duration subjects will be discussed.

Immunizations challenge healthcare personnel and affects immunization rates.

PubMed

Strohfus, Pamela K; Kim, Susan C; Palma, Sara; Duke, Russell A; Remington, Richard; Roberts, Caleb

2017-02-01

This study measured 1. medical office immunization rates and 2. health care personnel competency in managing vaccine practices before and after evidence-based immunization education was provided. This descriptive study compared 32 family medicine and pediatric offices and 178 medical assistants, licensed practical nurses, registered nurses, nurse practitioners, and physicians in knowledge-based testing pre-education, post-education, and 12-months post-education. Immunization rates were assessed before and 18-months post-education. Immunization rates increased 10.3% - 18months post-education; knowledge increased 7.8% - 12months post-education. Family medicine offices, licensed practical nurses, and medical assistants showed significant knowledge deficits before and 12-months post-education. All demographic groups scored less in storage/handling 12-months post-education. This study is one of the first studies to identify competency challenges in effective immunization delivery among medical assistants, licensed practical nurses, and family medicine offices. Formal and continuous education in immunization administration and storage/handling is recommended among these select groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Immune responses to bioengineered organs

PubMed Central

Ochando, Jordi; Charron, Dominique; Baptista, Pedro M.; Uygun, Basak E.

2017-01-01

Purpose of review Organ donation in the United States registered 9079 deceased organ donors in 2015. This high percentage of donations allowed organ transplantation in 29 851 recipients. Despite increasing numbers of transplants performed in comparison with previous years, the numbers of patients that are in need for a transplant increase every year at a higher rate. This reveals that the discrepancy between the demand and availability of organs remains fundamental problem in organ transplantation. Recent findings Development of bioengineered organs represents a promising approach to increase the pool of organs for transplantation. The technology involves obtaining complex three-dimensional scaffolds that support cellular activity and functional remodeling though tissue recellularization protocols using progenitor cells. This innovative approach integrates cross-thematic approaches from specific areas of transplant immunology, tissue engineering and stem cell biology, to potentially manufacture an unlimited source of donor organs for transplantation. Summary Although bioengineered organs are thought to escape immune recognition, the potential immune reactivity toward each of its components has not been studied in detail. Here, we summarize the host immune response toward different progenitor cells and discuss the potential implications of using nonself biological scaffolds to develop bioengineered organs. PMID:27926545

Toll immune signal activates cellular immune response via eicosanoids.

PubMed

Shafeeq, Tahir; Ahmed, Shabbir; Kim, Yonggyun

2018-07-01

Upon immune challenge, insects recognize nonself. The recognition signal will propagate to nearby immune effectors. It is well-known that Toll signal pathway induces antimicrobial peptide (AMP) gene expression. Eicosanoids play crucial roles in mediating the recognition signal to immune effectors by enhancing humoral immune response through activation of AMP synthesis as well as cellular immune responses, suggesting a functional cross-talk between Toll and eicosanoid signals. This study tested a cross-talk between these two signals. Two signal transducing factors (MyD88 and Pelle) of Toll immune pathway were identified in Spodoptera exigua. RNA interference (RNAi) of either SeMyD88 or SePelle expression interfered with the expression of AMP genes under Toll signal pathway. Bacterial challenge induced PLA 2 enzyme activity. However, RNAi of these two immune factors significantly suppressed the induction of PLA 2 enzyme activity. Furthermore, RNAi treatment prevented gene expression of cellular PLA 2 . Inhibition of PLA 2 activity reduced phenoloxidase activity and subsequent suppression in cellular immune response measured by hemocyte nodule formation. However, immunosuppression induced by RNAi of Toll signal molecules was significantly reversed by addition of arachidonic acid (AA), a catalytic product of PLA 2 . The addition also significantly reduced the enhanced fungal susceptibility of S. exigua treated by RNAi against two Toll signal molecules. These results indicate that there is a cross-talk between Toll and eicosanoid signals in insect immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of primary immunization coverage of infants under universal immunization programme in an urban area of bangalore city using cluster sampling and lot quality assurance sampling techniques.

PubMed

K, Punith; K, Lalitha; G, Suman; Bs, Pradeep; Kumar K, Jayanth

2008-07-01

Is LQAS technique better than cluster sampling technique in terms of resources to evaluate the immunization coverage in an urban area? To assess and compare the lot quality assurance sampling against cluster sampling in the evaluation of primary immunization coverage. Population-based cross-sectional study. Areas under Mathikere Urban Health Center. Children aged 12 months to 23 months. 220 in cluster sampling, 76 in lot quality assurance sampling. Percentages and Proportions, Chi square Test. (1) Using cluster sampling, the percentage of completely immunized, partially immunized and unimmunized children were 84.09%, 14.09% and 1.82%, respectively. With lot quality assurance sampling, it was 92.11%, 6.58% and 1.31%, respectively. (2) Immunization coverage levels as evaluated by cluster sampling technique were not statistically different from the coverage value as obtained by lot quality assurance sampling techniques. Considering the time and resources required, it was found that lot quality assurance sampling is a better technique in evaluating the primary immunization coverage in urban area.

Effect of HBIG combined with hepatitis B vaccine on blocking HBV transmission between mother and infant and its effect on immune cells.

PubMed

Gong, Junling; Liu, Xing

2018-01-01

The effect of hepatitis B immune globulin (HBIG) combined with hepatitis B vaccine on blocking hepatitis B virus (HBV) transmission between mother and infant and its effect on immune cells were studied. Ninety newborn infants confirmed to be HBV surface antigen (HBsAg)-positive were divided equally into three groups. Group A newborns received the hepatitis B vaccine at 0, 1 and 6 months after birth (10 µg/time). Group B newborns received an intramuscular injection of 100 IU HBIG 2 h after birth before the same treatment as group A. Mothers of group C newborns received three gluteus maxinus injections of 200 IU HBIG. The newborns in group C got the same treatment as group B. The blocking effect of HBV transmission between mother and infant was evaluated, and cell immune function was assessed. There were significant differences in comparison of blocking success rates between group A and B, and between group A and C as well (p<0.05). At the end of 12 months follow-up, the CD4 + level and CD4 + /CD8 + ratio in group C were higher thanthose in group A and B (p<0.05). In addition, the level of CD8 + T lymphocyte in group C was lower than those in group A and B (p<0.05). In comparison of levels of CD4 + T lymphocyte at the end of 12 months follow-up and 24 h after birth, the differences were significant (p<0.05) in bothgroup B and C. The differences of IFN-γ levels betweengroups B/C and group A were significant (p<0.05). Forthose newborn infants born to mothers who were positivefor both HBsAg and HBeAg, HBIG intervention formothers during late pregnancy, together with combinedtreatment of HBIG and hepatitis B vaccine for infants, gavebetter blocking result of HBV transmission.

Control of adaptive immunity by the innate immune system.

PubMed

Iwasaki, Akiko; Medzhitov, Ruslan

2015-04-01

Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.

Private sector contribution to childhood immunization: Sri Lankan experience.

PubMed

Agampodi, S B; Amarasinghe, D A C L

2007-04-01

The main service provider for childhood immunization in Sri Lanka is the government sector. However, utilization of private sector for childhood immunization is increasing rapidly. Existing national immunization data does not routinely include statistics on private sector immunization delivery adequately. To estimate the proportion of children immunized in the private sector; describe socio-demographic characteristics of private sector users and compare these with government sector users. A community-based crosssectional descriptive study was conducted using a pre-tested interviewer-administered structured questionnaire. This was done in the Colombo municipal council area using the WHO 30 cluster methodology. The total number of households in the sample was 553. Out of the 5,028 total immunizations reported in the present study, around one-third (2,544) was obtained through the private sector. Nineteen percent (104) of children were exclusively immunized from the private sector. The distribution of usual immunization provider was - government sector 72.3% (400) and private sector 27.7% (153). Significant differences were observed (P < 0.001) between private and government sector users with regard to family income, social class, ethnicity, religion and educational level of the mother. The age-appropriate immunization among the 12- to 23-month age group was 92.3% (144) in the government sector, whereas it was 95% (38) in the private sector. Among the 24- to 35-month age group, it was 91.7% (121) and 92.7% (76) respectively. The age-adjusted immunization coverage rates were almost same among the government and private sector users except for the measles vaccine, where the private sector users had significantly (P = 0.016) higher coverage. Utilization of private sector immunization services is high in the Colombo municipal council area.

A MOUSE TEST FOR MEASURING THE IMMUNIZING POTENCY OF ANTIRABIES VACCINES

PubMed Central

Webster, Leslie T.

1939-01-01

1. A quantitative practical mouse test is described for measuring the immunizing potency of antirabies vaccines. 2. Virulent virus, injected intraperitoneally as a vaccine, immunized mice within 10 days and for a period of at least 9 months. Demonstrable neutralizing antibodies accompanied this immunity. Virus given subcutaneously failed to immunize as effectively. The margin between immunizing and infecting dose of vaccine was small. 3. Commercial vaccines containing virulent virus prepared for the treatment of man gave results similar to those obtained with laboratory virus. 4. Commercial vaccines inactivated with phenol and prepared for the treatment of man in general failed to immunize mice. None contained virulent virus. The phenolized preparation from one commercial firm, however, as also the chloroformized preparation from another, immunized mice consistently when given intraperitoneally in quantities approximating 5 times that advocated per gm. of body weight in man. 5. Commercial canine vaccines inactivated with phenol proved non-virulent and failed to immunize mice. 6. Commercial canine vaccines inactivated with chloroform (Kelser) proved non-virulent but capable of immunizing mice provided a single intraperitoneal injection of 2 to 5 times that prescribed for dogs per gm. of body weight was given. 7. Chloroformized vaccines proved irritative to the peritoneum of mice. PMID:19870893

Immunity by equilibrium.

PubMed

Eberl, Gérard

2016-08-01

The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice

PubMed Central

Adams, Jessica M.; Otero-Corchon, Veronica; Hammond, Geoffrey L.; Veldhuis, Johannes D.; Qi, Nathan

2015-01-01

Distinct male and female patterns of pituitary GH secretion produce sexually differentiated hepatic gene expression profiles, thereby influencing steroid and xenobiotic metabolism. We used a fully automated system to obtain serial nocturnal blood samples every 15 minutes from cannulated wild-type (WT) and somatostatin knockout (Sst-KO) mice to determine the role of SST, the principal inhibitor of GH release, in the generation of sexually dimorphic GH pulsatility. WT males had lower mean and median GH values, less random GH secretory bursts, and longer trough periods between GH pulses than WT females. Each of these parameters was feminized in male Sst-KO mice, whereas female Sst-KO mice had higher GH levels than all other groups, but GH pulsatility was unaffected. We next performed hepatic mRNA profiling with high-density microarrays. Male Sst-KO mice exhibited a globally feminized pattern of GH-dependent mRNA levels, but female Sst-KO mice were largely unaffected. Among the differentially expressed female-predominant genes was Serpina6, which encodes corticosteroid-binding globulin (CBG). Increased CBG was associated with elevated diurnal peak plasma corticosterone in unstressed WT females and both sexes of Sst-KO mice compared with WT males. Sst-KO mice also had exaggerated ACTH and corticosterone responses to acute restraint stress. However, consistent with their lack of phenotypic signs of excess glucocorticoids, cerebrospinal fluid concentrations of free corticosterone in Sst-KO mice were not elevated. In summary, SST is necessary for the prolonged interpulse troughs that define masculinized pituitary GH secretion. SST also contributes to sexual dimorphism of the hypothalamic-pituitary-adrenal axis via GH-dependent regulation of hepatic CBG production. PMID:25551181

Trained immunity: a program of innate immune memory in health and disease

PubMed Central

Netea, Mihai G.; Joosten, Leo A.B.; Latz, Eicke; Mills, Kingston H.G.; Natoli, Gioacchino; Stunnenberg, Hendrik G.; O’Neill, Luke A.J.; Xavier, Ramnik J.

2016-01-01

The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed trained immunity or innate immune memory. Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases. PMID:27102489

Immunization of children at risk of infection with human immunodeficiency virus.

PubMed Central

Moss, William J.; Clements, C. John; Halsey, Neal A.

2003-01-01

This paper reviews the English language literature on the safety, immunogenicity and effectiveness in children infected with the human immunodeficiency virus (HIV) of vaccines currently recommended by WHO for use in national immunization programmes. Immunization is generally safe and beneficial for children infected with HIV, although HIV-induced immune suppression reduces the benefit compared with that obtained in HIV-uninfected children. However, serious complications can occur following immunization of severely immunocompromised children with bacillus Calmette-Gu rin (BCG) vaccine. The risk of serious complications attributable to yellow fever vaccine in HIV-infected persons has not been determined. WHO guidelines for immunizing children with HIV infection and infants born to HIV-infected women differ only slightly from the general guidelines. BCG and yellow fever vaccines should be withheld from symptomatic HIV-infected children. Only one serious complication (fatal pneumonia) has been attributed to measles vaccine administered to a severely immunocompromised adult. Although two HIV-infected infants have developed vaccine-associated paralytic poliomyelitis, several million infected children have been vaccinated and the evidence does not suggest that there is an increased risk. The benefits of measles and poliovirus vaccines far outweigh the potential risks in HIV-infected children. The policy of administering routine vaccines to all children, regardless of possible HIV exposure, has been very effective in obtaining high immunization coverage and control of preventable diseases. Any changes in this policy would have to be carefully examined for a potential negative impact on disease control programmes in many countries. PMID:12640478

Immune evasion, immunopathology and the regulation of the immune system.

PubMed

Sorci, Gabriele; Cornet, Stéphane; Faivre, Bruno

2013-02-13

Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths) that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

A novel mutation causing complete thyroxine-binding globulin deficiency (TBG-CD-Negev) among the Bedouins in southern Israel.

PubMed

Miura, Y; Hershkovitz, E; Inagaki, A; Parvari, R; Oiso, Y; Phillip, M

2000-10-01

T4-binding globulin (TBG) is the major thyroid hormone transport protein in human serum. Inherited TBG abnormalities do not usually alter the metabolic status and are transmitted in X-linked inheritance. A high prevalence of complete TBG deficiency (TBG-CD) has been reported among the Bedouin population in the Negev (southern Israel). In this study we report a novel single mutation causing complete TBG deficiency due to a deletion of the last base of codon 38 (exon 1), which led to a frame shift resulting in a premature stop at codon 51 and a presumed truncated peptide of 50 residues. This new variant of TBG (TBG-CD-Negev) was found among all of the patients studied. We conclude that a single mutation may account for TBG deficiency among the Bedouins in the Negev. This report is the first to describe a mutation in a population with an unusually high prevalence of TBG-CD.

Low dose anti-thymocyte globulin reduces chronic graft-versus-host disease incidence rates after matched unrelated donor transplantation.

PubMed

Tandra, Anand; Covut, Fahrettin; Cooper, Brenda; Creger, Richard; Brister, Lauren; McQuigg, Bernadette; Caimi, Paolo; Malek, Ehsan; Tomlinson, Ben; Lazarus, Hillard M; Otegbeye, Folashade; Kolk, Merle; de Lima, Marcos; Metheny, Leland

2017-12-04

Anti-thymocyte globulin (ATG) is often added to hematopoietic stem cell transplant conditioning regimens to prevent graft rejection and reduce graft-versus-host disease (GVHD). Doses used in retrospective and prospective clinical trials have ranged from 2.5 to 20 mg/kg with rates of grade II-IV acute GVHD and chronic GVHD up to 40 and 60%, respectively. We retrospectively compared outcomes in recipients of matched unrelated donor (MUD) grafts given low dose rabbit ATG IV 3 mg/kg (n = 52) versus recipients of matched related donor (MRD) grafts (n = 48) without ATG. One year cumulative incidence of chronic GVHD was 25.2% in the MUD group versus 33.3% in the MRD group (p = .5). One-year cumulative incidence of extensive chronic GVHD was 9.6% in the MUD group versus 26.6% in the MRD group (p = .042). Our analysis supports the use of low dose ATG in MUD transplantation as an effective therapy to prevent chronic GVHD.

Universal immunity to influenza must outwit immune evasion

PubMed Central

Quiñones-Parra, Sergio; Loh, Liyen; Brown, Lorena E.; Kedzierska, Katherine; Valkenburg, Sophie A.

2014-01-01

Although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. Currently available vaccines elicit strain-specific antibody (Ab) responses to the surface haemagglutinin (HA) and neuraminidase (NA) proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. Thus, there is a great need for cross-protective or “universal” influenza vaccines to overcome the necessity for annual immunization against seasonal influenza and to provide immunity to reduce the severity of infection with pandemic or outbreak viruses. It is well established that natural influenza infection can provide cross-reactive immunity that can reduce the impact of infection with distinct influenza type A strains and subtypes, including H1N1, H3N2, H2N2, H5N1, and H7N9. The key to generating universal influenza immunity through vaccination is to target functionally-conserved regions of the virus, which include epitopes on the internal proteins for cross-reactive T cell immunity or on the HA stem for broadly reactive Ab responses. In the wake of the 2009 H1N1 pandemic, broadly neutralizing antibodies (bnAbs) have been characterized and isolated from convalescent and vaccinated individuals, inspiring development of new vaccination techniques to elicit such responses. Induction of influenza-specific T cell responses through vaccination has also been recently examined in clinical trials. Strong evidence is available from human and animal models of influenza to show that established influenza-specific T cell memory can reduce viral shedding and symptom severity. However, the published evidence also shows that CD8+ T cells can efficiently select immune escape mutants early after influenza virus infection. Here, we discuss universal immunity to influenza viruses mediated by both cross-reactive T cells and Abs, the mechanisms of immune evasion in influenza, and propose how to counteract

Effect of Excoecaria agallocha on non-specific immune responses and disease resistance of Oreochromis niloticus against Streptococcus agalactiae.

PubMed

Laith, A A; Mazlan, A G; Effendy, A W; Ambak, M A; Nurhafizah, W W I; Alia, A S; Jabar, A; Najiah, M

2017-06-01

The current study was designed to evaluate the effects of Excoecaria agallocha leaf extracts on immune mechanisms and resistance of tilapia, Oreochromis niloticus, after challenge with Streptococcus agalactiae. Fish were divided into 6 groups; groups 1-5 fed with E. agallocha leaf extracts at 10, 20, 30, 40 and 50mgkg -1 level, respectively. Group 6 were fed without extract addition and acted as control. E. agallocha extracts were administered as feed supplement in fish diet for 28days and the hematological, immunological, and growth performance studies were conducted. Fish were infected with S. agalactiae at a dose of 15×105CFUmL -1 and the total white blood cell (WBC), phagocytosis and respiratory burst activities of leukocytes, serum bactericidal activity, lysozyme, total protein, albumin, and globulin levels were monitored and mortalities recorded for 15days post infection. Results revealed that feeding O. niloticus with 50mgkg -1 of E. agallocha enhanced WBC, phagocytic, respiratory burst, serum bactericidal and lysozyme activities on day 28 pre-challenge and on 3rd, 6th, 9th, 12th and 15th day post-challenge as compared to control. Total protein and albumin were not enhanced by E. agallocha diet. E. agallocha increased the survival of fish after challenge with S. agalactiae. The highest mortality rate (97%) was observed in control fish and the lowest mortality (27%) was observed with group fed with 50mgkg -1 extract. The results indicate that dietary intake of E. agallocha methanolic leaf extract in O. niloticus enhances the non-specific immunity and disease resistance against S. agalactiae pathogen. Copyright © 2017. Published by Elsevier Ltd.

An evaluation of immunization education resources by family medicine residency directors.

PubMed

Nowalk, Mary Patricia; Zimmerman, Richard K; Middleton, Donald B; Sherwood, Roger A; Ko, Feng-Shou; Kimmel, Sanford R; Troy, Judith A

2007-01-01

Immunization is a rapidly evolving field, and teachers of family medicine are responsible for ensuring that they and their students are knowledgeable about the latest vaccine recommendations. A survey was mailed to 456 family medicine residency directors across the United States to obtain their evaluation of immunization resources developed by the Society of Teachers of Family Medicine's Group on Immunization Education. Frequencies, measures of central tendency, and differences between responses from 2001 to 2005 were analyzed. Directors of 261 (57%) family medicine residencies responded, with >80% reporting satisfaction with immunization teaching resources. The popularity of bound resources decreased from 2001 to 2005, while immunization Web sites increased in importance. The journal supplement, "Vaccines Across the Lifespan, 2005" was less frequently read in 2005 than its predecessor published in 2001, but quality ratings remained high. Use of the Web site, www.ImmunizationEd.org, and the Shots software for both desktop and handheld computers has increased since their creation. Electronic immunization teaching resources are increasingly popular among family medicine residencies. As the field continues to change, the use of electronic resources is expected to continue, since they are easily updated and, in the case of www.ImmunizationEd.org and Shots software, are available free of charge.

Immunity's fourth dimension: approaching the circadian-immune connection.

PubMed

Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

2012-12-01

The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Trends in Outcomes and Hospitalization Charges of Infant Botulism in the United States: A Comparative Analysis Between Kids' Inpatient Database and National Inpatient Sample.

PubMed

Opila, Tamara; George, Asha; El-Ghanem, Mohammad; Souayah, Nizar

2017-02-01

New therapeutic strategies, including immune globulin intravenous, have emerged in the past two decades for the management of botulism. However, impact on outcomes and hospitalization charges among infants (aged ≤1 year) with botulism in the United States is unknown. We analyzed the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) for in-hospital outcomes and charges for infant botulism cases from 1997 to 2009. Demographics, discharge status, mortality, length of stay, and hospitalization charges were reported from the two databases and compared. Between 1997 and 2009, 504 infant hospitalizations were captured in KID', and 340 hospitalizations from NIS, for comparable years. A significant decrease was observed in mean length of stay for 'KID (P < 0.01); a similar decrease was observed for the NIS. The majority of patients were discharged to home. Despite an initial decrease after 1997, an increasing trend was observed for 'KID/NIS mean hospital charges from 2000 to 2009 (from $57,659/$56,309 to $143,171/$106,378; P < 0.001/P < 0.001). A linear increasing trend was evident when examining mean daily hospitalization charges for both databases. In conducting a subgroup analysis of the 'KID database, the youngest patients with infantile botulism (≤1.9 months) displayed the highest average number of procedures during their hospitalization (P < .001) and the highest rate of mechanical ventilation (P < .001), compared with their older counterparts. Infant botulism cases have demonstrated a significant increase in hospitalization charges over the years despite reduced length of stay. Additionally, there were significantly higher daily adjusted hospital charges and an increased rate of routine discharges for immune globulin intravenous-treated patients. More controlled studies are needed to define the criteria for cost-effective use of intravenous immune globulin in the population with infant botulism. Copyright © 2016 Elsevier Inc. All

BERNA: a century of immunobiological innovation.

PubMed

Cryz, S J

1999-10-01

At the time the Swiss Serum and Vaccine Institute Berne (BERNA) was found in 1898, few vaccines or immune globulins were available. This short list included vaccines against cholera, typhoid fever, plague, smallpox and rabies and equine anti-tetanus and diphtheria immune globulins. Furthermore, their use was restricted due to limited production capacity, uncertainty regarding safety and no public health infrastructure to promote their utilization. Today, safe and effective vaccines exist for more than 30 infectious diseases while human hyperimmune globulins exist to treat or prevent rabies, tetanus, respiratory syncytial virus, cytomegalovirus, hepatitis A, hepatitis B, and herpes virus (Varicella zoster) infections. Throughout its 100 years of existence, BERNA has played a key role in the evolution of the field by introducing novel technology leading to safer, and more efficacious vaccines. It was a pioneer in the development of freeze dried smallpox vaccine free from bacterial contamination. The Salmonella typhi Ty21a typhoid fever vaccine strain demonstrated that oral immunization against enteric bacterial pathogens was not only feasible, but could be accomplished with a virtual lack of attendant adverse reactions. This finding has served as an impetus to develop other live attenuated bacterial strains not only as vaccines, but also as vectors for vaccine antigens and gene therapy. One such example is Vibrio cholerae CVD 103-HgR, the first live vaccine for human use derived through recombinant DNA technology. Subsequent studies have shown that these two vaccine strains can be combined without sacrificing safety or immunogenicity, setting the cornerstone for combined orally administered vaccines. Recently, a novel vaccine antigen delivery system, termed virosomes, has been utilized to construct hepatitis A and influenza vaccines. Such vaccines elicit fewer local adverse reactions than their classical counterparts and display enhanced immunogenicity. Virosome

Mathematical modeling the radiation effects on humoral immunity

NASA Astrophysics Data System (ADS)

Smirnova, O. A.

A mathematical model of humoral immune response in nonirradiated and irradiated mammals is developed. It is based on conventional theories and experimental facts in this field. The model is a system of nonlinear differential equations which describe the dynamics of concentrations of antibody and antigen molecules, immunocompetent B lymphocytes, and the rest blood lymphocytes, as well as the bone-marrow lymphocyte precursors. The interaction of antigen molecules with antibodies and with antibody-like receptors on immunocompetent cells is also incorporated. The model quantitatively reproduces the dynamics of the humoral immune response to the T-independent antigen (capsular antigen of plague microbe) in nonirradiated mammals (CBA mice). It describes the peculiarities of the humoral immune response in CBA mice exposed to acute radiation before or after introducing antigen. The model predicts an adaptation of humoral immune system to low dose rate chronic irradiation in the result of which the intensity of immune response relaxes to a new, lower than normal, stable level. The mechanisms of this phenomenon are revealed. The results obtained show that the developed model, after the appropriate identification, can be used to predict the effects of acute and low-level long-term irradiation on the system of humoral immunity in humans. Employment of the mathematical model identified in the proper way should be important in estimating the radiation risk for cosmonauts and astronauts on long space missions such as a voyage to Mars or a lunar colony.

Endocannabinoids and the Immune System in Health and Disease.

PubMed

Cabral, Guy A; Ferreira, Gabriela A; Jamerson, Melissa J

2015-01-01

Endocannabinoids are bioactive lipids that have the potential to signal through cannabinoid receptors to modulate the functional activities of a variety of immune cells. Their activation of these seven-transmembranal, G protein-coupled receptors sets in motion a series of signal transductional events that converge at the transcriptional level to regulate cell migration and the production of cytokines and chemokines. There is a large body of data that supports a functional relevance for 2-arachidonoylglycerol (2-AG) as acting through the cannabinoid receptor type 2 (CB2R) to inhibit migratory activities for a diverse array of immune cell types. However, unequivocal data that supports a functional linkage of anandamide (AEA) to a cannabinoid receptor in immune modulation remains to be obtained. Endocannabinoids, as typical bioactive lipids, have a short half-life and appear to act in an autocrine and paracrine fashion. Their immediate effective action on immune function may be at localized sites in the periphery and within the central nervous system. It is speculated that endocannabinoids play an important role in maintaining the overall "fine-tuning" of the immune homeostatic balance within the host.

The twilight of immunity: emerging concepts in aging of the immune system.

PubMed

Nikolich-Žugich, Janko

2018-01-01

Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

Primary Prevention and Compliance Toward Childhood Immunizations.

ERIC Educational Resources Information Center

Peterson, Lizette

This paper discusses the success of methods used in the community to increase immunization levels among children. Using a population-wide model, data were obtained from a combined, city-county health department in Missouri. While the methods used by free school clinics and public clinics were found to be effective methods in promoting…

Low capacity of erythrocytes to bind with immune complexes via C3b receptor in patients with systemic lupus erythematosus: correlation with pathological proteinuria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nojima, Y.; Terai, C.; Minota, S.

1985-01-01

Erythrocytes from 51 patients with systemic lupus erythematosus and 75 controls were tested for the capacity to bind aggregated human gamma-globulin labeled with radioiodine in the presence of complement. Both in patients and controls, a trimodal distribution of binding capacity was observed. Low (less than 9% of the added radioactivity), intermediate (9-17%), and high binding (more than 17%) were observed in 13, 58, and 29% in controls and in 49, 43 and 8% in lupus patients. The low binding capacity of erythrocytes persisted even after patients entered remission following steroid therapy. A genetic control of binding capacity was supported bymore » familial surveys. Prevalence of pathological proteinuria was significantly higher in patients with low binding capacity than those with intermediate or high binding capacity (16/25 vs 7/26, P less than 0.01). These results indicate that an impaired physiological disposal of immune complexes via the erythrocyte C3b receptor in lupus patients may contribute to the development of renal involvement.« less

Evaluation of Primary Immunization Coverage of Infants Under Universal Immunization Programme in an Urban Area of Bangalore City Using Cluster Sampling and Lot Quality Assurance Sampling Techniques

PubMed Central

K, Punith; K, Lalitha; G, Suman; BS, Pradeep; Kumar K, Jayanth

2008-01-01

Research Question: Is LQAS technique better than cluster sampling technique in terms of resources to evaluate the immunization coverage in an urban area? Objective: To assess and compare the lot quality assurance sampling against cluster sampling in the evaluation of primary immunization coverage. Study Design: Population-based cross-sectional study. Study Setting: Areas under Mathikere Urban Health Center. Study Subjects: Children aged 12 months to 23 months. Sample Size: 220 in cluster sampling, 76 in lot quality assurance sampling. Statistical Analysis: Percentages and Proportions, Chi square Test. Results: (1) Using cluster sampling, the percentage of completely immunized, partially immunized and unimmunized children were 84.09%, 14.09% and 1.82%, respectively. With lot quality assurance sampling, it was 92.11%, 6.58% and 1.31%, respectively. (2) Immunization coverage levels as evaluated by cluster sampling technique were not statistically different from the coverage value as obtained by lot quality assurance sampling techniques. Considering the time and resources required, it was found that lot quality assurance sampling is a better technique in evaluating the primary immunization coverage in urban area. PMID:19876474

Winter distribution and abundance of Snowy Plovers in eastern North America and the West Indies

USGS Publications Warehouse

Elliott-Smith, Elise; Haig, Susan M.; Ferland, C.L.; Gorman, Leah

2004-01-01

Serum protein changes were studied in immune and nonimmune pigeons infected with three different strains of Trichomonas gallinae. Strain I (nonvirulent) produced no change in the relative concentration of serum components. Strains II (oral canker) and III (Jones' Barn) produced decreases in albumin and alpha globulins, and increases in beta and gamma globulins between the 7th and 20th days post infection. Birds infected with strain II began to return to normal by the 20th day, while all those infected with strain III were dead between 10 and 14 days post infection. Two serum protein patterns resulted from infection of immune birds with the Jones' Barn strain. One showed no change in relative protein concentrations and no tissue invasion by the parasite while the other was similar to that seen in nonimmune birds infected with a strain producing oral canker. These also showed evidence of tissue invasion by the parasite. It was concluded that tissue invasion was necessary to evoke a quantitative change in serum protein concentrations.

Immune modulation following immunization with polyvalent vaccines in dogs.

PubMed

Strasser, Alois; May, Bettina; Teltscher, Andrea; Wistrela, Eva; Niedermüller, Hans

2003-08-15

A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer.

Prognostic value of pretreatment albumin/globulin ratio in digestive system cancers: A meta-analysis.

PubMed

Guo, Hui-Wen; Yuan, Tang-Zhan; Chen, Jia-Xi; Zheng, Yang

2018-01-01

The albumin/globulin ratio (AGR) has been widely reported to be a potential predictor of prognosis in digestive system cancers (DSCs), but convincing conclusions have not been made. Therefore, herein, we performed a meta-analysis of relevant studies regarding this topic to evaluate the prognostic value of AGR in patients with DSCs. Three databases, including PubMed, EMBase, and Web of science, were searched comprehensively for eligible studies through September 8, 2017. The outcomes of interest included overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). In our meta-analysis, pooled analysis of 13 studies with 9269 patients showed that a low AGR was significantly correlated with poor OS (HR = 1.94; 95% CI: 1.57-2.38; P <0.001). Five studies with 6538 participants involved DFS, and our pooled analysis of these studies also demonstrated that there was a significant association of a low AGR with worse DFS (HR = 1.49; 95% CI: 1.10 to 2.00; P < 0.001). In addition, only 2 studies referred to CSS, and we also detected a significant relationship between a low AGR and worse CSS from the results of our meta-analysis. In summary, a low pretreatment AGR was related to unfavorable survival in human digestive system cancers. A low pretreatment AGR may be a useful predictive prognostic biomarker in human digestive system cancers.

[Changes in molecular forms of sex hormone binding globulin during menstrual cycle and menopause].

PubMed

Fonseca, M E; Masón, M; Ochoa, R; Hernández-V, M; Zárate, A

1996-11-01

Sex hormone binding globulin (SHBG) is a glycoprotein that transports mainly androgens and estrogens regulating the amount of free and bound hormone which in turn plays a role in the metabolic balance. It is also known that estrogens increase the hepatic production of SHBG which circulates in various molecular forms containing different amounts of sialic acid as the main component of carbohydrates. In the present work we studied physiological variations of molecular forms of SHBG during the normal menstrual cycle and the menopause. During the follicular phase the form 54 KD was the predominant variant, in the periovulatory period was isomers 90 KD, and during the luteal phase corresponded to both 54 and 90 KD. In the menopause dimeric form of 90 KD corresponded to the major proportion and was present a higher molecular forms of 115-135 KD. Following estrogen therapy the chromatographic profile changed as to that observed during the menstrual cycle. Important changes in the proportion of sialic acid were observed in each of the phases of menstrual cycle and following estrogen replacement. And increase in the amount of sialic acid corresponded to higher estrogen concentrations. It is concluded that SHBG concentrations varies during the menstrual cycle according the estrogen levels which in addition regulates the proportion of molecular forms and sialic acid containt.

Pharmacokinetic and pharmacodynamic studies of two different rabbit antithymocyte globulin dosing regimens: results of a randomized trial.

PubMed

Büchler, Matthias; Longuet, Hélène; Lemoine, Roxane; Herr, Florence; Gatault, Philippe; Thibault, Gilles; Ternant, David; Foulon, Christine; Pilorge, Bernadette; Lemay, Djamila; Sung, Crystal; Halimi, Jean-Michel; Baron, Christophe; Lebranchu, Yvon

2013-03-01

Rabbit antithymocyte globulin (rATG; Thymoglobulin(®)) is currently used to prevent acute rejection in kidney transplantation. The dose and regimen of rATG have not been optimized. Moreover, the impact of different treatment regimens on T-cell phenotype reconstitution remains unknown. We conducted a prospective randomized study of 17 renal transplant patients to determine the pharmacokinetics of total and active (bound to human cells) rATG and T-cell phenotype reconstitution after rATG administration. Patients received rATG at a total dose of 6mg/kg, administered either as 1.5mg/kg/day on days 0-3 (Group 1, n=8) or 3mg/kg on days 0 and 3 (Group 2, n=9). All patients received tacrolimus, mycophenolate mofetil and steroids. Blood samples were assayed for total rATG by enzyme linked immunosorbent assay and active rATG by flow cytometry. Maximum concentrations and terminal half-lives were similar between the two groups but at month 3 Group 1 had significantly lower values for total rATG (concentration was 6.2±1.1μg/mL versus 10.2±2.9μg/mL in Group 2, p=0.027) and total rATG dose-normalized AUC (374±83dayg/mL versus 508±149dayg/mL in Group 2, p=0.046). Time to sub-therapeutic levels (<1μg/mL) of active rATG was significantly shorter in Group 1 (18.75±6.9days versus 20±7.5days in Group 2, p<0.001). rATG induced significant depletion followed by slow reconstitution of CD3(+), CD4(+) and CD8(+) cells, with no marked differences between groups. B-cell count was unaffected, whereas CD3(-)CD56(+) NK-cell depletion was observed in both groups. rATG induced a significant decrease in the proportion of naïve CD4(+) T-cells, which plateaued after month 1 in Group 1 and after month 6 in Group 2. The proportion of central memory CD4(+) T-cells increased to a similar extent in both groups (Group 1: 38±18% at baseline, 74±23% at one year, p=0.009; Group 2: 32±14% at baseline, 65±14% at one year, p=0.001). In conclusion, our results suggest that the dosing regimen for r

Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

PubMed Central

Pye, Ruth; Patchett, Amanda; McLennan, Elspeth; Thomson, Russell; Carver, Scott; Fox, Samantha; Pemberton, David; Kreiss, Alexandre; Baz Morelli, Adriana; Silva, Anabel; Pearse, Martin J.; Corcoran, Lynn M.; Belov, Katherine; Hogg, Carolyn J.; Woods, Gregory M; Lyons, A. Bruce

2018-01-01

Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol®) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity

PubMed Central

Rosado, Maria Manuela; Simkó, Myrtill; Mattsson, Mats-Olof; Pioli, Claudio

2018-01-01

In recent years, the effects of electromagnetic fields (EMFs) on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while “respecting” the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing. PMID:29632855

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity.

PubMed

Rosado, Maria Manuela; Simkó, Myrtill; Mattsson, Mats-Olof; Pioli, Claudio

2018-01-01

In recent years, the effects of electromagnetic fields (EMFs) on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while "respecting" the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing.

Immune oncology, immune responsiveness and the theory of everything.

PubMed

Turan, Tolga; Kannan, Deepti; Patel, Maulik; Matthew Barnes, J; Tanlimco, Sonia G; Lu, Rongze; Halliwill, Kyle; Kongpachith, Sarah; Kline, Douglas E; Hendrickx, Wouter; Cesano, Alessandra; Butterfield, Lisa H; Kaufman, Howard L; Hudson, Thomas J; Bedognetti, Davide; Marincola, Francesco; Samayoa, Josue

2018-06-05

Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem.

[Plant immune system: the basal immunity].

PubMed

Shamraĭ, S N

2014-01-01

Plants have an efficient system of innate immunity which is based on the effective detection of potentially harmful microorganisms and rapid induction of defense responses. The first level of plant immunity is the basal immunity which is induced by the conserved molecular structures of microbes such as bacterial flagellins or fungal chitin, or molecules that result from the interaction of plants with pathogens, for example oligosaccharides and peptides ("danger signals"). Plants recognize these inducers through receptors localized to the plasma membrane, represented mainly receptor-like protein kinases or receptor-like proteins. Activation of the receptor by a ligand triggers a complex network of signaling events which eventually cause an array of plant defense responses to prevent further spread of the pathogen.

Tuberculosis disease diagnosis using artificial immune recognition system.

PubMed

Shamshirband, Shahaboddin; Hessam, Somayeh; Javidnia, Hossein; Amiribesheli, Mohsen; Vahdat, Shaghayegh; Petković, Dalibor; Gani, Abdullah; Kiah, Miss Laiha Mat

2014-01-01

There is a high risk of tuberculosis (TB) disease diagnosis among conventional methods. This study is aimed at diagnosing TB using hybrid machine learning approaches. Patient epicrisis reports obtained from the Pasteur Laboratory in the north of Iran were used. All 175 samples have twenty features. The features are classified based on incorporating a fuzzy logic controller and artificial immune recognition system. The features are normalized through a fuzzy rule based on a labeling system. The labeled features are categorized into normal and tuberculosis classes using the Artificial Immune Recognition Algorithm. Overall, the highest classification accuracy reached was for the 0.8 learning rate (α) values. The artificial immune recognition system (AIRS) classification approaches using fuzzy logic also yielded better diagnosis results in terms of detection accuracy compared to other empirical methods. Classification accuracy was 99.14%, sensitivity 87.00%, and specificity 86.12%.

DNA Immunization

PubMed Central

Wang, Shixia; Lu, Shan

2013-01-01

DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed. PMID:24510291

Maternal immune status in pregnancy is related to offspring's immune responses and atopy risk.

PubMed

Herberth, G; Hinz, D; Röder, S; Schlink, U; Sack, U; Diez, U; Borte, M; Lehmann, I

2011-08-01

The influence of maternal immune responses in pregnancy on children's immune competence and the development of atopic diseases later in life are poorly understood. To determine potential maternal effects on the maturation of children's immune system and resulting disease risks, we analysed immune responses in mother-child pairs in a prospective birth cohort study. Within the Lifestyle and Environmental factors and their Influence on Newborns Allergy risk (LINA) study, concentrations of Th1/Th2/Th17 and inflammatory cytokines/chemokines as well as IgE were measured in phytohemagglutinin and lipopolysaccharide stimulated maternal blood in the 34th week of gestation and in corresponding children's blood at birth and 1 year after (n = 353 mother-child pairs). Information on atopic outcomes during the first year of life was obtained from questionnaires. Concentrations of inflammatory markers, excepting TNF-α, were manifold higher in cord blood samples compared with maternal blood. Th1/Th2 cytokines were lower in children's blood with a Th2 bias at birth. Maternal inflammatory parameters (MCP-1, IL-10, TNF-α) in pregnancy showed an association with corresponding cytokines blood levels in children at the age of one. High maternal IgE concentrations in pregnancy were associated with increased children's IgE at birth and at the age of one, whereas children's atopic dermatitis (AD) was determined by maternal AD. Maternal inflammatory cytokines during pregnancy correlate with children's corresponding cytokines at the age of one but are not related to IgE or AD. While maternal IgE predicts children's IgE, AD in children is only associated with maternal disease. © 2011 John Wiley & Sons A/S.

Temperature-responsive release of cortisol from its binding globulin: a protein thermocouple.

PubMed

Cameron, Angus; Henley, David; Carrell, Robin; Zhou, Aiwu; Clarke, Anthony; Lightman, Stafford

2010-10-01

Only 5% of circulating cortisol is active and unbound to carrier proteins. Because cortisol levels vary rapidly due to the pulsatile nature of cortisol secretion, the dynamics of cortisol binding are critical determinants of tissue levels of free cortisol and consequent hormonal signaling. The major glucocorticoid carrier protein is corticosteroid binding globulin (CBG), a member of the serpin family that undergoes conformational changes to bind and release hormones. This mechanism has been noted to be temperature responsive, and we have now investigated the effects of temperature on the binding of human CBG to both cortisol and progesterone. Recombinant human CBG was synthesized and used for binding studies with cortisol and progesterone between 34 and 43 C. Binding was monitored by recording the change in intrinsic protein fluorescence. Binding of the steroids to the other major carrier, serum albumin, was measured in a similar manner. There was no effect of temperature on the interaction between human serum albumin and either cortisol or progesterone. The association of both cortisol and progesterone with CBG is more than three orders of magnitude greater than that with HSA, and this interaction was extremely responsive to changes in temperature. The affinity of both cortisol and progesterone for CBG drops approximately 16-fold as temperature increases from 35 to 42 C. This study clearly shows that even within the clinically relevant range of temperatures found in humans, CBG acts as a protein thermocouple that is exquisitely sensitive to temperature change and will release cortisol in response to fever or external sources of heat. This has major implications for our understanding of cortisol regulation in febrile patients.

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

PubMed

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

Pineal-adrenal-immune system relationship under thermal stress: effect on physiological, endocrine, and non-specific immune response in goats.

PubMed

Sejian, Veerasamy; Srivastava, Rajendra Swaroop

2010-12-01

The purpose of the investigation was to observe the pineal-adrenal-immune system relationships and their influence on non-specific immune response in female goats under short-term thermal stress. Six female goats had been exposed to 40°C and 60% relative humidity in the psychrometric chamber for 17 days. Blood samples were obtained on days 0 and 10 to establish control and thermal stress effects, respectively. Chemical adrenalectomy was achieved by injecting metyrapone (100 mg/kg body weight) followed by exogenous melatonin treatment (0.1 mg/kg body weight) from 11th to 17th day of experiment. Thermal stress significantly (P≤0.05) altered the physiological responses. Metyrapone and melatonin treatment significantly (P≤0.05) reduced the thermal-stress-induced increase in plasma concentrations of cortisol and corticosterone while significantly (P≤0.05) increased the plasma melatonin on days 11 and 17. Furthermore, these treatments significantly (P<0.05) increased the phagocytic activity of neutrophils as compared to both control and thermal exposure values from 11-17 days of experiment. The data generated from this study help us to understand the functional relationship between pineal, adrenal, and immune system, and how this relationship modifies the non-specific immune response for the well being of goats during thermal stress.

Immunization Action Coalition

MedlinePlus

... Email CDC: nipinfo@cdc.gov Contact: State Immunization Managers Email IAC: admin@immunize.org This page was ... STATE INFORMATION State Websites State Laws State Immunization Managers >> view all SUBSCRIBE SUPPORT IAC TECHNICALLY SPEAKING TRANSLATE ...

Protection of rats against dental caries by passive immunization with hen-egg-yolk antibody (IgY).

PubMed

Otake, S; Nishihara, Y; Makimura, M; Hatta, H; Kim, M; Yamamoto, T; Hirasawa, M

1991-03-01

Hen-egg-yolk antibody (IgY) was prepared against Streptococcus mutans MT8148 serotype c that was cultivated in medium containing sucrose, and it was used in passive caries-immunity studies. Specific pathogen-free rats infected with S. mutans MT8148 (c) and fed with a cariogenic diet containing more than 2% immune yolk powder developed significantly lower caries scores than did the ones infected with the same strain and fed with a diet containing only control yolk powder obtained from non-immunized hens. Similar results were obtained in an experiment with rats infected with S. mutans JC-2 (c) strain. Rats provided a diet supplemented with 0.5% immune water-soluble protein fraction containing S. mutans-specific IgY and challenged with S. mutans MT8148 exhibited significantly fewer caries lesions, compared with control rats on the normal diet.

The Asp(327)Asn polymorphism in the sex hormone-binding globulin gene modifies the association of soy food and tea intake with endometrial cancer risk.

PubMed

Xu, Wang Hong; Zheng, Wei; Cai, Qiuyin; Cheng, Jia-Rong; Cai, Hui; Xiang, Yong-Bing; Shu, Xiao Ou

2008-01-01

We evaluated the interactive effect of polymorphisms in the sex hormone-binding globulin (SHBG) gene with soy isoflavones, tea consumption, and dietary fiber on endometrial cancer risk in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 controls. Genotyping of polymorphisms was performed by using TaqMan (Applied Biosystems, Foster City, CA) assays (rs6259) or the Affymetrix MegAllele Targeted Genotyping System (Affymetrix, Inc., US) (rs13894, rs858521, and rs2955617). Dietary information was obtained using a validated food frequency questionnaire. A logistic regression model was employed to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found that the Asp(327)Asn (rs6259) polymorphism was associated with decreased risk of endometrial cancer, particularly among postmenopausal women (OR = 0.79, 95% CI = 0.62-1.00). This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at Asp(327)Asn (rs6259), particularly premenopausal women (P(interaction) = 0.06 and 0.02, respectively, for soy isoflavones and tea intake). This study suggests that gene-diet interaction may play an important role in the etiology of endometrial cancer risk.

Evaluation of health status of horses immunized with snake venom and montanide adjuvants, IMS 3012 (nanoparticle), ISA 206 and ISA 35 (emulsion based) during polyvalent snake antivenom production: hematological and biochemical assessment.

PubMed

Waghmare, A B; Salvi, N C; Deopurkar, R L; Shenoy, P A; Sonpetkar, J M

2014-05-01

Several biochemical and hematological changes in horses are observed during production of snake antivenom. Although conventional adjuvants like Freund's (Complete and Incomplete) are good immunopotentiators, they produce considerable local reactions in animals. Variety of commercial adjuvants, like montanide adjuvants, having high immunopotentiation and showing lesser side effects are available. The prime objective during antivenom production is to strike a balance between safety of immunized horses and efficacy of the product. In our earlier work, efficacy of montanide group of adjuvants in antivenom production has already been established. The aim of the present work was to assess the safety parameters in horses, viz.: biochemical and hematological, during production of snake antivenom. In the present study, 33 new horses were randomly divided into four groups and hyperimmunized using mixture of snake venoms, viz.: Cobra venom, Russell's viper venom, Krait venom and Echis venom along with montanide adjuvants, IMS 3012, ISA 206, ISA 35 and Incomplete Freund's adjuvant as a control adjuvant; through subcutaneous route at intervals of two weeks. During the immunization period, biochemical and hematological parameters were monitored at 0th, 14th, 21st, 30th and 42nd weeks. The mean hemoglobin values dropped slightly during initial immunization but subsequently regained to normal levels. The mean serum total protein values and globulin levels showed an increment in all the four groups, compared to day zero, vice-versa a slight drop was observed in albumin levels. No significant changes were observed in serum creatinine, bilirubin, alkaline phosphatase and blood urea nitrogen values. Finally, we conclude that montanide adjuvants could be a safer alternative to the conventional adjuvants for primary phase of immunization in antivenom production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of treatment with probiotics as water additives on tilapia (Oreochromis niloticus) growth performance and immune response.

PubMed

Zhou, Xuxia; Tian, Ziqiang; Wang, Yanbo; Li, Weifen

2010-09-01

A feeding trial was conducted for 40 days to delineate the effect of treatment with probiotics as water additives on tilapia (Oreochromis niloticus) growth performance and immune response. About 360 juveniles were randomly distributed into four treatment groups, each with three replicates. Different probiotics (T-1, Bacillus subtilis B10; T-2, Bacillus coagulans B16; T-3, Rhodopseudomonas palustris G06) were added to the water of tanks at final concentration of 1 x 10(7) cfu ml(-1) every 2 days, with no probiotic added to control tanks. At the end of the feeding trial, fish treated with B. coagulans B16 (T-2) and R. palustris G06 (T-3) had significantly (P < 0.05) higher final weight, daily weight gain, and specific growth rate compared with those treated with B. subtilis B10 (T-1) and those without probiotics (control). The highest (P < 0.05) content of total serum protein was found in T-2 compared with that in T-1, T-3, and the control. However, albumin concentration and albumin/globulin ratio were not affected by the probiotics treatments. Compared with the control, probiotic supplementation remarkably improved activities of superoxide dismutase and catalase (P < 0.05). T-2 fish exhibited higher average myeloperoxidase activity than the control, T-1, and T-3 groups. Regarding serum lysozyme content in tilapia, assays showed no difference (P > 0.05) among the treatment groups. Furthermore, probiotics treatments remarkably increased respiratory burst activity compared with control, with T-2 showing higher values than T-1 and T-3. This indicated that treatment with probiotics, B. coagulans B16 and R. palustris G06, as water additives could be used to enhance immune and health status, thereby improving growth performance of O. niloticus.

Immune System Quiz

MedlinePlus

... Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

Assessing barriers to immunization.

PubMed

Niederhauser, Victoria; Ferris, Catherine

2016-05-03

Parental barriers to childhood immunizations vary among countries, states and communities. There is a plethora of studies that exist to examine barriers to immunizations including many intervention studies designed to improve immunization rates in children. Often, intervention studies designed to minimize barriers and increase immunization uptake among children lack the inclusion of a standardized instrument to measure accurately parental barriers to childhood immunizations before and after interventions. The Searching for Hardships and Obstacles To Shots (SHOTS) survey is a standardized survey instrument to measure parental barriers to childhood immunizations. In several studies, the SHOTS survey has demonstrated consistent reliability and has been validated in diverse populations. The inclusion of the SHOTS survey instrument in studies to examine barriers to childhood immunization will provide researchers and clinicians with a better understanding of parents' individualized barriers to immunizations. Furthermore, use of the SHOTS survey instrument to collect information about parental barriers to immunizations can lead to targeted interventions to minimize these obstacles at the individual and community level and to help us to achieve our national, state and community childhood immunization goals.

[Autoantibody formation against the antigens of the synaptonemal complex in the syngeneic immunization of male Mus musculus].

PubMed

Dadashev, S Ia; Gorach, G G; Kolomiets, O L

1994-01-01

Male mice were immunized with the suspension of synaptonemal complexes (SC) isolated from mouse spermatocytes nuclei. The indirect immunofluorescent analysis showed the active binding of sera obtained from immunized mice to SC of mouse spermatocyte spreads. At early and mid-pachytene, SC can be clearly identified in 19 autosome bivalents and in sex chromosome bivalent. According to the electron microscopic analysis, all structural elements of SC bind antibodies. Metaphase chromosomes were not stained with the immune sera. Specificity of interaction between SC components and antibodies was confirmed in a series of control experiments. Analysis of sera obtained from mice after their syngeneic immunization with isolated SC fraction suggested that certain mouse SC components induce the formation of autoantibodies. This, in turn, suggests that these SC components are meiosis-specific.

Immune Receptors and Co-receptors in Antiviral Innate Immunity in Plants.

PubMed

Gouveia, Bianca C; Calil, Iara P; Machado, João Paulo B; Santos, Anésia A; Fontes, Elizabeth P B

2016-01-01

Plants respond to pathogens using an innate immune system that is broadly divided into PTI (pathogen-associated molecular pattern- or PAMP-triggered immunity) and ETI (effector-triggered immunity). PTI is activated upon perception of PAMPs, conserved motifs derived from pathogens, by surface membrane-anchored pattern recognition receptors (PRRs). To overcome this first line of defense, pathogens release into plant cells effectors that inhibit PTI and activate effector-triggered susceptibility (ETS). Counteracting this virulence strategy, plant cells synthesize intracellular resistance (R) proteins, which specifically recognize pathogen effectors or avirulence (Avr) factors and activate ETI. These coevolving pathogen virulence strategies and plant resistance mechanisms illustrate evolutionary arms race between pathogen and host, which is integrated into the zigzag model of plant innate immunity. Although antiviral immune concepts have been initially excluded from the zigzag model, recent studies have provided several lines of evidence substantiating the notion that plants deploy the innate immune system to fight viruses in a manner similar to that used for non-viral pathogens. First, most R proteins against viruses so far characterized share structural similarity with antibacterial and antifungal R gene products and elicit typical ETI-based immune responses. Second, virus-derived PAMPs may activate PTI-like responses through immune co-receptors of plant PTI. Finally, and even more compelling, a viral Avr factor that triggers ETI in resistant genotypes has recently been shown to act as a suppressor of PTI, integrating plant viruses into the co-evolutionary model of host-pathogen interactions, the zigzag model. In this review, we summarize these important progresses, focusing on the potential significance of antiviral immune receptors and co-receptors in plant antiviral innate immunity. In light of the innate immune system, we also discuss a newly uncovered layer of

Implementation of pertussis immunization in health-care personnel.

PubMed

Walther, Kathi; Burckhardt, Marie-Anne; Erb, Thomas; Heininger, Ulrich

2015-04-21

Infection with Bordetella pertussis is most severe in young infants who frequently acquire it from adults. Pertussis immunization in adults 25-29 years of age and all adults in close contact with infants <6 months was introduced in Switzerland in 2012. We immediately implemented this new recommendation in our hospital with a vaccination campaign. Between April 2012 and March 2013 we provided information about the campaign to our staff through several channels and offered appointments for counseling and immunization. After checking indications and contraindications of responding health-care personnel (HCP), informed consent for tetanus-diphtheria-acellular pertussis component (Tdap) immunization was obtained. Specific adverse events (AE) were self-assessed by standardized diaries for 7 days. Statistical analyses were performed using a t-test and Mann-Whitney U-tests SPSS (V21). Of 852 HCP eligible for pertussis immunization, 427 (51%) responded. Of these, 72 (17%) had already received Tdap <10 years ago, 304 (71%) received Tdap now, 38 (9%) were scheduled for vaccination and 12 (3%) declined. Diaries were returned by 272 (89%) of 304 vaccinees; 56 HCP reported ≥1 local AE, most frequently local swelling (8%), redness (2%), redness and swelling (7%), and fever (5=2%); no serious AE occurred. Comprehensive efforts were needed to achieve pertussis immunization coverage of ≥49% among all HCP in our institution. Good tolerability of the vaccine and continuous and individual information to HCP about the rationale and benefits of pertussis immunization contributed to this partial success, but increased efforts are needed to mobilize non-responding HCP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

PubMed

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

Electrophoretic serum protein fraction profile during the different physiological phases in Comisana ewes.

PubMed

Piccione, G; Alberghina, D; Marafioti, S; Giannetto, C; Casella, S; Assenza, A; Fazio, F

2012-08-01

The aim of this study was to evaluate the influence of different physiological phases on serum total proteins and their fractions of ten Comisana ewes housed in Mediterranean area. From each animal, blood samples were collected at different physiological phases: late pregnancy, post-partum, early, mid-, end lactation and dry period. On all samples serum total proteins were determined by the biuret method, and albumin, α-globulins, β(1) -globulins, β(2) -globulins and γ-globulins concentrations were assessed using an automated system. One-way repeated measures analysis of variance was applied to determine the significant effect of different physiological phases on the parameters studied. During the late pregnancy and post-partum, total proteins, β1- and β2-globulins and γ-globulins showed the highest values. Starting from post-partum, α-globulins increased to reach their peaks in mid-lactation. Early lactation was characterized by low γ-globulins values. The increase in serum albumin concentration and the drop in some globulin fractions determined the significant increase in albumin/globulin ratio. The obtained results contributed to improve the knowledge on electrophoretic profile during the different physiological phases in ewes, confirming that pregnancy and lactation periods affect the protein metabolism. Particularly, serum protein fractions pattern could give information about dehydration, plasma volume expansion and hepatic function, which occur during the different physiological phases. Dynamics of the protein profile - from pregnancy to dry period - which are provided by our results, could be considered as guidelines for the management strategies to guarantee the nutritional needs of these animals during the different physiological phases and to avoid a decline of productive performance and consequently an economic loss. © 2011 Blackwell Verlag GmbH.

[The effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mother].

PubMed

Kong, H H; Seo, S A; Shin, C O; Im, K I

1993-06-01

Acanthamoeba culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalitis (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive immunity on the active immunization in offspring mice have not been demonstrated. This experiment was done to observe the effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mothers. Acanthamoeba culbertsoni was cultured in the CGV medium axenically. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba culbertsoni trophozoites 1 x 10(6) each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated intranasally with 1 x 10(4) trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T cell/Ly2+ T cell ratio was increased in the transferred immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of immunization.

A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice.

PubMed

Fonseca, Jairo A; McCaffery, Jessica N; Kashentseva, Elena; Singh, Balwan; Dmitriev, Igor P; Curiel, David T; Moreno, Alberto

2017-05-31

Malaria remains a considerable burden on public health. In 2015, the WHO estimates there were 212 million malaria cases causing nearly 429,000 deaths globally. A highly effective malaria vaccine is needed to reduce the burden of this disease. We have developed an experimental vaccine candidate (PyCMP) based on pre-erythrocytic (CSP) and erythrocytic (MSP1) stage antigens derived from the rodent malaria parasite P. yoelii. Our protein-based vaccine construct induces protective antibodies and CD4 + T cell responses. Based on evidence that viral vectors increase CD8 + T cell-mediated immunity, we also have tested heterologous prime-boost immunization regimens that included human adenovirus serotype 5 vector (Ad5), obtaining protective CD8 + T cell responses. While Ad5 is commonly used for vaccine studies, the high prevalence of pre-existing immunity to Ad5 severely compromises its utility. Here, we report the use of the novel simian adenovirus 36 (SAd36) as a candidate for a vectored malaria vaccine since this virus is not known to infect humans, and it is not neutralized by anti-Ad5 antibodies. Our study shows that the recombinant SAd36PyCMP can enhance specific CD8 + T cell response and elicit similar antibody titers when compared to an immunization regimen including the recombinant Ad5PyCMP. The robust immune responses induced by SAd36PyCMP are translated into a lower parasite load following P. yoelii infectious challenge when compared to mice immunized with Ad5PyCMP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immune cell phenotype and function in sepsis

PubMed Central

Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

2015-01-01

Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis. The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of non extracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed. A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8 and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes and the cell function. PMID:26529661

IMMUNE CELL PHENOTYPE AND FUNCTION IN SEPSIS.

PubMed

Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

2016-03-01

Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis.The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of nonextracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed.A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes, but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8, and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes, and the cell function.

Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay▿

PubMed Central

Kennedy, Richard; Pankratz, V. Shane; Swanson, Eric; Watson, David; Golding, Hana; Poland, Gregory A.

2009-01-01

Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin. PMID:19535540

Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

PubMed

Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Harrison, Linda; Decker, Luc; Khamduang, Woottichai; Tierney, Camlin; Salvadori, Nicolas; Cressey, Tim R; Sirirungsi, Wasna; Achalapong, Jullapong; Yuthavisuthi, Prapap; Kanjanavikai, Prateep; Na Ayudhaya, Orada P; Siriwachirachai, Thitiporn; Prommas, Sinart; Sabsanong, Prapan; Limtrakul, Aram; Varadisai, Supang; Putiyanun, Chaiwat; Suriyachai, Pornnapa; Liampongsabuddhi, Prateung; Sangsawang, Suraphan; Matanasarawut, Wanmanee; Buranabanjasatean, Sudanee; Puernngooluerm, Pichit; Bowonwatanuwong, Chureeratana; Puthanakit, Thanyawee; Klinbuayaem, Virat; Thongsawat, Satawat; Thanprasertsuk, Sombat; Siberry, George K; Watts, Diane H; Chakhtoura, Nahida; Murphy, Trudy V; Nelson, Noele P; Chung, Raymond T; Pol, Stanislas; Chotivanich, Nantasak

2018-03-08

Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log 10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in

Technological and Organizational Context around Immunization Reporting and Interoperability in Minnesota

PubMed Central

Rajamani, Sripriya; Roche, Erin; Soderberg, Karen; Bieringer, Aaron

2014-01-01

Background: Immunization information systems (IIS) operate in an evolving health care landscape with technology changes driven by initiatives such as the Centers for Medicare and Medicaid Services EHR incentive program, promoting adoption and use of electronic health record (EHR) systems, including standards-based public health reporting. There is flux in organizational affiliations to support models such as accountable care organizations (ACO). These impact institutional structure of how reporting of immunizations occurs and the methods adopted. Objectives: To evaluate the technical and organizational characteristics of healthcare provider reporting of immunizations to public health in Minnesota and to assess the adoption of standardized codes, formats and transport. Methods: Data on organizations and reporting status was obtained from Minnesota IIS (Minnesota Immunization Information Connection: MIIC) by collating information from existing lists, specialized queries and review of annual reports. EHR adoption data of clinics was obtained in collaboration with informatics office supporting the Minnesota e-Health Initiative. These data from various sources were merged, checked for quality to create a current state assessment of immunization reporting and results validated with subject matter experts. Results: Standards-based reporting of immunizations to MIIC increased to 708 sites over the last 3 years. A growth in automated real-time reporting occurred in 2013 with 143 new sites adopting the method. Though the uptake of message standards (HL7) has increased, the adoption of current version of HL7 and web services transport remains low. The EHR landscape is dominated by a single vendor (used by 40% of clinics) in the state. There is trend towards centralized reporting of immunizations with an organizational unit reporting for many sites ranging from 4 to 140 sites. Conclusion: High EHR adoption in Minnesota, predominance of a vendor in the market, and centralized

Nucleic Acid Immunity.

PubMed

Hartmann, G

2017-01-01

Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to

Morphostructure of Immune System Organs in Cattle of Different Age.

PubMed

Gasisova, A I; Atkenova, A B; Ahmetzhanova, N B; Murzabekova, L M; Bekenova, A C

2017-04-01

This article provides comprehensive consideration of the age-dependent morphofunctional state of organs and tissues of the immune system (thymus, spleen, superficial and deep lymph nodes) in cattle. The morphofunctional maturity of organs and tissues of the immune system in cattle will be taken into account in various experimental studies, preventive and therapeutic measures. Performed analysis provides description of the spleen formation as well as the thymus and lymph nodes in post-natal ontogenesis and the macro- and microscopic structure of lymphoid cells and macrophages. The obtained results can be used to study immune responses of the thymus, spleen, lymph nodes in the pathological immunogenesis and may serve as a basis for development of recommendations related to diagnosis and treatment of diseases of the cattle immune system. The morphofunctional state of organs and tissues of the immune system in cattle was first studied with regard to the age dynamics. Based on the immunohistological studies, this article described the distribution and topography of immunocompetent cells (T lymphocytes, B lymphocytes and macrophages) and proliferative activity of lymphoid cells in the lymphoid organs and tissues in cattle. © 2016 Blackwell Verlag GmbH.

Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

NASA Astrophysics Data System (ADS)

Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

1999-04-01

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

NASA Technical Reports Server (NTRS)

Sastry, Jagannadha K.

1997-01-01

Our proposed experiments included: (1) immunzing mice with synthetic peptides; (2) preparing spleen and lymph node cells; (3) growing them under conventional conditions as well as in the rotatory vessel in appropriate medium reconstituting with synthetic peptides and/or cytokines as needed; and (4) comparing at regular time intervals the specific CTL activity as well as helper T-cell activity (in terms of both proliferative responses and cytokine production) using established procedures in my laboratory. We further proposed that once we demonstrated the merit of rotatory vessel technology to achieve desired results, these studies would be expanded to include immune cells from non-human primates (rhesus monkeys and chimpanzees) and also humans. We conducted a number of experiments to determine CTL induction by the synthetic peptides corresponding to antigenic proteins in HIV and HPV in different mouse strains that express MHC haplotypes H-2b or H-2d. We immunized mice with 100 ug of the synthetic peptide, suspended in sterile water, and emulsified in CFA (1:1). The immune lymph node cells obtained after 7 days were restimulated by culturing in T25 flask, HARV-10, or STLV-50, in the presence of the peptide at 20 ug/ml. The results from the 5'Cr-release assay consistently revealed complete abrogation of CTL activity of cells grown in the bioreactors (both HARV and STLV), while significant antigen-specific CTL activity was observed with cells cultured in tissue culture flasks. Thus, overall the data we generated in this study proved the usefulness of the NASA-developed developed technology for understanding the known immune deficiency during space travel. Additionally, this ex vivo microgravity technology since it mimics effectively the in vivo situation, it is also useful in understanding immune disorders in general. Thus, our proposed studies in TMC-NASA contract round II application benefit from data generated in this TMC-NASA contract round I study.

[Immune system and tumors].

PubMed

Terme, Magali; Tanchot, Corinne

2017-02-01

Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

CMV immune evasion and manipulation of the immune system with aging.

PubMed

Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

2017-06-01

Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to

Immunization Schedule

MedlinePlus

... third dose may be needed, depending on the brand of vaccine used in previous Hib immunizations. PCV ... third dose may be needed, depending on the brand of vaccine used in previous RV immunizations. 6 ...

Who needs a shot ... a review of tetanus immunity in the West of Ireland.

PubMed

Moughty, Adrian; Donnell, John O; Nugent, Mary

2013-12-01

Tetanus is a rare disease but, in the era of widespread vaccination, largely a preventable one. Immunization programmes in childhood are felt to offer lifelong immunity but it is known that with increased age immunity wanes. We sought to assess immunity in a sample of patients presenting for conditions unrelated to injury to the emergency department covering an area in the West of Ireland. A convenience sample of 216 patients, who presented to the emergency department for complaints unrelated to injury, requiring blood tests for their management was obtained. Using the Protetanus QuickStick® all samples were analysed. No statistical difference between men and women in terms of tetanus immunity (p=0.94) but significant reduction in immunity with increasing age (p<0.001). Those non-immune tended to be older with mean age of 66 years compared to mean age of 46 year for immune. Using logarithmic regression analysis an increase in age of 10 years was associated with 50% reduction in immunity. National guidelines should incorporate this data and explicitly advocate the use of booster doses of tetanus toxoid outside of the normal vaccination programme especially in the elderly.

Impact of Pharmacist Immunization Authority on Seasonal Influenza Immunization Rates Across States.

PubMed

Drozd, Edward M; Miller, Laura; Johnsrud, Michael

2017-08-01

The goal of this study was to investigate the impact on immunization rates of policy changes that allowed pharmacists to administer influenza immunizations across the United States. Influenza immunization rates across states were compared before and after policy changes permitting pharmacists to administer influenza immunizations. The study used Behavioral Risk Factor Surveillance System (BRFSS) survey data on influenza immunization rates between 2003 and 2013. Logistic regression models were constructed and incorporated adjustments for the complex sample design of the BRFSS to predict the likelihood of a person receiving an influenza immunization based on various patient health, demographic, and access to care factors. Overall, as states moved to allow pharmacists to administer influenza immunizations, the odds that an adult resident received an influenza immunization rose, with the effect increasing over time. The average percentage of people receiving influenza immunizations in states was 35.1%, rising from 32.2% in 2003 to 40.3% in 2013. The policy changes were associated with a long-term increase of 2.2% to 7.6% in the number of adults aged 25 to 59 years receiving an influenza immunization (largest for those aged 35-39 years) and no significant change for those younger or older. These findings suggest that pharmacies and other nontraditional settings may offer accessible venues for patients when implementing other public health initiatives. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Serum corticosteroid binding globulin expression is modulated by fasting in polar bears (Ursus maritimus).

PubMed

Chow, Brian A; Hamilton, Jason; Cattet, Marc R L; Stenhouse, Gordon; Obbard, Martyn E; Vijayan, Mathilakath M

2011-01-01

Polar bears (Ursus maritimus) from several subpopulations undergo extended fasting during the ice-free season. However, the animals appear to conserve protein despite the prolonged fasting, though the mechanisms involved are poorly understood. We hypothesized that elevated concentrations of corticosteroid binding globulin (CBG), the primary cortisol binding protein in circulation, lead to cortisol resistance and provide a mechanism for protein conservation during extended fasting. The metabolic state (feeding vs. fasting) of 16 field sampled male polar bears was determined based on their serum urea to creatinine ratio (>25 for feeding vs. <5 for fasting). There were no significant differences in serum cortisol levels between all male and female polar bears sampled. Serum CBG expression was greater in lactating females relative to non-lactating females and males. CBG expression was significantly higher in fasting males when compared to non-fasting males. This leads us to suggest that CBG expression may serve as a mechanism to conserve protein during extended fasting in polar bears by reducing systemic free cortisol concentrations. This was further supported by a lower serum glucose concentration in the fasting bears. As well, a lack of an enhanced adrenocortical response to acute capture stress supports our hypothesis that chronic hunger is not a stressor in this species. Overall, our results suggest that elevated serum CBG expression may be an important adaptation to spare proteins by limiting cortisol bioavailability during extended fasting in polar bears. Copyright © 2010 Elsevier Inc. All rights reserved.

In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo

2009-01-01

Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We alsomore » screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [{sup 3}H]5{alpha}-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 {mu}M concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.« less

Antithymocyte globulins in renal transplantation-from lymphocyte depletion to lymphocyte activation: The doubled-edged sword.

PubMed

Bamoulid, Jamal; Crépin, Thomas; Courivaud, Cécile; Rebibou, Jean-Michel; Saas, Philippe; Ducloux, Didier

2017-07-01

Compelling data suggest that lymphocyte depletion following T cell depleting therapy may induce prolonged CD4 T cell lymphopenia and trigger lymphocyte activation in some patients. These profound and non-reversible immune changes in T cell pool subsets are the consequence of both impaired thymic renewal and peripheral homeostatic proliferation. Chronic viral challenges by CMV play a major role in these immune alterations. Even when the consequences of CD4 T cell lymphopenia have been now well described, recent studies shed new light on the clinical consequences of immune activation. In this review, we will first focus on the mechanisms involved in T cell pool reconstitution after T cell depletion and further consider the clinical consequences of ATG-induced T cell activation and senescence in renal transplant recipients. Copyright © 2017 Elsevier Inc. All rights reserved.

Construction of High-Quality Camel Immune Antibody Libraries.

PubMed

Romão, Ema; Poignavent, Vianney; Vincke, Cécile; Ritzenthaler, Christophe; Muyldermans, Serge; Monsion, Baptiste

2018-01-01

Single-domain antibodies libraries of heavy-chain only immunoglobulins from camelids or shark are enriched for high-affinity antigen-specific binders by a short in vivo immunization. Thus, potent binders are readily retrieved from relatively small-sized libraries of 10 7 -10 8 individual transformants, mostly after phage display and panning on a purified target. However, the remaining drawback of this strategy arises from the need to generate a dedicated library, for nearly every envisaged target. Therefore, all the procedures that shorten and facilitate the construction of an immune library of best possible quality are definitely a step forward. In this chapter, we provide the protocol to generate a high-quality immune VHH library using the Golden Gate Cloning strategy employing an adapted phage display vector where a lethal ccdB gene has to be substituted by the VHH gene. With this procedure, the construction of the library can be shortened to less than a week starting from bleeding the animal. Our libraries exceed 10 8 individual transformants and close to 100% of the clones harbor a phage display vector having an insert with the length of a VHH gene. These libraries are also more economic to make than previous standard approaches using classical restriction enzymes and ligations. The quality of the Nanobodies that are retrieved from immune libraries obtained by Golden Gate Cloning is identical to those from immune libraries made according to the classical procedure.

Induction of protective immunity against toxoplasmosis in mice by immunization with Toxoplasma gondii RNA.

PubMed

Dimier-Poisson, Isabelle; Aline, Fleur; Bout, Daniel; Mévélec, Marie-Noëlle

2006-03-06

Toxoplasma gondii enters the mucosal surfaces of the host, and so immunity at these sites is of major interest. Due to the compartmentalization of the immune response, systemic immunization does not induce high levels of immunity at mucosal surfaces. Intranasal immunization has been shown to be very effective in inducing both systemic and mucosal immune responses. Immunization with mRNA can induce both humoral and cell-mediated immune responses, both of which are important in conferring immunity to T. gondii. The efficacy of RNA vaccination by the nasal route with T. gondii RNA was evaluated. We assessed the percentage of cumulative survival after an oral challenge with a lethal dose of T. gondii cysts (40 cysts), and the number of brain cysts following a challenge with a sublethal dose of T. gondii 76 K cysts (15 cysts). Vaccinated mice were found to be significantly better protected than non-immunized mice after a challenge with a lethal dose of cysts; and a challenge with a sublethal dose also resulted in fewer brain cysts than in non-immunized mice. Sera and intestinal secretions of immunized mice recognized T. gondii antigens, suggesting that a specific humoral immune response may occur. Moreover, a specific lymphoproliferative response observed in cervical lymph nodes may confer protection. These preliminary findings suggest that RNA vaccination by a mucosal route could be feasible.

Immunization coverage among Hispanic ancestry, 2003 National Immunization Survey.

PubMed

Darling, Natalie J; Barker, Lawrence E; Shefer, Abigail M; Chu, Susan Y

2005-12-01

The Hispanic population is increasing and heterogeneous (Hispanic refers to persons of Spanish, Hispanic, or Latino descent). The objective was to examine immunization rates among Hispanic ancestry for the 4:3:1:3:3 series (> or = 4 doses diphtheria, tetanus toxoids, and pertussis vaccine; > or = 3 doses poliovirus vaccine; > or = 1 doses measles-containing vaccine; > or = 3 doses Haemophilus influenzae type b vaccine; and > or = 3 doses hepatitis B vaccine). The National Immunization Survey measures immunization coverage among 19- to 35-month-old U.S. children. Coverage was compared from combined 2001-2003 data among Hispanics and non-Hispanic whites using t-tests, and among Hispanic ancestry using a chi-square test. Hispanics were categorized as Mexican, Mexican American, Central American, South American, Puerto Rican, Cuban, Spanish Caribbean (primarily Dominican Republic), other, and multiple ancestry. Children of Hispanic ancestry increased from 21% in 1999 to 25% in 2003. These Hispanic children were less well immunized than non-Hispanic whites (77.0%, +/-2.1% [95% confidence interval] compared to 82.5%, +/-1.1% (95% CI) > in 2003). Immunization coverage did not vary significantly among Hispanics of varying ancestries (p=0.26); however, there was substantial geographic variability. In some areas, immunization coverage among Hispanics was significantly higher than non-Hispanic whites. Hispanic children were less well immunized than non-Hispanic whites; however, coverage varied notably by geographic area. Although a chi-square test found no significant differences in coverage among Hispanic ancestries, the range of coverage, 79.2%, +/-5.1% for Cuban Americans to 72.1%, +/-2.4% for Mexican descent, may suggest a need for improved and more localized monitoring among Hispanic communities.

Characterization of immune response to Eimeria tenella antigens in a natural immunity model with hosts which differ serologically at the B locus of the major histocompatibility complex.

PubMed Central

Brake, D A; Fedor, C H; Werner, B W; Miller, T J; Taylor, R L; Clare, R A

1997-01-01

A model to simulate natural immunity to Eimeria tenella was developed in three chicken lines which differ at the B locus of the major histocompatibility complex. Homozygous, 1-day-old chicks of the B19B19, B24B24, or B30B30 genotype were trickle immunized by being orally fed a small infectious dose of E. tenella oocysts for 5 consecutive days. These naturally exposed birds were then challenged at different times between 5 and 24 days after the final dose, and the level of protection was assessed 6 days after challenge, using body weight gain and intestinal lesion scores. The duration of immunity in naturally exposed birds differed among the major histocompatibility complex lines. Trickle immunization of the B19B19 haplotype afforded the longest and strongest level of protection compared to the other two haplotypes tested. In addition, in vitro splenic and peripheral blood lymphocyte proliferative responses in trickle-immunized birds were measured against sporozoite, merozoite, and tissue culture-derived E. tenella parasite antigens isolated from the recently described SB-CEV-1/F7 established cell line. The lymphocytes obtained from B19B19 birds trickle immunized responded in vitro to the E. tenella-infected SB-CEV-1/F7 tissue culture-derived parasite antigen. Furthermore, antigen-specific immune responses appeared earlier in immune, challenged B19B19 birds than in their naive, challenged counterparts. The development of a model simulating natural immunization will serve as a foundation to further characterize both humoral and cell-mediated responses to E. tenella tissue culture-derived parasite antigens and to better understand host protective immune responses to avian coccidiosis. PMID:9119452

Mesenchymal stem cells: immune evasive, not immune privileged

PubMed Central

Ankrum, James A.; Ong, Joon Faii; Karp, Jeffrey M.

2014-01-01

The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or ‘immune privileged’; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief ‘hit and run’ mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens. PMID:24561556

Plant immunity against viruses: antiviral immune receptors in focus

PubMed Central

Calil, Iara P.

2017-01-01

Abstract Background Among the environmental limitations that affect plant growth, viruses cause major crop losses worldwide and represent serious threats to food security. Significant advances in the field of plant–virus interactions have led to an expansion of potential strategies for genetically engineered resistance in crops during recent years. Nevertheless, the evolution of viral virulence represents a constant challenge in agriculture that has led to a continuing interest in the molecular mechanisms of plant–virus interactions that affect disease or resistance. Scope and Conclusion This review summarizes the molecular mechanisms of the antiviral immune system in plants and the latest breakthroughs reported in plant defence against viruses. Particular attention is given to the immune receptors and transduction pathways in antiviral innate immunity. Plants counteract viral infection with a sophisticated innate immune system that resembles the non-viral pathogenic system, which is broadly divided into pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity. An additional recently uncovered virus-specific defence mechanism relies on host translation suppression mediated by a transmembrane immune receptor. In all cases, the recognition of the virus by the plant during infection is central for the activation of these innate defences, and, conversely, the detection of host plants enables the virus to activate virulence strategies. Plants also circumvent viral infection through RNA interference mechanisms by utilizing small RNAs, which are often suppressed by co-evolving virus suppressors. Additionally, plants defend themselves against viruses through hormone-mediated defences and activation of the ubiquitin–26S proteasome system (UPS), which alternatively impairs and facilitates viral infection. Therefore, plant defence and virulence strategies co-evolve and co-exist; hence, disease development is largely dependent on

Plant immunity against viruses: antiviral immune receptors in focus.

PubMed

Calil, Iara P; Fontes, Elizabeth P B

2017-03-01

Among the environmental limitations that affect plant growth, viruses cause major crop losses worldwide and represent serious threats to food security. Significant advances in the field of plant-virus interactions have led to an expansion of potential strategies for genetically engineered resistance in crops during recent years. Nevertheless, the evolution of viral virulence represents a constant challenge in agriculture that has led to a continuing interest in the molecular mechanisms of plant-virus interactions that affect disease or resistance. This review summarizes the molecular mechanisms of the antiviral immune system in plants and the latest breakthroughs reported in plant defence against viruses. Particular attention is given to the immune receptors and transduction pathways in antiviral innate immunity. Plants counteract viral infection with a sophisticated innate immune system that resembles the non-viral pathogenic system, which is broadly divided into pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity. An additional recently uncovered virus-specific defence mechanism relies on host translation suppression mediated by a transmembrane immune receptor. In all cases, the recognition of the virus by the plant during infection is central for the activation of these innate defences, and, conversely, the detection of host plants enables the virus to activate virulence strategies. Plants also circumvent viral infection through RNA interference mechanisms by utilizing small RNAs, which are often suppressed by co-evolving virus suppressors. Additionally, plants defend themselves against viruses through hormone-mediated defences and activation of the ubiquitin-26S proteasome system (UPS), which alternatively impairs and facilitates viral infection. Therefore, plant defence and virulence strategies co-evolve and co-exist; hence, disease development is largely dependent on the extent and rate at which these opposing

Chapter 2: Innate Immunity

PubMed Central

Turvey, Stuart E.; Broide, David H.

2009-01-01

Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

The Immune System: Basis of so much Health and Disease: 2. Innate Immunity.

PubMed

Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

2017-03-01

The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covering innate immunity. Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

PubMed

Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

2017-04-01

The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

Immunohistochemical analysis of cytokeratin and human milk fat globulin expression in mucinous carcinoma of the skin.

PubMed

Ohnishi, Takamitsu; Takizawa, Hajime; Watanabe, Shinichi

2002-01-01

Mucinous carcinoma of the skin (MCS) is a rare epithelial tumor which arises primarily in the skin. Metastatic MC from extracutaneous sites, especially breast or colon, mimics MCS and cannot be differentiated from MCS by routine histology alone. Nine cases of MCS were analyzed immunohistochemically using monoclonal antibodies against cytokeratins (CKs) and human milk fat globulin 1 (HMFG) in order to clarify their nature and compare the immunophenotypes with those of other MCs studied in the literature. Expression of simple epithelial CKs in most of the tumor cells of all cases studied and co-expression of simple and stratified epithelial CKs in some tumor cells of two cases were recognized. CK 20 expression could not detected in any tumor cells. Focal HMFG expression in the luminal or outer surface of the nests was observed in three cases. From CKs expression, MCS was speculated to differentiated mainly toward the secretory cells of the sweat glands, and some tumor cells toward the transient portion between the dermal duct and the secretory portion. Focal HMFG expression suggested either a consequence of malignant transformation or apocrine differentiation. No expression of CK 20 in MCS suggests that we may exclude the diagnosis of metastatic colorectal MC which expressed CK 20.

Genetic variants determining body fat distribution and sex hormone-binding globulin among Chinese female young adults.

PubMed

Shi, Juan; Li, Lijuan; Hong, Jie; Qi, Lu; Cui, Bin; Gu, Weiqiong; Zhang, Yifei; Miao, Lin; Wang, Rui; Wang, Weiqing; Ning, Guang

2014-11-01

Measures of body fat distribution (i.e. waist : hip ratio [WHR]) are major risk factors for diabetes, independent of overall adiposity. The genetic variants related to body fat distribution show sexual dimorphism and particularly affect females. Substantial literature supports a role for sex hormone-binding globulin (SHBG) in the maintenance of glucose homeostasis. The aim of the present study was to examine the association of the genetic risk score of body fat distribution with SHBG levels and insulin resistance in young (14-30 years) Chinese females. In all, 675 young Chinese females were evaluated in the present study. A genetic risk score (GRS) was calculated on the basis of 12 established variants associated with body fat distribution. The main outcome variable was serum SHBG levels and homeostasis model assessment of insulin resistance (HOMA-IR). The GRS of body fat distribution was significantly associated with decreasing serum SHBG levels (P = 0.018), independent of body mass index and WHR. In addition, the GRS and SHBG showed additive effects on HOMA-IR (P = 0.004). The GRS of body fat distribution reflects serum SHBG levels, and the GRS and SHBG jointly influence the risk of insulin resistance. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Pericarditis mediated by respiratory syncytial virus in a hematopoietic stem cell transplant patient.

PubMed

Rubach, M P; Pavlisko, E N; Perfect, J R

2013-08-01

We describe a case of pericarditis and large pericardial effusion in a 63-year-old African-American man undergoing autologous hematopoietic stem cell transplant for multiple myeloma. Pericardial tissue biopsy demonstrated fibrinous pericarditis, and immunohistochemistry stains were positive for respiratory syncytial virus. The patient improved with oral ribavirin and intravenous immune globulin infusions. © 2013 John Wiley & Sons A/S.

In immune defense: redefining the role of the immune system in chronic disease.

PubMed

Rubinow, Katya B; Rubinow, David R

2017-03-01

The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

PubMed

Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

2017-12-01

Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

Tolerance induction of IgG+ memory B cells by T cell-independent type II antigens.

PubMed

Haniuda, Kei; Nojima, Takuya; Ohyama, Kyosuke; Kitamura, Daisuke

2011-05-15

Memory B cells generated during a T cell-dependent immune response rapidly respond to a secondary immunization by producing abundant IgG Abs that bind cognate Ag with high affinity. It is currently unclear whether this heightened recall response by memory B cells is due to augmented IgG-BCR signaling, which has only been demonstrated in the context of naive transgenic B cells. To address this question, we examined whether memory B cells can respond in vivo to Ags that stimulate only through BCR, namely T cell-independent type II (TI-II) Ags. In this study, we show that the TI-II Ag (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll cannot elicit the recall response in mice first immunized with the T cell-dependent Ag NP-chicken γ-globulin. Moreover, the NP-Ficoll challenge in vivo as well as in vitro significantly inhibits a subsequent recall response to NP-chicken γ-globulin in a B cell-intrinsic manner. This NP-Ficoll-mediated tolerance is caused by the preferential elimination of IgG(+) memory B cells binding to NP with high affinity. These data indicate that BCR cross-linking with a TI-II Ag does not activate IgG(+) memory B cells, but rather tolerizes them, identifying a terminal checkpoint of memory B cell differentiation that may prevent autoimmunity.

Passive immunization of mice pups through oral immunization of dams with a plant-derived vaccine.

PubMed

Walmsley, Amanda M; Kirk, Dwayne D; Mason, Hugh S

2003-03-03

Passive immunization plays an important role in protecting young mammals against pathogens before the maturation of their own immune systems. Although many reports have shown active immunization of animals and human through the use of plant-derived vaccines, only one report has given evidence of passive immunization of offspring through oral immunization of parents using plant-derived vaccines. In this case, a challenge alone provided the evidence of passive immunization and the mechanism through which this occurred was not investigated. This report describes the first step in elucidating the mechanism of passive immunization of offspring through actively immunizing the female parent through an orally delivered, plant-derived vaccine. The authors found passive immunization of offspring was caused by transfer of antigen-specific IgG through either transplacental transfer or ingesting colostrum. Future studies will investigate the roles of transplacental antibody transfer and ingesting colostrum in passive immunization and the possible involvement of IgA in this immunization route.

Patterns of HIV/SIV Prevention and Control by Passive Antibody Immunization.

PubMed

Yamamoto, Hiroyuki; Matano, Tetsuro

2016-01-01

Neutralizing antibody (NAb) responses are promising immune effectors for control of human immunodeficiency virus (HIV) infection. Protective activity and mechanisms of immunodeficiency virus-specific NAbs have been increasingly scrutinized in animals infected with simian immunodeficiency virus (SIV), chimeric simian/human immunodeficiency virus (SHIV) and related viruses. Studies on such models have unraveled a previously underscored protective potential against in vivo immunodeficiency virus replication. Pre-challenge NAb titers feasibly provide sterile protection from SIV/SHIV infection by purging the earliest onset of viral replication and likely modulate innate immune cell responses. Sufficient sub-sterile NAb titers after established infection also confer dose-dependent reduction of viremia, and in certain earlier time frames augment adaptive immune cell responses and even provide rebound-free viral control. Here, we provide an overview of the obtained patterns of SIV/SHIV protection and viral control by various types of NAb passive immunizations and discuss how these notions may be extrapolated to NAb-based clinical control of HIV infection.

Immune System

EPA Science Inventory

A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

Local immunization program for susceptible-infected-recovered network epidemic model

NASA Astrophysics Data System (ADS)

Wu, Qingchu; Lou, Yijun

2016-02-01

The immunization strategies through contact tracing on the susceptible-infected-recovered framework in social networks are modelled to evaluate the cost-effectiveness of information-based vaccination programs with particular focus on the scenario where individuals belonging to a specific set can get vaccinated due to the vaccine shortages and other economic or humanity constraints. By using the block heterogeneous mean-field approach, a series of discrete-time dynamical models is formulated and the condition for epidemic outbreaks can be established which is shown to be not only dependent on the network structure but also closely related to the immunization control parameters. Results show that increasing the immunization strength can effectively raise the epidemic threshold, which is different from the predictions obtained through the susceptible-infected-susceptible network framework, where epidemic threshold is independent of the vaccination strength. Furthermore, a significant decrease of vaccine use to control the infectious disease is observed for the local vaccination strategy, which shows the promising applications of the local immunization programs to disease control while calls for accurate local information during the process of disease outbreak.

γδ T cell and other immune cells crosstalk in cellular immunity.

PubMed

He, Ying; Wu, Kangni; Hu, Yongxian; Sheng, Lixia; Tie, Ruxiu; Wang, Binsheng; Huang, He

2014-01-01

γδ T cells have been recognized as effectors with immunomodulatory functions in cellular immunity. These abilities enable them to interact with other immune cells, thus having the potential for treatment of various immune-mediated diseases with adoptive cell therapy. So far, the interactions between γδ T cell and other immune cells have not been well defined. Here we will discuss the interactivities among them and the perspective on γδ T cells for their use in immunotherapy could be imagined. The understanding of the crosstalk among the immune cells in immunopathology might be beneficial for the clinical application of γδ T cell.

Photodynamic therapy for cancer and activation of immune response

NASA Astrophysics Data System (ADS)

Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.

2010-02-01

Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors (TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study.

Immune Response And Anamnestic Immune Response In Children After A 3-Dose Primary Hepatitis B Vaccination.

PubMed

Afzal, Muhammad Faheem; Sultan, Muhammad Ashraf; Saleemi, Ahmad Imran

2016-01-01

Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response & anamnestic immune response in children, 9 months-10 years of age, after a 3dose primary Hepatitis B vaccination. This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, documented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum antiHBsAb by ELIZA was measured. Children with antiHBs titers ≥10 mIU/mL were considered to be immune. Those with anti HBsAb levels <10 mIU/mL were offered a booster dose of infant recombinant hepatitis B vaccine. The second serum sample was obtained 21-28 days following the administration of the booster dose and the anamnestic immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Of the 200 children, protective antibody response was found in 58%. Median serological response was 18.60 (range 2.82 - 65.15). Antibody levels were found to have a statistically significant ( pvalue 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vacci ne was administered to all nonresponders, with each registering a statistically significant (pvalue 0.00) anamnestic response. The vaccination schedule with short dosage interval was unable to provide protection to 42% of the study population

Predictors of immune function in space flight

NASA Astrophysics Data System (ADS)

Shearer, William T.; Zhang, Shaojie; Reuben, James M.; Lee, Bang-Ning; Butel, Janet S.

2007-02-01

Of all of the environmental conditions of space flight that might have an adverse effect upon human immunity and the incidence of infection, space radiation stands out as the single-most important threat. As important as this would be on humans engaged in long and deep space flight, it obviously is not possible to plan Earth-bound radiation and infection studies in humans. Therefore, we propose to develop a murine model that could predict the adverse effects of space flight radiation and reactivation of latent virus infection for humans. Recent observations on the effects of gamma and latent virus infection demonstrate latent virus reactivation and loss of T cell mediated immune responses in a murine model. We conclude that using this small animal method of quantitating the amounts of radiation and latent virus infection and resulting alterations in immune responses, it may be possible to predict the degree of immunosuppression in interplanetary space travel for humans. Moreover, this model could be extended to include other space flight conditions, such as microgravity, sleep deprivation, and isolation, to obtain a more complete assessment of space flight risks for humans.

Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.

PubMed

Lichtenauer, Michael; Mildner, Michael; Werba, Gregor; Beer, Lucian; Hoetzenecker, Konrad; Baumgartner, Andrea; Hasun, Matthias; Nickl, Stefanie; Mitterbauer, Andreas; Zimmermann, Matthias; Gyöngyösi, Mariann; Podesser, Bruno Karl; Klepetko, Walter; Ankersmit, Hendrik Jan

2012-01-01

Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.

Cancer immunoediting by the innate immune system in the absence of adaptive immunity

PubMed Central

O’Sullivan, Timothy; Saddawi-Konefka, Robert; Vermi, William; Koebel, Catherine M.; Arthur, Cora; White, J. Michael; Uppaluri, Ravi; Andrews, Daniel M.; Ngiow, Shin Foong; Teng, Michele W.L.; Smyth, Mark J.; Schreiber, Robert D.

2012-01-01

Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting. PMID:22927549

[Mucosal immunity with emphasis on urinary tract immunity and diabetes].

PubMed

Krejsek, J; Kudlová, M; Kolácková, M; Novosad, J

2008-05-01

Protective immune response in urinary tract is frequently impaired in patients with diabetes. Immunity in this mucosal compartment displays unique characteristics; e.g. absence of physiological microflora and lack of mucus. Pathogens are identified by the PRR receptors expressed on both epithelial and immune cells. Inflammatory response characterised by the acumulation ofgranulocytes is followed. Both protective and harm characteristics of inflammatory response are inseparable linked and delineated by gene polymorphisms in PRR receptors.

An immune-related lncRNA signature for patients with anaplastic gliomas.

PubMed

Wang, Wen; Zhao, Zheng; Yang, Fan; Wang, Haoyuan; Wu, Fan; Liang, Tingyu; Yan, Xiaoyan; Li, Jiye; Lan, Qing; Wang, Jiangfei; Zhao, Jizong

2018-01-01

We investigated immune-related long non-coding RNAs (lncRNAs) that may be exploited as potential therapeutic targets in anaplastic gliomas. We obtained 572 lncRNAs and 317 immune genes from the Chinese Glioma Genome Atlas microarray and constructed immune-related lncRNAs co-expression networks to identify immune-related lncRNAs. Two additional datasets (GSE16011, REMBRANDT) were used for validation. Gene set enrichment analysis and principal component analysis were used for functional annotation. Immune-lncRNAs co-expression networks were constructed. Nine immune-related lncRNAs (SNHG8, PGM5-AS1, ST20-AS1, LINC00937, AGAP2-AS1, MIR155HG, TUG1, MAPKAPK5-AS1, and HCG18) signature was identified in patients with anaplastic gliomas. Patients in the low-risk group showed longer overall survival (OS) and progression-free survival than those in the high-risk group (P < 0.0001; P < 0.0001). Additionally, patients in the high-risk group displayed no-deletion of chromosomal arms 1p and/or 19q, isocitrate dehydrogenase wild-type, classical and mesenchymal TCGA subtype, G3 CGGA subtype, and lower Karnofsky performance score (KPS). Moreover, the signature was an independent factor and was significantly associated with the OS (P = 0.000, hazard ratio (HR) = 1.434). These findings were further validated in two additional datasets (GSE16011, REMBRANDT). Low-risk and high-risk groups displayed different immune status based on principal components analysis. Our results showed that the nine immune-related lncRNAs signature has prognostic value for anaplastic gliomas.

Validation of Procedures for Monitoring Crewmember Immune Function SDBI-1900, SMO-015 - Integrated Immune

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Nehlsen-Cannarella, Sandra; Morukov, Boris; Pierson, Duane; Sams, Clarence

2007-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk from prolonged immune dysregulation during space flight are not yet determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight condition. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flight-compatible immune monitoring strategy. Characterization of the clinical risk and the development of a monitoring strategy are necessary prerequisite activities prior to validating countermeasures. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers immune system. Pre-flight, in-flight and post-flight assessments of immune status, immune function, viral reactivation and physiological stress will be performed. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter landing day assessments. The overall status of the immune system during flight (activation

Pattern dynamics of the reaction-diffusion immune system.

PubMed

Zheng, Qianqian; Shen, Jianwei; Wang, Zhijie

2018-01-01

In this paper, we will investigate the effect of diffusion, which is ubiquitous in nature, on the immune system using a reaction-diffusion model in order to understand the dynamical behavior of complex patterns and control the dynamics of different patterns. Through control theory and linear stability analysis of local equilibrium, we obtain the optimal condition under which the system loses stability and a Turing pattern occurs. By combining mathematical analysis and numerical simulation, we show the possible patterns and how these patterns evolve. In addition, we establish a bridge between the complex patterns and the biological mechanism using the results from a previous study in Nature Cell Biology. The results in this paper can help us better understand the biological significance of the immune system.

Immunization Equity.

PubMed

Hinman, Alan R; McKinlay, Mark A

2015-12-01

Health inequities are the unjust differences in health among different social groups. Unfortunately, inequities are the norm, both in terms of health status and access to, and use of, health services. Childhood immunizations reduce the incidence of vaccine-preventable diseases and represent a cost-effective way to foster health equity. This paper reflects a 2015 review of data from surveys conducted in developing countries from 2005 to 2011 that show significant inequities in immunization coverage and discusses several initiatives currently underway (including Gavi, the Vaccine Alliance) that are directed at increasing childhood immunizations or reducing or abolishing overall health inequities. These initiatives have already had a significant impact on disease burden and childhood mortality and give rise to optimism that health disparities may further be reduced and health equity achieved as a result of investments made in immunization. Copyright © 2015 2015 by American Journal of Preventive Medicine and Els. Published by Elsevier Inc. All rights reserved.

[Immune granulomatous inflammation as the body's adaptive response].

PubMed

Paukov, V S; Kogan, E A

2014-01-01

Based on their studies and literature analysis, the authors offer a hypothesis for the adaptive pattern of chronic immune granulomatous inflammation occurring in infectious diseases that are characterized by the development of non-sterile immunity. The authors' proposed hypothesis holds that not every chronic inflammation is a manifestation of failing defenses of the body exposed to a damaging factor. By using tuberculosis and leprosy as an example, the authors show the insolvency of a number of existing notions of the pathogenesis and morphogenesis of epithelioid-cell and leprous granulomas. Thus, the authors consider that resident macrophages in tuberculosis maintain their function to kill mycobacteria; thereby the immune system obtains information on the antigenic determinants of the causative agents. At the same time, by consuming all hydrolases to kill mycobacteria, the macrophage fails to elaborate new lysosomes for the capacity of the pathogens to prevent them from forming. As a result, the lysosome-depleted macrophage transforms into an epithelioid cell that, maintaining phagocytic functions, loses its ability to kill the causative agents. It is this epithelioid cell where endocytobiosis takes place. These microorganisms destroy the epithelioid cell and fall out in the area of caseating granuloma necrosis at regular intervals. Some of them phagocytize epithelioid cells to maintain non-sterile immunity; the others are killed by inflammatory macrophages. The pathogenesis and morphogenesis of leprous granuloma, its tuberculous type in particular, proceed in a fundamentally similar way. Thus, non-sterile immunity required for tuberculosis, leprosy, and, possibly, other mycobacterioses is maintained.

Instant Childhood Immunization Schedule

MedlinePlus

... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension.

PubMed

Agrawal, Babita; Singh, Shakti; Gupta, Nancy; Li, Wen; Vedi, Satish; Kumar, Rakesh

2017-07-27

Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world's population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas. Human beings are not immunologically naïve because they are continually exposed to various environmental microbes and antigens, creating large populations of memory T cells. Heterologous immunity occurs when this pool of memory T cells cross-react against a new pathogen in an individual. Such heterologous immunity could influence the outcome when an individual is infected by a pathogen. We have recently made an unexpected finding that adenoviruses, a common environmental pathogen and an experimental vaccine vector, can induce robust cross-reactive immune responses against multiple antigens of HCV. Our unique finding of previously uncharacterized heterologous immunity against HCV opens new avenues to understand HCV pathogenesis and develop effective vaccines.

Origins of adaptive immunity.

PubMed

Liongue, Clifford; John, Liza B; Ward, Alister

2011-01-01

Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

Immune Profiling of Premalignant Lesions in Patients With Lynch Syndrome.

PubMed

Chang, Kyle; Taggart, Melissa W; Reyes-Uribe, Laura; Borras, Ester; Riquelme, Erick; Barnett, Reagan M; Leoni, Guido; San Lucas, F Anthony; Catanese, Maria T; Mori, Federica; Diodoro, Maria G; You, Y Nancy; Hawk, Ernest T; Roszik, Jason; Scheet, Paul; Kopetz, Scott; Nicosia, Alfredo; Scarselli, Elisa; Lynch, Patrick M; McAllister, Florencia; Vilar, Eduardo

2018-04-16

Colorectal carcinomas in patients with Lynch syndrome (LS) arise in a background of mismatch repair (MMR) deficiency, display a unique immune profile with upregulation of immune checkpoints, and response to immunotherapy. However, there is still a gap in understanding the pathogenesis of MMR-deficient colorectal premalignant lesions, which is essential for the development of novel preventive strategies for LS. To characterize the immune profile of premalignant lesions from a cohort of patients with LS. Whole-genome transcriptomic analysis using next-generation sequencing was performed in colorectal polyps and carcinomas of patients with LS. As comparator and model of MMR-proficient colorectal carcinogenesis, we used samples from patients with familial adenomatous polyposis (FAP). In addition, a total of 47 colorectal carcinomas (6 hypermutants and 41 nonhypermutants) were obtained from The Cancer Genome Atlas (TCGA) for comparisons. Samples were obtained from the University of Texas MD Anderson Cancer Center and "Regina Elena" National Cancer Institute, Rome, Italy. All diagnoses were confirmed by genetic testing. Polyps were collected at the time of endoscopic surveillance and tumors were collected at the time of surgical resection. The data were analyzed from October 2016 to November 2017. Assessment of the immune profile, mutational signature, mutational and neoantigen rate, and pathway enrichment analysis of neoantigens in LS premalignant lesions and their comparison with FAP premalignant lesions, LS carcinoma, and sporadic colorectal cancers from TCGA. The analysis was performed in a total of 28 polyps (26 tubular adenomas and 2 hyperplastic polyps) and 3 early-stage LS colorectal tumors from 24 patients (15 [62%] female; mean [SD] age, 48.12 [15.38] years) diagnosed with FAP (n = 10) and LS (n = 14). Overall, LS polyps presented with low mutational and neoantigen rates but displayed a striking immune activation profile characterized by CD4 T cells

Effectiveness analyses may underestimate protection of infants after group C meningococcal immunization.

PubMed

Vu, David M; Kelly, Dominic; Heath, Paul T; McCarthy, Noel D; Pollard, Andrew J; Granoff, Dan M

2006-07-15

Group C meningococcal conjugate-vaccine effectiveness in the United Kingdom declines from ~90% in the first year to 0% between 1 and 4 years after immunization in infants immunized at 2, 3, and 4 months of age and to 61% in toddlers given a single dose. Confidence intervals are wide, and the extent of protection is uncertain. Serum samples were obtained from children 3-5 years of age who were participants in a preschool booster-vaccine trial. Serum bactericidal activity was measured with human complement. Group C anticapsular antibody concentrations were measured by a radioantigen binding assay. Passive protection was analyzed in an infant rat bacteremia model. Serum samples from UK children who had been immunized 2-3 years earlier as infants or toddlers had higher levels of radioantigen binding, bactericidal activity, and passive protection than did historical control serum samples from unimmunized children (P<.05). A higher proportion of children immunized as infants had serum bactericidal activity titers > or =1 : 4 (considered to be protective) than those immunized as toddlers (61% vs. 24%; P<.01), but there were no significant differences in the proportion of serum samples conferring passive protection (50% and 41%, respectively; P=.4). We found no evidence of lower immunity in children immunized as infants than as toddlers. On the basis of serum bactericidal activity and/or passive protection, 40%-50% of both age groups are protected at 2-3 years after immunization, which was significantly greater than in unimmunized historical controls (<5%).

Comparison of immunization rates of adults ages 65 years and older managed within two nurse practitioner-owned clinics with national immunization rates.

PubMed

Wright, Wendy L; Morrell, Elise; Lee, Jennie; Cuellar, Norma Graciela; White, Patricia

2017-07-01

Adults ages ≥65 years are at increased risk for infectious diseases. Ensuring these individuals are fully vaccinated is imperative. The purpose of this study was to assess the immunization rates of adults ages ≥65 years managed by nurse practitioners (NPs) and compare the results with national immunization rates and Healthy People 2020 goals. A convenience sample of adults ages ≥65 years was obtained from two NP-managed clinics. The vaccine records of each subject were reviewed for documentation of having received five vaccines (tetanus, diphtheria, and pertussis; influenza; pneumococcal polysaccharide vaccine 23; pneumococcal conjugate vaccine 13; and herpes zoster vaccine). One hundred and fifty females (70.8%) and 62 males (29.2%) met inclusion criteria. NP-managed patients had higher immunization rates than the national averages across all five major vaccines. The herpes zoster vaccination rates exceeded the recommendations from Healthy People 2020 whereas pneumococcal and influenza rates were below. The stocking of vaccines within the NP-managed clinics, direct billing to Medicare for Part D vaccines, and previsit care planning likely contributed to the high vaccination rates. These high immunization rates in patients managed by NPs provide support for the important role that NPs play in the care of older adults. ©2017 American Association of Nurse Practitioners.

Immunity, ageing and cancer

PubMed Central

Derhovanessian, Evelyna; Solana, Rafael; Larbi, Anis; Pawelec, Graham

2008-01-01

Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient. PMID:18816370

Antibody response and maternal immunity upon boosting PRRSV-immune sows with experimental farm-specific and commercial PRRSV vaccines.

PubMed

Geldhof, Marc F; Van Breedam, Wander; De Jong, Ellen; Lopez Rodriguez, Alfonso; Karniychuk, Uladzimir U; Vanhee, Merijn; Van Doorsselaere, Jan; Maes, Dominiek; Nauwynck, Hans J

2013-12-27

The porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure in sows and respiratory disease in pigs of all ages. Despite the frequent use of vaccines to maintain PRRSV immunity in sows, little is known on how the currently used vaccines affect the immunity against currently circulating and genetically divergent PRRSV variants in PRRSV-immune sows, i.e. sows that have a pre-existing PRRSV-specific immunity due to previous infection with or vaccination against the virus. Therefore, this study aimed to assess the capacity of commercially available attenuated/inactivated PRRSV vaccines and autogenous inactivated PRRSV vaccines - prepared according to a previously optimized in-house protocol - to boost the antibody immunity against currently circulating PRRSV variants in PRRSV-immune sows. PRRSV isolates were obtained from 3 different swine herds experiencing PRRSV-related problems, despite regular vaccination of gilts and sows against the virus. In a first part of the study, the PRRSV-specific antibody response upon booster vaccination with commercial PRRSV vaccines and inactivated farm-specific PRRSV vaccines was evaluated in PRRSV-immune, non-pregnant replacement sows from the 3 herds. A boost in virus-neutralizing antibodies against the farm-specific isolate was observed in all sow groups vaccinated with the corresponding farm-specific inactivated vaccines. Use of the commercial attenuated EU type vaccine boosted neutralizing antibodies against the farm-specific isolate in sows derived from 2 farms, while use of the commercial attenuated NA type vaccine did not boost farm-specific virus-neutralizing antibodies in any of the sow groups. Interestingly, the commercial inactivated EU type vaccine boosted farm-specific virus-neutralizing antibodies in sows from 1 farm. In the second part of the study, a field trial was performed at one of the farms to evaluate the booster effect of an inactivated farm-specific vaccine and a commercial

Immunization of complex networks

NASA Astrophysics Data System (ADS)

Pastor-Satorras, Romualdo; Vespignani, Alessandro

2002-03-01

Complex networks such as the sexual partnership web or the Internet often show a high degree of redundancy and heterogeneity in their connectivity properties. This peculiar connectivity provides an ideal environment for the spreading of infective agents. Here we show that the random uniform immunization of individuals does not lead to the eradication of infections in all complex networks. Namely, networks with scale-free properties do not acquire global immunity from major epidemic outbreaks even in the presence of unrealistically high densities of randomly immunized individuals. The absence of any critical immunization threshold is due to the unbounded connectivity fluctuations of scale-free networks. Successful immunization strategies can be developed only by taking into account the inhomogeneous connectivity properties of scale-free networks. In particular, targeted immunization schemes, based on the nodes' connectivity hierarchy, sharply lower the network's vulnerability to epidemic attacks.

Japanese Encephalitis Surveillance and Immunization - Asia and Western Pacific Regions, 2016.

PubMed

Heffelfinger, James D; Li, Xi; Batmunkh, Nyambat; Grabovac, Varja; Diorditsa, Sergey; Liyanage, Jayantha B; Pattamadilok, Sirima; Bahl, Sunil; Vannice, Kirsten S; Hyde, Terri B; Chu, Susan Y; Fox, Kimberley K; Hills, Susan L; Marfin, Anthony A

2017-06-09

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis.

PubMed

Pishel, Iryna; Shytikov, Dmytro; Orlova, Tatiana; Peregudov, Alex; Artyuhov, Igor; Butenko, Gennadij

2012-04-01

The emergence of immune disorders in aging is explained by many factors, including thymus dysfunction, decrease in the proportion and function of naïve T cells, and so forth. There are several approaches to preventing these changes, such as thymus rejuvenation, stem cells recovery, modulation of hormone production, and others. Our investigations of heterochronic parabiosis have shown that benefits of a young immune system, e.g., actively working thymus and regular migration of young hematopoietic stem cells between parabiotic partners, appeared unable to restore the immune system of the old partner. At the same time, we have established a progressive immune impairment in the young heterochronic partners. The mechanism of age changes in the immune system in this model, which may lead to reduced life expectancy, has not been fully understood. The first age-related manifestation in the young partners observed 3 weeks after the surgery was a dramatic increase of CD8(+)44(+) cells population in the spleen. A detailed analysis of further changes revealed a progressive decline of most immunological functions observable for up to 3 months after the surgery. This article reviews possible mechanisms of induction of age-related changes in the immune system of young heterochronic partners. The data obtained suggest the existence of certain factors in the old organisms that trigger aging, thus preventing the rejuvenation process.

[Relationship between BCG immunization coverage and the immunization delivery system in the Tama area of Tokyo].

PubMed

Sugishita, Yoshiyuki; Hayashi, Kunihiko; Mori, Toru; Horiguchi, Itsuko; Marui, Eiji

2012-03-01

The BCG immunization has long been performed in Japan. Although the BCG immunization service is the responsibility of the municipality, the manner in which the BCG immunization is delivered differs from municipality to municipality. The purpose of this study was to clarify how the different manner of the BCG immunization delivery systems influenced the BCG immunization coverage. The study of BCG immunization coverage was conducted in the Tama area located in the western suburbs of Tokyo in 2004. The birth data and the immunization history by the age of 3 years were collected in the three-year-old health check-up from a total of 2,341 children residing in the Tama area. Based on the age at immunization for each child, the BCG immunization coverage was calculated according to the types of the BCG immunization delivery system. The immunization types were defined as follows; the BCG immunization given on the occasion of the mass health check-up (Group 1); the exclusive mass BCG immunization in a monthly service (Group 2); the exclusive mass BCG immunization in a bimonthly service (Group 3); the exclusive mass BCG immunization in services of fewer than every two months (Group 4); and the immunization given on an individual basis by a general practitioner (Group 5). A univariate analysis was performed to examine the relationship between the BCG immunization coverage by the age of 6 months and the difference among the BCG immunization delivery systems, followed by a multivariate regression analysis to adjust for the factors related to the demography, health care services and the socio-economic status of the municipalities. Unadjusted odds ratios and adjusted odds ratios for BCG unimmunized children under the age of 6 months by the BCG immunization delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR 1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82, adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj

The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis

PubMed Central

Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H.; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Barberio, Manuela Terranova; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D.; Nestle, Frank O.

2015-01-01

Summary Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analysing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets, and uncovered insights into genetic control for regulatory T cells. This dataset also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. PMID:25772697

The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

PubMed

Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

2015-04-09

Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Barriers to immunization among children of HIV-infected mothers in Kolkata, India: a qualitative study.

PubMed

Sensarma, Pinaki; Bhandari, Subhasis; Kutty, V Raman

2015-03-01

More than one fourth of children of HIV-infected mothers living in Kolkata city are not completely immunized by 12 months of age. This qualitative study aims to explore the barriers to immunization of these children as perceived by their caregivers and the local health care service providers. In-depth interviews were conducted after obtaining written informed consent. Audio recording and hand-recorded notes were used with permission. The transcripts were coded and analyzed using grounded theory. Deteriorating socioeconomic status, tightening of time schedule of caregivers due to illness in the family, stigma, discrimination, and lack of awareness about immunization prove to be major barriers for immunization of the HIV-exposed children. Interplay of these factors coupled with harassment and negative attitudes of service providers toward HIV-affected/HIV-infected people also impede immunization. The intervention efforts need to address these social barriers and adverse life events to improve immunization coverage. © 2013 APJPH.

Enhancement of Th1 immune responses to recombinant influenza nucleoprotein by Ribi adjuvant.

PubMed

Cargnelutti, Diego E; Sanchez, María A V; Alvarez, Paula; Boado, Lorena; Mattion, Nora; Scodeller, Eduardo A

2013-04-01

A broad coverage influenza vaccine against multiple viral strains based on the viral nucleoprotein (NP) is a goal pursued by many laboratories. If the goal is to formulate the vaccine with recombinant NP it is essential to count on adjuvants capable of inducing cellular immunity. This work have studied the effect of the monophosphoryl lipid A and trehalose dimycolate, known as the Ribi Adjuvant System (RAS), in the immune response induced in mice immunized with recombinant NP. The NP was formulated with RAS and used to immunize BALB/c mice. Immunizations with NP-RAS increased the humoral and cellular immune responses compared to unadjuvanted NP. The predominant antibody isotype was IgG2a, suggesting the development of a Th1 response. Analysis of the cytokines from mice immunized with NP-RAS showed a significant increase in the production of IFN-g and a decreased production of IL-10 and IL-4 compared to controls without RAS. These results are similar to those usually obtained using Freund’s adjuvant, known to induce Th1 and CTL responses when co-administered with purified proteins, and suggest that a similar approach may be possible to enhance the performance of a T-cell vaccine containing NP.

Immune system

USDA-ARS?s Scientific Manuscript database

This chapter is an update on the swine Immune System. It will be Chapter 16 in the 11th Edition (2018) of Diseases of Swine. The chapter outlines all aspects of the swine immune system in development and in responses to infection and vaccination. It illustrates the tremendous influence that the immu...

Structure-informed insights for NLR functioning in plant immunity.

PubMed

Sukarta, Octavina C A; Slootweg, Erik J; Goverse, Aska

2016-08-01

To respond to foreign invaders, plants have evolved a cell autonomous multilayered immune system consisting of extra- and intracellular immune receptors. Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) mediate recognition of pathogen effectors inside the cell and trigger a host specific defense response, often involving controlled cell death. NLRs consist of a central nucleotide-binding domain, which is flanked by an N-terminal CC or TIR domain and a C-terminal leucine-rich repeat domain (LRR). These multidomain proteins function as a molecular switch and their activity is tightly controlled by intra and inter-molecular interactions. In contrast to metazoan NLRs, the structural basis underlying NLR functioning as a pathogen sensor and activator of immune responses in plants is largely unknown. However, the first crystal structures of a number of plant NLR domains were recently obtained. In addition, biochemical and structure-informed analyses revealed novel insights in the cooperation between NLR domains and the formation of pre- and post activation complexes, including the coordinated activity of NLR pairs as pathogen sensor and executor of immune responses. Moreover, the discovery of novel integrated domains underscores the structural diversity of NLRs and provides alternative models for how these immune receptors function in plants. In this review, we will highlight these recent advances to provide novel insights in the structural, biochemical and molecular aspects involved in plant NLR functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune Disorder HSCT Protocol

ClinicalTrials.gov

2017-11-17

Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

STUDIES ON THE ANTIGENIC PROPERTIES OF COMPLEMENT

PubMed Central

Klein, Paul G.; Burkholder, Peter M.

1960-01-01

Evidence is presented to show that guinea pig complement fixed on sensitized sheep red cells acts as a specific agglutinogen. Agglutinating antibodies that react with cell-fixed complement can be produced by immunizing rabbits with a complex of stromata-amboceptor-complement or with guinea pig serum globulin. These agglutinins can be removed by precipitation with guinea pig serum. They are, therefore, distinct from immunoconglutinins. PMID:14409702

Cellular Sites of Immunologic Unresponsiveness*

PubMed Central

Chiller, Jacques M.; Habicht, Gail S.; Weigle, William O.

1970-01-01

The reconstitution of the immune response of lethally irradiated mice to human γ-globulin is dependent on the synergistic action of bone marrow with thymus cells. Immunologic unresponsiveness appears to involve a functional defect at each of these cellular levels, inasmuch as neither bone marrow nor thymus cells from unresponsive donors are capable of demonstrating synergism in combination with their normal counterpart. PMID:4192271

Innate immune memory in plants.

PubMed

Reimer-Michalski, Eva-Maria; Conrath, Uwe

2016-08-01

The plant innate immune system comprises local and systemic immune responses. Systemic plant immunity develops after foliar infection by microbial pathogens, upon root colonization by certain microbes, or in response to physical injury. The systemic plant immune response to localized foliar infection is associated with elevated levels of pattern-recognition receptors, accumulation of dormant signaling enzymes, and alterations in chromatin state. Together, these systemic responses provide a memory to the initial infection by priming the remote leaves for enhanced defense and immunity to reinfection. The plant innate immune system thus builds immunological memory by utilizing mechanisms and components that are similar to those employed in the trained innate immune response of jawed vertebrates. Therefore, there seems to be conservation, or convergence, in the evolution of innate immune memory in plants and vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune drug discovery from venoms.

PubMed

Jimenez, Rocio; Ikonomopoulou, Maria P; Lopez, J Alejandro; Miles, John J

2018-01-01

This review catalogues recent advances in knowledge on venoms as standalone therapeutic agents or as blueprints for drug design, with an emphasis on venom-derived compounds that affects the immune system. We discuss venoms and venom-derived compounds that affect total immune cell numbers, immune cell proliferation, immune cell migration, immune cell phenotype and cytokine secretion. Identifying novel compounds that 'tune' the system, up-regulating the immune response during infectious disease and cancer and down-regulating the immune response during autoimmunity, will greatly expand the tool kit of human immunotherapeutics. Targeting these pathways may also open therapeutic options that alleviate symptoms of envenomation. Finally, combining recent advances in venomics with progress in low cost, high-throughput screening platforms will no doubt yield hundreds of prototype immune modulating compounds in the coming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying patterns of immune-related disease: use in disease prevention and management.

PubMed

Dietert, Rodney R; Zelikoff, Judith T

2010-05-01

Childhood susceptibility to diseases linked with immune dysfunction affects over a quarter of the pediatric population in some countries. While this alone is a significant health issue, the actual impact of immune-related diseases extends over a lifetime and involves additional secondary conditions. Some comorbidities are well known (e.g., allergic rhinitis and asthma). However, no systematic approach has been used to identify life-long patterns of immune-based disease where the primary condition arises in childhood. Such information is useful for both disease prevention and treatment approaches. Recent primary research papers as well as review articles were obtained from PubMed, Chem Abstracts, Biosis and from the personal files of the authors. Search words used were: the diseases and conditions shown Figs. 1 and 2 in conjunction with comorbid, comorbidities, pediatric, childhood, adult, immune, immune dysfunction, allergy, autoimmune, inflammatory, infectious, health risks, environment, risk factors. Childhood diseases such as asthma, type-1 diabetes, inflammatory bowel disease, respiratory infections /rhinitis, recurrent otitis media, pediatric celiac, juvenile arthritis and Kawasaki disease are examples of significant childhood health problems where immune dysfunction plays a significant role. Each of these pediatric diseases is associated with increased risk of several secondary conditions, many of which appear only later in life. To illustrate, four prototypes of immune-related disease patterns (i.e., allergy, autoimmunity, inflammation and infectious disease) are shown as tools for: 1) enhanced disease prevention; 2) improved management of immune-based pediatric diseases; and 3) better recognition of underlying pediatric immune dysfunction. Identification of immune-related disease patterns beginning in childhood provides the framework for examining the underlying immune dysfunctions that can contribute to additional diseases in later life. Many pediatric

Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

PubMed

Lim, Theam Soon; Chan, Soo Khim

2016-01-01

Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Immune-based therapies.

PubMed

Lein, B

1995-12-01

Several immune-based HIV therapy studies presented at the Interscience Conference on Antimicrobial Agents Chemotherapy (ICAAC) are summarized. These studies involve the following therapies: HIV-IT, a gene therapy approach to augmenting the body's anti-HIV responses; interferon-alpha n3, a new formulation of alpha interferon with fewer toxicities; transfer of immune responses from one individual to another, also called passive immune therapy; and interleukin-2 (IL-2) in combination with protease inhibitors.

Sex hormone-binding globulin b expression in the rainbow trout ovary prior to sex differentiation.

PubMed

Pérez, Claudio; Araneda, Cristian; Estay, Francisco; Díaz, Nelson F; Vizziano-Cantonnet, Denise

2018-04-01

Salmonids have two sex hormone-binding globulin (Shbg) paralogs. Shbga is mainly expressed in the liver, while Shbgb is secreted by the granulosa cells of the rainbow trout ovary. Coexpression of shbgb and the gonadal aromatase cyp19a1a mRNAs been observed in granulosa cells, suggesting a physiological coordination between Shbgb expression and estrogen synthesis. As estrogens are essential for female sex determination in the fish ovary, we propose that Shbgb participates in early ovarian differentiation, either by binding with estrogen or through another mechanism that remains to be discovered. To elucidate this potential role, monosex populations of female trout were studied during the molecular ovarian differentiation period (28-56 dpf). shbgb mRNA expression was measured using qPCR and compared with expression of genes for other ovarian markers (cyp19a1a, foxl2, follistatin, and estrogen receptors). shbgb transcript expression was detected during the final stages of embryonic development (21-26 dpf) and during molecular ovarian differentiation (32-52 dpf) after hatching (which occurred at 31 dpf). In situ hybridization localized shbgb transcription to the undifferentiated ovary at 42 dpf, and shbgb and cyp19a1a mRNA showed similar expression patterns. These results suggest that Shbgb is involved in early ovarian differentiation, supporting an important role for the salmonid shbgb gene in sex determination. Copyright © 2017 Elsevier Inc. All rights reserved.

A randomized trial of maternal influenza immunization decision-making: A test of persuasive messaging models.

PubMed

Frew, Paula M; Kriss, Jennifer L; Chamberlain, Allison T; Malik, Fauzia; Chung, Yunmi; Cortés, Marielysse; Omer, Saad B

2016-08-02

We sought to examine the effectiveness of persuasive communication interventions on influenza vaccination uptake among black/African American pregnant women in Atlanta, Georgia. We recruited black/African American pregnant women ages 18 to 50 y from Atlanta, GA to participate in a prospective, randomized controlled trial of influenza immunization messaging conducted from January to April 2013. Eligible participants were randomized to 3 study arms. We conducted follow-up questionnaires on influenza immunization at 30-days post-partum with all groups. Chi-square and t tests evaluated group differences, and outcome intention-to-treat assessment utilized log-binomial regression models. Of the 106 enrolled, 95 women completed the study (90% retention), of which 31 were randomly assigned to affective messaging intervention ("Pregnant Pause" video), 30 to cognitive messaging intervention ("Vaccines for a Healthy Pregnancy" video), and 34 to a comparison condition (receipt of the Influenza Vaccine Information Statement). The three groups were balanced on baseline demographic characteristics and reported health behaviors. At baseline, most women (63%, n = 60) reported no receipt of seasonal influenza immunization during the previous 5 y. They expressed a low likelihood (2.1 ± 2.8 on 0-10 scale) of obtaining influenza immunization during their current pregnancy. At 30-days postpartum follow-up, influenza immunization was low among all participants (7-13%) demonstrating no effect after a single exposure to either affective messaging (RR = 1.10; 95% CI: 0.30-4.01) or cognitive messaging interventions (RR = 0.57; 95% CI: 0.11-2.88). Women cited various reasons for not obtaining maternal influenza immunizations. These included concern about vaccine harm (47%, n = 40), low perceived influenza infection risk (31%, n = 26), and a history of immunization nonreceipt (24%, n = 20). The findings reflect the limitations associated with a single exposure to varying maternal influenza

A randomized trial of maternal influenza immunization decision-making: A test of persuasive messaging models

PubMed Central

Frew, Paula M.; Kriss, Jennifer L.; Chamberlain, Allison T.; Malik, Fauzia; Chung, Yunmi; Cortés, Marielysse; Omer, Saad B.

2016-01-01

ABSTRACT Objective: We sought to examine the effectiveness of persuasive communication interventions on influenza vaccination uptake among black/African American pregnant women in Atlanta, Georgia. Methods: We recruited black/African American pregnant women ages 18 to 50 y from Atlanta, GA to participate in a prospective, randomized controlled trial of influenza immunization messaging conducted from January to April 2013. Eligible participants were randomized to 3 study arms. We conducted follow-up questionnaires on influenza immunization at 30-days post-partum with all groups. Chi-square and t tests evaluated group differences, and outcome intention-to-treat assessment utilized log-binomial regression models. Results: Of the 106 enrolled, 95 women completed the study (90% retention), of which 31 were randomly assigned to affective messaging intervention (“Pregnant Pause” video), 30 to cognitive messaging intervention (“Vaccines for a Healthy Pregnancy” video), and 34 to a comparison condition (receipt of the Influenza Vaccine Information Statement). The three groups were balanced on baseline demographic characteristics and reported health behaviors. At baseline, most women (63%, n = 60) reported no receipt of seasonal influenza immunization during the previous 5 y. They expressed a low likelihood (2.1 ± 2.8 on 0-10 scale) of obtaining influenza immunization during their current pregnancy. At 30-days postpartum follow-up, influenza immunization was low among all participants (7-13%) demonstrating no effect after a single exposure to either affective messaging (RR = 1.10; 95% CI: 0.30-4.01) or cognitive messaging interventions (RR = 0.57; 95% CI: 0.11-2.88). Women cited various reasons for not obtaining maternal influenza immunizations. These included concern about vaccine harm (47%, n = 40), low perceived influenza infection risk (31%, n = 26), and a history of immunization nonreceipt (24%, n = 20). Conclusion: The findings reflect the limitations

Your Child's Immunization Record

MedlinePlus

Your Child’s Immunization Record It’s important to keep up-to-date records of all your child’s immunizations, beginning at birth and continuing through ... receives a vaccination by filling in the date. Record of Immunizations Date Given: Where Given: Reaction: Hepatitis ...

Factors Associated With Provider Reporting of Child and Adolescent Vaccination History to Immunization Information Systems: Results From the National Immunization Survey, 2006-2012.