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Sample records for acquired humoral immunity

  1. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact.

    PubMed

    Scholz, Jean L; Crowley, Jenni E; Tomayko, Mary M; Steinel, Natalie; O'Neill, Patrick J; Quinn, William J; Goenka, Radhika; Miller, Juli P; Cho, Yun Hee; Long, Vatana; Ward, Chris; Migone, Thi-Sau; Shlomchik, Mark J; Cancro, Michael P

    2008-10-07

    We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.

  2. Humoral immune response to the heat-labile enterotoxin of Escherichia coli in naturally acquired diarrhea and antitoxin determination by passive immune hemolysis.

    PubMed Central

    Evans, D J; Ruiz-Palacios, G; Evans, D E; DuPont, H L; Pickering, L K; Olarte, J

    1977-01-01

    Acute- and convalescent-phase sera from 132 students attending a university in rural Mexico were assayed for antibody against the heat-labile enterotoxin (LT) of Escherichia coli by neutralization of LT activity in the Y-1 adrenal cell assay and by passive immune hemolysis of LT-sensitized sheep erythrocytes. The two titration methods produced comparable results with respect to antitoxin responses detected. An inverse relationship was found between acute geometric mean antitoxin titer and the occurrence of diarrhea associated with LT-producing E. coli, especially in newly arrived students from the U.S.A. A significant correlation (P less than 0.00 5) was found between a rise in antitoxin titer detectable by the passive immune hemolysis technique and diarrhea with LT-producing E. coli isolated. Thus, humoral antitoxin titers appear to be a useful indicator of immune status with respect to enterotoxigenic (LT) E. coli diarrhea. PMID:330395

  3. Vaccination to gain humoral immune memory

    PubMed Central

    Sarkander, Jana; Hojyo, Shintaro; Tokoyoda, Koji

    2016-01-01

    The concept of immune memory forms the biological basis for vaccination programs. Despite advancements in the field of immune memory and vaccination, most current vaccines are evaluated by magnitude of antigen-specific antibody titers in serum or mucosa after vaccination. It has been shown, however, that antibody-mediated humoral immune memory is established regardless of the magnitude and duration of immune reactions, suggesting that assessment of vaccine efficacy should be performed for several years after vaccination. This long-term investigation is disadvantageous for prevalent and pandemic infections. Long-lived memory plasma cells and memory helper T cells which contribute to humoral immune memory are generated in the bone marrow after migration of memory cell precursors through bloodstream. Thus, it may be a novel evaluation strategy to assess the precursors of memory cells in the blood in the early phase of the immune reaction(s). We here review recent advances on the generation and maintenance of immune memory cells involved in humoral immunity and introduce a current concept of direct and short-term assessment of humoral immune memory formation upon vaccination as a correlate of protection. PMID:28090322

  4. Humoral innate immune response and disease

    PubMed Central

    Shishido, Stephanie N.; Varahan, Sriram; Yuan, Kai; Li, Xiangdong; Fleming, Sherry D.

    2012-01-01

    The humoral innate immune response consists of multiple components, including the naturally occurring antibodies (NAb), pentraxins and the complement and contact cascades. As soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. However, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathogy. Many studies have examined the relationship between humoral immunity and autoimmune disorders. This review focuses on the interactions between the humoral components and their role in promoting the pathogenesis of bacterial and viral infections and chronic diseases such as atherosclerosis and cancer. Understanding the beneficial and detrimental aspects of the individual components and the interactions between proteins which regulate the innate and adaptive response will provide therapeutic targets for subsequent studies. PMID:22771788

  5. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    PubMed Central

    Crill, Wayne D.; Hughes, Holly R.; Trainor, Nicole B.; Davis, Brent S.; Whitney, Matt T.; Chang, Gwong-Jen J.

    2012-01-01

    Dengue viruses (DENV) are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF). Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1) DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT) with this cross-reactivity reduced (CRR) vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naїve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine-induced immune responses. PMID

  6. The immortality of humoral immunity.

    PubMed

    Elgueta, Raul; de Vries, Victor C; Noelle, Randolph J

    2010-07-01

    Decades of high-titered antibody are sustained due to the persistence of memory B cells and long-lived plasma cells (PCs). The differentiation of each of these subsets is antigen- and T-cell driven and is dependent on signals acquired and integrated during the germinal center response. Inherent in the primary immune response must be the delivery of signals to B cells to create these populations, which have virtual immortality. Differences in biology and chemotactic behavior disperse memory B cells and long-lived PCs to a spectrum of anatomic sites. Each subset must rely on survival factors that can support their longevity. This review focuses on the generation of each of these subsets, their survival, and renewal, which must occur to sustain serological memory. In this context, we discuss the role of antigen, bystander inflammation, and cellular niches. The contribution of BAFF (B-cell activating factor belonging to the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) to the persistence of memory B cells and PCs are also detailed. Insights that have been provided over the past few years in the regulation of long-lived B-cell responses will have profound impact on vaccine development, the treatment of pre-sensitized patients for organ transplantation, and therapeutic interventions in both antibody- and T-cell-mediated autoimmunity.

  7. Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites: Naturally Acquired Humoral Immune Response and B-Cell Epitope Mapping in Brazilian Amazon Inhabitants.

    PubMed

    Rodrigues-da-Silva, Rodrigo Nunes; Soares, Isabela Ferreira; Lopez-Camacho, Cesar; Martins da Silva, João Hermínio; Perce-da-Silva, Daiana de Souza; Têva, Antônio; Ramos Franco, Antônia Maria; Pinheiro, Francimeire Gomes; Chaves, Lana Bitencourt; Pratt-Riccio, Lilian Rose; Reyes-Sandoval, Arturo; Banic, Dalma Maria; Lima-Junior, Josué da Costa

    2017-01-01

    The cell-traversal protein for ookinetes and sporozoites (CelTOS), a highly conserved antigen involved in sporozoite motility, plays an important role in the traversal of host cells during the preerythrocytic stage of Plasmodium species. Recently, it has been considered an alternative target when designing novel antimalarial vaccines against Plasmodium falciparum. However, the potential of Plasmodium vivax CelTOS as a vaccine target is yet to be explored. This study evaluated the naturally acquired immune response against a recombinant P. vivax CelTOS (PvCelTOS) (IgG and IgG subclass) in 528 individuals from Brazilian Amazon, as well as the screening of B-cell epitopes in silico and peptide assays to associate the breadth of antibody responses of those individuals with exposition and/or protection correlates. We show that PvCelTOS is naturally immunogenic in Amazon inhabitants with 94 individuals (17.8%) showing specific IgG antibodies against the recombinant protein. Among responders, the IgG reactivity indexes (RIs) presented a direct correlation with the number of previous malaria episodes (p = 0.003; r = 0.315) and inverse correlation with the time elapsed from the last malaria episode (p = 0.031; r = -0.258). Interestingly, high responders to PvCelTOS (RI > 2) presented higher number of previous malaria episodes, frequency of recent malaria episodes, and ratio of cytophilic/non-cytophilic antibodies than low responders (RI < 2) and non-responders (RI < 1). Moreover, a high prevalence of the cytophilic antibody IgG1 over all other IgG subclasses (p < 0.0001) was observed. B-cell epitope mapping revealed five immunogenic regions in PvCelTOS, but no associations between the specific IgG response to peptides and exposure/protection parameters were found. However, the epitope (PvCelTOSI136-E143) was validated as a main linear B-cell epitope, as 92% of IgG responders to PvCelTOS were also responders to this peptide sequence. This

  8. Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites: Naturally Acquired Humoral Immune Response and B-Cell Epitope Mapping in Brazilian Amazon Inhabitants

    PubMed Central

    Rodrigues-da-Silva, Rodrigo Nunes; Soares, Isabela Ferreira; Lopez-Camacho, Cesar; Martins da Silva, João Hermínio; Perce-da-Silva, Daiana de Souza; Têva, Antônio; Ramos Franco, Antônia Maria; Pinheiro, Francimeire Gomes; Chaves, Lana Bitencourt; Pratt-Riccio, Lilian Rose; Reyes-Sandoval, Arturo; Banic, Dalma Maria; Lima-Junior, Josué da Costa

    2017-01-01

    The cell-traversal protein for ookinetes and sporozoites (CelTOS), a highly conserved antigen involved in sporozoite motility, plays an important role in the traversal of host cells during the preerythrocytic stage of Plasmodium species. Recently, it has been considered an alternative target when designing novel antimalarial vaccines against Plasmodium falciparum. However, the potential of Plasmodium vivax CelTOS as a vaccine target is yet to be explored. This study evaluated the naturally acquired immune response against a recombinant P. vivax CelTOS (PvCelTOS) (IgG and IgG subclass) in 528 individuals from Brazilian Amazon, as well as the screening of B-cell epitopes in silico and peptide assays to associate the breadth of antibody responses of those individuals with exposition and/or protection correlates. We show that PvCelTOS is naturally immunogenic in Amazon inhabitants with 94 individuals (17.8%) showing specific IgG antibodies against the recombinant protein. Among responders, the IgG reactivity indexes (RIs) presented a direct correlation with the number of previous malaria episodes (p = 0.003; r = 0.315) and inverse correlation with the time elapsed from the last malaria episode (p = 0.031; r = −0.258). Interestingly, high responders to PvCelTOS (RI > 2) presented higher number of previous malaria episodes, frequency of recent malaria episodes, and ratio of cytophilic/non-cytophilic antibodies than low responders (RI < 2) and non-responders (RI < 1). Moreover, a high prevalence of the cytophilic antibody IgG1 over all other IgG subclasses (p < 0.0001) was observed. B-cell epitope mapping revealed five immunogenic regions in PvCelTOS, but no associations between the specific IgG response to peptides and exposure/protection parameters were found. However, the epitope (PvCelTOSI136-E143) was validated as a main linear B-cell epitope, as 92% of IgG responders to PvCelTOS were also responders to this peptide sequence. This

  9. The humoral immune system of anadromous fish.

    PubMed

    Zwollo, Patty

    2017-01-03

    The immune system of anadromous fish is extremely complex, a direct consequence of their diadromous nature. Hormone levels fluctuate widely throughout their life cycle, as fish move between fresh and salt water. This poses major challenges to the physiology of anadromous fish, including adaptation to very different saline environments, distinct pathogen fingerprints, and different environmental stressors. Elevated cortisol and sex hormone levels inhibit B lymphopoiesis and IgM(+) antibody responses, while catecholamines, growth hormones and thyroid hormones are generally stimulatory and enhance the humoral immune response. Immunological memory in the form of long-lived plasma cells likely plays important roles in health and survival during the life cycle of anadromous fishes. This review discusses some of the complex immune-endocrine pathways in anadromous fish, focusing on essential roles for B lineage cells in the successful completion of their life cycle. A discussion is included on potential differences in immuno-competence between wild and hatchery-raised fish.

  10. Regulation of humoral immunity by complement.

    PubMed

    Carroll, Michael C; Isenman, David E

    2012-08-24

    The complement system of innate immunity is important in regulating humoral immunity largely through the complement receptor CR2, which forms a coreceptor on B cells during antigen-induced activation. However, CR2 also retains antigens on follicular dendritic cells (FDCs). Display of antigen on FDCs is critical for clonal selection and affinity maturation of activated B cells. This review will discuss the role of complement in adaptive immunity in general with a focus on the interplay between CR2-associated antigen on B cells with CR2 expressed on FDCs. This latter interaction provides an opportunity for memory B cells to sample antigen over prolonged periods. The cocrystal structure of CR2 with its ligand C3d provides insight into how the complement system regulates access of antigen by B cells with implications for therapeutic manipulations to modulate aberrant B cell responses in the case of autoimmunity.

  11. Humoral immune response to the antigen administered as an immune complex.

    PubMed

    Marusić, M; Marusić-Galesić, S; Pokrić, B

    1992-12-01

    Antigen (HSA) bound in immune complexes at equivalence with syngeneic anti-HSA antibodies elicit much stronger humoral immune response then soluble HSA. On the other hand, administration of immune complexes formed with xenogeneic (rabbit) anti-HSA antibodies suppressed humoral immune response against HSA, but not against rabbit IgG in mice. We suggest that immunization with antigen bound in immune complex might represent a powerful tool in enhancing humoral immune responses.

  12. Eosinophils: important players in humoral immunity.

    PubMed

    Berek, C

    2016-01-01

    Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. Recently, however, it has become clear that eosinophils also play crucial non-inflammatory roles in the generation and maintenance of adaptive immune responses. Eosinophils, being a major source of the plasma cell survival factor APRIL (activation and proliferation-induced ligand), are essential not only for the long-term survival of plasma cells in the bone marrow, but also for the maintenance of these cells in the lamina propria which underlies the gut epithelium. At steady state under non-inflammatory conditions eosinophils are resident cells of the gastrointestinal tract, although only few are present in the major organized lymphoid tissue of the gut - the Peyer's patches (PP). Surprisingly, however, lack of eosinophils abolishes efficient class-switching of B cells to immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are required to generate and to maintain mucosal IgA plasma cells, and as a consequence their absence leads to a marked reduction of IgA both in serum and in the gut-associated lymphoid tissues (GALT). Eosinophils thus have an essential part in long-term humoral immune protection, as they are crucial for the longevity of antibody-producing plasma cells in the bone marrow and, in addition, for gut immune homeostasis.

  13. Variability in Humoral Immunity to Measles Vaccine: New Developments

    PubMed Central

    Haralambieva, Iana H.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Whitaker, Jennifer A.; Poland, Gregory A.

    2015-01-01

    Despite the existence of an effective measles vaccine, resurgence in measles cases in the United States and across Europe has occurred, including in individuals vaccinated with two doses of the vaccine. Host genetic factors result in inter-individual variation in measles vaccine-induced antibodies, and play a role in vaccine failure. Studies have identified HLA and non-HLA genetic influences that individually or jointly contribute to the observed variability in the humoral response to vaccination among healthy individuals. In this exciting era, new high-dimensional approaches and techniques including vaccinomics, systems biology, GWAS, epitope prediction and sophisticated bioinformatics/statistical algorithms, provide powerful tools to investigate immune response mechanisms to the measles vaccine. These might predict, on an individual basis, outcomes of acquired immunity post measles vaccination. PMID:26602762

  14. 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.

  15. Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

    PubMed

    Halder, Sumita; Mehta, Ashish K; Mediratta, Pramod K; Sharma, Krishna K

    2011-08-01

    The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity.

  16. Age effects on B cells and humoral immunity in humans

    PubMed Central

    Frasca, Daniela; Diaz, Alain; Romero, Maria; Landin, Ana Marie; Blomberg, Bonnie B

    2010-01-01

    Both humoral and cellular immune responses are impaired in aged individuals, leading to decreased vaccine responses. Although T cell defects occur, defects in B cells play a significant role in age-related humoral immune changes. The ability to undergo class switch recombination (CSR), the enzyme for CSR, AID (activation-induced cytidine deaminase) and the transcription factor E47 are all decreased in aged stimulated B cells. We here present an overview of age-related changes in human B cell markers and functions, and also discuss some controversies in the field of B cell aging. PMID:20728581

  17. Cryptosporidiosis in the acquired immune deficiency syndrome.

    PubMed

    Cooper, D A; Wodak, A; Marriot, D J; Harkness, J L; Ralston, M; Hill, A; Penny, R

    1984-10-01

    Cryptosporidiosis was found in a patient with the acquired immune deficiency syndrome. The microbiological and morphological features of this newly recognized opportunistic infection are distinctive and diagnostic.

  18. Acquired immune deficiency syndrome: review.

    PubMed

    Scully, C; Cawson, R A; Porter, S R

    1986-07-19

    Acquired immunodeficiency syndrome (AIDS) is reviewed for dental practitioners, with an emphasis on oral findings; the clinical course, diagnosis, reporting, treatment, prognosis, transmission, and epidemiology are also covered. HIV infection has an incubation period that may be associated with glandular fever, a prodrome called AIDS-Related Complex (ARC) characterized by lymphadenopathy, low fever, weight loss, night sweats, diarrhea, oral candidosis, nonproductive cough and recurrent infections. AIDS is characterized by opportunistic infections. Over 50% present with pneumocystis carinii pneumonia, 21% with Kaposi's sarcoma, and 6% have both. The AIDS virus causes direct neurological symptoms in some cases. Oral candidosis (thrush) in a young male without a local cause such as xerostomia or immune suppression is strongly suggestive of AIDS. Other oral manifestations are severe herpes simplex, varicella-zoster, Epstein-Barr virus, cytomegalovirus, venereal warts, aphthous ulceration, mycobacterial oral ulcers, oral histoplasmosis, sinusitis and osteomyelitis of the jaw. Hairy leukoplakia, usually seen on the lateral border of the tongue, is probably caused by Epstein-Barr virus. Kaposi's sarcoma, an endothelial cell tumor, is characteristic of AIDS, and in 50% of patients is oral or perioral. Cervical lymph node enlargement will be seen in those with ARC as well as AIDS. No guidelines have been issued by the Department of Health and Social Security for dental surgeons in the UK for reporting AIDS cases. Although HIV virions have been isolated from saliva, there are no known incidents of transmission via saliva. HIV is less likely to be transmitted by needle stick injuries than, for example hepatitis B (25% risk), especially if the blood is from a carrier rather than a full blown AIDS case.

  19. Humoral immune responses in foetal sheep.

    PubMed Central

    Fahey, K J; Morris, B

    1978-01-01

    A total of fifty-two foetal sheep between 49 and 126 days gestation were injected with polymeric and monomeric flagellin, dinitrophenylated monomeric flagellin, chicken red blood cells, ovalbumin, ferritin, chicken gamma-globulin and the somatic antigens of Salmonella typhimurium in a variety of combinations. Immune responses were followed in these animals by taking serial blood samples from them through indwelling vascular cannulae and measuring the circulating titres of antibody. Of the antigens tested, ferritin induced immune responses in the youngest foetuses. A short time later in gestation, the majority of foetuses responded to chicken red blood cells, polymeric flagellin, monomeric flagellin and dinitrophenylated monomeric flagellin. Only older foetuses responded regularly to chicken gamma-globulin and ovalbumin. However, antibodies to all these antigens were first detected over the relatively short period of development between 64 and 82 days gestation and this made it difficult to define any precise order in the development of immune responsiveness. Of the antigens tested only the somatic antigens of S. typhimurium failed to induce a primary antibody response during foetal life. The character and magnitude of the antibody responses in foetuses changed throughout in utero development. Both the total amount of antibody produced and the duration of the response increased with foetal age. Foetuses younger than 87 days gestation did not synthesize 2-mercaptoethanol resistant antibodies or IgG1 immunoglobulin to any of the antigens tested, whereas most foetuses older than this regularly did so. PMID:711249

  20. Acquired Immunity to Pathogenic Fungi.

    DTIC Science & Technology

    1977-06-01

    colonization of the nasal cavity, oral cavity or rectal area of the bacteria free guinea pigs. We allowed the infected animals (primary) to continue...canis, or T. mentagrophytes was able to colonize the bacteria free 6I tract, oral cavity, nasal cavity or lungs of2the girmfree rats: only T...the normal mice. The implanted thymus appeared-to suppress immunity to systemic candidiasis that was present in the athymic nude mice. We are going to

  1. Humoral and cellular immunity in chromium picolinate-supplemented lambs.

    PubMed

    Dallago, B S L; McManus, C M; Caldeira, D F; Campeche, A; Burtet, R T; Paim, T P; Gomes, E F; Branquinho, R P; Braz, S V; Louvandini, H

    2013-08-01

    The effects of oral supplementation of chromium picolinate (CrPic) on humoral and cellular immunity in sheep were investigated. Twenty-four male lambs divided into four treatments and received different dosages of CrPic: placebo (0), 0.250, 0.375, and 0.500 mg of chromium/animal/day during 84 days. The base ration was Panicum maximum cv Massai hay and concentrate. Blood samples were collected fortnightly for total and differential leukocyte counts. On days 28 and 56, the lambs were challenged with chicken ovalbumin I.M. Serum samples were collected on days 46 and 74 and subjected to an indirect enzyme-linked immunosorbent assay to measure IgG anti-ovalbumin. The cell-mediated immune response was determined by a delay-type hypersensitivity test using phytohemagglutinin. CrPic did not significantly affect humoral immunity in lambs but there was a negative effect on cellular immunity (P < 0.05) as Cr supplementation increased. Therefore, the level of Cr supplementation for lambs must be better studied to address its effect on stressed animals or the possible toxic effects of Cr on the animal itself or its immune system.

  2. Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis

    PubMed Central

    Negm, Ola H.; Hamed, Mohamed R.; Dilnot, Elizabeth M.; Shone, Clifford C.; Marszalowska, Izabela; Lynch, Mark; Loscher, Christine E.; Edwards, Laura J.; Tighe, Patrick J.; Wilcox, Mark H.

    2015-01-01

    Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost. PMID:26178385

  3. Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis.

    PubMed

    Negm, Ola H; Hamed, Mohamed R; Dilnot, Elizabeth M; Shone, Clifford C; Marszalowska, Izabela; Lynch, Mark; Loscher, Christine E; Edwards, Laura J; Tighe, Patrick J; Wilcox, Mark H; Monaghan, Tanya M

    2015-09-01

    Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost.

  4. Insights into the naturally acquired immune response to Plasmodium vivax malaria.

    PubMed

    Longley, Rhea J; Sattabongkot, Jetsumon; Mueller, Ivo

    2016-02-01

    Plasmodium vivax is the most geographically widespread of the malaria parasites causing human disease, yet it is comparatively understudied compared with Plasmodium falciparum. In this article we review what is known about naturally acquired immunity to P. vivax, and importantly, how this differs to that acquired against P. falciparum. Immunity to clinical P. vivax infection is acquired more quickly than to P. falciparum, and evidence suggests humans in endemic areas also have a greater capacity to mount a successful immunological memory response to this pathogen. Both of these factors give promise to the idea of a successful P. vivax vaccine. We review what is known about both the cellular and humoral immune response, including the role of cytokines, antibodies, immunoregulation, immune memory and immune dysfunction. Furthermore, we discuss where the future lies in terms of advancing our understanding of naturally acquired immunity to P. vivax, through the use of well-designed longitudinal epidemiological studies and modern tools available to immunologists.

  5. Humor.

    PubMed

    Woodbury-Fariña, Michel A; Antongiorgi, Joalex L

    2014-12-01

    Humor has not been taken as seriously as it should be. Humor has many positive effects in the daily lives of patients and clinicians need to take advantage of these. Many indices of stress are attenuated and this serves to improve the therapeutic alliance. Freudian, rational emotive therapy, and kleinian views are presented, as well as examples of how to use playful therapy. In addition, advice on how to develop humor is given.

  6. The clinical impact of humoral immunity in pediatric renal transplantation.

    PubMed

    Chaudhuri, Abanti; Ozawa, Mikki; Everly, Matthew J; Ettenger, Robert; Dharnidharka, Vikas; Benfield, Mark; Mathias, Robert; Portale, Anthony; McDonald, Ruth; Harmon, William; Kershaw, David; Vehaskari, V Matti; Kamil, Elaine; Baluarte, H Jorge; Warady, Bradley; Li, Li; Sigdel, Tara K; Hsieh, Szu-chuan; Dai, Hong; Naesens, Maarten; Waskerwitz, Janie; Salvatierra, Oscar; Terasaki, Paul I; Sarwal, Minnie M

    2013-03-01

    The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.

  7. The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

    PubMed Central

    Chaudhuri, Abanti; Ozawa, Mikki; Everly, Matthew J.; Ettenger, Robert; Dharnidharka, Vikas; Benfield, Mark; Mathias, Robert; Portale, Anthony; McDonald, Ruth; Harmon, William; Kershaw, David; Vehaskari, V. Matti; Kamil, Elaine; Baluarte, H. Jorge; Warady, Bradley; Li, Li; Sigdel, Tara K.; Hsieh, Szu-chuan; Dai, Hong; Naesens, Maarten; Waskerwitz, Janie; Salvatierra, Oscar; Terasaki, Paul I.

    2013-01-01

    The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study. PMID:23449533

  8. Cellular and humoral immunity in subacute sclerosing panencephalitis.

    PubMed Central

    Dhib-Jalbut, S S; Abdelnoor, A M; Haddad, F S

    1981-01-01

    Cellular and humoral immunity was studied in 26 patients with subacute sclerosing panencephalitis. Results were compared with those of 14 normal controls and 11 patients suffering from other neurological disorders. It was shown that cellular and humoral immune responses are adequate in subacute sclerosing panencephalitis. The persistently elevated levels of serum immunoglobulin G (IgG) and IgA indicated a persistent infection, and their progressive rise in later stages correlated with the progressive nature of the illness. IgG progressively increased with the clinical stage in the cerebrospinal fluid unaccompanied by a corresponding rise in the measles antibody titer. This suggests that antigenic determinants other than those tested play a role in the production of IgG in the cerebrospinal fluid. The progressive increase in the ratio of cerebrospinal fluid to serum IgG with the advance of the disease suggests synthesis of IgG locally in the central nervous system. Elevated measles antibody titer in serum and cerebrospinal fluid is a consistent aid in the diagnosis of subacute sclerosing panencephalitis. It is more specific in cerebrospinal fluid than in serum. Its level did not vary significantly with the clinical stages or duration of illness. Depressed serum complement activity has been detected in some subacute sclerosing panencephalitis patients in whom serum levels of the third and fourth components of the complement were normal. PMID:6973545

  9. Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases

    PubMed Central

    Zhang, Yi; Li, Jun; Zhang, Ya-Min; Zhang, Xiao-Ming; Tao, Juan

    2015-01-01

    Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) is one of the receptors of B cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL). TACI is a regulator in the immune responses. TACI inhibits B cell expansion and promotes the differentiation and survival of plasma cells. The mechanisms underlying these effects probably involve changed expressions of some crucial molecules, such as B lymphocyte induced maturation protein-1 (Blimp-1) and inducible T-cell costimulator ligand (ICOSL) in B cells and/or plasma cells. However, abnormal TACI signaling may relate to autoimmune disorders. Common variable immune deficiency (CVID) patients with heterozygous mutations in TACI alleles increase susceptibility to autoimmune diseases. Taci−/− mice and BAFF transgenic mice both develop signs of human SLE. These findings that indicate inappropriate levels of TACI signaling may disrupt immune system balance, thereby promoting the development of autoimmune diseases. In this review, we summarize the basic characteristics of the TACI ligands BAFF and APRIL, and detail the research findings on the role of TACI in humoral immunity. We also discuss the possible mechanisms underlying the susceptibility of CVID patients with TACI mutations to autoimmune diseases and the role of TACI in the pathogenesis of SLE. PMID:25866827

  10. 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.

  11. Antibody-antigen kinetics constrain intracellular humoral immunity

    PubMed Central

    Bottermann, Maria; Lode, Heidrun Elisabeth; Watkinson, Ruth E.; Foss, Stian; Sandlie, Inger; Andersen, Jan Terje; James, Leo C.

    2016-01-01

    During infection with non-enveloped viruses, antibodies stimulate immunity from inside cells by activating the cytosolic Fc receptor TRIM21. This intracellular humoral response relies on opsonized viral particles reaching the cytosol intact but the antigenic and kinetic constraints involved are unknown. We have solved the structure of a potent TRIM21-dependent neutralizing antibody in complex with human adenovirus 5 hexon and show how these properties influence immune activity. Structure-guided mutagenesis was used to generate antibodies with 20,000-fold variation in affinity, on-rates that differ by ~50-fold and off-rates by >175-fold. Characterization of these variants during infection revealed that TRIM21-dependent neutralization and NFκB activation was largely unaffected by on-rate kinetics. In contrast, TRIM21 antiviral activity was exquisitely dependent upon off-rate, with sub-μM affinity antibodies nevertheless unable to stimulate signaling because of fast dissociation kinetics. These results define the antibody properties required to elicit an efficient intracellular immune response during viral infection. PMID:27881870

  12. Innate and acquired bacteriophage-mediated immunity

    PubMed Central

    Barr, Jeremy J.; Youle, Merry; Rohwer, Forest

    2013-01-01

    We recently described a novel, non-host-derived, phage-mediated immunity active at mucosal surfaces, the main site of pathogen entry in metazoans. In that work, we showed that phage T4 adheres to mucus glycoproteins via immunoglobulin-like domains displayed on its capsid. This adherence positions the phage in mucus surfaces where they are more likely to encounter and kill bacteria, thereby benefiting both the phage and its metazoan host. We presented this phage-metazoan symbiosis based on an exclusively lytic model of phage infection. Here we extend our bacteriophage adherence to mucus (BAM) model to consider the undoubtedly more complex dynamics in vivo. We hypothesize how mucus-adherent phages, both lytic and temperate, might impact the commensal microbiota as well as protect the metazoan epithelium from bacterial invasion. We suggest that BAM may provide both an innate and an acquired antimicrobial immunity. PMID:24228227

  13. Characterization of the Humoral Immune Response against Gnathostoma binucleatum in Patients Clinically Diagnosed with Gnathostomiasis

    PubMed Central

    Zambrano-Zaragoza, José Francisco; Durán-Avelar, Ma de Jesús; Messina-Robles, Maud; Vibanco-Pérez, Norberto

    2012-01-01

    Gnathostomiasis is an emerging systemic parasitic disease acquired by consuming raw or uncooked fresh-water fish infected with the advanced third-stage larvae of Gnathostoma spp. This disease is endemic to the Pacific region of Mexico, and one of its etiologic agents has been identified as Gnathostoma binucleatum. We characterized the humoral immune response of patients clinically diagnosed with gnathostomiasis by detecting total IgM, IgE, and IgG class and subclasses against a crude extract of the parasite by Western blotting. Our results do not show differences in the antigens recognized by IgM and IgE. However, we found that the specific humoral immune response is caused mainly by IgG, specifically IgG4. We found that 43%, 65.2%, 54.1%, and 26.3% of the patients recognize the 37-kD, 33-kD, 31-kD, and 24-kDa antigens, suggesting that the 33-kD antigen is the immunodominant antigen of G. binucleatum. PMID:22665606

  14. Evasion and Interactions of the Humoral Innate Immune Response in Pathogen Invasion, Autoimmune Disease, and Cancer

    PubMed Central

    Rettig, Trisha A.; Harbin, Julie N.; Harrington, Adelaide; Dohmen, Leonie; Fleming, Sherry D.

    2015-01-01

    The humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. To persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. Disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases. This review will examine how gram positive bacteria, viruses, cancer, and the autoimmune conditions Systemic Lupus Erythematosus and Anti-phospholipid syndrome, interact with these immune system components. Through examining evasion techniques it becomes clear that interplay between these three systems exists. By exploring the interplay and the evasion/disruption of the humoral innate immune system, we can develop a better understanding of pathogenic infections, cancer, and autoimmune disease development. PMID:26145788

  15. Chronic pediatric pulmonary disease and primary humoral antibody based immune disease.

    PubMed

    Dosanjh, A

    2011-04-01

    Chronic inflammation of the larger airways is a common occurrence in children. A number of factors such as younger age, premature birth, male gender, exposure to environmental smoke or pollution, and crowded housing can increase a child's susceptibility to chronic lung disease. Chronic bronchitis may be caused by an underlying humoral immunodeficiency if the clinical course is recurrent or prolonged. Primary humoral immunodeficiency accounts for approximately 70% of all immunodeficiencies. The differential of chronic bronchitis also includes Cystic Fibrosis, ciliary defects and immune cellular and phagocytic defects. This review will summarize the most common humoral antibody based immune based deficiencies associated with chronic pulmonary disease.

  16. The cellular and humoral immunity assay in patients with complicated urolithiasis

    PubMed Central

    Ceban, E; Banov, P; Galescu, A; Tanase, D

    2017-01-01

    Especially complicated, renal lithiasis contributes to the general inflammatory syndrome development that interferes with nonspecific, humoral and cellular immune system. The surgical treatment of nephrolithiasis is closely related to drug therapy of urinary infection, one of the reasons being the reduction of the immune status. The work is performed by evaluating the immunological status preoperatively in 58 patients with complicated lithiasis. The analysis of the status in these patients demonstrated that complicated urolithiasis results in significant changes in the immune system, these changes being expressed at the cellular and humoral level of immunity. PMID:28255384

  17. Assessing humoral and cell-mediated immune response in Hawaiian green turtles, Chelonia mydas

    USGS Publications Warehouse

    Work, T.M.; Balazs, G.H.; Rameyer, R.A.; Chang, S.P.; Berestecky, J.

    2000-01-01

    Seven immature green turtles, Chelonia mydas, captured from Kaneohe Bay on the island of Oahu were used to evaluate methods for assessing their immune response. Two turtles each were immunized intramuscularly with egg white lysozyme (EWL) in Freunda??s complete adjuvant, Gerbu, or ISA-70; a seventh turtle was immunized with saline only and served as a control. Humoral immune response was measured with an indirect enzyme linked immunosorbent assay (ELISA). Cell-mediated immune response was measured using in vitro cell proliferation assays (CPA) using whole blood or peripheral blood mononuclear cells (PBM) cultured with concanavalin A (ConA), phytohaemagglutinin (PHA), or soluble egg EWL antigen. All turtles, except for one immunized with Gerbu and the control, produced a detectable humoral immune response by 6 weeks which persisted for at least 14 weeks after a single immunization. All turtles produced an anamnestic humoral immune response after secondary immunization. Antigen specific cell-mediated immune response in PBM was seen in all turtles either after primary or secondary immunization, but it was not as consistent as humoral immune response; antigen specific cell-mediated immune response in whole blood was rarely seen. Mononuclear cells had significantly higher stimulation indices than whole blood regardless of adjuvant, however, results with whole blood had lower variability. Both Gerbu and ISA-70 appeared to potentiate the cell-mediated immune response when PBM or whole blood were cultured with PHA. This is the first time cell proliferation assays have been compared between whole blood and PBM for reptiles. This is also the first demonstration of antigen specific cell-mediated response in reptiles. Cell proliferation assays allowed us to evaluate the cell-mediated immune response of green turtles. However, CPA may be less reliable than ELISA for detecting antigen specific immune response. Either of the three adjuvants appears suitable to safely elicit a

  18. Specific humoral and cellular immunity induced by Trypanosoma cruzi DNA immunization in a canine model

    PubMed Central

    2013-01-01

    Chagas disease has a high incidence in Mexico and other Latin American countries. Because one of the most important known methods of prevention is vector control, which has been effective only in certain areas of South America, the development of a vaccine to protect people at risk has been proposed. In this study, we assessed the cellular and humoral immune response generated following immunization with pBCSP and pBCSSP4 plasmids containing the genes encoding a trans-sialidase protein (present in all three forms of T. cruzi) and an amastigote specific glycoprotein, respectively, in a canine model. Thirty-five beagle dogs were divided randomly into 5 groups (n = 7) and were immunized twice intramuscularly with 500 μg of pBCSSP4, pBCSP, pBk-CMV (empty plasmid) or saline solution. Fifteen days after the last immunization the 4 groups were infected intraperitoneally with 500 000 metacyclic trypomastigotes. The fifth group was unimmunized/infected. The parasitaemia in the immunized/infected dogs was for a shorter period (14 vs. 29 days) and the parasite load was lower. The concentration of IgG1 (0.612 ± 0.019 O.D.) and IgG2 (1.167 ± 0.097 O.D.) subclasses was measured (absorbance) 15 days after the last immunization with both recombinant plasmids, the majority of which were IgG2. The treatment of parasites using the serum from dogs immunized with pBCSP and pBCSSP4 plasmids produced 54% (± 11.8) and 68% (± 21.4) complement-mediated lysis, respectively. At 12 h post immunization, an increase in cytokines was not observed; however, vaccination with pBCSSP4 significantly increased the levels of IFN-γ and IL-10 at 9 months post-infection. The recombinant plasmid immunization stimulated the spleen cell proliferation showing a positive stimulatory index above 2.0. In conclusion, immunization using both genes effectively induces a humoral and cellular immune response. PMID:23497041

  19. Humoral immune responses of amphioxus Branchiostoma belcheri to challenge with Escherichia coli.

    PubMed

    Pang, Qiuxiang; Zhang, Shicui; Liu, Xuemei; Wu, Di

    2006-08-01

    Humoral parameters of amphioxus Branchiostoma belcheri, including lysozyme, antimicrobial activity, microbial agglutinin and haemagglutinins were measured before and after challenge with Escherichia coli. Humoral fluids from unchallenged B. belcheri had lysozyme, antimicrobial, microbial agglutinating and haemagglutinating activities, which may represent part of the baseline level of innate immunity in this organism. After challenge with E. coli, the lysozyme activity, growth-inhibiting activities against E. coli and Vibrio alginolyticus, microbial agglutinating activities against Micrococcus lysodeikticus, Bacillus subtilis and Staphylococus aureus, and haemagglutinating activities against rabbit and human A and O erythrocytes in the humoral fluids were all increased significantly. In contrast, the agglutinating activities against Vibrio harveyi and E. coli and the haemagglutinating activity against human B erythrocytes in the humoral fluids were reduced in response to E. coli challenge. It appears that the humoral fluids of B. belcheri contain components that are able to differentiate different microbes and different human blood cell types.

  20. Characterization of the effect of Cr(VI) on humoral innate immunity using Drosophila melanogaster.

    PubMed

    Pragya, P; Shukla, A K; Murthy, R C; Abdin, M Z; Kar Chowdhuri, D

    2015-11-01

    With the advancement of human race, different anthropogenic activities have heaped the environment with chemicals that can cause alteration in the immune system of exposed organism. As a first line of barrier, the evolutionary conserved innate immunity is crucial for the health of an organism. However, there is paucity of information regarding in vivo assessment of the effect of environmental chemicals on innate immunity. Therefore, we examined the effect of a widely used environmental chemical, Cr(VI), on humoral innate immune response using Drosophila melanogaster. The adverse effect of Cr(VI) on host humoral response was characterized by decreased gene expression of antimicrobial peptides (AMPs) in the exposed organism. Concurrently, a significantly decreased transcription of humoral pathway receptors (Toll and PGRP) and triglyceride level along with inhibition of antioxidant enzyme activities were observed in exposed organism. This in turn weakened the immune response of exposed organism that was manifested by their reduced resistance against bacterial infection. In addition, overexpression of the components of humoral immunity particularly Diptericin benefits Drosophila from Cr(VI)-induced humoral immune-suppressive effect. To our knowledge, this is the first report regarding negative impact of an environmental chemical on humoral innate immune response of Drosophila along with subsequent protection by AMPs, which may provide novel insight into host-chemical interactions. Also, our data validate the utility and sensitivity of Drosophila as a model that could be used for screening the possible risk of environmental chemicals on innate immunity with minimum ethical concern that can be further extrapolated to higher organisms.

  1. Immunology of chronic generalized periodontitis. 1. Estimation of cellular and humoral immune status.

    PubMed

    Anil, S; Hari, S; Remani, P; Vijaykumar, T

    1990-01-01

    Cell-mediated and humoral immune responses were assessed in forty patients with chronic generalized periodontitis (CGP), and in an equal number of control subjects. The cell mediated immunity assessed by enumeration of total rosette forming cells [TRFC] and high affinity rosette forming cells [HARFC], were found to be slightly depressed in CGP patients compared controls. The humoral immune response was assessed by estimation of serum immunoglobulins G,A,M,D and E by single radial immunodiffusion technique (RID). Except IgD all the other immunoglobulins were found to be elevated significantly. These immunological derangements found in CGP patients may be the cause or effect of the disease process.

  2. Cell-mediated and humoral immune response in diabetic patients with periodontitis.

    PubMed

    Anil, S; Remani, P; Vijayakumar, T; Hari, S

    1990-07-01

    Cell-mediated and humoral immune responses were assessed in 50 patients with type II or non-insulin-dependent diabetes mellitus and 50 nondiabetic patients with periodontitis. The values were compared with those of 50 age and sex-matched control subjects. The cell-mediated immunity assessed by enumerating the total and high-affinity rosette-forming cells of the patient did not show any significant variation from that of the normal control subjects. The humoral immune response was assessed by estimating serum immunoglobulins G, A, M, D, and E by single radial immunodiffusion. Except IgD, all other immunoglobulins were found to be elevated significantly in both diabetic and nondiabetic subjects. The alteration in humoral immune response may be the cause or the effect of periodontitis. The defective host response reported in diabetic patients may be responsible for the increased incidence of periodontitis in diabetic patients as compared to nondiabetic patients.

  3. IL17-Producing γδ T Cells May Enhance Humoral Immunity during Pulmonary Pseudomonas aeruginosa Infection in Mice

    PubMed Central

    Pan, Tingting; Tan, Ruoming; Li, Meiling; Liu, Zhaojun; Wang, Xiaoli; Tian, Lijun; Liu, Jialin; Qu, Hongping

    2016-01-01

    The host acquired immune response, especially the humoral immunity, plays key roles in preventing bacterial pneumonia in the lung. Our previous research demonstrated that interleukin 17-producing γδ T cells (IL17-γδ T cells) have a protective effect on the early innate immune response during acute pulmonary Pseudomonas aeruginosa infection. However, whether IL17-γδ T cells also play a role in humoral immunity is unknown. In this study, an acute pulmonary P. aeruginosa infection model was established in wild-type and γδ TCR−/− C57BL/6 mice. The expression of IL-17 on γδ T cells isolated from infected lung tissues increased rapidly and peaked at day 7 after acute infection with P. aeruginosa. Compared with wild-type infected mice, the levels of total immunoglobulins including IgA, IgG, and IgM in the serum and BALF were significantly decreased in γδ TCR−/− mice, with the exception of IgM in the BALF. Moreover, CD69 expression in B cells from the lungs and spleen and the level of BAFF in the plasma were also decreased in γδ TCR−/− mice. IL17-γδ T cell transfusion significantly improved the production of immunoglobulins, B cell activation and BAFF levels in γδ TCR−/− mice compared with γδ TCR−/− mice without transfusion; this effect was blocked when cells were pretreated with an IL-17 antibody. Together, these data demonstrate that IL17-γδ T cells are involved in CD19+ B cell activation and the production of immunoglobulins during acute pulmonary P. aeruginosa infection. Thus, we conclude that IL17-γδ T cells may facilitate the elimination of bacteria and improve survival through not only innate immunity but also humoral immunity. PMID:27999768

  4. The evolution of resistance through costly acquired immunity.

    PubMed Central

    Boots, Michael; Bowers, Roger G.

    2004-01-01

    We examine the evolutionary dynamics of resistance to parasites through acquired immunity. Resistance can be achieved through the innate mechanisms of avoidance of infection and reduced pathogenicity once infected, through recovery from infection and through remaining immune to infection: acquired immunity. We assume that each of these mechanisms is costly to the host and find that the evolutionary dynamics of innate immunity in hosts that also have acquired immunity are quantitatively the same as in hosts that possess only innate immunity. However, compared with resistance through avoidance or recovery, there is less likely to be polymorphism in the length of acquired immunity within populations. Long-lived organisms that can recover at intermediate rates faced with fast-transmitting pathogens that cause intermediate pathogenicity (mortality of infected individuals) are most likely to evolve long-lived acquired immunity. Our work emphasizes that because whether or not acquired immunity is beneficial depends on the characteristics of the disease, organisms may be selected to only develop acquired immunity to some of the diseases that they encounter. PMID:15209105

  5. Mucosal Immunization with Liposome-Nucleic Acid Adjuvants Generates Effective Humoral and Cellular Immunity

    PubMed Central

    Henderson, Angela; Propst, Katie; Kedl, Ross; Dow, Steven

    2012-01-01

    Development of effective new mucosal vaccine adjuvants has become a priority with the increase in emerging viral and bacterial pathogens. We previously reported that cationic liposomes complexed with non-coding plasmid DNA (CLDC) were effective parenteral vaccine adjuvants. However, little is known regarding the ability of liposome-nucleic acid complexes to function as mucosal vaccine adjuvants, or the nature of the mucosal immune responses elicited by mucosal liposome-nucleic acid adjuvants. To address these questions, antibody and T cell responses were assessed in mice following intranasal immunization with CLDC-adjuvanted vaccines. The effects of CLDC adjuvant on antigen uptake, trafficking, and cytokine responses in the airways and draining lymph nodes were also assessed. We found that mucosal immunization with CLDC-adjuvanted vaccines effectively generated potent mucosal IgA antibody responses, as well as systemic IgG responses. Notably, mucosal immunization with CLDC adjuvant was very effective in generating strong and sustained antigen-specific CD8+ T cell responses in the airways of mice. Mucosal administration of CLDC vaccines also induced efficient uptake of antigen by DCs within the mediastinal lymph nodes. Finally, a killed bacterial vaccine adjuvanted with CLDC induced significant protection from lethal pulmonary challenge with Burkholderia pseudomallei. These findings suggest that liposome-nucleic acid adjuvants represent a promising new class of mucosal adjuvants for non-replicating vaccines, with notable efficiency at eliciting both humoral and cellular immune responses following intranasal administration. PMID:21600950

  6. The role of B cells and humoral immunity in Mycobacterium tuberculosis infection

    PubMed Central

    Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M.; Casadevall, Arturo; Flynn, JoAnne

    2014-01-01

    Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. PMID:25458990

  7. On the relationship between meningococcal transmission dynamics and disease: remarks on humoral immunity.

    PubMed

    Guzzetta, Giorgio; Manfredi, Piero; Gasparini, Roberto; Panatto, Donatella; Edmunds, W John

    2009-05-26

    We consider a model for the transmission dynamics of Neisseria meningitidis which incorporates the humoral immunity hypothesis in an explicit way. The "humoral immunity" hypothesis states that individuals will experience significantly different risks of invasive disease depending on whether they are experiencing their first infection episode, or a subsequent one. The model is fitted to the Stonehouse-Danbury carriage data and to UK disease data. For serogroup C (B) the risk of disease during the first infection episode results to be 100 (400) times higher compared to subsequent ones. Moreover the best-fit corresponds to the situation where N. lactamica essentially always confers cross-protection.

  8. Acquired and innate immunity to polyaromatic hydrocarbons

    SciTech Connect

    Yusuf, Nabiha Timares, Laura; Seibert, Megan D.; Xu Hui; Elmets, Craig A.

    2007-11-01

    Polyaromatic hydrocarbons are ubiquitous environmental pollutants that are potent mutagens and carcinogens. Researchers have taken advantage of these properties to investigate the mechanisms by which chemicals cause cancer of the skin and other organs. When applied to the skin of mice, several carcinogenic polyaromatic hydrocarbons have also been shown to interact with the immune system, stimulating immune responses and resulting in the development of antigen-specific T-cell-mediated immunity. Development of cell-mediated immunity is strain-specific and is governed by Ah receptor genes and by genes located within the major histocompatibility complex. CD8{sup +} T cells are effector cells in the response, whereas CD4{sup +} T cells down-regulate immunity. Development of an immune response appears to have a protective effect since strains of mice that develop a cell-mediated immune response to carcinogenic polyaromatic hydrocarbons are less likely to develop tumors when subjected to a polyaromatic hydrocarbon skin carcinogenesis protocol than mice that fail to develop an immune response. With respect to innate immunity, TLR4-deficient C3H/HeJ mice are more susceptible to polyaromatic hydrogen skin tumorigenesis than C3H/HeN mice in which TLR4 is normal. These findings support the hypothesis that immune responses, through their interactions with chemical carcinogens, play an active role in the prevention of chemical skin carcinogenesis during the earliest stages. Efforts to augment immune responses to the chemicals that cause tumors may be a productive approach to the prevention of tumors caused by these agents.

  9. Humoral and Cellular Immunity Changed after Traumatic Brain Injury in Human Patients.

    PubMed

    Wang, Jia-Wei; Li, Jin-Ping; Song, Ying-Lun; Zhao, Qi-Huang

    2017-01-01

    Previous studies have suggested that there is a disproportionally higher risk of infection following traumatic brain injury (TBI). This predisposition to infection may be driven by a poorly understood, brain-specific response in the immune system after TBI. However, there is a lack of studies that have fully characterized TBI patients to understand the relationship between TBI and peripheral immune function. In the present study, markers for humoral immunity and cellular immunity were measured for up to 2 weeks in the peripheral blood of 37 patients with TBI in order to elucidate the time course and the type of the peripheral immune response following TBI. 12 relatively healthy individuals without TBI and other neurological diseases were enrolled into the control group. Our data indicated that TBI could induce significant changes in humoral immunity characterized by a decrease in IgG and IgM levels and an increase in the complements C3 and C4 levels in comparison with the control group. Moreover, compared with the control group, a significant reduction in peripheral blood CD3(+) and CD3(+)CD4(+) lymphocyte counts occurred early (days 1-3) following the onset of trauma. These results provide evidence that TBI is associated with substantial changes in humoral immunity and cellular immunity, which may explain the high incidence of infection encountered in these patients.

  10. Repeatedly administered antidepressant drugs modulate humoral and cellular immune response in mice through action on macrophages

    PubMed Central

    Kozlowski, Michael; Bryniarski, Pawel; Strobel, Spencer; Bryk, Agata; Myszka, Michal; Tyszka, Anna; Kuszmiersz, Piotr; Nowakowski, Jaroslaw; Filipczak-Bryniarska, Iwona

    2016-01-01

    Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive

  11. Humoral fingerprinting of immune responses: “super-resolution”, high-dimensional serology

    PubMed Central

    Lau, William W.; Tsang, John S.

    2016-01-01

    In a recent study, Chung et al. report the development of a high-dimensional approach to assess humoral responses to immune perturbation that goes beyond antibody neutralization and titers. This approach enables the identification of potentially novel correlates and mechanisms of protective immunity to HIV vaccination, thus offering a glimpse of how dense phenotyping of serological responses coupled with bioinformatics analysis could lead to much-sought-after markers of protective vaccination responses. PMID:26830541

  12. Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus.

    PubMed

    Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter; Jensen, Trine Hammer; Jensen, Tove Dannemann; Aasted, Bent; Blixenkrone-Møller, Merete

    2009-07-30

    The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV. The DNA vaccine-induced immunity protected the natural host against disease development.

  13. Progressive multifocal leukoencephalopathy occurring with the acquired immune deficiency syndrome.

    PubMed

    England, J D; Hsu, C Y; Garen, P D; Goust, J M; Biggs, P J

    1984-08-01

    A 33-year-old homosexual man with symptoms and signs of a focal brain process was subsequently found to have an acquired immune deficiency syndrome (AIDS) with biopsy-proven progressive multifocal leukoencephalopathy. This report reemphasizes the association of progressive multifocal leukoencephalopathy with AIDS and probably is best viewed as another example of an opportunistic CNS infection complicating deficient cell-mediated immunity.

  14. Defining the humoral immune response to infectious agents using high-density protein microarrays

    PubMed Central

    Vigil, Adam; Davies, D Huw; Felgner, Philip L

    2010-01-01

    A major component of the adaptive immune response to infection is the generation of protective and long-lasting humoral immunity. Traditional approaches to understanding the host’s humoral immune response are unable to provide an integrated understanding of the antibody repertoire generated in response to infection. By studying multiple antigenic responses in parallel, we can learn more about the breadth and dynamics of the antibody response to infection. Measurement of antibody production following vaccination is also a gauge for efficacy, as generation of antibodies can protect from future infections and limit disease. Protein microarrays are well suited to identify, quantify and compare individual antigenic responses following exposure to infectious agents. This technology can be applied to the development of improved serodiagnostic tests, discovery of subunit vaccine antigen candidates, epidemiologic research and vaccine development, as well as providing novel insights into infectious disease and the immune system. In this review, we will discuss the use of protein microarrays as a powerful tool to define the humoral immune response to bacteria and viruses. PMID:20143947

  15. Influence of pathological progression on the balance between cellular and humoral immune responses in bovine tuberculosis

    PubMed Central

    Welsh, Michael D; Cunningham, Rodat T; Corbett, David M; Girvin, R Martyn; McNair, James; Skuce, Robin A; Bryson, David G; Pollock, John M

    2005-01-01

    Studies of tuberculosis have suggested a shift in dominance from a T helper type 1 (Th1) towards a Th2 immune response that is associated with suppressed cell-mediated immune (CMI) responses and increased humoral responses as the disease progresses. In this study a natural host disease model was used to investigate the balance of the evolving immune response towards Mycobacterium bovis infection in cattle with respect to pathogenesis. Cytokine analysis of CD4 T-cell clones derived from M. bovis-infected animals gave some indication that there was a possible relationship between enhanced pathogenesis and an increased ratio of Th0 [interleukin-4-positive/interferon-γ-positive (IL-4+/IFN-γ+)] clones to Th1 (IFN-γ+) clones. All animals developed strong antimycobacterial CMI responses, but depressed cellular responses were evident as the disease progressed, with the IFN-γ test failing to give consistently positive results in the latter stages. Furthermore, a stronger Th0 immune bias, depressed in vitro CMI responses, elevated levels of IL-10 expression and enhanced humoral responses were also associated with increased pathology. In minimal disease, however, a strong Th1 immune bias was maintained and an anti-M. bovis humoral response failed to develop. It was also seen that the level of the anti-M. bovis immunoglobulin G1 (IgG1) isotype antibody responses correlated with the pathology scores, whereas CMI responses did not have as strong a relationship with the development of pathology. Therefore, the development and maintenance of a Th1 IFN-γ response is associated with a greater control of M. bovis infection. Animals progressing from a Th1-biased to a Th0-biased immune response developed more extensive pathology and performed less well in CMI-based diagnostic tests but developed strong IgG1 humoral responses. PMID:15606800

  16. The humoral immune response induced by snake venom toxins.

    PubMed

    da Silva, Wilmar Dias; Tambourgi, Denise V

    2011-10-01

    This review summarizes the key contributions to our knowledge regarding the immune response induced by snake venom toxins, focusing particularly on the production of antibodies and their venom-neutralizing effects. We cover the past and present state of the art of anti-snake venom production, followed by an overview of the venomous snakes and their venoms. The toxic properties of relevant snake venom toxins are approached in some details, with particular emphasis on the molecular domains responsible for binding to cells or plasma components in victims. The interactions of these domains are also reviewed, particularly the putatively relevant epitopes, along with the immune system and the resulting antibodies. We also review trials aimed at reducing the quantities of non-relevant antibodies in the antivenoms by substituting whole venoms with purified toxins to immunize animals, or the immunogenicity of the heterologous antivenom antibodies by humanizing their molecules.

  17. Cellular and humoral immune abnormalities in Gulf War veterans.

    PubMed Central

    Vojdani, Aristo; Thrasher, Jack D

    2004-01-01

    We examined 100 symptomatic Gulf War veterans (patients) and 100 controls for immunologic assays. The veterans and controls were compared for the percentage of T cells (CD3); B cells (CD19); helper:suppressor (CD4:CD8) ratio; natural killer (NK) cell activity; mitogenic response to phytohemagglutin (PHA) and pokeweed mitogen (PWM); level of immune complexes; myelin basic protein (MBP) and striated and smooth muscle autoantibodies; and antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 (HSV-1), HSV-2, human herpes Type 6 (HHV-6), and Varicella zoster virus (VZV). The percentage of T cells in patients versus controls was not significantly different, whereas a significantly higher proportion of patients had elevated T cells compared with controls. The percentage of B cells was significantly elevated in the patients versus the controls. The NK cell (NK) activity was significantly decreased in the patients (24.8 +/- 16.5 lytic units) versus the controls (37.3 +/- 26.4 lytic units). The percentage of patients with lower than normal response to PHA and PWM was significantly different from controls. Immune complexes were significantly increased in the patients (53.1 +/- 18.6, mean +/- SD) versus controls (34.6 +/- 14.3). Autoantibody titers directed against MBP and striated or smooth muscle were significantly greater in patients versus controls. Finally, the patients had significantly greater titers of antibodies to the viruses compared with the controls (p < 0.001). These immune alterations were detected 2-8 years after participation in the Gulf War. The immune alterations are consistent with exposure to different environmental factors. We conclude that Gulf War syndrome is a multifaceted illness with immune function alterations that may be induced by various factors and are probably associated with chronic fatigue syndrome. PMID:15175170

  18. Passive transfer of naturally acquired specific immunity against West Nile Virus to foals in a semi-feral pony herd.

    PubMed

    Wilkins, Pamela A; Glaser, Amy L; McDonnell, Sue M

    2006-01-01

    Horses naturally exposed to West Nile Virus (WNV) or vaccinated against WNV develop humoral immunity thought to be protective against development of clinical disease in exposed or infected animals. No reports evaluate the efficacy of passive transfer of naturally acquired specific WNV humoral immunity from dam to foal. The purpose of this study was to investigate passive transfer of naturally acquired immunity to WNV to foals born in a herd of semi-feral ponies, not vaccinated against WNV, in an endemic area, with many dams having seroconverted because of natural exposure. Microwell serum neutralization titers against WNV were determined in all mares and foals. Serum IgG concentration was determined in foals by serial radial immunodiffusion. Differences in IgG concentration between seropositive and seronegative foals were examined by means of the Mann-Whitney U-test. Linear regression was used to evaluate the association between mare and foal titers. Seventeen mare-foal pairs were studied; 1 foal had inadequate IgG concentration. IgG concentration was not different between seronegative and seropositive foals (P = .24). Mare and foal titers were significantly correlated in foals with adequate passive transfer of immunity (Spearman's rho = .84; P < .001); >90% of the foal's titer was explained by the mare's titer (R2 = 0.91; P < .001). Passive transfer of specific immunity to WNV is present in pony foals with adequate passive transfer of immunity born to seroconverted mares.

  19. The effects of ochratoxin/aluminosilicate interaction on the tissues and humoral immune response of broilers.

    PubMed

    Santin, Elizabeth; Paulillo, Antonio C; Maiorka, Paulo C; Alessi, Antonio C; Krabbe, Everton L; Maiorka, Alex

    2002-02-01

    This study aimed to evaluate the effect of dietary ochratoxin, in the presence or absence of aluminosilicate, on the histology of the bursa of Fabricius, liver and kidneys, and on the humoral immune response of broilers vaccinated against Newcastle disease virus. The exposure of birds to 2 p.p.m. ochratoxin, in the presence or absence of aluminosilicate, reduced their humoral immune response and the number of mitotic cells in the bursa. The relative weight of the livers of the birds exposed to this toxin was increased and, microscopically, there was hepatocyte vacuolation and megalocytosis with accompanying hyperplasia of the biliary epithelium. The kidneys showed hypertrophy of the renal proximal tubular epithelium, with thickening of the glomerular basement membrane. Aluminosilicate did not ameliorate the deleterious effects of the ochratoxin.

  20. The Early Humoral Immune Response to Bacillus anthracis Toxins in Patients Infected with Cutaneous Anthrax

    DTIC Science & Technology

    2011-01-01

    RESEARCH ARTICLE The early humoral immune response to Bacillus anthracis toxins in patients infected with cutaneous anthrax Karen E. Brenneman 1•2...Editor: Patrick Brennan Keywords anthrax; lethal factor; edema factor; protective antigen. Introduction Abstract Bacillus anthracis, the...Anthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive spore-forming microorganism whose mani- festations in humans depend on the

  1. Effects of 60-Hz electric fields on specific humoral and cellular components of the immune system

    SciTech Connect

    Morris, J.E.; Phillips, R.D.

    1982-01-01

    Humoral and cellular functions of the immune system of Swiss-Webster mice were evaluated after exposure to 60-Hz electric fields at 100 kV/m. No significant differences were observed in primary antibody response to keyhole limpet hemocyanin (precipitating antibody levels) between exposed (30 or 60 days) and control mice, nor were there significant changes in mitogen-stimulation response of spleen cells from mice similarly exposed for 90 or 150 days when compared to sham-exposed animals.

  2. Effects of fenbendazole on the murine humoral immune system.

    PubMed

    Landin, Ana Marie; Frasca, Daniela; Zaias, Julia; Van der Put, Elaine; Riley, Richard L; Altman, Norman H; Blomberg, Bonnie B

    2009-05-01

    Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the experimental use of mice until at least 6 wk after treatment should be considered.

  3. Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria

    PubMed Central

    Zander, Ryan A.; Guthmiller, Jenna J.; Graham, Amy C.; Burke, Bradly E.; Carr, Daniel J.J.

    2016-01-01

    CD4 T cell-dependent antibody responses are essential for limiting Plasmodium parasite replication and the severity of malaria; however, the factors that regulate humoral immunity during highly inflammatory, Th1-biased systemic infections are poorly understood. Using genetic and biochemical approaches, we show that Plasmodium infection-induced type I interferons limit T follicular helper accumulation and constrain anti-malarial humoral immunity. Mechanistically we show that CD4 T cell-intrinsic type I interferon signaling induces T-bet and Blimp-1 expression, thereby promoting T regulatory 1 responses. We further show that the secreted effector cytokines of T regulatory 1 cells, IL-10 and IFN-γ, collaborate to restrict T follicular helper accumulation, limit parasite-specific antibody responses, and diminish parasite control. This circuit of interferon-mediated Blimp-1 induction is also operational during chronic virus infection and can occur independently of IL-2 signaling. Thus, type I interferon-mediated induction of Blimp-1 and subsequent expansion of T regulatory 1 cells represent generalizable features of systemic, inflammatory Th1-biased viral and parasitic infections that are associated with suppression of humoral immunity. PMID:27732671

  4. Humoral immune response to a recombinant hemoplasma antigen in experimental 'Candidatus Mycoplasma turicensis' infection.

    PubMed

    Novacco, Marilisa; Wolf-Jäckel, Godelind; Riond, Barbara; Hofmann-Lehmann, Regina

    2012-06-15

    'Candidatus Mycoplasma turicensis' is a feline hemoplasma species that was isolated in a cat with hemolytic anemia. PCR has been widely used to investigate and diagnose 'Candidatus Mycoplasma turicensis' infection, but so far, little is known about the humoral immune response in infected cats. Recently, enzyme-linked immunosorbent assays (ELISA) were developed to monitor anti-feline hemoplasma antibodies. The aim of the present study was to investigate the humoral immune response in cats experimentally infected with 'Candidatus Mycoplasma turicensis' and to monitor the influence of the pre-administration of methylprednisolone and subsequent antibiotic treatment. Serum and plasma samples from 15 specified pathogen-free cats infected with 'Candidatus Mycoplasma turicensis' were analyzed by ELISA. Seroconversion was demonstrated in all cats, and the antibodies remained detectable until the end of the study (up to 100 weeks post-exposure). In some cats, the ELISA seemed more sensitive and better able to demonstrate exposure to 'Candidatus Mycoplasma turicensis' than PCR. The peak antibody level occurred after the peak of the bacterial blood loads. The methylprednisolone administrations were associated with increased antibody levels, while antibiotic treatment, particularly with doxycycline, resulted in a decrease in antibody levels. Additionally, preliminary data indicated that three of four seropositive cats were protected from bacteremia after a subsequent challenge. In conclusion, the ELISA was found to be a useful tool to investigate the humoral immune response in hemoplasma-infected cats and a desirable addition to PCR to study the pathogenesis of hemoplasma infections.

  5. Humoral immune response to Bacteroides gingivalis fimbrial antigen in mice.

    PubMed Central

    Ogawa, T; Shimauchi, H; Kusumoto, Y; Hamada, S

    1990-01-01

    Bacteroides gingivalis fimbrial antigen incorporated into liposomes, but not in Tris-HCl buffer, significantly raised the levels of anti-fimbriae antibodies in serum, particularly of the IgG class, after oral primary and booster immunizations in BALB/c mice. An approximately linear relationship was observed between the dose of fimbrial antigen and the level of fimbriae-specific antibodies produced; antibody production reached its maximum at an immunization dosage of 500 micrograms of fimbriae per mouse. Fimbriae-specific antibody production was enhanced by use of a semi-synthetic adjuvant, a stearoyl derivative of sodium beta-N-acetylglucosaminyl-(1----4)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-(L) - stearoyl-(D)-meso-diamino-pimelic acid-(D)-amide-D-alanine (GM)-53) in liposomes. High anti-fimbriae antibody levels in serum and saliva were maintained for several months in the mice that had received two orally administered boosters of fimbrial antigen with GM-53 in liposomes. Salivary anti-fimbriae antibody levels, particularly of the IgA class, were markedly raised. PMID:1968885

  6. Cellular and humoral immunity in chronic equine laminitis.

    PubMed

    Steelman, Samantha M; Johnson, Daisy; Wagner, Bettina; Stokes, Ashleym; Chowdhary, Bhanu P

    2013-06-15

    Chronic equine laminitis causes persistent pain and lameness in affected animals and often necessitates euthanasia when pain management strategies become ineffective. Published studies as well as anecdotal reports suggest that this chronic inflammatory disease is associated with systemic alterations in immune responsiveness, perhaps involving an autoimmune component. We investigated this broad hypothesis by measuring a variety of immune indicators in healthy control horses (CON) and horses with chronic laminitis (LMN). We found that white blood cells from LMN horses produced more IFNγ than did cells from CON horses when stimulated in vitro with polyinosinic-polycytidylic acid [poly(I:C)], possibly due to an elevated number of circulating monocytes. No differences between groups were observed in plasma concentrations of IgG, IgA, IgM, IgE, or rheumatoid factor. Laminar tissue from LMN horses expressed elevated levels of keratinocyte damage-related genes as well as inflammatory cytokines and chemokines, which corresponded with a modest amount of neutrophil infiltration as shown by histological staining of fixed tissue and accumulation of neutrophil elastase protein. Taken together, our results do not support the hypothesis of an autoimmune component in chronic laminitis, although the strong induction of neutrophil chemokines and the presence of tissue neutrophils suggests that this cell type is likely involved in perpetuating the inflammation and tissue damage associated with this disease.

  7. Novel protein targets of the humoral immune response to Listeria monocytogenes infection in rabbits.

    PubMed

    Yu, Wei Ling; Dan, Hanhong; Lin, Min

    2007-07-01

    The role of the humoral immune response in protective immunity against listerial infection has been overlooked and is essentially unknown. This study aimed to discover the protein targets of Listeria monocytogenes that elicit an antibody response following infection in a rabbit model. A genomic expression library for L. monocytogenes was constructed and differentially screened to identify genes encoding proteins that reacted with antiserum from rabbits infected with live L. monocytogenes serotype 4b (RalphaL), but not with that from animals immunized with heat-killed bacteria (RalphaK). Thirty-one clones expressing proteins that reacted exclusively with RalphaL were identified and sequenced. Sequence analysis, together with Western blot analysis of the proteins expressed from positive clones, led to the identification of eight L. monocytogenes proteins as targets of humoral immune responses during listerial infection: three internalin members (InlA, InlD and InlC2) and five novel proteins of unknown function (designated IspA, IspB, IspC, IspD and IspE, respectively). Exhibition of humoral immune responses to these proteins in actively infected rabbits but not in animals receiving heat-killed L. monocytogenes suggested that they were induced or significantly upregulated in vivo during infection and thus are important in Listeria pathogenesis. With the exception of antibodies to InlA, this is the first demonstration of antibodies to the other seven proteins in infected hosts. These immunogenic proteins may be useful candidates for elucidation of the role of antibodies in protective immunity in the context of listerial infection, as well as potential targets for serodiagnostic reagents and vaccine and drug development.

  8. An Acquired Taste: Children's Perceptions of Humor and Teasing in Verbal Irony

    ERIC Educational Resources Information Center

    Pexman, Penny M.; Glenwright, Melanie; Krol, Andrea; James, Tammy

    2005-01-01

    Around 5 or 6 years of age, children begin to recognize that speakers who make ironic remarks do not believe what they literally say, but children of the same age do not show appreciation for the humor function of irony (Dews et al., 1996; Harris & Pexman, 2003). We investigated 7- to 10-year-old children's interpretations of verbal irony and…

  9. Teaching AIDS: A Resource Guide on Acquired Immune Deficiency Syndrome.

    ERIC Educational Resources Information Center

    Quackenbush, Marcia; Sargent, Pamela

    This document is a resource guide designed for teachers, youth leaders, and health educators as a practical and relevant approach to integrating information on Acquired Immune Deficiency Syndrome (AIDS) into their existing courses. The curriculum is written in language appropriate for teenagers, junior college students, and the young adult…

  10. CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses.

    PubMed

    Chevalier, Nina; Jarrossay, David; Ho, Edwin; Avery, Danielle T; Ma, Cindy S; Yu, Di; Sallusto, Federica; Tangye, Stuart G; Mackay, Charles R

    2011-05-15

    High expression of CXCR5 is one of the defining hallmarks of T follicular helper cells (T(FH)), a CD4 Th cell subset that promotes germinal center reactions and the selection and affinity maturation of B cells. CXCR5 is also expressed on 20-25% of peripheral blood human central memory CD4 T cells (T(CM)), although the definitive function of these cells is not fully understood. The constitutive expression of CXCR5 on T(FH) cells and a fraction of circulating T(CM) suggests that CXCR5(+) T(CM) may represent a specialized subset of memory-type T(FH) cells programmed for homing to follicles and providing B cell help. To verify this assumption, we analyzed this cell population and show its specialized function in supporting humoral immune responses. Compared with their CXCR5(-) T(CM) counterparts, CXCR5(+) T(CM) expressed high levels of the chemokine CXCL13 and efficiently induced plasma cell differentiation and Ig secretion. We found that the distinct B cell helper qualities of CXCR5(+) T(CM) were mainly due to high ICOS expression and pronounced responsiveness to ICOS ligand costimulation together with large IL-10 secretion. Furthermore, B cell helper attributes of CXCR5(+) T(CM) were almost exclusively acquired on cognate interaction with B cells, but not with dendritic cells. This implies that a preferential recruitment of circulating CXCR5(+) T(CM) to CXCL13-rich B cell follicles is required for the promotion of a quick and efficient protective secondary humoral immune response. Taken together, we propose that CXCR5(+) T(CM) represent a distinct memory cell subset specialized in supporting Ab-mediated immune responses.

  11. Humoral and cellular immunity in cosmonauts after the ISS missions

    NASA Astrophysics Data System (ADS)

    Rykova, M. P.; Antropova, E. N.; Larina, I. M.; Morukov, B. V.

    Spaceflight effects on the immune system were studied in 30 cosmonauts flown onto the International Space Station (ISS) for long- (125-195 d, n=15) and short-term (8-10 d, n=15) missions. Immunological investigations before launch and after landing were performed by using methods for quantitative and functional evaluation of the immunologically competent cells. Specific assays include: peripheral leukocyte distribution, natural killer (NK) cell cytotoxic activity, phagocytic activity of monocytes and granulocytes, proliferation of T-cells in response to a mitogen, levels of immunoglobulins IgA, IgM, IgG, virus-specific antibody and cytokine in serum. It was noticed that after long-term spaceflights the percentage of NK (CD3-/CD16+/CD56+) cells was significantly reduced compared with pre-flight data (p<0.05) and NK activity was suppressed by 20-85% as compared with pre-flight data in 12 out of 15 cosmonauts. T-lymphocyte activity was decreased by 25-39% as compared with pre-flight data in 5 out of 13 cosmonauts. However, the relative number of CD3+, CD4+ and CD8+ T-cells did not change. The functional activity of NK and T-cells decreased in some of the cosmonauts after short-term missions. On the other hand, a moderate trend upward of NK cytotoxic activity and proliferative activity of T-cells was observed in some individuals. Concentrations immunoglobulins (IgA, IgM, IgG) and levels of M and G antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes virus type 6 (HV6) in serum did not reveal significant changes after long- and short-term flights. Concentrations of cytokines (IL- 1β, IL-2, IL-4 and TNF- α) in serum changed in an apparently random manner as compared with values before long- and short-term missions. Despite the fact that many improvements have been made to the living conditions of aboard the ISS our investigations demonstrate the remarkable depression of the immunological function after the ISS missions

  12. The Role of B Cells and Humoral Immunity in Mycobacterium tuberculosis Infection

    PubMed Central

    Kozakiewicz, Lee; Phuah, Jiayao; Flynn, JoAnne

    2014-01-01

    Tuberculosis (TB) remains a serious threat to public health, causing 2 million deaths annually world-wide. The control of TB has been hindered by the requirement of long duration of treatment involving multiple chemotherapeutic agents, the increased susceptibility to Mycobacterium tuberculosis infection in the HIV-infected population, and the development of multi-drug resistant and extensively resistant strains of tubercle bacilli. An efficacious and cost-efficient way to control TB is the development of effective anti-TB vaccines. This measure requires thorough understanding of the immune response to M. tuberculosis. While the role of cell-mediated immunity in the development of protective immune response to the tubercle bacillus has been well established, the role of B cells in this process is not clearly understood. Emerging evidence suggests that B cells and humoral immunity can modulate the immune response to various intracellular pathogens, including M. tuberculosis. These lymphocytes form conspicuous aggregates in the lungs of tuberculous humans, non-human primates, and mice, which display features of germinal center B cells. In murine TB, it has been shown that B cells can regulate the level of granulomatous reaction, cytokine production, and the T cell response. This chapter discusses the potential mechanisms by which specific functions of B cells and humoral immunity can shape the immune response to intracellular pathogens in general, and to M. tuberculosis in particular. Knowledge of the B cell-mediated immune response to M. tuberculosis may lead to the design of novel strategies, including the development of effective vaccines, to better control TB. PMID:23468112

  13. Cellular and humoral local immune responses in sheep experimentally infected with Oestrus ovis (Diptera: Oestridae).

    PubMed

    Tabouret, Guillaume; Lacroux, Caroline; Andreoletti, Olivier; Bergeaud, Jean Paul; Hailu-Tolosa, Yacob; Hoste, Hervé; Prevot, Françoise; Grisez, Christelle; Dorchies, Philippe; Jacquiet, Philippe

    2003-01-01

    Cellular and humoral local responses were investigated following repetitive artificial Oestrus ovis infections in lambs. The presence of larvae induced a huge local recruitment of either leucocytes (T and B lymphocytes, macrophages) or granulocytes (eosinophils, mast cells and globule leucocytes). This cellular response was more pronounced in the ethmoid and sinus (development sites of second and third instar larvae) than in the septum or turbinates where first instar larvae migrate. Infected lambs produced Oestrus ovis specific IgG and IgA antibodies in their mucus. This local humoral response was mainly directed against larval salivary gland antigens and not against larval digestive tract antigens. Compared to the control animals, the sinusal mucosa of infected animals was extremely thickened and the epithelium exhibited hyperplasia, metaplasia and eosinophilic exocytosis. The possible roles of these local immune responses in the regulation of O. ovis larvae populations in sheep are discussed.

  14. Swiprosin-1/EFhd2 limits germinal center responses and humoral type 2 immunity.

    PubMed

    Brachs, Sebastian; Turqueti-Neves, Adriana; Stein, Merle; Reimer, Dorothea; Brachvogel, Bent; Bösl, Michael; Winkler, Thomas; Voehringer, David; Jäck, Hans-Martin; Mielenz, Dirk

    2014-11-01

    Activated B cells are selected for in germinal centers by regulation of their apoptosis. The Ca2+ -binding cytoskeletal adaptor protein Swiprosin-1/EFhd2 (EFhd2) can promote apoptosis in activated B cells. We therefore hypothesized that EFhd2 might limit humoral immunity by repressing both the germinal center reaction and the expected enhancement of immune responses in the absence of EFhd2. Here, we established EFhd2(-/-) mice on a C57BL/6 background, which revealed normal B- and T-cell development, basal Ab levels, and T-cell independent type 1, and T-cell independent type 2 responses. However, T cell-dependent immunization with sheep red blood cells and infection with the helminth Nippostrongylus brasiliensis (N.b) increased production of antibodies of multiple isotypes, as well as germinal center formation in EFhd2(-/-) mice. In addition, serum IgE levels and numbers of IgE+ plasma cells were strongly increased in EFhd2(-/-) mice, both after primary as well as after secondary N.b infection. Finally, mixed bone marrow chimeras unraveled an EFhd2-dependent B cell-intrinsic contribution to increased IgE plasma cell numbers in N.b-infected mice. Hence, we established a role for EFhd2 as a negative regulator of germinal center-dependent humoral type 2 immunity, with implications for the generation of IgE.

  15. The humoral immune response of the Tasmanian devil (Sarcophilus harrisii) against horse red blood cells.

    PubMed

    Kreiss, Alexandre; Wells, Barrie; Woods, Gregory M

    2009-07-15

    The Tasmanian devil (Sarcophilus harrisii) is under threat of extinction due to a fatal infectious neoplastic disease, named Devil Facial Tumour Disease. Tumours are transferred as allografts between animals and no effective immune response or host resistance to the disease has been detected, raising interest in the immune function of the species. To investigate whether Tasmanian devils had a competent humoral immune response, four devils were immunised with horse red blood cells (HRBC) either intraperitoneally or subcutaneously. Antibody responses were measured by direct and indirect haemagglutination assays for a period of up to 40 weeks. Primary responses were well defined, but secondary responses were prominent only in the devils immunised subcutaneously. All devils showed evidence for a memory antibody response following a booster given 32 weeks after the first injection and this was more evident with the subcutaneous route. Tasmanian devils tested were capable of mounting a humoral immune response against HRBC and the subcutaneous injection in the presence of the adjuvant Montanide was a safe and effective route.

  16. The Murine Humoral Immune Response to Hepatitis B Surface Antigen: Idiotype Network Pathways.

    NASA Astrophysics Data System (ADS)

    Schick, Michael Roy

    Recognition of a wide spectrum in disease outcomes following Hepatitis B Virus (HBV) infection has led to the suggestion that individual differences may be due to characteristics of the immune response. HBV, a hepatotropic virus, is not directly cytopathic to the host hepatocytes but the cellular damage which does not occur may be due to the host's own immune response. It is this variety in immune response capabilities following natural infection or vaccination which led to the present study in which the murine humoral immune response to hepatitis B surface antigen (HBsAg) was examined. Following immunization with purified HBsAg an anti-HBs response could be detected in 19 inbred strains of mice. The response, which varied among the strains, was linked to the major histocompatibility complex (MHC). Among high responders to HBsAg were two strains in which a poor response to a single epitope could be detected. Although quantitatively serum from these strains resembled serum from other high responders, there was a major difference in the qualitative aspects. Included within this study was the role of idotype networks within the murine anti-HBs response. By directly targeting HBsAg-specific B cells within the framework of an idiotype network by an Ab-2, it was possible to circumvent T cell-dependent regulation of an immune response. In each of five inbred strains of mice immunized with a polyclonal rabbit Ab-2 an Ab-3 population with HBsAg-specificity (Ab -1^') was induced. These mice were also immunized with HBsAg resulting in a higher anti-HBs response as compared to HBsAg immunization alone in all of the strains tested except for one. The response in this strain, normally a low responder to HBsAg, indicated that the mechanisms for genetic restriction of the anti -HBs response was still active, although it was not apparent during anti-Id immunization. The effects of an anti-Id on the murine antibody response to HBsAg may lead to insights on the presence of idiotype

  17. Cell-mediated and humoral immune responses in patients with localized juvenile periodontitis.

    PubMed

    Anil, S; Hari, S; Remani, P; Vijayakumar, T; Ankathil, R

    1990-03-01

    Cell-mediated and humoral immune responses were assessed in 21 patients with localized juvenile periodontitis (LJP), and in an equal number of control subjects. The cell-mediated immunity, assessed by enumeration of total rosette forming cells [TRFC] and high affinity rosette forming cells [HARFC], was found to be depressed in LJP patients compared to controls. Estimation of serum immunoglobulins G,A,M,D and E levels were done using single radial immunodiffusion. All the immunoglobulins except IgD were found to be elevated significantly in LJP patients. The defective immune response found in LJP patients may be the cause or effect of the disease process. Further investigations are necessary to determine whether these defects are genetically controlled.

  18. Humoral immune response of the small-spotted catshark, Scyliorhinus canicula.

    PubMed

    Crouch, Kathryn; Smith, Lauren E; Williams, Rebecca; Cao, Wei; Lee, Mike; Jensen, Allan; Dooley, Helen

    2013-05-01

    Cartilaginous fishes are the oldest group in which an adaptive immune system based on immunoglobulin-superfamily members is found. This manuscript compares humoral immune function in small-spotted catshark (Scyliorhinus canicula) with that described for spiny dogfish (Squalus acanthias), another member of the Squalomorphi superorder, and nurse shark, the model for humoral immunity in elasmobranchs and a member of the Galeomorphi superorder. Although small-spotted catshark and nurse shark are separated by over 200 million years we found that immunoglobulin isoforms are well conserved between the two species. However, the plasma protein profile of small-spotted catshark was most similar to that of spiny dogfish, with low levels of pentameric IgM, and IgNAR present as a multimer in plasma rather than a monomer. We show that an antigen-specific monomeric IgM response, with a profile similar to that described previously for nurse sharks, can be raised in small-spotted catshark. Lacking polyclonal or monoclonal antibody reagents for detecting catshark IgNAR we investigated phage-display and recombinant Fc-fusion protein expression as alternative methods to look for an antigen-specific response for this isotype. However, we could find no evidence of an antigen-specific IgNAR in the animals tested using either of these techniques. Thus, unlike nurse sharks where antigen-specific monomeric IgM and IgNAR appear together, it seems there may be a temporal or complete 'uncoupling' of these isotypes during a humoral response in the small-spotted catshark.

  19. Evaluation of encapsulated Newcastle disease virus liposomes using various phospholipids administered to improve chicken humoral immunity.

    PubMed

    Tseng, Li-Ping; Chiou, Chwei-Jang; Deng, Ming-Chung; Lin, Mei-Hsiu; Pan, Ryh-Nan; Huang, Yi-You; Liu, Der-Zen

    2009-11-01

    We propose the adjuvant effects of phospholipid liposome compositions using intranasal inoculation of a liposomal-Newcastle disease virus (NDV) vaccine in chickens. The immunogenicity of three liposome formulations was determined in chickens using the hemagglutination-inhibition (HI) test, nasal secretory immunoglobulin A and serum immunoglobulin A (IgG) antibody titers using the enzyme-linked immunosorbent assay. The immune response against NDV antigens was determined after immunization with neutral charged liposomes composed of egg phosphatidylcholine (EPC) (60 micromol), cholesterol (Chol) (15 micromol), and EPC-liposomes (EPC-Lip), which elicited strong systemic (serum) and local (nasal) humoral responses. However, the intranasal administration with cationic charged liposomes composed of EPC (30 micromol), stearylamine (SA) (15 micromol), Chol (15 micromol), and SA-liposomes (SA-Lip) induced poor humoral immune responses. Only the vaccine formulated with anionic charged liposomes composed of EPC (30 micromol), dipalmitoylphosphatidylserine (15 micromol), Chol (15 micromol), and phosphatidylserine-liposomes (PS-Lip) elicited the highest titers of HI antibodies. These are the first results to suggest that antigen delivery using EPC-Lip is very useful in enhancing antibody production at the mucosal site and in serum.

  20. NF-κB/Rel Proteins and the Humoral Immune Responses of Drosophila melanogaster

    PubMed Central

    Ganesan, Sandhya; Aggarwal, Kamna; Paquette, Nicholas; Silverman, Neal

    2011-01-01

    Nuclear Factor-κB (NF-κB)/Rel transcription factors form an integral part of innate immune defenses and are conserved throughout the animal kingdom. Studying the function, mechanism of activation and regulation of these factors is crucial for understanding host responses to microbial infections. The fruit fly Drosophila melanogaster has proved to be a valuable model system to study these evolutionarily conserved NF-κB mediated immune responses. Drosophila combats pathogens through humoral and cellular immune responses. These humoral responses are well characterized and are marked by the robust production of a battery of anti-microbial peptides. Two NF-κB signaling pathways, the Toll and the IMD pathways, are responsible for the induction of these antimicrobial peptides. Signal transduction in these pathways is strikingly similar to that in mammalian TLR pathways. In this chapter, we discuss in detail the molecular mechanisms of microbial recognition, signal transduction and NF-κB regulation, in both the Toll and the IMD pathways. Similarities and differences relative to their mammalian counterparts are discussed, and recent advances in our understanding of the intricate regulatory networks in these NF-κB signaling pathways are also highlighted. PMID:20852987

  1. Maternal antibody transfer can lead to suppression of humoral immunity in developing zebra finches (Taeniopygia guttata).

    PubMed

    Merrill, Loren; Grindstaff, Jennifer L

    2014-01-01

    Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female's plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring's humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipopolysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring's humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17-28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for the offspring.

  2. A novel mode of induction of the humoral innate immune response in Drosophila larvae

    PubMed Central

    Kenmoku, Hiroyuki

    2017-01-01

    ABSTRACT Drosophila adults have been utilized as a genetically tractable model organism to decipher the molecular mechanisms of humoral innate immune responses. In an effort to promote the utility of Drosophila larvae as an additional model system, in this study, we describe a novel aspect of an induction mechanism for innate immunity in these larvae. By using a fine tungsten needle created for manipulating semi-conductor devices, larvae were subjected to septic injury. However, although Toll pathway mutants were susceptible to infection with Gram-positive bacteria as had been shown for Drosophila adults, microbe clearance was not affected in the mutants. In addition, Drosophila larvae were found to be sensitive to mechanical stimuli with respect to the activation of a sterile humoral response. In particular, pinching with forceps to a degree that might cause minor damage to larval tissues could induce the expression of the antifungal peptide gene Drosomycin; notably, this induction was partially independent of the Toll and immune deficiency pathways. We therefore propose that Drosophila larvae might serve as a useful model to analyze the infectious and non-infectious inflammation that underlies various inflammatory diseases such as ischemia, atherosclerosis and cancer. PMID:28250052

  3. DNAk is a dominant epitope in the humoral immune response of channel catfish (Ictalurus punctatus) to Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination remains a viable alternative for bacterial disease protection in fish; however additional work is required to understand the mechanisms of adaptive immunity in the channel catfish. To assess the humoral immune response to Flavobacterium columnare; a group of channel catfish were first im...

  4. System-Wide Associations between DNA-Methylation, Gene Expression, and Humoral Immune Response to Influenza Vaccination

    PubMed Central

    Zimmermann, Michael T.; Oberg, Ann L.; Grill, Diane E.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; Kennedy, Richard B.; Poland, Gregory A.

    2016-01-01

    Failure to achieve a protected state after influenza vaccination is poorly understood but occurs commonly among aged populations experiencing greater immunosenescence. In order to better understand immune response in the elderly, we studied epigenetic and transcriptomic profiles and humoral immune response outcomes in 50–74 year old healthy participants. Associations between DNA methylation and gene expression reveal a system-wide regulation of immune-relevant functions, likely playing a role in regulating a participant’s propensity to respond to vaccination. Our findings show that sites of methylation regulation associated with humoral response to vaccination impact known cellular differentiation signaling and antigen presentation pathways. We performed our analysis using per-site and regionally average methylation levels, in addition to continuous or dichotomized outcome measures. The genes and molecular functions implicated by each analysis were compared, highlighting different aspects of the biologic mechanisms of immune response affected by differential methylation. Both cis-acting (within the gene or promoter) and trans-acting (enhancers and transcription factor binding sites) sites show significant associations with measures of humoral immunity. Specifically, we identified a group of CpGs that, when coordinately hypo-methylated, are associated with lower humoral immune response, and methylated with higher response. Additionally, CpGs that individually predict humoral immune responses are enriched for polycomb-group and FOXP2 transcription factor binding sites. The most robust associations implicate differential methylation affecting gene expression levels of genes with known roles in immunity (e.g. HLA-B and HLA-DQB2) and immunosenescence. We believe our data and analysis strategy highlight new and interesting epigenetic trends affecting humoral response to vaccination against influenza; one of the most common and impactful viral pathogens. PMID:27031986

  5. Hibernation is associated with depression of T-cell independent humoral immune responses in the 13-lined ground squirrel.

    PubMed

    Bouma, Hjalmar R; Henning, Robert H; Kroese, Frans G M; Carey, Hannah V

    2013-03-01

    Mammalian hibernation consists of periods of low metabolism and body temperature (torpor), interspersed by euthermic arousal periods. The function of both the innate and adaptive immune system is suppressed during hibernation. In this study, we analyzed the humoral adaptive immune response to a T-cell independent (TI-2) and a T-cell dependent (TD) antigen. Thirteen-lined ground squirrels were immunized in summer or during hibernation with either a TI-2 or TD antigen on day 0 and day 14. Blood was drawn on day 0, 7, 14, 21 and 28. Both types of antigens induced a significant rise in antibody titer in summer animals. Much to our surprise, however, only immunization with the TD antigen, and not with the TI-2 antigen induced a humoral response in hibernators. Flow cytometric analysis of CD4 (helper T-lymphocytes), CD8 (cytotoxic T-lymphocytes) and CD45RA (B-lymphocytes) in blood, spleen and lymph nodes ruled out massive apoptosis as explanation of the absent TI humoral response during hibernation. Rather, reduced TI-2 stimulation of B-lymphocytes, possibly due to lowered serum complement during torpor, may explain the reduced antibody production in response to a TI-2 antigen. These results demonstrate that hibernation diminishes the capacity to induce a TI-2 humoral immune response, while the capacity to induce a humoral response to a TD antigen is maintained.

  6. pH-sensitive carbonate apatite nanoparticles as DNA vaccine carriers enhance humoral and cellular immunity.

    PubMed

    He, Pan; Takeshima, Shin-nosuke; Tada, Seiichi; Akaike, Toshihiro; Ito, Yoshihiro; Aida, Yoko

    2014-10-29

    To demonstrate the potential of pH-sensitive carbonate apatite (CO₃Ap) nanoparticles as DNA vaccine carriers to enhance vaccination efficacy, we examined the humoral and cellular immune responses of C57BL/6 mice immunized with the plasmid expression vector pCI-neo encoding the full-length soluble ovalbumin (OVA) (pCI-neo-sOVA), pCI-neo-sOVA/CO₃Ap complexes, or pCI-neo/CO₃Ap complexes as a control. Mice immunized with a low dose of pCI-neo-sOVA-loaded CO₃Ap (10 μg) produced ex vivo splenocyte proliferation after stimulation with CD8 T-cell but not CD4 T-cell epitopes and a delayed-type-hypersensitivity reaction more efficiently than mice in the other groups. Furthermore, mice receiving this immunization generated the same levels of OVA-specific antibodies and interferon (IFN)-γ secretion after CD8 T-cell and CD4 T-cell epitope challenges as those in mice treated with 100 μg of free pCI-neo-sOVA, whereas mice injected with a high dose of pCI-neo-sOVA-loaded CO₃Ap (100 μg) or with control plasmids produced negligible levels of OVA-specific antibodies or IFN-γ. Therefore, our results showed that 10 μg of pCI-neo-sOVA delivered by CO₃Ap strongly elicited humoral and cellular immune responses. This study is the first to demonstrate the promising potential of CO₃Ap nanoparticles for DNA vaccine delivery.

  7. Effect of carotenoid β-cryptoxanthin on cellular and humoral immune response in rabbit.

    PubMed

    Ghodratizadeh, Soroush; Kanbak, Güngör; Beyramzadeh, Mojtaba; Dikmen, Zeliha Gunnur; Memarzadeh, Salar; Habibian, Reza

    2014-03-01

    Beta-cryptoxanthin (b-Cr) is a pro-vitamin A and one of the major carotenoids that can be commonly found in mammalian serum and tissues. Foods rich in certain fatty acids are known to be effective to gain a healthy immune system. In the present study, we evaluated the effect of b-Cr on rabbit humoral and cellular immune responses to have a better vision about the mechanism of effect of carotenoids on immune system. Twenty rabbits were randomly divided into five groups (4 per group): Groups consisted of: 1) control group (normal saline; 2) b-Cr (control); 3) vaccine control; 4) 5 mg/kg b-Cr o.p. + vaccine; 5) 10 mg/kg b-Cr o.p. + vaccine. Blood samples were obtained from the marginal ear artery at three time points: days 0, 14 and 21 of the study. Blood CD4+ and CD8+ lymphocytes and Serum Immunoglobulin and Cytokines content were evaluated. Results show that b-Cr administration increased the blood CD4+ lymphocytes count (P > 0.01). Serum IgG, IgM and IgA levels increased (P > 0.05) following b-Cr administration. b-Cr treatment increased serum IL-4 levels (P > 0.05). According to presented results, b-Cr may increase the humoral immunity in mammals. So, it would possible has a potentially beneficial effect on health and on prevention of the immunity related diseases.

  8. Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection.

    PubMed

    Elsner, Rebecca A; Hastey, Christine J; Olsen, Kimberly J; Baumgarth, Nicole

    2015-07-01

    Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host's ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long

  9. Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

    PubMed Central

    Makidon, Paul E.; Janczak, Katarzyna W.; Blanco, Luz P.; Swanson, Benjamin; Smith, Douglas M.; Pham, Tiffany; Szabo, Zsuzsanna; Kukowska-Latallo, Jolanta F.; Baker, James R.

    2014-01-01

    Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses. PMID:24532579

  10. Humoral immune response to an antigen from Porphyromonas gingivalis 381 in periodontal disease.

    PubMed Central

    Kurihara, H; Nishimura, F; Nakamura, T; Nakagawa, M; Tanimoto, I; Nomura, Y; Kokeguchi, S; Kato, K; Murayama, Y

    1991-01-01

    The humoral immune responses of patients with periodontitis were evaluated to characterize the host response to Porphyromonas gingivalis. A sonic extract of P. gingivalis 381 from whole cells was fractionated by gel chromatography and ion-exchange chromatography. The fractionated extracts were evaluated by Western blot (immunoblot) analyses with patient sera. A dominant antigen was identified from the sonic extract with an apparent molecular mass of 53 kDa. The 53-kDa protein antigen (Ag53) was purified by affinity chromatography by using a monoclonal antibody. Ag53 was detected on the vesicle surface of P. gingivalis 381 by immunoelectron microscopy by using the monoclonal antibody and was detected as a major protein in the outer membrane and in vesicles by Western blot analysis. Monoclonal antibody cross-reactivity to Ag53 in the sonic extracts of P. gingivalis ATCC 33277, P. gingivalis 1021, and Porphyromonas endodontalis ATCC 35406 was revealed. Seventy-seven patients with periodontitis were examined for their responses to Ag53. Serum immunoglobulin G (IgG) from 54 patients reacted strongly to Ag53; however, serum IgG from the remaining 23 patients did not exhibit detectable reactivity at all to Ag53, even though the patients had high serum IgG titers to the sonic extract. Ag53 is a new marker that represents an interesting aspect of the humoral immune response to P. gingivalis in patients with periodontitis. Images PMID:1855992

  11. Humoral immune response and coated or uncoated oxygenators during cardiopulmonary bypass surgery

    PubMed Central

    Karakisi, Sedat Ozan; Bozok, Şahin; Ergene, Şaban; İlhan, Gökhan; Karamustafa, Hakan; Tufekci, Nebiye; Kunt, Ayşe Gül; Şener, Erol; Çankaya, İdil; Kocakulak, Mustafa; Muşabak, Uğur; Sargon, Mustafa Fevzi

    2016-01-01

    Summary Aim: To investigate and compare uncoated and phosphorylcholine-coated oxygenators in terms of induction of humoral immune response during coronary artery bypass surgery. Methods: A total of 20 consecutive patients who underwent coronary artery bypass surgery were randomly distributed into two groups according to the type of oxygenator used during surgery. Group 1 consisted of 10 patients who were operated on using phosphorylcholine-coated oxygenators. Group 2 contained 10 patients who underwent surgery using uncoated oxygenators. Blood and oxygenator fibre samples were obtained and compared in terms of immunoglobulins (IgG, IgM), complements (C3c, C4), serum total protein and albumin levels using electron microscopy and flow cytometry. Results: In group 1, levels of IgM, IgG, total protein and serum albumin were significantly increased at the end of cardiopulmonary bypass (CPB) compared to those at the beginning of CPB. In group 2, C3c and C4 levels at the beginning of CPB were found to be significantly higher than at the end. Electron microscopic examination of oxygenator fibres demonstrated that phosphorylcholine-coated fibres were less likely to be adsorbed by serum proteins and complements than the uncoated fibres. Conclusion: Our results indicate that phosphorylcholine-coated oxygenators seemed to induce humoral immune response to a lesser extent than uncoated oxygenators during coronary artery bypass procedures. PMID:27841912

  12. Improvement influenza HA2 DNA vaccine cellular and humoral immune responses with Mx bio adjuvant.

    PubMed

    Soleimani, Sina; Shahsavandi, Shahla; Maddadgar, Omid

    2017-03-01

    Immunization with DNA vaccines as a novel alternative to conventional vaccination strategy requires adjuvant for improving vaccine efficacy. The conserved immunogenic HA2 subunit, which harbors neutralizing epitopes is a promising vaccine candidate against influenza viruses. In this study, for the first time we explore the idea of using host interferon inducible Mx protein to increase the immunogenicity of HA2 H9N2 influenza DNA vaccine. The potency and safety of the Mx adjuvanted-HA2 vaccine was evaluated in BALB/c mice by different prime-boost strategies. To assess the effect of the vaccination on the virus clearance rate, mice were challenged with homologous influenza virus. Administration of the adjuvanted vaccine and boosting with the same regimen could effectively enhance both humoral and cellular immune responses in treated mice. These data demonstrated that Mx as host defense peptide can be potentiated for improving influenza vaccine efficacy.

  13. What are the commonalities governing the behavior of humoral immune recognitive repertoires?

    PubMed

    Cohn, Melvin

    2006-01-01

    The humoral repertoire of immune systems is large, random and somatically selected. It is derived from a germline selected repertoire by a variety of diversification mechanisms, complementation of subunits, mutation and gene conversion. However derived, the end-product must be able to recognize and rid a vast variety of pathogens. This is accomplished by viewing antigens as combinatorials of epitopes, an astuce that permits a small repertoire to respond sufficiently rapidly to a vast antigenic universe. A somatically generated repertoire, however, requires a solution to two problems. First, a somatic mechanism for a self-nonself discrimination has to be put in place. Second, the repertoire has to be coupled to the effector mechanisms in a coherent fashion. The rules governing these two mechanisms are species-independent and delineate the parameters of all immune repertoires, whatever the somatic mechanism used to generate them.

  14. Heterogeneity in cellular and humoral immune responses against Toxoplasma gondii antigen in humans

    PubMed Central

    FATOOHI, A F; COZON, G J N; GONZALO, P; MAYENCON, M; GREENLAND, T; PICOT, S; PEYRON, F

    2004-01-01

    Protection against Toxoplasma gondii in infected patients is mainly attributed to cellular immunity. We here attempt to improve the characterization of the proteins that induce cellular immunity in naturally infected patients. Cellular immunity was evaluated by flow cytometry after 7 days of blood culture from 31 chronically T. gondii infected and 8 noninfected pregnant women, in the presence of soluble T. gondii antigen (ST-Ag) or fractionated proteins from ST-Ag, separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Blood cultures from infected patients with ST-Ag induced 39·5 ± 12·7% of activated (CD25+) CD4+ T cells using flow cytometry. This contrasts with the absence of activated CD4+ T cells after either culture with PBS or in blood cultures from noninfected women. The protein fraction between 21 and 41·9 kD induced the highest response (14·7 ± 10·0%). Blood samples from 20 infected and 5 uninfected women were cultured in presence of 12 protein subfractions of 2–208 kD. The highest frequencies of response among infected patients were seen with fractions (Fr) 26–31·9 kD (C.I. 85–100%) and Fr 32–36·9 kD (C.I. 77–100%). Although we note a good concordance between cellular and humoral response, Western blot analysis of ST-Ag does not completely predict the panel of proteins recognized by cellular immunity. Two-dimensional separation of the ST-Ag revealed more than 200 protein spots in these fractions. However, only two proteins in the 20–40 kD range induced a significant humoral response. Further studies are necessary to determine which proteins in the Fr 26–31·9 kD and 32–36·9 kD are superior immunogens for cellular responses. PMID:15147357

  15. Heterogeneity in cellular and humoral immune responses against Toxoplasma gondii antigen in humans.

    PubMed

    Fatoohi, A F; Cozon, G J N; Gonzalo, P; Mayencon, M; Greenland, T; Picot, S; Peyron, F

    2004-06-01

    Protection against Toxoplasma gondii in infected patients is mainly attributed to cellular immunity. We here attempt to improve the characterization of the proteins that induce cellular immunity in naturally infected patients. Cellular immunity was evaluated by flow cytometry after 7 days of blood culture from 31 chronically T. gondii infected and 8 noninfected pregnant women, in the presence of soluble T. gondii antigen (ST-Ag) or fractionated proteins from ST-Ag, separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Blood cultures from infected patients with ST-Ag induced 39.5 +/- 12.7% of activated (CD25+) CD4+ T cells using flow cytometry. This contrasts with the absence of activated CD4+ T cells after either culture with PBS or in blood cultures from noninfected women. The protein fraction between 21 and 41.9 kD induced the highest response (14.7 +/- 10.0%). Blood samples from 20 infected and 5 uninfected women were cultured in presence of 12 protein subfractions of 2-208 kD. The highest frequencies of response among infected patients were seen with fractions (Fr) 26-31.9 kD (C.I. 85-100%) and Fr 32-36.9 kD (C.I. 77-100%). Although we note a good concordance between cellular and humoral response, Western blot analysis of ST-Ag does not completely predict the panel of proteins recognized by cellular immunity. Two-dimensional separation of the ST-Ag revealed more than 200 protein spots in these fractions. However, only two proteins in the 20-40 kD range induced a significant humoral response. Further studies are necessary to determine which proteins in the Fr 26-31.9 kD and 32-36.9 kD are superior immunogens for cellular responses.

  16. Searching for the cause of the acquired immune deficiency syndrome.

    PubMed

    Leavitt, R D

    1984-02-01

    An outbreak of unexplained immune deficiency associated with opportunistic infection and Kaposi's sarcoma is occurring in the USA and other parts of the world. Affected individuals with what had come to be known as the acquired immune deficiency syndrome (AIDS) have a high mortality. Epidemiological features suggest the presence of a transmissable agent, but no responsible agent has yet been identified. Homosexual and bisexual men make up 75% of these affected individuals. Cytomegalovirus, Epstein Barr and herpes simplex viruses, organisms that commonly affect male homosexuals, may produce some features of AIDS. Individually or collectively, however, they can not account for the emergence of a previously unrecognized clinical syndrome. Hepatitis B is prevalent in patients with AIDS and may play a role as a co-factor in the disease. The properties of a number of other known viruses may provide a model for the pathogenesis of some features of the AIDS immunodeficiency. Newly described simian acquired immune deficiency syndrome (SAIDS) is the best available animal model. In man, the retrovirus, human T-cell leukemia virus (HTLV) may play a role in AIDS. However, HTLV or any other known virus cannot yet be assumed to cause AIDS. It is likely that an as yet unrecognized agent is the key causative agent of AIDS.

  17. Effect of nanovaccine chemistry on humoral immune response kinetics and maturation

    NASA Astrophysics Data System (ADS)

    Haughney, Shannon L.; Ross, Kathleen A.; Boggiatto, Paola M.; Wannemuehler, Michael J.; Narasimhan, Balaji

    2014-10-01

    Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry facilitated differential kinetics of development of antibody titers, avidity, and epitope specificity. The results provide new insights into the underlying role(s) of nanoparticle chemistry in providing long-lived humoral immunity and aid in the rational design of nanovaccine formulations to induce long-lasting and mature antibody responses.Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry

  18. Humoral and cellular immune responses after influenza vaccination in patients with postcancer fatigue

    PubMed Central

    Prinsen, Hetty; van Laarhoven, Hanneke WM; Pots, Jeanette M; Duiveman-de Boer, Tjitske; Mulder, Sasja F; van Herpen, Carla ML; Jacobs, Joannes FM; Leer, Jan Willem H; Bleijenberg, Gijs; Stelma, Foekje F; Torensma, Ruurd; de Vries, I Jolanda M

    2015-01-01

    The aim of this study was to compare humoral and cellular immune responses to influenza vaccination in cancer survivors with and without severe symptoms of fatigue. Severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer survivors were vaccinated against seasonal influenza. Humoral immunity was evaluated at baseline and post-vaccination by a hemagglutination inhibition assay. Cellular immunity was evaluated at baseline and post-vaccination by lymphocyte proliferation and activation assays. Regulatory T cells were measured at baseline by flow cytometry and heat-shock protein 90 alpha levels by ELISA. Comparable humoral immune responses were observed in fatigued and non-fatigued patients, both pre- and post-vaccination. At baseline, fatigued patients showed a significantly diminished cellular proliferation upon virus stimulation with strain H3N2 (1414 ± 1201 counts), and a trend in a similar direction with strain H1N1 (3025 ± 2339 counts), compared to non-fatigued patients (3099 ± 2401 and 5877 ± 4604 counts, respectively). The percentage of regulatory T lymphocytes was significantly increased (4.4 ± 2.1% versus 2.4 ± 0.8%) and significantly lower amounts of interleukin 2 were detected prior to vaccination in fatigued compared to non-fatigued patients (36.3 ± 44.3 pg/ml vs. 94.0 ± 45.4 pg/ml with strain H3N2 and 28.4 ± 44.0 pg/ml versus 74.5 ± 56.1 pg/ml with strain H1N1). Pre-vaccination heat-shock protein 90 alpha concentrations, post-vaccination cellular proliferation, and post-vaccination cytokine concentrations did not differ between both groups. In conclusion, influenza vaccination is favorable for severely fatigued cancer survivors and should be recommended when indicated. However, compared to non-fatigued cancer survivors, fatigued cancer survivors showed several significant differences in immunological reactivity at baseline, which warrants further investigation. PMID:25996472

  19. Humoral and cellular immune responses after influenza vaccination in patients with postcancer fatigue.

    PubMed

    Prinsen, Hetty; van Laarhoven, Hanneke W M; Pots, Jeanette M; Duiveman-de Boer, Tjitske; Mulder, Sasja F; van Herpen, Carla M L; Jacobs, Joannes F M; Leer, Jan Willem H; Bleijenberg, Gijs; Stelma, Foekje F; Torensma, Ruurd; de Vries, I Jolanda M

    2015-01-01

    The aim of this study was to compare humoral and cellular immune responses to influenza vaccination in cancer survivors with and without severe symptoms of fatigue. Severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer survivors were vaccinated against seasonal influenza. Humoral immunity was evaluated at baseline and post-vaccination by a hemagglutination inhibition assay. Cellular immunity was evaluated at baseline and post-vaccination by lymphocyte proliferation and activation assays. Regulatory T cells were measured at baseline by flow cytometry and heat-shock protein 90 alpha levels by ELISA. Comparable humoral immune responses were observed in fatigued and non-fatigued patients, both pre- and post-vaccination. At baseline, fatigued patients showed a significantly diminished cellular proliferation upon virus stimulation with strain H3N2 (1414 ± 1201 counts), and a trend in a similar direction with strain H1N1 (3025 ± 2339 counts), compared to non-fatigued patients (3099 ± 2401 and 5877 ± 4604 counts, respectively). The percentage of regulatory T lymphocytes was significantly increased (4.4 ± 2.1% versus 2.4 ± 0.8%) and significantly lower amounts of interleukin 2 were detected prior to vaccination in fatigued compared to non-fatigued patients (36.3 ± 44.3 pg/ml vs. 94.0 ± 45.4 pg/ml with strain H3N2 and 28.4 ± 44.0 pg/ml versus 74.5 ± 56.1 pg/ml with strain H1N1). Pre-vaccination heat-shock protein 90 alpha concentrations, post-vaccination cellular proliferation, and post-vaccination cytokine concentrations did not differ between both groups. In conclusion, influenza vaccination is favorable for severely fatigued cancer survivors and should be recommended when indicated. However, compared to non-fatigued cancer survivors, fatigued cancer survivors showed several significant differences in immunological reactivity at baseline, which warrants further investigation.

  20. Humoral and cellular immune responses to influenza vaccination in children with cancer receiving chemotherapy

    PubMed Central

    WONG-CHEW, ROSA MARÍA; FRÍAS, MARGARITA NAVA; GARCÍA-LEÓN, MIGUEL LEONARDO; ARRIAGA-PIZANO, LOURDES; SANSON, AURORA MEDINA; LOPEZ-MACÍAS, CONSTANTINO; ISIBASI, ARMANDO; SANTOS-PRECIADO, JOSÉ IGNACIO

    2012-01-01

    The immune response to influenza vaccination in children with cancer is controversial. The objective of this study was to characterize the cellular and humoral immune responses to an influenza vaccine in children with cancer who were receiving chemotherapy. In this study, children with cancer, who were not previously immunized, received an influenza vaccine via intramuscular injection. Blood samples were obtained prior to and at 4 weeks after immunization. Antibodies were measured using a hemagglutination inhibition (HI) assay. Cell-mediated immunity was measured by specific lymphoproliferation with 3H-thymidine incorporation and by measuring cell frequencies following staining with monoclonal antibodies (CD8, CD4, CD19, CD45RA and CD27) using flow cytometry following incubation with the influenza antigen for 5 days. Geometric mean titers (GMT), mean counts per minute (cpm), cell frequencies prior to and following vaccination and percentage patient responses were compared using the Mann-Whitney non-parametric U and Chi-square tests; where p<0.05 was considered to indicate a statistically significant result. A total of 56 children were included. Their mean age was 6.64±3.61 years. Acute lymphoblastic leukemia (ALL) was diagnosed in 75, solid tumors in 23 and lymphoma in 2% of the children. Subjects with titers ≥40 hemagglutination units (HU) increased from 43% prior to vaccination to 73% following vaccination (p=0.01), whereas the GMT increased from 31.35 [95% confidence interval (CI), 29–111] to 143.45 HU (95% CI, 284–640) following vaccination (p<0.001). An increase in CD45RA expression in CD8+ T cells was observed following vaccination (p=0.01). An increase in CD27 expression was observed in the CD4/8-negative cell population stimulated with the influenza antigen following vaccination (p<0.05). No serious adverse effects were observed. An increase in the seropositivity rate and GMT values following influenza vaccination were also observed. Influenza

  1. Modulation of host immunity and reproduction by horizontally acquired Wolbachia.

    PubMed

    Pigeault, Romain; Braquart-Varnier, Christine; Marcadé, Isabelle; Mappa, Gaëtan; Mottin, Elmina; Sicard, Mathieu

    2014-11-01

    The Wolbachia are symbiotic bacteria vertically transmitted from one host generation to another. However, a growing amount of data shows that horizontal transfers of Wolbachia also frequently occur within and between host species. The consequences of the arrival of new symbionts on host physiology can be studied by their experimental introduction in asymbiotic hosts. After experimental transfers of the eight major isopod Wolbachia strains in the isopod Porcellio dilatatus only two of them (wCon and wDil) were found to (1) have no pathogenic effect on the host and (2) be able to pass vertically to the host offspring. In the present work, we studied the influence of these two strains, able to complete an horizontal transfer, on immunity and reproduction of P. dilatatus at two stages of the transfer: (1) in recipient hosts that encounter the symbionts: to test the influence of symbiont when acquired during host life and (2) in vertically infected offspring: to test the influence of a symbiotic interaction occurring all lifelong. The impact of Wolbachia varied depending on the stage: there were clearer effects in vertically infected individuals than in those that acquired the symbionts during their lives. Moreover, the two Wolbachia strains showed contrasted effects: the strain wCon tended to reduce the reproductive investment but to maintain or increase immune parameters whilst wDil had positive effects on reproductive investment but decreased the investment in some immune parameters. These results suggest that horizontally acquisition of Wolbachia can influence the balance between host immune and reproductive traits.

  2. Alteration of antioxidant defense status precedes humoral immune response abnormalities in macrosomia

    PubMed Central

    Haddouche, Mustapha; Aribi, Mourad; Moulessehoul, Soraya; Smahi, Mohammed Chems-Eddine Ismet; Lammani, Mohammed; Benyoucef, Mohammed

    2011-01-01

    Summary Background This study aimed to investigate whether the anomalies affecting the antioxidant and humoral immune defenses could start at birth and to check whether the decrease in antioxidant defenses may precede the immune abnormalities in macrosomic newborns. Material/Methods Thirty macrosomic and 30 sex-matched control newborns were recruited for a retrospective case-control study at the Maghnia Maternity Hospital of Tlemcen Department (Algeria). Results The serum IgG levels were similar in both groups. However, plasma ORAC, albumin, vitamin E, SOD, CAT and GSH-Px levels were significantly decreased in macrosomic as compared to control newborns, yet no difference was observed after adjustment for weight. Additionally, serum concentrations of complement C3, MDA and XO were significantly higher in macrosomic as compared to controls before adjustment for weight. Moreover, macrosomia was significantly associated with high levels of complement C3 (OR=8, p=0.002); whereas no association with those of IgG was observed (OR<1, p>0.05). Furthermore, macrosomia was significantly associated with low levels of ORAC (OR=4.96, p=0.027), vitamin E (OR=4.5, p=0.018), SOD (OR=6.88, p=0.020) and CAT (OR=5.67, p=0.017), and with high levels of MDA (OR=10.29, p=0.005). Conclusions Abnormalities of the humoral defense system in excessive weight could be preceded by alterations of the anti-oxidative defense and by inflammatory response and activation of innate immunity at birth. Additionally, excessive weight could be a potential factor contributing to decreased anti-oxidative capacity and increased oxidative stress. PMID:22037745

  3. Effect of nanovaccine chemistry on humoral immune response kinetics and maturation.

    PubMed

    Haughney, Shannon L; Ross, Kathleen A; Boggiatto, Paola M; Wannemuehler, Michael J; Narasimhan, Balaji

    2014-11-21

    Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry facilitated differential kinetics of development of antibody titers, avidity, and epitope specificity. The results provide new insights into the underlying role(s) of nanoparticle chemistry in providing long-lived humoral immunity and aid in the rational design of nanovaccine formulations to induce long-lasting and mature antibody responses.

  4. Transcutaneous DNA immunization following waxing-based hair depilation elicits both humoral and cellular immune responses

    PubMed Central

    Xiao, Gang; Li, Xinran; Kumar, Amit; Cui, Zhengrong

    2012-01-01

    Previously, we showed that transcutaneous (TC) DNA immunization by applying plasmid DNA onto a mouse skin area wherein the hair follicles were induced into growth stage by plucking the hair using warm waxing induced strong and functional antigen-specific antibody responses. In the present study, using plasmids that encode β-galactosidase gene or ovalbumin (OVA) gene, we showed that this mode of TC DNA immunization not only induced specific antibody responses, but also induced antigen-specific cytotoxic T lymphocyte responses. In fact, TC DNA immunization using a plasmid that encodes OVA gene prevented the growth of OVA-expressing B16-OVA tumor cells in the immunized mice. Moreover, we provided additional evidence supporting that hair follicles are essential for this mode of TC DNA immunization. PMID:22771558

  5. Plasmodium vivax Pre-Erythrocytic–Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses

    PubMed Central

    Molina, Douglas M.; Finney, Olivia C.; Arevalo-Herrera, Myriam; Herrera, Socrates; Felgner, Philip L.; Gardner, Malcolm J.; Liang, Xiaowu; Wang, Ruobing

    2012-01-01

    The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy− individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic–stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy− donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria. PMID:22826492

  6. The humoral response in TCR alpha-/- mice. Can gammadelta-T cells support the humoral immune response?

    PubMed

    Lindroth, K; Troye-Blomberg, M; Singh, M; Dieli, F; Ivanyi, J; Fernández, C

    2002-03-01

    An optimal humoral response requires T-cell help; however, it has been questioned if this help comes exclusively from alphabeta-T cells or whether gammadelta-T cells also contribute. We have attempted to answer this question by studying the humoral response in T-cell receptor alpha-chain knockout (alpha-/-) mice, which lack the alphabetaT cell subset. Two model antigens were used to characterize the response: the thymus-independent (TI) antigen native dextran B512 (Dx), and the thymus-dependent (TD) antigen heat shock protein (HSP65) from Mycobacterium tuberculosis. When challenged with Dx, the alpha-/- mice elicited a strong antibody response and formed rudimentary germinal centres (GCs), a T-cell dependent reaction. In contrast, the humoral response to HSP65 was poor. However, alpha-/- mice became primed when challenged with HSP65, because when supplemented with wild-type thymocytes, the antigen-primed animals were able to mount a stronger response than the nonprimed ones when challenged with HSP65. A crucial step seems to be the collaboration between gammadeltaT cells and antigen presenting cells (APCs), as splenocytes from alpha-/- mice were able to respond to HSP65 in an environment containing primed-APCs. Based on these results, we propose a model for B-cell activation in the alpha-/- mice.

  7. Acquired TTP: ADAMTS13 meets the immune system.

    PubMed

    Verbij, Fabian C; Fijnheer, Rob; Voorberg, Jan; Sorvillo, Nicoletta

    2014-11-01

    The majority of the patients affected by acquired thrombotic thrombocytopenic purpura (TTP) develop autoantibodies directed towards ADAMTS13 that interfere with its von Willebrand Factor (VWF) processing activity. B cell responses have been shown to primarily target the spacer domain of ADAMTS13 thereby prohibiting the binding of ADAMTS13 to the VWF A2 domain. In this review we summarize recent knowledge gained on the immune recognition and processing of ADAMTS13 by antigen-presenting cells (APCs). HLA-DRB1*11 has been identified as a risk factor for acquired TTP. Analysis of MHC class II/peptide complexes of ADAMTS13 pulsed dendritic cells have shown that the CUB2 domain derived peptide FINVAPHAR is preferentially presented on HLA-DRB1*11. Based on these findings we propose a model for the initiation of the autoimmune reactivity against ADAMTS13 in previously healthy individuals. We hypothesize that mimicry between a pathogen-derived peptide and the CUB2 derived FINVAPHAR-peptide might contribute to the onset of acquired TTP.

  8. Interaction of menstrual cycle phase and sexual activity predicts mucosal and systemic humoral immunity in healthy women.

    PubMed

    Lorenz, Tierney K; Demas, Gregory E; Heiman, Julia R

    2015-12-01

    Several studies have documented shifts in humoral immune parameters (e.g., immunoglobulins) across the menstrual cycle in healthy women. It is thought that these shifts may reflect dynamic balancing between reproduction and pathogen defense, as certain aspects of humoral immunity may disrupt conception and may be temporarily downregulated at ovulation. If so, one could expect maximal cycle-related shifts of humoral immunity in individuals invested in reproduction - that is, women who are currently sexually active - and less pronounced shifts in women who are not reproductively active (i.e., abstinent). We investigated the interaction of sexual activity, menstrual cycle phase, and humoral immunity in a sample of 32 healthy premenopausal women (15 sexually active, 17 abstinent). Participants provided saliva samples during their menses, follicular phase, ovulation (as indicated by urine test for LH surge), and luteal phase, from which IgA was assayed. Participants also provided blood samples at menses and ovulation, from which IgG was assayed. Sexually active participants provided records of their frequency of sexual activity as well as condom use. At ovulation, sexually active women had higher IgG than abstinent women (d=0.77), with women reporting regular condom use showing larger effects (d=0.63) than women reporting no condom use (d=0.11). Frequency of sexual activity predicted changes in IgA (Cohen's f(2)=0.25), with women reporting high frequency of sexual activity showing a decrease in IgA at ovulation, while women reporting low frequency or no sexual activity showing an increase in IgA at ovulation. Taken together, these findings support the hypothesis that shifts in humoral immunity across the menstrual cycle are associated with reproductive effort, and could contribute to the mechanisms by which women's physiology navigates tradeoffs between reproduction and immunity.

  9. Effect of humoral immunity on HIV-1 dynamics with virus-to-target and infected-to-target infections

    NASA Astrophysics Data System (ADS)

    Elaiw, A. M.; Raezah, A. A.; Alofi, A. S.

    2016-08-01

    We consider an HIV-1 dynamics model by incorporating (i) two routes of infection via, respectively, binding of a virus to a receptor on the surface of a target cell to start genetic reactions (virus-to-target infection), and the direct transmission from infected cells to uninfected cells through the concept of virological synapse in vivo (infected-to-target infection); (ii) two types of distributed-time delays to describe the time between the virus or infected cell contacts an uninfected CD4+ T cell and the emission of new active viruses; (iii) humoral immune response, where the HIV-1 particles are attacked by the antibodies that are produced from the B lymphocytes. The existence and stability of all steady states are completely established by two bifurcation parameters, R 0 (the basic reproduction number) and R 1 (the viral reproduction number at the chronic-infection steady state without humoral immune response). By constructing Lyapunov functionals and using LaSalle's invariance principle, we have proven that, if R 0 ≤ 1 , then the infection-free steady state is globally asymptotically stable, if R 1 ≤ 1 < R 0 , then the chronic-infection steady state without humoral immune response is globally asymptotically stable, and if R 1 > 1 , then the chronic-infection steady state with humoral immune response is globally asymptotically stable. We have performed numerical simulations to confirm our theoretical results.

  10. Impact of the blood meal on humoral immunity and microbiota in the gut of female Culicoides sonorensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although Culicoides sonorensis is an important vector of orbiviruses that cause significant disease in domestic and wild ruminants in the USA, little is known about factors contributing to midge vector competence. In other vectors such as mosquitoes, interactions between the humoral immune response,...

  11. [The humoral and cell-mediated immune response induced by the NIVGRIP inactivated influenza vaccine].

    PubMed

    Mihail, A; Steiner, N; Berca, C; Jucu, V; Muşat, G

    1988-01-01

    A comparative study was conducted in patients vaccinated with the NIVGRIP trivalent inactivated influenza vaccine and in placebo receiving controls on the kinetics of the serum hemagglutination inhibiting (HAI) antibodies and the neutralizing secretory antibodies in the nasopharyngeal secretions (NPS), of the blastic transformation of lymphocytes index, of the rosette formation index and of the serum immunoglobulins. A significant rise of the H.A.I. and the neutralizing secretory antibodies as well as of the blastic transformation of lymphocytes index was recorded after stimulation with the influenza vaccine. There were no significant changes in controls. No significant variations of the blastic transformation of lymphocytes index after stimulation with P.P.D. and of the rosette formation index were recorded in both investigated groups. Serum immunoglobulin titres showed significant variations in vaccinated as well as in control groups. The results point out the stimulating effect of the NIVGRIP inactivated influenza vaccine on both humoral and cell mediated immune responses.

  12. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients.

    PubMed

    Cho, Michael Jeffrey; Lo, Agnes S Y; Mao, Xuming; Nagler, Arielle R; Ellebrecht, Christoph T; Mukherjee, Eric M; Hammers, Christoph M; Choi, Eun-Jung; Sharma, Preety M; Uduman, Mohamed; Li, Hong; Rux, Ann H; Farber, Sara A; Rubin, Courtney B; Kleinstein, Steven H; Sachais, Bruce S; Posner, Marshall R; Cavacini, Lisa A; Payne, Aimee S

    2014-06-19

    Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies (autoAbs) against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3 antibodies (Abs) from four PV patients and identify pathogenic VH1-46 autoAbs from all four patients. Unexpectedly, VH1-46 autoAbs had relatively few replacement mutations. We reverted antibody somatic mutations to their germline sequences to determine the requirement of mutations for autoreactivity. Three of five VH1-46 germline-reverted Abs maintain Dsg3 binding, compared with zero of five non-VH1-46 germline-reverted Abs. Site-directed mutagenesis of VH1-46 Abs demonstrates that acidic amino-acid residues introduced by somatic mutation or heavy chain VDJ recombination are necessary and sufficient for Dsg3 binding. Our data suggest that VH1-46 autoantibody gene usage is commonly found in PV because VH1-46 Abs require few to no mutations to acquire Dsg3 autoreactivity, which may favour their early selection. Common VH gene usage indicates common humoral immune responses, even among unrelated patients.

  13. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients

    PubMed Central

    Cho, Michael Jeffrey; Lo, Agnes S.Y.; Mao, Xuming; Nagler, Arielle R.; Ellebrecht, Christoph T.; Mukherjee, Eric M.; Hammers, Christoph M.; Choi, Eun-Jung; Sharma, Preety M.; Uduman, Mohamed; Li, Hong; Rux, Ann H.; Farber, Sara A.; Rubin, Courtney B.; Kleinstein, Steven H.; Sachais, Bruce S.; Posner, Marshall R.; Cavacini, Lisa A.; Payne, Aimee S.

    2014-01-01

    Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3 antibodies from four PV patients and identify pathogenic VH1-46 autoantibodies from all four patients. Unexpectedly, VH1-46 autoantibodies had relatively few replacement mutations. We reverted antibody somatic mutations to their germline sequences to determine the requirement of mutations for autoreactivity. Three of five VH1-46 germline-reverted antibodies maintain Dsg3 binding, compared to zero of five non-VH1-46 germline-reverted antibodies. Site-directed mutagenesis of VH1-46 antibodies demonstrate that acidic amino acid residues introduced by somatic mutation or heavy chain VDJ recombination are necessary and sufficient for Dsg3 binding. Our data suggest that VH1-46 autoantibody gene usage is commonly found in PV because VH1-46 antibodies require few to no mutations to acquire Dsg3 autoreactivity, which may favor their early selection. Common VH gene usage indicates common humoral immune responses, even among unrelated patients. PMID:24942562

  14. Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: an 8-year follow-up study in a single centre.

    PubMed

    Gregorek, H; Chrzanowska, K H; Michałkiewicz, J; Syczewska, M; Madaliński, K

    2002-11-01

    During an 8-year period of observation, defects of immune responses were characterized and monitored in 40 of 50 Polish children with Nijmegen breakage syndrome referred to the Children's Memorial Health Institute in Warsaw. The following parameters were determined at diagnosis: (1) concentrations of serum IgM, IgG, IgA; (2) concentrations of IgG subclasses; and (3) lymphocyte subpopulations. In addition, naturally acquired specific antibodies against Streptococcus pneumoniae were determined in 20 patients with a history of recurrent respiratory infections. During follow-up, total serum immunoglobulins and IgG subclasses were monitored systematically in 17 patients who did not receive immunomodulatory therapy. Moreover, anti-HBs antibody response was measured after vaccination of 20 children against HBV. We found that the immune deficiency in NBS is profound, highly variable, with a tendency to progress over time. Systematic monitoring of the humoral response, despite good clinical condition, is essential for early medical intervention.

  15. Profiling the Humoral Immune Response of Acute and Chronic Q Fever by Protein Microarray*

    PubMed Central

    Vigil, Adam; Chen, Chen; Jain, Aarti; Nakajima-Sasaki, Rie; Jasinskas, Algimantas; Pablo, Jozelyn; Hendrix, Laura R.; Samuel, James E.; Felgner, Philip L.

    2011-01-01

    Antigen profiling using comprehensive protein microarrays is a powerful tool for characterizing the humoral immune response to infectious pathogens. Coxiella burnetii is a CDC category B bioterrorist infectious agent with worldwide distribution. In order to assess the antibody repertoire of acute and chronic Q fever patients we have constructed a protein microarray containing 93% of the proteome of Coxiella burnetii, the causative agent of Q fever. Here we report the profile of the IgG and IgM seroreactivity in 25 acute Q fever patients in longitudinal samples. We found that both early and late time points of infection have a very consistent repertoire of IgM and IgG response, with a limited number of proteins undergoing increasing or decreasing seroreactivity. We also probed a large collection of acute and chronic Q fever patient samples and identified serological markers that can differentiate between the two disease states. In this comparative analysis we confirmed the identity of numerous IgG biomarkers of acute infection, identified novel IgG biomarkers for acute and chronic infections, and profiled for the first time the IgM antibody repertoire for both acute and chronic Q fever. Using these results we were able to devise a test that can distinguish acute from chronic Q fever. These results also provide a unique perspective on isotype switch and demonstrate the utility of protein microarrays for simultaneously examining the dynamic humoral immune response against thousands of proteins from a large number of patients. The results presented here identify novel seroreactive antigens for the development of recombinant protein-based diagnostics and subunit vaccines, and provide insight into the development of the antibody response. PMID:21817167

  16. Effect of fresh frozen plasma and gammaglobulin on humoral immunity in neonatal sepsis.

    PubMed Central

    Acunas, B A; Peakman, M; Liossis, G; Davies, E T; Bakoleas, B; Costalos, C; Gamsu, H R; Vergani, D

    1994-01-01

    Fresh frozen plasma and intravenous immunoglobulin are used as prophylaxis against, and for the treatment of, neonatal infection. It is assumed that any beneficial effect is mediated through the humoral immune factors contained in each preparation. The effect of fresh frozen plasma and intravenous immunoglobulin on humoral immune markers (immunoglobulins and IgG subclasses, complement components and activation products, and C reactive protein) was investigated over a 24 hour period after their randomised administration to 67 infants with suspected infection. Thirty infants without suspicion of infection were studied as controls. Compared with control infants, infants with suspected infection had increased concentrations of C reactive protein, reduced concentrations of fibronectin, and increased concentrations of the complement activation marker C3d, but similar concentrations of IgG, IgG subclasses, IgA, and IgM. After intravenous immunoglobulin treatment (500 mg/kg) concentrations of total IgG and all IgG subclasses increased, as did IgA and complement component C4. Concentrations of C reactive protein decreased after intravenous immunoglobulin treatment and were significantly lower than baseline after 24 hours. In contrast, no change in IgG or IgG subclass concentrations occurred after fresh frozen plasma administration. At 24 hours after fresh frozen plasma administration, concentrations of IgA, IgM, and C4 were significantly higher than baseline and serum IgA was significantly higher than in infants tested 24 hours after intravenous immunoglobulin treatment. These results confirm the rational basis for intravenous immunoglobulin treatment but question the value of fresh frozen plasma, particularly in the light of its attendant problems as an untreated blood product. PMID:8198411

  17. IGKC and FcγR genotypes and humoral immunity to HER2 in breast cancer.

    PubMed

    Pandey, Janardan P; Kistner-Griffin, Emily; Black, Laurel; Namboodiri, Aryan M; Iwasaki, Motoki; Kasuga, Yoshio; Hamada, Gerson S; Tsugane, Shoichiro

    2014-02-01

    Immunoglobulin κ constant (IGKC) gene has recently been identified as a strong prognostic marker in several human solid tumors, including breast cancer. Although the mechanisms underlying the IGKC signature are not yet known, identification of tumor-infiltrating plasma cells as the source of IGKC expression strongly suggests a role for humoral immunity in breast cancer progression. The primary aim of the present investigation was to determine whether the genetic variants of IGKC, KM (κ marker) allotypes, are risk factors for breast cancer, and whether they influence the magnitude of humoral immunity to epidermal growth factor receptor 2 (HER2), which is overexpressed in 25-30% of breast cancer patients and is associated with poor prognosis. Using a matched case-control design, we genotyped a large (1719 subjects) study population from Japan and Brazil for KM alleles. Both cases and controls in this study population had been previously characterized for GM (γ marker) and Fcγ receptor (FcγR) alleles, and the cases had also been characterized for anti-HER2 antibodies. Conditional logistic regression analysis of the data showed that KM1 allele additively contributed to the risk of breast cancer in the Japanese subjects from Nagano: Compared to KM3 homozygotes, KM1 homozygotes were almost twice as likely to develop breast cancer (OR=1.77, CI 1.06-2.95). Additionally, KM genotypes-individually and in particular epistatic combinations with FcγRIIa genotypes-contributed to the magnitude of anti-HER2 antibody responsiveness in the Japanese patients. This is the first report implicating KM alleles in the immunobiology of breast cancer.

  18. In Vivo Delivery of Antigens by Adenovirus Dodecahedron Induces Cellular and Humoral Immune Responses to Elicit Antitumor Immunity

    PubMed Central

    Villegas-Mendez, Ana; Garin, Marina I; Pineda-Molina, Estela; Veratti, Eugenia; Bueren, Juan A; Fender, Pascal; Lenormand, Jean-Luc

    2010-01-01

    Cancer vaccines based on virus-like particles (VLPs) vectors may offer many advantages over other antigen-delivery systems and represent an alternative to the ex vivo cell therapy approach. In this study, we describe the use of penton-dodecahedron (Pt-Dd) VLPs from human adenovirus type 3 (Ad3) as cancer vaccine vehicle for specific antigens, based on its unique cellular internalization properties. WW domains from the ubiquitin ligase Nedd4 serve as an adapter to bind the antigen to Pt-Dd. By engineering fusion partners of WW with the model antigen ovalbumin (OVA), Pt-Dd can efficiently deliver WW-OVA in vitro and the Pt-Dd/WW complex can be readily internalized by dendritic cells (DCs). Immunization with WW-OVA/Pt-Dd results in 90% protection against B16-OVA melanoma implantation in syngeneic mice. This high level of protection correlates with the development of OVA-specific CD8+ T cells. Moreover, vaccination with WW-OVA Pt-Dd induces robust humoral responses in mice as shown by the high levels of anti-OVA antibodies (Abs) detected in serum. Importantly, treatment of mice bearing B16-OVA tumors with WW-OVA/Pt-Dd results in complete tumor regression in 100% of cases. Thus, our data supports a dual role of Pt-Dd as antigen-delivery vector and natural adjuvant, able to generate integrated cellular and humoral responses of broad immunogenic complexity to elicit specific antitumor immunity. Antigen delivery by Pt-Dd vector is a promising novel strategy for development of cancer vaccines with important clinical applications. PMID:20179681

  19. In vivo delivery of antigens by adenovirus dodecahedron induces cellular and humoral immune responses to elicit antitumor immunity.

    PubMed

    Villegas-Mendez, Ana; Garin, Marina I; Pineda-Molina, Estela; Veratti, Eugenia; Bueren, Juan A; Fender, Pascal; Lenormand, Jean-Luc

    2010-05-01

    Cancer vaccines based on virus-like particles (VLPs) vectors may offer many advantages over other antigen-delivery systems and represent an alternative to the ex vivo cell therapy approach. In this study, we describe the use of penton-dodecahedron (Pt-Dd) VLPs from human adenovirus type 3 (Ad3) as cancer vaccine vehicle for specific antigens, based on its unique cellular internalization properties. WW domains from the ubiquitin ligase Nedd4 serve as an adapter to bind the antigen to Pt-Dd. By engineering fusion partners of WW with the model antigen ovalbumin (OVA), Pt-Dd can efficiently deliver WW-OVA in vitro and the Pt-Dd/WW complex can be readily internalized by dendritic cells (DCs). Immunization with WW-OVA/Pt-Dd results in 90% protection against B16-OVA melanoma implantation in syngeneic mice. This high level of protection correlates with the development of OVA-specific CD8(+) T cells. Moreover, vaccination with WW-OVA Pt-Dd induces robust humoral responses in mice as shown by the high levels of anti-OVA antibodies (Abs) detected in serum. Importantly, treatment of mice bearing B16-OVA tumors with WW-OVA/Pt-Dd results in complete tumor regression in 100% of cases. Thus, our data supports a dual role of Pt-Dd as antigen-delivery vector and natural adjuvant, able to generate integrated cellular and humoral responses of broad immunogenic complexity to elicit specific antitumor immunity. Antigen delivery by Pt-Dd vector is a promising novel strategy for development of cancer vaccines with important clinical applications.

  20. AAV-mediated delivery of optogenetic constructs to the macaque brain triggers humoral immune responses.

    PubMed

    Mendoza, Skyler D; El-Shamayleh, Yasmine; Horwitz, Gregory D

    2017-02-15

    Gene delivery to the primate central nervous system via recombinant adeno-associated viral vectors (AAV) allows neurophysiologists to control and observe neural activity precisely. A current limitation of this approach is variability in vector transduction efficiency. Low levels of transduction can foil experimental manipulations, prompting vector readministration. The ability to make multiple vector injections into the same animal, even in cases where successful vector transduction has already been achieved, is also desirable. However, vector readministration has consequences for humoral immunity and gene delivery that depend on vector dosage and route of administration in complex ways. As part of optogenetic experiments in rhesus monkeys, we analyzed blood sera collected before and after AAV injections into the brain and quantified neutralizing antibodies to AAV using an in vitro assay. We found that injections of AAV1 and AAV9 vectors elevated neutralizing antibody titers consistently. These immune responses were specific to the serotype injected and were long lasting. These results demonstrate that optogenetic manipulations in monkeys trigger immune responses to AAV capsids, suggesting that vector readministration may have a higher likelihood of success by avoiding serotypes injected previously.

  1. Effects of endosulfan on humoral and cell-mediated immune responses in rats

    SciTech Connect

    Banerjee, B.D.; Hussain, Q.Z.

    1987-03-01

    Endosulfan (6,7,8,9,10,10a-hexa-chloro-1,5,5a,6,9,9a-hexahydro, 6,9-methano-2,4,3-benzodioxathiepin-3-oxide), a polycyclic chlorinated hydrocarbon of cyclodien group, is a well known insecticide. Food is the main source of exposure of the general population to endosulfan. The physical, chemical as well as toxicological effects of endosulfan in experimental animals have been reported by various workers. However, the reports regarding the effect of endosulfan on immune system are not available. In view of its widespread use there is an urgent need to investigate the immunotoxicological effect of endosulfan in mammals for the safety evaluation of this insecticide. This has, therefore, prompted the authors to investigate the effect of endosulfan on immune system employing albino rats as the experimental animals. Included in this report are their preliminary findings on humoral and cell-mediated immune responses in rats exposed to sub-chronic doses of endosulfan.

  2. Antiparasite treatments reduce humoral immunity and impact oxidative status in raptor nestlings

    PubMed Central

    Hanssen, Sveinn Are; Bustnes, Jan Ove; Schnug, Lisbeth; Bourgeon, Sophie; Johnsen, Trond Vidar; Ballesteros, Manuel; Sonne, Christian; Herzke, Dorte; Eulaers, Igor; Jaspers, Veerle L B; Covaci, Adrian; Eens, Marcel; Halley, Duncan J; Moum, Truls; Ims, Rolf Anker; Erikstad, Kjell Einar

    2013-01-01

    Parasites are natural stressors that may have multiple negative effects on their host as they usurp energy and nutrients and may lead to costly immune responses that may cause oxidative stress. At early stages, animals may be more sensitive to infectious organisms because of their rapid growth and partly immature immune system. The objective of this study was to explore effects of parasites by treating chicks of two raptor species (northern goshawk Accipiter gentilis and white-tailed sea eagle Haliaeetus albicilla) against both endoparasites (internal parasites) and ectoparasites (external parasites). Nests were either treated against ectoparasites by spraying with pyrethrin or left unsprayed as control nests. Within each nest, chicks were randomly orally treated with either an antihelminthic medication (fenbendazole) or sterile water as control treatment. We investigated treatment effects on plasma (1) total antioxidant capacity TAC (an index of nonenzymatic circulating antioxidant defenses), (2) total oxidant status TOS (a measure of plasmatic oxidants), and (3) immunoglobulin levels (a measure of humoral immune function). Treatment against ectoparasites led to a reduction in circulating immunoglobulin plasma levels in male chicks. TOS was higher when not receiving any parasite reduction treatment and when receiving both endo- and ectoparasitic reduction treatment compared with receiving only one treatment. TAC was higher in all treatment groups, when compared to controls. Despite the relatively low sample size, this experimental study suggests complex but similar relationships between treatment groups and oxidative status and immunoglobulin levels in two raptor species. PMID:24455145

  3. Effects of intraperitoneal lead and cadmium on the humoral immune response of Salmo trutta

    SciTech Connect

    O'Neill, J.G.

    1981-07-01

    In the present study the effects of i.p. dosed lead (Pb) and cadium (Cd) on humoral antibody levels were examined in brown trout, Salmo trutta, immunized with MS2 bacteriophage. Earlier work had shown that the live MS2 virus was a primary immunogen and highly immunogenic, while non-pathogenic in fishes. Further, the antibody response could be quantified by a sensitive and reproducible technique. The i.p. route of heavy metal challenge was utilized to remove the complications presented by the environmental modifications of the toxicity of these metals and their passage through the gills of the fish. It was apparent that single i.p. doses of Pb and Cd resulted in a substantial reduction of antibody titre in MS2-immunized trout and that within the time limits of the experiment there was no recovery. However, only in the case of the two lethal concentrations was antibody totally eliminated from the sera and death ensued. Cd-exposure suppressed those responses mediated by T-lymphocytes and macrophages. A reduction in the number of B-like cells, as well as the loss of helper and memory cell activity, could have been responsible for reducing antibody titre in Pb- and Cd-dosed trout. A reduction in the number and activity of immune effector cells would also account for the Cd-dose dependent suppression of the antibody response after a rechallenge with MS2.

  4. Studies in chronic lymphocytic leukaemia II. Lymphocyte markers, cellular and humoral immunity and the effect of treatment.

    PubMed Central

    Bazerbashi, M. B.; Chanarin, I.; Denman, A. M.

    1980-01-01

    Observations were made on 15 patients with chronic lymphocytic leukaemia, 3 with non-Hodgkin's lymphoma, and 18 healthy controls. These include characterization of lymphocytes, assessment of humoral and cell-mediated immunity and the effect of treatment. Those responding to therapy showed a disappearance of 'null' lymphocytes from the blood with improvement in clinical and haematological parameters. Their immune capacity, however, remained unchanged or continued to deteriorate. PMID:7393803

  5. Introduction and immunopathogenesis of acquired immune deficiency syndrome.

    PubMed

    Sudharshan, S; Biswas, Jyotirmay

    2008-01-01

    India has a large number of patients with acquired immune deficiency syndrome (AIDS), the third largest population of this group in the world. This disease was first described in patients with Pneumocystis pneumonia in 1981. Ocular lesions can occur at any stage of the disease but are more commonly seen at the late stages. Human immunodeficiency virus (HIV), the causative agent of AIDS is a retrovirus with RNA genome and a unique 'Reverse transcriptase enzyme' and is of two types, HIV-1 and 2. Most human diseases are caused by HIV-1. The HIV-1 subtypes prevalent in India are A, B and C. They act predominantly by reducing the CD4+ cells and thus the patient becomes susceptible to opportunistic infections. High viral titers in the peripheral blood during primary infection lead to decrease in the number of CD4+ T lymphocytes. Onset of HIV-1-specific cellular immune response with synthesis of HIV-1 specific antibodies leads to the decline of plasma viral load and chronification of HIV-1 infection. However, the asymptomatic stage of infection may lead to persistent viral replication and a rapid turnover of plasma virions which is the clinical latency. During this period, there is further decrease in the CD4+ counts which makes the patient's immune system incapable of controlling opportunistic pathogens and thus life-threatening AIDS-defining diseases emerge. Advent of highly active antiretroviral treatment (HAART) has revolutionized the management of AIDS though there is associated increased development of immune recovery uveitis in a few of these patients.

  6. Characterization of naturally-occurring humoral immunity to AAV in sheep.

    PubMed

    Tellez, Joseph; Van Vliet, Kim; Tseng, Yu-Shan; Finn, Jonathan D; Tschernia, Nick; Almeida-Porada, Graça; Arruda, Valder R; Agbandje-McKenna, Mavis; Porada, Christopher D

    2013-01-01

    AAV vectors have shown great promise for clinical gene therapy (GT), but pre-existing human immunity against the AAV capsid often limits transduction. Thus, testing promising AAV-based GT approaches in an animal model with similar pre-existing immunity could better predict clinical outcome. Sheep have long been used for basic biological and preclinical studies. Moreover, we have re-established a line of sheep with severe hemophilia A (HA). Given the impetus to use AAV-based GT to treat hemophilia, we characterized the pre-existing ovine humoral immunity to AAV. ELISA revealed naturally-occurring antibodies to AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. For AAV2, AAV8, and AAV9 these inhibit transduction in a luciferase-based neutralization assay. Epitope mapping identified peptides that were common to the capsids of all AAV serotypes tested (AAV2, AAV5, AAV8 and AAV9), with each animal harboring antibodies to unique and common capsid epitopes. Mapping using X-ray crystallographic AAV capsid structures demonstrated that these antibodies recognized both surface epitopes and epitopes located within regions of the capsid that are internal or buried in the capsid structure. These results suggest that sheep harbor endogenous AAV, which induces immunity to both intact capsid and to capsid epitopes presented following proteolysis during the course of infection. In conclusion, their clinically relevant physiology and the presence of naturally-occurring antibodies to multiple AAV serotypes collectively make sheep a unique model in which to study GT for HA, and other diseases, and develop strategies to circumvent the clinically important barrier of pre-existing AAV immunity.

  7. Humoral immune response against contractile proteins (actin and myosin) during cardiovascular disease.

    PubMed

    De Scheerder, I K; De Buyzere, M; Delanghe, J; Maas, A; Clement, D L; Wieme, R

    1991-08-01

    Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute myocardial infarction (n = 28, AMI), valve surgery (n = 35, VALVE), coronary bypass surgery (n = 35, CABG), and peripheral vascular surgery (n = 14, VASC). Anti-actin and anti-myosin antibodies were determined on admission and serially during a period of 90 days. Anti-actin and anti-myosin immune response (IgG, IgM) was expressed comparing absorbance of the patients' serum with a reference serum. In the different patient groups significantly (P less than 0.01) higher anti-actin and anti-myosin antibody concentrations were found on admission compared with age-matched control groups. During follow-up, all patient groups except the vascular surgery group showed a significant immune response against actin and myosin, with an immune response ratio (peak/admission) for AMA IgG and IgM respectively of 2.12 and 2.40 in the VALVE group, 1.30 and 1.99 in the CABG group, 1.42 and 1.48 in the AMI group and 1.66 and 1.25 in the MYO group; and for AAA IgG and IgM respectively of 1.57 and 3.00 in the VALVE group, 1.54 and 1.64 in the CABG group, 1.25 and 1.07 in the AMI group, and 1.42 and 1.42 in the MYO group. A significant correlation between pre-cardiac injury and peak post-cardiac injury anti-myosin and anti-actin autoantibody levels could be demonstrated suggesting that pre-injury sensitization to these antigens plays an important role in evoking post-cardiac injury immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Characterization of Naturally-Occurring Humoral Immunity to AAV in Sheep

    PubMed Central

    Tellez, Joseph; Van Vliet, Kim; Tseng, Yu-Shan; Finn, Jonathan D.; Tschernia, Nick; Almeida-Porada, Graça; Arruda, Valder R.; Agbandje-McKenna, Mavis; Porada, Christopher D.

    2013-01-01

    AAV vectors have shown great promise for clinical gene therapy (GT), but pre-existing human immunity against the AAV capsid often limits transduction. Thus, testing promising AAV-based GT approaches in an animal model with similar pre-existing immunity could better predict clinical outcome. Sheep have long been used for basic biological and preclinical studies. Moreover, we have re-established a line of sheep with severe hemophilia A (HA). Given the impetus to use AAV-based GT to treat hemophilia, we characterized the pre-existing ovine humoral immunity to AAV. ELISA revealed naturally-occurring antibodies to AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. For AAV2, AAV8, and AAV9 these inhibit transduction in a luciferase-based neutralization assay. Epitope mapping identified peptides that were common to the capsids of all AAV serotypes tested (AAV2, AAV5, AAV8 and AAV9), with each animal harboring antibodies to unique and common capsid epitopes. Mapping using X-ray crystallographic AAV capsid structures demonstrated that these antibodies recognized both surface epitopes and epitopes located within regions of the capsid that are internal or buried in the capsid structure. These results suggest that sheep harbor endogenous AAV, which induces immunity to both intact capsid and to capsid epitopes presented following proteolysis during the course of infection. In conclusion, their clinically relevant physiology and the presence of naturally-occurring antibodies to multiple AAV serotypes collectively make sheep a unique model in which to study GT for HA, and other diseases, and develop strategies to circumvent the clinically important barrier of pre-existing AAV immunity. PMID:24086458

  9. Evaluation of Humoral Immunity to Mycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development

    PubMed Central

    Niki, Mamiko; Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Ohta, Ken; Inoue, Manabu; Niki, Makoto; Kaneko, Yukihiro; Morimoto, Kozo; Kurashima, Atsuyuki; Kitada, Seigo; Matsumoto, Sohkichi; Suzuki, Koichi; Hoshino, Yoshihiko

    2015-01-01

    Although tuberculosis remains a major global health problem, Bacille Calmette-Guérin (BCG) is the only available vaccine. However, BCG has limited applications, and a more effective vaccine is needed. Cellular mediated immunity (CMI) is thought to be the most important immune response for protection against Mycobacterium tuberculosis (Mtb). However, the recent failure of a clinical trial for a booster BCG vaccine and increasing evidence of antibody-mediated immunity prompted us to evaluate humoral immunity to Mtb-specific antigens. Using Enzyme-Linked ImmunoSpot and Enzyme-Linked ImmunoSorbent Assays, we observed less correlation of both CMI and IgG titers with patient clinical status, including serum concentration of C reactive protein. However, IgA titers against Mtb were significantly correlated with clinical status, suggesting that specific IgA antibodies protect against Mtb proliferation. In addition, in some cases, IgA antibody titers were significantly associated with the serum concentration of total albumin, which supports the idea that humoral immunity can be influenced by the nutritional status. Based on these observations, we propose that the induction of humoral immunity should be included as an option in TB vaccine development strategies. PMID:26568961

  10. The relationship between undernutrition and humoral immune status in children with pneumonia in Papua New Guinea.

    PubMed

    Cripps, Allan W; Otczyk, Diana C; Barker, Jane; Lehmann, Deborah; Alpers, Michael P

    2008-01-01

    Malnutrition is a significant risk factor for childhood infectious diseases in developing countries, including Papua New Guinea (PNG). Whilst the mechanisms are not fully understood there is little doubt that impairment of immune function is a major contributing factor in enhancing disease susceptibility in malnourished children. This susceptibility has been clearly shown for pneumonia in PNG. The aim of this study was to examine the effect of undernutrition on the humoral immune profile in children less than 60 months of age with pneumonia. The study was cross-sectional with measurements of nutritional status and parameters of the immune response being assessed simultaneously. The children were grouped according to age for the purpose of comparative analysis. The children were from the Goroka region of the Eastern Highlands Province of PNG and had been admitted to hospital with moderate-severe pneumonia. They were classified as undernourished (less than 80% weight for age) or nourished (greater than or equal to 80% weight for age). Serum albumin, IgG, IgA and IgM and salivary albumin and IgA were measured. Antibodies to nontypeable Haemophilus influenzae outer membrane protein and Escherichia coli O antigen were also determined in serum and saliva. Undernourished children aged less than 49 months had lower levels of serum albumin than nourished children throughout this age range. Lower values of salivary IgA were observed in infants (less than 13 months of age) than in older children, with a larger proportion of younger children having no detectable IgA. The age-related immunological profile was similar in undernourished and nourished children. At different age intervals the concentration of immunoglobulins in serum and saliva from undernourished children was generally found to be less than or the same as that from nourished children. In most cases undernourished children had lower levels of specific antibodies than nourished children but for some antibodies in

  11. Role of vitamin D in acquired immune and autoimmune diseases.

    PubMed

    Delvin, Edgard; Souberbielle, Jean-Claude; Viard, Jean-Paul; Salle, Bernard

    2014-08-01

    Vitamin D has been attributed roles in the pathogenesis and prevention of several diseases such as cancer, cardiovascular disease, multiple sclerosis, diabetes, autism and autoimmune diseases. The concomitant expression of the 25-hydroxyvitamin D3-1α-hydroxylase and of the vitamin D3 receptor in animal and human tissues and organs other than bone supports this paradigm. Translated into the clinical field, meta-analyses and systematic reviews have also revealed an association between vitamin D insufficiency or deficiency and non-osseous diseases. Although relying on the large databases, they are diverse in nature and involve participants of varying age and evolving in different environments. Furthermore, they do not allow any analysis of a possible causal relationship between vitamin D supplementation and clinical outcomes. Following a brief historical account, this review addresses these caveats, and gives examples of randomized controlled trials conducted in the fields of acquired immune and autoimmune diseases.

  12. Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination.

    PubMed

    Li, Yingying; Zhou, Ming; Luo, Zhaochen; Zhang, Yachun; Cui, Min; Chen, Huanchun; Fu, Zhen F; Zhao, Ling

    2017-04-01

    Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. There is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination. In this study, a recombinant rabies virus (RABV) that expressed murine interleukin-7 (IL-7), referred to here as rLBNSE-IL-7, was constructed, and its effectiveness was evaluated in a mouse model. rLBNSE-IL-7 induced higher rates of T follicular helper (Tfh) cells and germinal center (GC) B cells from draining lymph nodes (LNs) than the parent virus rLBNSE. Interestingly, rLBNSE-IL-7 improved the percentages of long-lived memory B cells (Bmem) in the draining LNs and plasma cells (PCs) in the bone marrow (BM) for up to 360 days postimmunization (dpi). As a result of the presence of the long-lived PCs, it also generated prolonged virus-neutralizing antibodies (VNAs), resulting in better protection against a lethal challenge than that seen with rLBNSE. Moreover, consistent with the increased numbers of Bmem and PCs after a boost with rLBNSE, rLBNSE-IL-7-immunized mice promptly produced a more potent secondary anti-RABV neutralizing antibody response than rLBNSE-immunized mice. Overall, our data suggest that overexpressing IL-7 improved the induction of long-lasting primary and secondary antibody responses post-RABV immunization.IMPORTANCE Extending humoral immune responses using adjuvants is an important method to develop long-lasting and efficient vaccines against rabies. However, little information is currently available regarding prolonged immunological

  13. Adult Drosophila melanogaster evolved for antibacterial defense invest in infection-induced expression of both humoral and cellular immunity genes

    PubMed Central

    2011-01-01

    Background While the transcription of innate immunity genes in response to bacterial infection has been well-characterised in the Drosophila model, we recently demonstrated the capacity for such transcription to evolve in flies selected for improved antibacterial defense. Here we use this experimental system to examine how insects invest in constitutive versus infection-induced transcription of immunity genes. These two strategies carry with them different consequences with respect to energetic and pleiotropic costs and may be more or less effective in improving defense depending on whether the genes contribute to humoral or cellular aspects of immunity. Findings Contrary to expectation we show that selection preferentially increased the infection-induced expression of both cellular and humoral immunity genes. Given their functional roles, infection induced increases in expression were expected for the humoral genes, while increases in constitutive expression were expected for the cellular genes. We also report a restricted ability to improve transcription of immunity genes that is on the order of 2-3 fold regardless of total transcription level of the gene. Conclusions The evolved increases in infection-induced expression of the cellular genes may result from specific cross talk with humoral pathways or from generalised strategies for enhancing immunity gene transcription. A failure to see improvements in constitutive expression of the cellular genes suggests either that increases might come at too great a cost or that patterns of expression in adults are decoupled from the larval phase where increases would be most effective. The similarity in fold change increase across all immunity genes may suggest a shared mechanism for the evolution of increased transcription in small, discrete units such as duplication of cis-regulatory elements. PMID:21859495

  14. Do all creatures possess an acquired immune system of some sort?

    PubMed

    Rimer, Jacob; Cohen, Irun R; Friedman, Nir

    2014-03-01

    Recent findings have provided evidence for the existence of non-vertebrate acquired immunity. We survey these findings and propose that all living organisms must express both innate and acquired immunity. This is opposed to the paradigm that only vertebrates manifest the two forms of immune mechanism; other species are thought to use innate immunity alone. We suggest new definitions of innate and acquired immunity, based on whether immune recognition molecules are encoded in the inherited genome or are generated through somatic processes. We reason that both forms of immunity are similarly ancient, and have co-evolved in response to lifestyle, cost-benefit tradeoffs and symbiosis versus parasitism. However, different species have evolved different immune solutions that are not necessarily genetically related, but serve a similar general function - allowing individuals to learn from their own immune experience; survival of species is contingent on the acquired immune experience of its individuals.

  15. Autopsy pathology in the acquired immune deficiency syndrome.

    PubMed Central

    Reichert, C. M.; O'Leary, T. J.; Levens, D. L.; Simrell, C. R.; Macher, A. M.

    1983-01-01

    The acquired immune deficiency syndrome (AIDS) is a devastating new illness which appears to be sexually and parenterally transmissible. AIDS was first described in the male homosexual community; however, the disease has more recently been described among intravenous drug abusers, Haitians, hemophiliacs, and others. The etiologic agent is unknown. AIDS may represent an infection by a previously undescribed organism, a mutant of a known microorganism, or a multifactorial combination of environmental, immunologic, and genetic factors. As a consequence of the disease's seemingly irreversible ablation of the cell-mediated immune system, AIDS victims succumb to a variety of infections and/or unusual neoplasms. In its fully developed form, mortality approaches 100%. At autopsy the gross and microscopic pathology of the syndrome can be divided into three general categories: 1) morphologic manifestations of profound lymphoid depletion; 2) infections, usually with mixed opportunistic pathogens; and 3) unusual neoplasms, most frequently Kaposi's sarcoma or high-grade lymphomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 PMID:6311021

  16. Humoral and cellular immune responses to matrix protein of measles virus in subacute sclerosing panencephalitis.

    PubMed Central

    Dhib-Jalbut, S; McFarland, H F; Mingioli, E S; Sever, J L; McFarlin, D E

    1988-01-01

    The immune response to matrix (M) protein of measles virus was examined in patients with subacute sclerosing panencephalitis (SSPE) and controls. Antibodies specific for M and nucleocapsid (NC) proteins in 11 serum and 8 cerebrospinal fluid (CSF) samples from patients with SSPE were quantitated by enzyme-linked immunosorbent assay by using affinity-purified measles virus proteins. Geometric mean anti-NC antibody titers were higher in the serum (6.58 +/- 0.98 [mean +/- standard deviation]) and CSF (4.38 +/- 0.74) of SSPE patients compared with controls. Anti-M antibodies were present in the serum and CSF of all SSPE samples tested but in titers lower than those of anti-NC antibodies. Geometric mean anti-M antibody titer was 3.35 +/- 0.53 in sera from patients with SSPE compared with 3.05 +/- 0.66 in sera from patients with other neurological diseases and 3.12 +/- 0.74 in sera from healthy individuals. Geometric mean anti-M antibody titer was 2.59 +/- 0.86 in the CSF of eight patients with SSPE compared with a mean less than 1.00 for patients with other neurological disease (controls). Intrathecal synthesis of anti-M or anti-NC antibodies was established in four patients with SSPE. The cellular immune responses to M, F, HA, and NC proteins were examined in four of the patients with SSPE by lymphoproliferation and were not significantly different from those in five healthy controls. The results demonstrate humoral and cellular immune responses to M protein in patients with SSPE and indicate that it is unlikely that a defect in the immune response to this virus component accounts for the disease process in the patients studied. Images PMID:3373575

  17. Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis.

    PubMed Central

    Smith, P D; Ohura, K; Masur, H; Lane, H C; Fauci, A S; Wahl, S M

    1984-01-01

    The ineffective immune response in patients with the acquired immune deficiency syndrome (AIDS) contributes to severe and widespread infections and unrestricted growth by certain tumors. To determine whether monocyte dysfunction contributes to this immunosuppressed condition, we investigated monocyte chemotaxis in patients with AIDS. Using three different chemotactic stimuli, N-formylmethionylleucylphenylalanine, lymphocyte-derived chemotactic factor, and C5a des Arg, we studied the chemotactic responses of monocytes from seven homosexual men with AIDS, three homosexuals with lymphadenopathy and an abnormal immunological profile, seven healthy homosexual men, and 23 heterosexual control individuals. Monocytes from each of the AIDS patients with Kaposi's sarcoma and/or opportunistic infection exhibited a marked reduction in chemotaxis to all stimuli compared with the healthy control subjects. The reduced chemotactic responses were observed over a wide range of concentrations for each stimulus. Monocytes from AIDS patients who had clinically apparent opportunistic infection(s) exhibited a greater reduction in monocyte migration to all three stimuli than monocytes from the AIDS patient with only Kaposi's sarcoma. Monocytes from each of three homosexuals with lymphadenopathy and an abnormal immunological profile exhibited decreased chemotactic responses that were intermediate between those of the AIDS patients and the healthy heterosexual control subjects. In contrast to these findings, monocytes from each of seven healthy homosexuals exhibited normal chemotactic responses to the same stimuli. In addition, monocytes from AIDS patients exhibited reduced chemotaxis to soluble products of Giardia lamblia, one of several protozoan parasites prevalent in AIDS patients. Thus the immune abnormality in AIDS, previously thought to involve only the T-, B-, and natural killer lymphocytes, extends to the monocyte-macrophage. Defective monocyte migratory function may contribute to

  18. Characterization of effector components from the humoral and cellular immune response stimulated by melanoma cells exhibiting modified IGF-1 expression.

    PubMed

    Zhu, Chaobin; Trabado, Séverine; Fan, Ye; Trojan, Jerzy; Lone, Yu-Chun; Giron-Michel, Julien; Duc, Huynh-Thien

    2015-03-01

    Modified melanoma B16 cells inhibited in their IGF-1 expression (B16MOD), on the contrary to the IGF-1 fully expressed parental wild-type (B16WT) counterpart, were shown to stimulate humoral as well as cellular immune responses. Among humoral components, the neutralizing and complement-fixing antibodies of IgM and essentially IgG2 (a+b) isotypes exhibited in vitro and in vivo effects upon tumour growth, while the IgG1 antibody isotype promoted enhanced tumour proliferation. As for the cellular immunity, it was found that the T CD8(+) lymphocyte subpopulation remained the main potent and long lasting immune active effector regulating tumour growth.

  19. Humoral immune response in patients with cerebral parenchymal cysticercosis treated with praziquantel.

    PubMed Central

    Estañol, B; Juárez, H; Irigoyen, M del C; González-Barranco, D; Corona, T

    1989-01-01

    The humoral immune response to treatment with praziquantel (PZQ) was studied in eight patients with parenchymal cerebral cysticercosis (CC). In the serum and in the cerebrospinal fluid (CSF) before, during and after the administration of the drug, the following were quantitated (a) levels of specific anticysticercous antibodies measured in optical densities by the ELISA method; (b) levels of IgG, IgM, IgA and IgE; (c) levels of complement fraction C3, C4; (d) presence of immune complexes; (e) total number of white blood cells in the CSF. It was found that after treatment with PZQ, the level of specific anticysticercous antibodies and the level of IgG rose significantly in the CSF but not in the blood. The levels of the fractions of the complement and the immunoglobulins IgM, IgA and IgE did not change significantly either in the serum or in the CSF. The blood-brain barrier was found ruptured in three patients before therapy and in five patients after the therapy as measured by the albumin index. Nevertheless, the IgG index showed that there was local production of IgG in five patients before treatment and in seven after the end of it. The relative specific antibody index was greater than 1.0 in five patients before therapy and in seven after therapy. This data strongly supports the idea that the specific antibodies are produced intrathecally and are not derived from the serum pool through a ruptured blood-brain barrier. It was concluded that patients with parenchymal CC have an elevation of specific anticysticercous probably due to a combination of a ruptured blood-brain barrier and intrathecal synthesis. The relatively small rupture of the blood-brain barrier and the high IgG and relative specific antibody index suggest that intrathecal synthesis is the most important mechanism. The humoral immune response may be of importance not only in the elimination of the parasite but also in the genesis of the illness. PMID:2703841

  20. Intraocular route of AAV2 vector administration defines humoral immune response and therapeutic potential

    PubMed Central

    Miller, Rehae; Han, Ping-Yang; Pang, Jijing; Dinculescu, Astra; Chiodo, Vince; Hauswirth, William W.

    2008-01-01

    Purpose Safety and efficiency are critical for successful gene therapy. Adeno-associated viral (AAV) vectors are commonly used for gene transfer in both human and animal studies. However, administration of AAV vectors can lead to development of neutralizing antibodies against the vector capsid, thus decreasing the efficiency of therapeutic gene transfer and preventing effective vector readministration. We investigated immune responses to different routes of ocular administration and readministration of AAV vectors, and the effect of previous exposure of AAV vector in one eye on the transduction efficacy of subsequent intraocular AAV-mediated gene delivery to the partner eye. Methods We tested two vector systems. One contained a cDNA encoding a secreted pigment epithelial derived factor (PEDF) cDNA under the control of a Cytomegalovirus (CMV) enhancer and chicken β-actin promoter (CBA; AAV2-CBA-PEDF) and was tested in a murine model of laser-induced choroidal neovascularization (CNV). The other vector contained a cDNA encoding the intracellular reporter green fluorescent protein (GFP) under the control of the same promoter (AAV2-CBA-GFP). Animals were divided into groups and received sequential injections at different combinations of either intravitreal or subretinal routes. CNV was evaluated by fluorescein angiographic choroidal flat-mount image analysis. The expression of GFP was analyzed in retinal sections by direct fluorescence imaging. Antibodies against AAV2 capsid and transgenes were analyzed by ELISA using serum samples collected before injection and different time points after the injection. Neutralizing antibodies were characterized by in vitro assays. Results Various ocular compartments responded to AAV administration differently. Intravitreal administration of AAV vectors, which resulted in transduction of inner retina (primarily retinal ganglion cells), generated a humoral immune response against AAV capsid that blocked vector expression upon

  1. Giardia duodenalis: analysis of humoral immune response in experimentally infected gerbils (Meriones unguiculatus).

    PubMed

    Argüello-García, R; Ortega-Pierres, M G

    1997-01-01

    In this work, we have analyzed the humoral immune response in Mongolian gerbils infected with Giardia duodenalis trophozoites of strains P-1 and WB. The course of infection in the animals was assessed by monitoring cyst shedding in feces, and serum samples were collected at weekly intervals to measure antibody levels by ELISA. Parallel studies were carried out to determine the patterns of total and surface antigens of the parasite recognized by antibodies using Western blot and radioimmunoprecipitation (RIP) assays with the use of homospecific enzyme conjugates. Typical patterns of cyst shedding were observed in the infected animals and cyst numbers per gram of feces were consistently higher in gerbils infected with WB strain. Antibody levels to G. duodenalis antigens were observed by week 2 post-infection and were still detectable 4 months after infection. G. duodenalis antigens showed a complex but quantitatively and qualitatively different recognition pattern by infection-induced antibodies in Western blot assays which related to infecting strain. However, RIP assays showed a more restricted and common pattern of recognition of surface antigens from either strain. Taken together, the data obtained in this study provides further information regarding direct comparisons among infecting strain, patterns of infectivity, and host immune response toward G. duodenalis antigens in the gerbil model.

  2. Studies on the humoral immune response to a synthetic vaccine against Plasmodium falciparum malaria.

    PubMed Central

    Salcedo, M; Barreto, L; Rojas, M; Moya, R; Cote, J; Patarroyo, M E

    1991-01-01

    A synthetic vaccine against the asexual blood stages of P. falciparum, the SPf 66 synthetic hybrid polymer, composed of peptides derived from three merozoite membrane proteins as well as one peptide from the sporozoite CS protein, has been developed by our group and tested in different protection assays in Aotus monkeys as well as in human volunteers. This study evaluates the humoral immune response induced by the SPf 66 protein vaccination in adult human volunteers from the Colombian Pacific coast as follows: determination of specific IgG antibody levels against SPf 66 by FAST-ELISA after each immunization; analysis of antibody reactivity with P. falciparum schizont lysates by immunoblots; and determination of the in vitro parasite growth inhibition. A clear boosting effect, dependent on time and dose, was observed in the antibody production kinetics. These antibodies also specifically recognize three proteins of the P. falciparum schizont lysate corresponding to the molecular weights of the proteins from which the amino acid sequence was derived. These sera were also capable of markedly inhibiting in vitro parasite growth. PMID:2015702

  3. Trypanosoma cruzi: H2 complex and genetic background influence on the humoral immune response against epimastigotes.

    PubMed

    Aguillón, J C; Hermosilla, T; Molina, M C; Morello, A; Repetto, Y; Orn, A; Ferreira, A

    2000-08-01

    Using A.SW, A.CA, B10.S and B10.M congenic mouse strains, we measured the IgG specific humoral immune responses against sonicated and live Trypanosoma cruzi epimastigotes. Genes located in the A background (A.SW and A.CA strains) mediate higher IgG responses against the parasite antigenic complexes than those located in the B background (strains B10.S and B10.M), regardless of the H2 haplotypes. Thus, non H2 genetic elements seem to be more important in determining differences in the total IgG immune response against T. cruzi. Whether a detectable H2 effect, in favor of the H2(s) haplotype, occurred in the A or B background, was contingent on the immunisation protocol used. Thus, the H2(s) haplotype mediates a higher IgG response in the A background, if immunised with live epimastigotes, and in the B background against sonicated epimastigotes. Most likely this represents a complex sequence of events, controlled by non-MHC genes, involving antigen handling and processing and depending on the physical form of antigen delivery.

  4. Association between microRNA polymorphisms and humoral immunity to hepatitis B vaccine.

    PubMed

    Xiong, Yongzhen; Chen, Shengli; Chen, Ruhong; Lin, Weiyan; Ni, Jindong

    2013-08-01

    To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-146a, miR-196a2, miR-27a, miR-26a-1, miR-124 and miR-149 genes are associated with immune response to hepatitis B vaccine. The genotype and allele frequencies of SNPs were compared between the non-responders (n=77) and responders (n=207). The associations of the genotypes with antibody levels were assessed in the responders. Significant associations were observed between SNPs in miR-146a and miR-26a-1 genes and non-response to hepatitis B vaccine (p<0.05). In addition, SNPs in miR-146a and miR-27a genes were associated with variations in levels of antibodies to hepatitis B antigen. Thus, specific SNPs in microRNAs (miRNAs) genes may affect status of the hepatitis B vaccine induced protective humoral immune response. They also suggest that the three miRNAs play a role in modulating antibody responses to hepatitis B vaccine.

  5. Humoral Immune Pressure Selects for HIV-1 CXC-chemokine Receptor 4-using Variants.

    PubMed

    Lin, Nina; Gonzalez, Oscar A; Registre, Ludy; Becerril, Carlos; Etemad, Behzad; Lu, Hong; Wu, Xueling; Lockman, Shahin; Essex, Myron; Moyo, Sikhulile; Kuritzkes, Daniel R; Sagar, Manish

    2016-06-01

    Although both C-C chemokine receptor 5 (CCR5)- and CXC chemokine receptor 4 (CXCR4)-using HIV-1 strains cause AIDS, the emergence of CXCR4-utilizing variants is associated with an accelerated decline in CD4+ T cells. It remains uncertain if CXCR4-using viruses hasten disease or if these variants only emerge after profound immunological damage. We show that exclusively CXCR4- as compared to cocirculating CCR5-utilizing variants are less sensitive to neutralization by both contemporaneous autologous plasma and plasma pools from individuals that harbor only CCR5-using HIV-1. The CXCR4-utilizing variants, however, do not have a global antigenic change because they remain equivalently susceptible to antibodies that do not target coreceptor binding domains. Studies with envelope V3 loop directed antibodies and chimeric envelopes suggest that the neutralization susceptibility differences are potentially influenced by the V3 loop. In vitro passage of a neutralization sensitive CCR5-using virus in the presence of autologous plasma and activated CD4+ T cells led to the emergence of a CXCR4-utilizing virus in 1 of 3 cases. These results suggest that in some but not necessarily all HIV-1 infected individuals humoral immune pressure against the autologous virus selects for CXCR4-using variants, which potentially accelerates disease progression. Our observations have implications for using antibodies for HIV-1 immune therapy.

  6. Efficiency of Matricaria chamomilla CH12 and number of doses of rabies vaccine on the humoral immune response in cattle.

    PubMed

    de Souza Reis, Luis Souza; Frazatti-Gallina, Neuza Maria; de Lima Paoli, Rosana; Giuffrida, Rogerio; Albas, Avelino; Oba, Eunice; Pardo, Paulo Eduardo

    2008-12-01

    This study evaluated the effect of Matricaria chamomilla and vaccination frequency on cattle immunization against rabies. Four groups (n = 15 /group) were treated with or without Matricaria chamomilla CH12 and vaccinated with one or two doses of rabies vaccine (30 day interval). No effect of chamomile was found on cattle immunization against rabies; however, antibody titers were protective in cattle vaccinated twice, while 93.3% of cattle vaccinated only once had titers under 0.5 UI/ml after 60 days. In conclusion, the use of chamomile did not alter the humoral immune response in cattle, and two vaccine doses are suggested for achieving protective antibody titers.

  7. Efficiency of Matricaria chamomilla CH12 and number of doses of rabies vaccine on the humoral immune response in cattle

    PubMed Central

    Frazatti-Gallina, Neuza Maria; de Lima Paoli, Rosana; Giuffrida, Rogerio; Albas, Avelino; Oba, Eunice; Pardo, Paulo Eduardo

    2008-01-01

    This study evaluated the effect of Matricaria chamomilla and vaccination frequency on cattle immunization against rabies. Four groups (n = 15 /group) were treated with or without Matricaria chamomilla CH12 and vaccinated with one or two doses of rabies vaccine (30 day interval). No effect of chamomile was found on cattle immunization against rabies; however, antibody titers were protective in cattle vaccinated twice, while 93.3% of cattle vaccinated only once had titers under 0.5 UI/ml after 60 days. In conclusion, the use of chamomile did not alter the humoral immune response in cattle, and two vaccine doses are suggested for achieving protective antibody titers. PMID:19043320

  8. Humoral and cellular immune responses to Yersinia pestis infection in long-term recovered plague patients.

    PubMed

    Li, Bei; Du, Chunhong; Zhou, Lei; Bi, Yujing; Wang, Xiaoyi; Wen, Li; Guo, Zhaobiao; Song, Zhizhong; Yang, Ruifu

    2012-02-01

    Plague is one of the most dangerous diseases and is caused by Yersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n = 65) recovered from Y. pestis infection during the past 16 years were investigated using a protein microarray and an enzyme-linked immunosorbent spot assay (ELISpot). The seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade ago, the antibody-positive rate still remains 69.5%. There is no difference in the antibody presence between gender, age, and infected years, but it seems to be associated with the F1 antibody titers during infection (r = 0.821; P < 0.05). Except F1 antibody, the antibodies against LcrV and YopD were detected in most of the patients, suggesting they could be the potential diagnostic markers for detecting the infection of F1-negative strains. Regarding cellular immunity, the cell number producing gamma interferon (IFN-γ), stimulated by F1 and LcrV, respectively, in vitro to the peripheral blood mononuclear cells of 7 plague patients and 4 negative controls, showed no significant difference, indicating F1 and LcrV are not dominant T cell antigens against plague for a longer time in humans. Our findings have direct implications for the future design and development of effective vaccines against Y. pestis infection and the development of new target-based diagnostics.

  9. Effect of ivermectin on the cellular and humoral immune responses of rabbits.

    PubMed

    Sajid, Muhammad Sohail; Iqbal, Zafar; Muhammad, Ghulam; Sandhu, Mansur Abdullah; Khan, Muhammad Nisar; Saqib, Muhammad; Iqbal, Muhammad Umair

    2007-05-01

    The objective of this paper is to determine the effect of ivermectin administration on cell mediated (CMI) and humoral immunity (HI) of rabbits. CMI against dinitrochlorobenzene (DNCB) and sheep red blood cells (SRBC) in rabbits was determined by delayed-type hypersensitivity and macrophage engulfment assay (MEA), respectively; whereas, HI to Pasteurella multocida B2 vaccine and SRBC was determined by indirect haemagglutination assay (IHA) and Jerne hemolytic plaque formation assay (JHPFA), respectively. The rabbits were divided into four major groups (A through D) each subdivided into four sub-groups (1 through 4). Rabbits of group A served as vehicle control while those of groups B, C and D were treated with ivermectin at the dose rates of 200 microg/kg, 400 microg/kg and 600 microg/kg b.w., respectively. Cellular immunity was determined in sub-groups 1 and 2 through DNCB and MEA, respectively while HI was determined in sub-groups 3 and 4 through IHA and JHPFA, respectively. The skin sensitivity to DNCB at 24 and 48 h and macrophage engulfment of SRBC were highest (P>0.05) in rabbits administered with 600 microg/kg b.w. The highest geometric mean titers (14.00+/-0.31) and number of plaque forming units (1860+/-0.75) were found in rabbits that received ivermectin at a dose of 600 microg/kg b.w. followed, in order by the groups that received 400 microg/kg, 200 microg/kg b.w. and controls. Leukocyte counts were significantly higher in ivermectin-treated groups (C and D) than group A (vehicle control) and B (ivermectin at the rate of 200 microg/kg). A graded dose immune response suggested an immunopotentiating effect of ivermectin at higher doses.

  10. Honey bee drones maintain humoral immune competence throughout all life stages in the absence of vitellogenin production.

    PubMed

    Gätschenberger, Heike; Gimple, Olaf; Tautz, Jürgen; Beier, Hildburg

    2012-04-15

    Drones are haploid male individuals whose major social function in honey bee colonies is to produce sperm and mate with a queen. In spite of their limited tasks, the vitality of drones is of utmost importance for the next generation. The immune competence of drones - as compared to worker bees - is largely unexplored. Hence, we studied humoral and cellular immune reactions of in vitro reared drone larvae and adult drones of different age upon artificial bacterial infection. Haemolymph samples were collected after aseptic and septic injury and subsequently employed for (1) the identification of immune-responsive peptides and/or proteins by qualitative proteomic analyses in combination with mass spectrometry and (2) the detection of antimicrobial activity by inhibition-zone assays. Drone larvae and adult drones responded with a strong humoral immune reaction upon bacterial challenge, as validated by the expression of small antimicrobial peptides. Young adult drones exhibited a broader spectrum of defence reactions than drone larvae. Distinct polypeptides including peptidoglycan recognition protein-S2 and lysozyme 2 were upregulated in immunized adult drones. Moreover, a pronounced nodulation reaction was observed in young drones upon bacterial challenge. Prophenoloxidase zymogen is present at an almost constant level in non-infected adult drones throughout the entire lifespan. All observed immune reactions in drones were expressed in the absence of significant amounts of vitellogenin. We conclude that drones - like worker bees - have the potential to activate multiple elements of the innate immune response.

  11. Gastrointestinal surgery and the acquired immune deficiency syndrome

    PubMed Central

    Weledji, Elroy P.; Nsagha, Dickson; Chichom, Alain; Enoworock, George

    2015-01-01

    Acquired immune-deficiency syndrome (AIDS) is becoming an increasing problem to the surgeon. The impact of HIV/AIDS on surgical practice include the undoubted risk to which the surgeon will expose him or herself, the atypical conditions that may be encountered and the outcome and long term benefit of the surgical treatment in view of disease progression. The two factors most associated with surgical outcome and poor wound healing were AIDS and poor performance status (ASA score). This article questions whether gastrointestinal surgical procedures can be safe and effective therapeutic measures in HIV/AIDS patients and if surgical outcome is worthy of the surgeon's ethical responsibility to treat. As HIV/AIDS patients are not a homogeneous group, with careful patient selection, emergency laparotomy for peritonitis confers worthwhile palliation. However, aggressive surgical intervention must be undertaken with caution and adequate peri-operative care is required. Symptomatic improvement of anorectal pathology may make delayed wound healing an acceptable complication. Alternatives to surgery can be contemplated for diagnosis, prophylaxis or palliation. PMID:25685343

  12. Humoral immune responses among mucosal and cutaneous leishmaniasis patients caused by Leishmania braziliensis.

    PubMed

    Valli, L C; Passos, V M; Dietze, R; Callahan, H L; Berman, J D; Grogl, M

    1999-12-01

    Mucosal leishmaniasis is arguably the most morbid sequelae of cutaneous leishmaniasis. The importance of early diagnosis for effective therapy, coupled with the difficulty of diagnosing the disease parasitologically, prompted this investigation of humoral immune markers of mucosal disease. Promastigote soluble antigens of Leishmania braziliensis, isolated from cutaneous and mucosal lesions, were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis; antigens were identified by immunoblotting with parasite-specific IgG antibody-positive sera of patients with mucosal disease (n = 18) and cutaneous disease (n = 23). For antigens of the cutaneous parasite WR 2095, mucosal sera generally reacted intensely to antigens of 75, 66, and 45 kDa and weakly to 48-50-kDa antigens, whereas cutaneous sera generally detected weakly the first 3 antigens and intensely the latter doublet. The data suggest that the transition from the cutaneous antigenic profile to a mucosal antigenic profile could be used to predict mucosal disease in approximately half of mucosal patients. An additional finding was that antibodies present in the sera of patients with mucosal disease labeled a 66-kDa peptide of normal human lip mucosa more intensely than did cutaneous sera. Autoimmune processes stimulated by the reaction of IgG, originally directed against the 66-kDa of L. braziliensis, to the 66-kDa antigen of mucosal tissue may contribute to the clinical presentation of mucosal leishmaniasis.

  13. Genetic control of the humoral immune response to avian egg white lysozymes in the chicken

    SciTech Connect

    Flanagan, M.P.

    1987-01-01

    Chickens from two closely related sublines, GHs-B6 and GHs-B13, differing serologically at the major histocompatibility complex, were significantly different in their humoral response to three avian egg white lysozymes. Specific antisera levels were measured by radioimmunoassay using /sup 125/I-labeled lysozymes. Antibodies elicited in response to these lysozymes are assumed to be directed against sites on these lysozymes where their amino acid sequence differs from that of the recipient G. domesticus egg white lysozyme (HEL). GHs-B6 birds produced a high level of antibody in response to immunization of turkey (TEL), pheasant (PhL) and guinea hen (GHL) lysozymes. GHs-B13 birds produced no detectable antibody to TEL, were intermediate in their response to PhL and equaled the antibody production of GHs-B6 birds in response to GHL. Antisera to each lysozyme were examined for crossreactivity with all other lysozymes by use of a competitive binding assay.

  14. Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue.

    PubMed

    Mingozzi, F; Chen, Y; Edmonson, S C; Zhou, S; Thurlings, R M; Tak, P P; High, K A; Vervoordeldonk, M J

    2013-04-01

    Antibodies against adeno-associated viral (AAV) vectors are highly prevalent in humans. Both preclinical and clinical studies showed that antibodies against AAV block transduction even at low titers, particularly when the vector is introduced into the bloodstream. Here we measured the neutralizing antibody (NAb) titer against AAV serotypes 2, 5, 6 and 8 in the serum and matched synovial fluid (SF) from rheumatoid arthritis patients. The titer in the SF was lower than that in the matched plasma samples, indicating a difference in distribution of NAb to AAV depending on the body fluid compartment. This difference was more evident for AAV2, against which higher titers were measured. Of all serotypes, anti-AAV5 antibodies were the least prevalent in both the serum and SF. We next evaluated the impact of B-cell depletion on anti-AAV antibodies in rheumatoid arthritis patients who received one or two courses of the anti-CD20 antibody rituximab as part of their disease management. A drop of NAb titer was observed in a subset of those subjects carrying NAb titers ≤1:1000; however, only in a minority of subjects titers dropped below 1:5. This work provides insights into strategies to overcome the limitation of pre-existing humoral immunity to AAV vectors.

  15. Humoral immunity to AAV vectors in gene therapy: challenges and potential solutions.

    PubMed

    Masat, Elisa; Pavani, Giulia; Mingozzi, Federico

    2013-06-01

    Gene transfer trials with adeno-associated virus (AAV) vectors have initiated to unveil the therapeutic potential of this approach, with some of the most exciting results coming from clinical studies of gene transfer for hemophilia B, congenital blindness, and the recent market approval of the first AAV-based gene therapy in Europe. With clinical development, however, some of the limitations of in vivo gene transfer have emerged; in particular the host immune system represents an important obstacle to be overcome in terms of both safety and efficacy of gene transfer in vivo with AAV vectors. Results in humans undergoing gene transfer indicate that capsid-specific T cell responses directed against transduced cells may limit the duration of transgene expression following AAV gene transfer, and similarly anti-AAV neutralizing antibodies can completely prevent transduction of a target tissue, resulting in lack of efficacy. Anti-AAV neutralizing antibodies are highly prevalent in humans, and the frequency of subjects with detectable titers can reach up to two thirds of the population. The approach to the problem of preexisting humoral immunity to AAV so far has been the exclusion of seropositive subjects, but this solution is far from being optimal. Several additional strategies have been proposed and tested in a variety of preclinical animal models. Future studies will help defining the optimal strategy, or combination of strategies, to successfully treat subjects with preexisting antibodies to AAV due to natural infection or to prior administration of AAV vectors. These advancements will likely have a significant impact on the field of gene transfer with AAV vectors.

  16. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    PubMed

    Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  17. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations

    PubMed Central

    Slike, Bonnie M.; Creegan, Matthew

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5–10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10–20 years post vaccination. This contrasted with a comparator group of adults, ages 35–49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112–3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program. PMID:28046039

  18. Trade-offs between acquired and innate immune defenses in humans

    PubMed Central

    McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  19. Hepatobiliary manifestations of the acquired immune deficiency syndrome.

    PubMed

    Cappell, M S

    1991-01-01

    Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these

  20. AIDS (Acquired Immune Deficiency Syndrome) and Employment Discrimination

    DTIC Science & Technology

    1987-09-30

    Protozoal and helminthic infections 1. Cryptosporidiosis 2. Pneumocystis carinii pneumonia (most common disease in AIDS victims) 3. Strongyloidosis 4...diagnosed with either a rare opportunistic infection (01), or cancer2 typically occurring only in individuals with severely compromised immune systems...disorder of the human immune system leading to enhanced susceptibility to particular opportunistic infections and certain cancers.5 In the immune

  1. The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

    PubMed Central

    Sintes, Jordi; Polentarutti, Nadia; Walland, A. Cooper; Yeiser, John R.; Cunha, Cristina; Lacerda, João F.; Salvatori, Giovanni; Blander, J. Magarian

    2016-01-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation–related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell–independent and T cell–dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens. PMID:27621420

  2. Trans-generational and neonatal humoral immune responses in West Greenland sledge dogs (Canis familiaris) exposed to organohalogenated environmental contaminants.

    PubMed

    Sonne, Christian; Larsen, Hans Jørgen S; Kirkegaard, Maja; Letcher, Robert J; Dietz, Rune

    2010-11-01

    Previous investigations in the Arctic have suggested OHC (organohalogen contaminant) induced immune toxic effects on e.g. polar bears (Ursus maritimus). We therefore studied the dietary impact from minke whale blubber (Balaenoptera acutorostrata), rich in polyunsaturated fatty acids and OHCs, on the humoral immunity of 7 captive West Greenland sledge dog (Canis familiaris) bitches and their 4 pups constituting a sentinel model species for polar bears. A control group was composed of 8 bitches and their 5 pups all fed pork (Suis scrofa) fat. The study included serum IgG measurements (bitches and pups) and specific immune responses towards tetanus toxoid (bitches) and diphtheria toxoid (pups) as well as influenza virus (pups). The analyses showed that IgG concentrations were non-significantly lowest in exposed bitches and pups (t-test: all p>0.05). In addition, significant lower antibody response was detected in exposed pups immunized with influenza virus at age 3 months (t-test: both p<0.05). No clear group differences were found for tetanus toxoid in bitches and diphtheria toxoid in pups. The results suggest that the humoral immune system of sledge dogs may be suppressed by the dietary blubber composition of OHCs and polyunsaturated fatty acids while a larger follow-up study is recommended in order to investigate this relationship further.

  3. Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria.

    PubMed

    Huang, Jing; Li, Xiangming; Coelho-dos-Reis, Jordana G A; Zhang, Min; Mitchell, Robert; Nogueira, Raquel Tayar; Tsao, Tiffany; Noe, Amy R; Ayala, Ramses; Sahi, Vincent; Gutierrez, Gabriel M; Nussenzweig, Victor; Wilson, James M; Nardin, Elizabeth H; Nussenzweig, Ruth S; Tsuji, Moriya

    2015-12-01

    In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-γ and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen.

  4. Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors

    PubMed Central

    Sobarzo, Ariel; Stonier, Spencer W.; Herbert, Andrew S.; Ochayon, David E.; Kuehne, Ana I.; Eskira, Yael; Fedida-Metula, Shlomit; Tali, Neta; Lewis, Eli C.; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Yavelsky, Victoria; Dye, John M.; Lobel, Leslie

    2016-01-01

    Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000–2001). Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections. PMID:27187443

  5. Evaluation of the humoral immune response to human leukocyte antigens in Brazilian renal transplant candidates.

    PubMed

    Saito, Patricia Keiko; Yamakawa, Roger Haruki; Aparecida, Erica Pereira; da Silva Júnior, Waldir Verissimo; Borelli, Sueli Donizete

    2014-01-01

    Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

  6. [Changes of humoral and cellular immunity in chronic hepatitis C patients of different staging].

    PubMed

    Masalova, O V; Abdulmedzhidova, A G; Morgunov, K V; Grishchenko, S V; Shkurko, T V; Lakina, E I; Kelli, E I; L'vov, D K; Kushch, A A

    2003-01-01

    The purpose of the present study was to investigate the influence produced by viral proteins in the hepatic cells and RNA of hepatitis C virus (HCV) on the indices of T- and B-cell response in 52 patients with chronic hepatitis C (CHC). A relative count of peripheral-blood lymphocytes (PBL), expressing antigens CD3+, CD4+, CD8+, CD16+, CD20+ and CD95+ was estimated. The repertoire of antibodies to HCV proteins was specified. The thus obtained data were compared with an activity and a disease stage by using the histological diagnosis and alanine-amino-transferase (ALT) level as well as with the presence of HCV RNA in the serum and viral protein of the liver. Such comparison of data and the use of the correlation analysis made it possible to establish that the antibodies to NS5 protein were detected reliably more often in patients with a more pronounced hepatic fibrosis, with a higher ALT activity and with expression of HCV proteins in the liver. At the same time, the presence of proteins in the liver and of RNA in the serum were accompanied by a more active humoral response to the non-structure proteins of NS4 and NS5 as well as by more profound discrepancies of the immunity T-cell chain (a lowered ratio of CD4+/CD8+ and a smaller content of CD95+). There were no differences between PBL of the studied populations in patients with various activities and an HCV stage. A relatively bigger quantity of CD95(+)--positive PBL was found to be reliably higher in patients with viremia but lower in those cases, in which HCV proteins were detected in the liver. This confirms the inhibiting ability of HCV proteins to the Fas-mediated apoptose of PBL in CHC patient.

  7. HIV-specific humoral and cellular immunity in rabbits vaccinated with recombinant human immunodeficiency virus-like gag-env particles

    SciTech Connect

    Haffar, O.K.; Smithgall, M.D.; Moran, P.A.; Travis, B.M.; Zarling, J.M.; Hu, S.L. )

    1991-08-01

    Recombinant human immunodeficiency virus type-1 (HIV-1)-like gag-env particles produced in mammalian cells were inoculated into two New Zealand white rabbits. In parallel, two control rabbits were inoculated with the homologous HIV-1 virions inactivated by ultraviolet light (uv) and psoralen treatments. The humoral and cellular immune responses to HIV-1 were evaluated for both groups of animals. Recombinant particles elicited humoral immunity that was specific for all the viral structural proteins. The antibodies recognized both denatured and nondenatured proteins. Moreover, the sera neutralized the in vitro infectivity of the homologous virus in CEM cells. Importantly, the recombinant particles also generated a T helper response by priming with the HIV proteins. Similar results were observed with inactivated virus immunization. Therefore, the authors results suggest that the recombinant HIV-like particles elicit functional humoral immunity as well as cellular immunity and represent a novel vaccine candidate for AIDS.

  8. Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

    PubMed

    Lambert, Nathaniel D; Haralambieva, Iana H; Kennedy, Richard B; Ovsyannikova, Inna G; Pankratz, Vernon Shane; Poland, Gregory A

    2015-03-15

    Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study (GWAS) to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific neutralizing antibodies. We identified rs2064479 in the HLA-DPB1 genetic region as being significantly associated with humoral immune response variations after rubella vaccination (P = 8.62 × 10(-8)). All other significant SNPs in this GWAS were located near the HLA-DPB1 gene (P ≤ 1 × 10(-7)). These findings demonstrate that polymorphisms in HLA-DPB1 are strongly associated with interindividual differences in neutralizing antibody levels to rubella vaccination and represent a validation of our previous HLA work.

  9. Effects of amoxicillin, ceftiofur, doxycycline, tiamulin and tulathromycin on pig humoral immune responses induced by erysipelas vaccination.

    PubMed

    Pomorska-Mól, M; Kwit, K; Wierzchosławski, K; Dors, A; Pejsak, Z

    2016-05-28

    It addition to their antimicrobial properties, antibiotics can influence the host immune system (modulation of cytokine secretion, antibody production and T-cell proliferation). In the present study, the authors studied the effects of therapeutic doses of amoxicillin (AMX), ceftiofur (CEF), doxycycline (DOXY), tiamulin (TIAM) and tulathromycin (TUL) on the postvaccinal immune response after pigs had been vaccinated against erysipelas. Because humoral immunity is considered as the most important in the protection against swine erysipelas, the present study focused on the interactions between antibiotics and postvaccinal humoral immunity. One hundred and five, eight-week-old pigs of both sexes were used. Specific antibodies to the Erysipelothrix rhusiopathiae antigen were determined using a commercial ELISA test. In pigs treated with DOXY or CEF or TIAM, a significant reduction in the number of positive pigs was observed four and six weeks after the second dose of vaccine, compared with the remaining vaccinated groups. In pigs treated with CEF, the ELISA score was significantly lower than in non-treated vaccinated pigs. While in vaccinated pigs treated with AMX or TUL, the ELISA score was significantly higher than in pigs treated with the remaining antibiotics and than in non-treated vaccinated controls. The results of the present study indicate that vaccination of pigs against erysipelas in the presence of antibiotics may result in a decrease (CEF, DOXY, TIAM) or enhancement (AMX, TUL) in the production of specific antibodies.

  10. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

    PubMed Central

    Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

    2016-01-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

  11. Humoral immunity and CD4+ Th1 cells are both necessary for a fully protective immune response upon secondary infection with Brucella melitensis.

    PubMed

    Vitry, Marie-Alice; Hanot Mambres, Delphine; De Trez, Carl; Akira, Shizuo; Ryffel, Bernhard; Letesson, Jean-Jacques; Muraille, Eric

    2014-04-15

    Brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. Given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. Efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against Brucella. In this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response following priming by the injection of heat-killed or live Brucella melitensis 16M. Using a panel of gene-deficient mice, we demonstrated that during a secondary recall response, both the Brucella-specific humoral response and CD4+ Th1 cells must act together to confer protective immunity in the spleen to B. melitensis infection. Humoral protective immunity is induced by the inoculation of both heat-killed and live bacteria, and its development does not require T cells, MyD88/IL-12p35 signaling pathways, or an activation-induced deaminase-mediated isotype switch. In striking contrast, the presence of memory IFN-γ-producing CD4+ Th1 cells requires the administration of live bacteria and functional MyD88/IL-12p35 pathways. In summary, our work identifies several immune markers closely associated with protective immune memory and could help to define a rational strategy to obtain an effective human vaccine against brucellosis.

  12. Influence of nematode Anguillicoloides crassus infestation on the cellular and humoral innate immunity in European eel (Anguilla anguilla L.)

    PubMed Central

    Terech-Majewska, Elżbieta; Siwicki, Andrzej K.

    2015-01-01

    Parasitic invasions are recognized as one of the primary factors responsible for decreasing populations of European eel. The aim of the present study was to determine the influence of infestation with the nematode Anguillicoloides crassus on the innate immunity in European eel (Anguilla anguilla). Anguillicoloides crassus parasitizes the swim bladder of this fish. Levels of the following immunological parameters were measured: spleen phagocyte respiratory burst activity, spleen phagocyte potential killing activity, pronephros lymphocyte proliferation stimulated by concanavaline A or lipopolisaccharide, plasma lysozyme and ceruloplasmin activity, total protein and immunoglobulin (Ig) serum levels. The analyses of the results of humoral and cellular immunity indicate that all studied parameters were statistically significant higher (p < 0.05) in non-infested fish compared to the ones with anguillicolosis except for ceruloplasmin level. These data suggest that the A. crassus infestation in European eel is responsible for a decreased immune response what could result in higher susceptibility to other pathogenic conditions. PMID:26557024

  13. Evaluation of innate, humoral and cell-mediated immunity in mice following in vivo implantation of electrospun polycaprolactone.

    PubMed

    McLoughlin, Colleen E; Smith, Matthew J; Auttachoat, Wimolnut; Bowlin, Gary L; White, Kimber L

    2012-06-01

    Electrospun polycaprolactone (EPCL) is currently being investigated for use in tissue engineering applications such as vascular grafts. However, the effects of electrospun polymers on systemic immune responses following in vivo exposure have not previously been examined. The work presented evaluates whether EPCL in either a microfibrous or nanofibrous form affects innate, humoral and/or cell-mediated immunity using a standard immunotoxicological testing battery. Holistic in vivo endpoints examined include the antibody-forming cell assay (AFC or plaque assay) and the delayed-type hypersensitivity response to Candida albicans. In addition, natural killer cell cytotoxic activity was assessed using an ex vivo assay and splenic cell population phenotypes were analyzed by flow cytometry for material exposure-related changes. Results indicated that 28 day subcutaneous implantation of EPCL, either in microfibrous or nanofibrous form, did not affect the systemic functions of the immune system in 12-16 week old female B6C3F1 mice.

  14. Recombinant measles viruses expressing single or multiple antigens of human immunodeficiency virus (HIV-1) induce cellular and humoral immune responses.

    PubMed

    Liniger, Matthias; Zuniga, Armando; Morin, Teldja Neige Azzouz; Combardiere, Behazine; Marty, Rene; Wiegand, Marian; Ilter, Orhan; Knuchel, Marlyse; Naim, Hussein Y

    2009-05-26

    Recombinant measles viruses (rMV) based on the live attenuated measles vaccine strain (MVb) expressing antigens of HIV-1 clade B were generated by reverse genetics. Recombinants expressing single or double antigens of HIV-1 (rMV-HIV) were genetically highly stable on human diploid cells. The production process of these viruses was essentially similar to the parental MV strain, yielding comparative end titers. Immunization of tg-mice by different regimens and formulations showed potent humoral and cellular immune responses against MV and HIV antigens. Recombinant MV-HIV expressing Gag protein conferred protective immunity in tg-mice after a high-dose pseudochallenge with recombinant vaccinia virus. In addition, rMV-HIV boosted anti-HIV antibodies, in the presence of pre-existing anti-vector antibodies.

  15. Host age as a determinant of naturally acquired immunity to Plasmodium falciparum.

    PubMed

    Baird, J K

    1995-03-01

    The usual course of infection by Plasmodium falciparum among adults who lack a history of exposure to endemic malaria is fulminant. The infection in adults living with hyper- to holoendemic malaria is chronic and benign. Naturally acquired immunity to falciparum malaria is the basis of this difference. Confusion surrounds an essential question regarding this process: What is its rate of onset? Opinions vary because of disagreement over the relationships between exposure to infection, antigenic polymorphism and naturally acquired immunity. In this review, Kevin Baird discusses these relationships against a backdrop of host age as a determinant of naturally acquired immunity to falciparum malaria.

  16. Heat killed multi-serotype Shigella immunogens induced humoral immunity and protection against heterologous challenge in rabbit model.

    PubMed

    Nag, Dhrubajyoti; Sinha, Ritam; Mitra, Soma; Barman, Soumik; Takeda, Yoshifumi; Shinoda, Sumio; Chakrabarti, M K; Koley, Hemanta

    2015-11-01

    Recently we have shown the homologous protective efficacy of heat killed multi-serotype Shigella (HKMS) immunogens in a guinea pig colitis model. In our present study, we have advanced our research by immunizing rabbits with a reduced number of oral doses and evaluating the host's adaptive immune responses. The duration of immunogenicity and subsequently protective efficacy was determined against wild type heterologous Shigella strains in a rabbit luminal model. After three successive oral immunizations with HKMS immunogens, serum and lymphocyte supernatant antibody titer against the heterologous shigellae were reciprocally increased and remained at an elevated level up to 180 days. Serogroup and serotype specific O-antigen of lipopolysaccharide and immunogenic proteins of heterologous challenge strains were detected by immunoblot assay. Up-regulation of IL-12p35, IFN-γ and IL-10 mRNA expression was detected in immunized rabbit peripheral blood mononuclear cells (PBMC) after stimulation with HKMS in vitro. HKMS-specific plasma cell response was confirmed by production of a relatively higher level of HKMS-specific IgG in immunized PBMC supernatant compared to control group. Furthermore, the immunized groups of rabbits exhibited complete protection against wild type heterologous shigellae challenge. Thus HKMS immunogens induced humoral and Th1-mediated adaptive immunity and provided complete protection in a rabbit model. These immunogens could be a broad spectrum non-living vaccine candidate for human use in the near future.

  17. Empirical evidence of cold stress induced cell mediated and humoral immune response in common myna ( Sturnus tristis)

    NASA Astrophysics Data System (ADS)

    Sandhu, Mansur A.; Zaib, Anila; Anjum, Muhammad S.; Qayyum, Mazhar

    2015-11-01

    Common myna ( Sturnus tristis) is a bird indigenous to the Indian subcontinent that has invaded many parts of the world. At the onset of our investigation, we hypothesized that the immunological profile of myna makes it resistant to harsh/new environmental conditions. In order to test this hypothesis, a number of 40 mynas were caught and divided into two groups, i.e., 7 and 25 °C for 14 days. To determine the effect of cold stress, cell mediated and humoral immune responses were assessed. The macrophage engulfment percentage was significantly ( P < 0.05) higher at 25 °C rather than 7 °C either co-incubated with opsonized or unopsonized sheep red blood cells (SRBC). Macrophage engulfment/cell and nitric oxide production behaved in a similar manner. However, splenic cells plaque formation, heterophil to lymphocyte (H/L) ratio, and serum IgM or IgG production remained non-significant. There was a significant increase of IgG antibody production after a second immunization by SRBC. To the best of our knowledge, these findings have never been reported in the progression of this bird's invasion in frosty areas of the world. The results revealed a strengthened humoral immune response of myna and made this bird suitable for invasion in the areas of harsh conditions.

  18. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.

    PubMed

    Jaillon, Sébastien; Moalli, Federica; Ragnarsdottir, Bryndis; Bonavita, Eduardo; Puthia, Manoj; Riva, Federica; Barbati, Elisa; Nebuloni, Manuela; Cvetko Krajinovic, Lidija; Markotic, Alemka; Valentino, Sonia; Doni, Andrea; Tartari, Silvia; Graziani, Giorgio; Montanelli, Alessandro; Delneste, Yves; Svanborg, Catharina; Garlanda, Cecilia; Mantovani, Alberto

    2014-04-17

    Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs.

  19. Missing the target: DNAk is a dominant epitope in the humoral immune response of channel catfish (Ictalurus punctatus) to Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination remains a viable alternative for bacterial disease protection in fish; however additional work is required to understand the mechanisms of adaptive immunity in the channel catfish. To assess the humoral immune response to Flavobacterium columnare; a group of channel catfish were first im...

  20. Low-Dose Priming Before Vaccination with the Phase I Chloroform-Methanol Residue Vaccine Against Q Fever Enhances Humoral and Cellular Immune Responses to Coxiella Burnetii

    DTIC Science & Technology

    2008-10-01

    Vaccination with the Phase I Chloroform-Methanol Residue Vaccine against Q Fever Enhances Humoral and Cellular Immune Responses to Coxiella burnetii David... I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are...inadvertently vaccinated. The phase I chloroform- methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers

  1. Erythema elevatum diutinum in acquired immune deficiency syndrome: Can it be an immune reconstitution inflammatory syndrome?

    PubMed Central

    Jose, Sheethal K; Marfatia, Yogesh S.

    2016-01-01

    A 47-year-old male with acquired immune deficiency syndrome (AIDS) presented with multiple hyperpigmented papules and nodules on both ankles, dorsum of bilateral feet and soles. It was associated with mild itching and pain. The patient was diagnosed with human immunodeficiency virus (HIV) in 2007. First-line antiretroviral therapy (ART) was started in 2009 to which he responded initially. He was shifted to second-line ART 11 months ago in March 2015 due to treatment failure as suggested by CD4 count of 50 cells/mm3. The present skin lesions started 2 months after the initiation of second-line ART. Differential diagnoses considered were Kaposi's sarcoma and immune reconstitution inflammatory syndrome (IRIS) related infections, but biopsy was suggestive of erythema elevatum diutinum (EED). Patient was started on oral dapsone 100 mg/day and increased to 200 mg/day to which he is responding gradually. In the present case, appearance of the lesions after initiation of second-line ART coupled with increase in CD4 count and decrease of viral load below undetectable level suggest that EED could be an IRIS. PMID:27190420

  2. Acquired immune deficiency syndrome (AIDS). Hypotheses on the etiology.

    PubMed

    Kelly, T A

    1984-08-01

    AIDS could be caused by a mutant hepatitis B virus or even a prion-like agent. Hepatitis B, as a retro-like virus, might induce cancerous cells, which, like other malignant cells, could produce substances that inhibit macrophages and their activation of T-cells. Hepatitis B, by reverse transcription, might become a provirus in or adjacent to the Ir gene of the major histocompatibility locus (MHC) altering the Ia antigen on macrophages and inhibiting the immune response. A prion could by reverse translation produce a similar effect on the Ir gene or by protein----protein replication create new antigenic proteins which could confuse immune signals from the macrophages to T-cells; create enzymes modifying existing antigenic determinants; and create proteins not recognized as "self" that could initiate a frank, but subtle autoimmune phenomenon. Any one, or an interaction of these events, could create a "negative autoimmunity": the immune system would attack itself.

  3. Hepatitis in children with acquired immune deficiency syndrome. Histopathologic and immunocytologic features.

    PubMed

    Duffy, L F; Daum, F; Kahn, E; Teichberg, S; Pahwa, R; Fagin, J; Kenigsberg, K; Kaplan, M; Fisher, S E; Pahwa, S

    1986-01-01

    Hepatic morphology and immunocytology were evaluated in 4 children with clinical and immunologic characteristics of the acquired immune deficiency syndrome or acquired immune deficiency syndrome related complex. All 4 children had hepatomegaly and increased serum alanine and aspartate aminotransferase activity. Both lobular and portal changes were noted. Lymphocytic infiltration, piecemeal necrosis, hepatocellular and bile duct damage, sinusoidal cell hyperplasia, and endothelialitis were prominent. Vesicular rosettes in sinusoidal lymphocytes and tubuloreticular structures in sinusoidal endothelial cells were demonstrated by electron microscopy. The lymphocytic infiltrate in both the lobular and portal spaces was characterized by a relative increase of cytotoxic/suppressor (T8) cells. Hepatitis may be a common feature of pediatric acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex. Although the histopathologic changes are consistent with chronic active hepatitis, the specific pathogenesis remains to be determined.

  4. Essential Roles of TIM-1 and TIM-4 Homologs in Adaptive Humoral Immunity in a Zebrafish Model.

    PubMed

    Xu, Xiao-Gang; Hu, Jing-Fang; Ma, Jun-Xia; Nie, Li; Shao, Tong; Xiang, Li-Xin; Shao, Jian-Zhong

    2016-02-15

    TIM-1 and TIM-4 proteins have become increasingly attractive for their critical functions in immune modulation, particularly in CD4(+) Th2 cell activation. Thus, these proteins were hypothesized to regulate adaptive humoral immunity. However, further evidence is needed to validate this hypothesis. This study describes the molecular and functional characteristics of TIM-1 and TIM-4 homologs from a zebrafish (Danio rerio) model (D. rerio TIM [DrTIM]-1 and DrTIM-4). DrTIM-1 and DrTIM-4 were predominantly expressed in CD4(+) T cells and MHC class II(+) APCs under the induction of Ag stimulation. Blockade or knockdown of both DrTIM-1 and DrTIM-4 significantly decreased Ag-specific CD4(+) T cell activation, B cell proliferation, Ab production, and vaccinated immunoprotection against bacterial infection. This result suggests that DrTIM-1 and DrTIM-4 serve as costimulatory molecules required for the full activation of adaptive humoral immunity. DrTIM-1 was detected to be a trafficking protein located in the cytoplasm of CD4(+) T cells. It can translocate onto the cell surface under stimulation by TIM-4-expressing APCs, which might be a precise regulatory strategy for CD4(+) T cells to avoid self-activation before APCs stimulation. Furthermore, a unique alternatively spliced soluble DrTIM-4 variant was identified to exert a negative regulatory effect on the proliferation of CD4(+) T cells. The above findings highlight a novel costimulatory mechanism underlying adaptive immunity. This study enriches the current knowledge on TIM-mediated immunity and provides a cross-species understanding of the evolutionary history of costimulatory systems throughout vertebrate evolution.

  5. EPSAH, an exopolysaccharide from Aphanothece halophytica GR02, improves both cellular and humoral immunity as a novel polysaccharide adjuvant.

    PubMed

    Zhu, Lei; Zhang, Fan; Yang, Li-Jun; Ge, Yang; Wei, Qing-Fang; Ou, Yu

    2016-07-01

    EPSAH is an exopolysaccharide from Aphanothece halophytica GR02. The present study was designed to evaluate its toxicity and adjuvant potential in the specific cellular and humoral immune responses in ovalbumin (OVA) in mice. EPSAH did not cause any mortality and side effects when the mice were administered subcutaneously twice at the dose of 50 mg·kg(-1). Hemolytic activity in vitro indicated that EPSAH was non-hemolytic. Splenocyte proliferation in vitro was assayed with different concentrations of EPSAH. The mice were immunized subcutaneously with OVA 0.1 mg alone or with OVA 0.1 mg dissolved in saline containing Alum (0.2 mg) or EPSAH (0.2, 0.4, or 0.8 mg) on Day 1 and 15. Two weeks later, splenocyte proliferation, natural killer (NK) cell activity, production of cytokines IL-2 from splenocytes, and serum OVA-specific antibody titers were measured. Phagocytic activity, production of pro-inflammatory cytokines IL-1 and IL-12 in mice peritoneal macrophages were also determined. EPSAH showed a dose-dependent stimulating effect on mitogen-induced proliferation. The Con A-, LPS-, and OVA-induced splenocyte proliferation and the serum OVA-specific IgG, IgG1, and IgG2a antibody titers in the immunized mice were significantly enhanced. EPSAH also significantly promoted the production of Th1 cytokine IL-2. Besides, EPSAH remarkably increased the killing activities of NK cells from splenocytes in the immunized mice. In addition, EPSAH enhanced phagocytic activity and the generation of pro-inflammatory cytokines IL-1 and IL-12 in macrophages. These results indicated that EPSAH had a strong potential to increase both cellular and humoral immune responses, particularly promoting the development of Th1 polarization.

  6. Galleria mellonella larvae are capable of sensing the extent of priming agent and mounting proportionatal cellular and humoral immune responses.

    PubMed

    Wu, Gongqing; Xu, Li; Yi, Yunhong

    2016-06-01

    Larvae of Galleria mellonella are useful models for studying the innate immunity of invertebrates or for evaluating the virulence of microbial pathogens. In this work, we demonstrated that prior exposure of G. mellonella larvae to high doses (1×10(4), 1×10(5) or 1×10(6) cells/larva) of heat-killed Photorhabdus luminescens TT01 increases the resistance of larvae to a lethal dose (50 cells/larva) of viable P. luminescens TT01 infection administered 48h later. We also found that the changes in immune protection level were highly correlated to the changes in levels of cellular and humoral immune parameters when priming the larvae with different doses of heat-killed P. luminescens TT01. Priming the larvae with high doses of heat-killed P. luminescens TT01 resulted in significant increases in the hemocytes activities of phagocytosis and encapsulation. High doses of heat-killed P. luminescens TT01 also induced an increase in total hemocyte count and a reduction in bacterial density within the larval hemocoel. Quantitative real-time PCR analysis showed that genes coding for cecropin and gallerimycin and galiomycin increased in expression after priming G. mellonella with heat-killed P. luminescens TT01. All the immune parameters changed in a dose-dependent manner. These results indicate that the insect immune system is capable of sensing the extent of priming agent and mounting a proportionate immune response.

  7. Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage

    PubMed Central

    Thomas, Susan N.; Rutkowski, Joseph M.; Pasquier, Miriella; Kuan, Emma L.; Alitalo, Kari; Randolph, Gwendalyn J.; Swartz, Melody A.

    2012-01-01

    Lymphatic vessels transport interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs), yet the contribution of peripheral lymphatic drainage to adaptive immunity remains poorly understood. We examined immune responses to dermal vaccination and contact hypersensitivity (CHS) challenge in K14-VEGFR-3-Ig mice, which lack dermal lymphatic capillaries and experience markedly depressed transport of solutes and dendritic cells from the skin to draining LNs. In response to dermal immunization, K14-VEGFR-3-Ig mice produced lower antibody titers. In contrast, although delayed, T cell responses were robust after 21 days, including high levels of antigen-specific CD8+ T cells and production of IFN-γ, IL-4 and IL-10 upon restimulation. T cell-mediated CHS responses were strong in K14-VEGFR-3-Ig mice, but importantly, their ability to induce CHS tolerance in the skin was impaired. Additionally, one-year-old mice displayed multiple signs of autoimmunity. These data suggest that lymphatic drainage plays more important roles in regulating humoral immunity and peripheral tolerance than in effector T cell immunity. PMID:22844119

  8. A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

    PubMed Central

    Dhanwani, Rekha; Zhou, Yanqin; Huang, Qinfeng; Verma, Vikram; Dileepan, Mythili; Ly, Hinh

    2015-01-01

    ABSTRACT Pichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein (NP [P]) gene of the influenza A/PR8 virus. The trisegmented viruses rP18tri-G/H and rP18tri-G/P showed slightly reduced growth in vitro and expressed HA and NP, respectively. Mice immunized with rP18tri-G/H were completely protected against lethal influenza virus challenge even 120 days after immunization. These rP18tri-based vectors could efficiently induce both neutralizing antibodies and antigen-specific T cell responses via different immunization routes. Interestingly, the immune responses were significantly increased upon a booster dose and remained at high levels even after three booster doses. In summary, we have developed a novel PICV-based live vaccine vector that can express foreign antigens to induce strong humoral and cell-mediated immunity and is ideal for a prime-and-boost vaccination strategy. IMPORTANCE We have developed a novel Pichinde virus (PICV)-based live viral vector, rP18tri, that packages three RNA segments and encodes as many as two foreign genes. Using the influenza virus HA and NP genes as model antigens, we show that this rP18tri vector can induce strong humoral and cellular immunity via different immunization routes and can lead to protection in mice. Interestingly, a booster dose further enhances the immune responses, a feature that distinguishes this from other known live viral vectors. In summary, our study demonstrates a unique feature of this

  9. Humoral immune response to oral rabies vaccination in raccoon kits: problems and implications.

    PubMed

    Fry, Tricia L; Vandalen, Kaci K; Shriner, Susan A; Moore, Susan M; Hanlon, Cathleen A; Vercauteren, Kurt C

    2013-06-10

    Little is known about the immunogenicity of RABORAL V-RG(®) (V-RG), an oral rabies vaccine, in raccoon kits (Procyon lotor). The objectives of this study were to characterize the immunogenicity of V-RG in young kits and investigate the potential impact of maternal antibodies on response to vaccination of nursing raccoon kits. Raccoon kits (n=30) were vaccinated at either 3 weeks of age, 7 weeks of age, or assigned as contact controls. Nineteen kits (73%) that were whelped by unvaccinated mothers responded to V-RG exposure (orally or indirect contact) by production of detectable rabies virus neutralizing antibodies (RVNA) while 7 (27%) kits did not respond to V-RG exposure. Four kits were whelped by a mother with high levels of RVNA and all four kits acquired maternal rabies antibodies. At approximately 9 months of age, all kits were inoculated with a killed rabies vaccine, IMRAB3(®). The kits which initially responded to V-RG oral vaccination or contact with vaccinated littermates demonstrated a rapid anamnestic response. In contrast, the V-RG non-responders and those with acquired maternal antibodies exhibited a primary immune response to IMRAB3(®), where RVNA levels were substantially lower on days 5 and 7 than the levels in the animals with an anamnestic response. These findings suggest that the naïve contact kits and the nonresponsive kits most likely remained susceptible to rabies virus infection whereas the ones demonstrating response to V-RG would not have been susceptible to a rabies virus infection.

  10. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice

    PubMed Central

    Barroso, Shana P. C.; Nico, Dirlei; Nascimento, Danielle; Santos, Ana Clara V.; Couceiro, José Nelson S. S.; Bozza, Fernando A.; Ferreira, Ana M. A.; Ferreira, Davis F.; Palatnik-de-Sousa, Clarisa B.; Souza, Thiago Moreno L.; Gomes, Andre M. O.; Silva, Jerson L.; Oliveira, Andréa C.

    2015-01-01

    Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling). Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus. PMID:26056825

  11. Circulating levels of the innate and humoral immune regulators CD14 and CD23 are associated with adult glioma.

    PubMed

    Zhou, Mi; Wiemels, Joseph L; Bracci, Paige M; Wrensch, Margaret R; McCoy, Lucie S; Rice, Terri; Sison, Jennette D; Patoka, Joseph S; Wiencke, John K

    2010-10-01

    Allergy history has been consistently inversely associated with glioma risk. Two serologic markers, soluble CD23 (sCD23) and soluble CD14 (sCD14), are part of the innate and adaptive humoral immune systems and modulate allergic responses in opposite directions, with sCD23 enhancing and sCD14 blunting inflammatory responses. We measured sCD23 and sCD14 in serum from blood that was drawn at a single time point from 1,079 glioma patients postdiagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 [highest versus lowest quartile odds ratio (OR), 3.94; 95% confidence interval (95% CI), 2.98-5.21] and low sCD23 (lowest versus highest quartile OR, 2.5; 95% CI, 1.89-3.23). Results were consistent across glioma histologic types and grades, but were strongest for glioblastoma. Whereas temozolomide treatment was not associated with either sCD14 or sCD23 levels among cases, those taking dexamethasone had somewhat lower sCD23 levels than those not taking dexamethasone. However, sCD23 was associated with case status regardless of dexamethasone treatment. These results augment the long-observed association between allergies and glioma and support a role for the innate and adaptive humoral functions of the immune system, in particular immunoregulatory proteins, in gliomagenesis.

  12. Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity.

    PubMed

    Chen, Shasha; Cai, Chenxu; Li, Zehua; Liu, Guangao; Wang, Yuande; Blonska, Marzenna; Li, Dan; Du, Juan; Lin, Xin; Yang, Meixiang; Dong, Zhongjun

    2017-02-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (TFH) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in TFH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient TFH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP.

  13. Humoral Immune Responses of Dengue Fever Patients Using Epitope-Specific Serotype-2 Virus-Like Particle Antigens

    PubMed Central

    Crill, Wayne D.; Hughes, Holly R.; Delorey, Mark J.; Chang, Gwong-Jen J.

    2009-01-01

    Dengue virus (DENV) is a serious mosquito-borne pathogen causing significant global disease burden, either as classic dengue fever (DF) or in its most severe manifestation dengue hemorrhagic fever (DHF). Nearly half of the world's population is at risk of dengue disease and there are estimated to be millions of infections annually; a situation which will continue to worsen with increasing expansion of the mosquito vectors and epidemic DF/DHF. Currently there are no available licensed vaccines or antivirals for dengue, although significant effort has been directed toward the development of safe and efficacious dengue vaccines for over 30 years. Promising vaccine candidates are in development and testing phases, but a better understanding of immune responses to DENV infection and vaccination is needed. Humoral immune responses to DENV infection are complex and may exacerbate pathogenicity, yet are essential for immune protection. In this report, we develop DENV-2 envelope (E) protein epitope-specific antigens and measure immunoglobulin responses to three distinct epitopes in DENV-2 infected human serum samples. Immunoglobulin responses to DENV-2 infection exhibited significant levels of individual variation. Antibody populations targeting broadly cross-reactive epitopes centered on the fusion peptide in structural domain II were large, highly variable, and greater in primary than in secondary DENV-2 infected sera. E protein domain III cross-reactive immunoglobulin populations were similarly variable and much larger in IgM than in IgG. DENV-2 specific domain III IgG formed a very small proportion of the antibody response yet was significantly correlated with DENV-2 neutralization, suggesting that the highly protective IgG recognizing this epitope in murine studies plays a role in humans as well. This report begins to tease apart complex humoral immune responses to DENV infection and is thus important for improving our understanding of dengue disease and immunological

  14. scFv from Antibody That Mimics gp43 Modulates the Cellular and Humoral Immune Responses during Experimental Paracoccidioidomycosis

    PubMed Central

    Jannuzzi, Grasielle Pereira; Tavares, Aldo Henrique F. P.; Kaihami, Gilberto Hideo; de Almeida, José Roberto Fogaça; de Almeida, Sandro Rogério; Ferreira, Karen Spadari

    2015-01-01

    Paracoccidioidomycosis (PCM), caused by Paracoccidioides species is a prevalent systemic and progressive mycosis that occurs in Latin America. It is caused by Paracoccidioides species. Immunization with dendritic cells transfected with a plasmid encoding the scFv (pMAC/PS-scFv) that mimics the main antigen of P. brasiliensis (gp43) confers protection in experimental PCM. DCs link innate and adaptive immunity by recognizing invading pathogens and selecting the type of effector T cell to mediate the immune response. Here, we showed that DC-pMAC/PS-scFv induces the activation of CD4+ and CD8+ T cells. Moreover, our results demonstrated that BALB/c mice infected with P. brasiliensis and treated with DC-pMAC/PS-scFv showed the induction of specific IgG production against gp43 and IFN-γ, IL-12 and IL-4 cytokines. Analysis of regional lymph nodes revealed increases in the expression of clec7a, myd88, tlr2, gata3 and tbx21, which are involved in the immune response. Taken together, our results indicate that the scFv modulates the humoral and cellular immune responses and presents epitopes to CD4+ and CD8+ T cells. PMID:26091522

  15. Impairment of the humoral and CD4(+) T cell responses in HTLV-1-infected individuals immunized with tetanus toxoid.

    PubMed

    Souza, Anselmo; Santos, Silvane; Carvalho, Lucas P; Grassi, Maria Fernanda R; Carvalho, Edgar M

    2016-08-01

    T cells from HTLV-1-infected individuals have a decreased ability to proliferate after stimulation with recall antigens. This abnormality may be due to the production of regulatory cytokine or a dysfunctional antigen presentation. The aims of this study were to evaluate the antibody production and cytokine expression by lymphocytes before and after immunization with tetanus toxoid (TT) and to evaluate the immune response of monocytes after stimulation with TT and frequency of dendritic cells (DC) subsets. HTLV-1 carriers (HC) and uninfected controls (UC) with negative serology for TT were immunized with TT, and the antibody titers were determined by ELISA as well as the cell activation markers expression by monocytes. The frequencies of DC subsets were determined by flow cytometry. Following immunization, the IgG anti-TT titers and the frequency of CD4(+) T cells expressing IFN-γ, TNF-α and IL-10 in response to TT were lower in the HC than in the UC. Additionally, monocytes from HC did not exhibit increased HLA-DR expression after stimulation with TT, and presented low numbers of DC subsets, therefore, it's necessary to perform functional studies with antigen-presenting cells. Collectively, our finding suggests that HC present an impairment of the humoral and CD4(+) T cell immune responses after vaccination.

  16. Early developmental exposures shape trade-offs between acquired and innate immunity in humans

    PubMed Central

    Georgiev, Alexander V.; Kuzawa, Christopher W.; McDade, Thomas W.

    2016-01-01

    Background and objectives Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. Methodology We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein–Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants’ birth (1983–4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. Results In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. Conclusions and implications Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women. PMID:27530543

  17. Endocrine disorders in Brazilian patients with acquired immune deficiency syndrome.

    PubMed

    Fontes, Rosita; Vangeloti, Andréa; Pires, Maria Lucia; Lima, Mário B C; Dimetz, Trude; Faulhaber, Marcelo; Faria, Raul; Meirelles, Ricardo M

    2003-01-01

    Acquired immunodeficiency syndrome (AIDS) was first reported in Brazil in 1980. In 1997, its incidence was 147 per million and then declined to 90 per million in 2000. Abnormalities of endocrine organ systems occur frequently in patients with AIDS. We evaluated mineralcorticoid, glucocorticoid, and thyroid hormone axes and glucose and insulin responses to a standardized oral glucose dose in healthy individuals; human immunodeficiency virus (HIV)-seropositive, asymptomatic individuals; HIV-infected patients with general lymphadenopathy, diarrhea, fever, fatigue, nocturnal sweating, and weight loss; and HIV-infected patients diagnosed with secondary infectious diseases or neoplasms. Baseline cortisol levels in the patients with AIDS were significantly higher than those in healthy control subjects. However, after adrenocorticotrophic hormone stimulation, cortisol levels were significantly lower in HIV-infected patients. Insulin concentrations were significantly higher after the glucose load in HIV-infected asymptomatic than in patients with AIDS. There were no significant differences in mineralocorticoid or thyroid function among groups.

  18. Evaluation of specific humoral immune response in pigs vaccinated with cell culture adapted classical swine fever vaccine

    PubMed Central

    Nath, Mrinal K.; Sarma, D. K.; Das, B. C.; Deka, P.; Kalita, D.; Dutta, J. B.; Mahato, G.; Sarma, S.; Roychoudhury, P.

    2016-01-01

    Aim: To determine an efficient vaccination schedule on the basis of the humoral immune response of cell culture adapted live classical swine fever virus (CSFV) vaccinated pigs and maternally derived antibody (MDA) in piglets of vaccinated sows. Materials and Methods: A cell culture adapted live CSFV vaccine was subjected to different vaccination schedule in the present study. Serum samples were collected before vaccination (day 0) and 7, 14, 28, 42, 56, 180, 194, 208, 270, 284 and 298 days after vaccination and were analyzed by liquid phase blocking enzyme-linked immunosorbent assay. Moreover, MDA titre was detected in the serum of piglets at 21 and 42 days of age after farrowing of the vaccinated sows. Results: On 28 days after vaccination, serum samples of 83.33% vaccinated pigs showed the desirable level of antibody titer (log10 1.50 at 1:32 dilution), whereas 100% animals showed log10 1.50 at 1:32 dilution after 42 days of vaccination. Animals received a booster dose at 28 and 180 days post vaccination showed stable high-level antibody titre till the end of the study period. Further, piglets born from pigs vaccinated 1 month after conception showed the desirable level of MDA up to 42 days of age. Conclusion: CSF causes major losses in pig industry. Lapinised vaccines against CSFV are used routinely in endemic countries. In the present study, a cell culture adapted live attenuated vaccine has been evaluated. Based on the level of humoral immune response of vaccinated pigs and MDA titer in piglets born from immunized sows, it may be concluded that the more effective vaccination schedule for prevention of CSF is primary vaccination at 2 months of age followed by booster vaccination at 28 and 180 days post primary vaccination and at 1 month of gestation. PMID:27057117

  19. Pathogen-Mimicking Polymeric Nanoparticles based on Dopamine Polymerization as Vaccines Adjuvants Induce Robust Humoral and Cellular Immune Responses.

    PubMed

    Liu, Qi; Jia, Jilei; Yang, Tingyuan; Fan, Qingze; Wang, Lianyan; Ma, Guanghui

    2016-04-06

    Aiming to enhance the immunogenicity of subunit vaccines, a novel antigen delivery and adjuvant system based on dopamine polymerization on the surface of poly(D,L-lactic-glycolic-acid) nanoparticles (NPs) with multiple mechanisms of immunity enhancement is developed. The mussel-inspired biomimetic polydopamine (pD) not only serves as a coating to NPs but also functionalizes NP surfaces. The method is facile and mild including simple incubation of the preformed NPs in the weak alkaline dopamine solution, and incorporation of hepatitis B surface antigen and TLR9 agonist unmethylated cytosine-guanine (CpG) motif with the pD surface. The as-constructed NPs possess pathogen-mimicking manners owing to their size, shape, and surface molecular immune-activating properties given by CpG. The biocompatibility and biosafety of these pathogen-mimicking NPs are confirmed using bone marrow-derived dendritic cells. Pathogen-mimicking NPs hold great potential as vaccine delivery and adjuvant system due to their ability to: 1) enhance cytokine secretion and immune cell recruitment at the injection site; 2) significantly activate and maturate dendritic cells; 3) induce stronger humoral and cellular immune responses in vivo. Furthermore, this simple and versatile dopamine polymerization method can be applicable to endow NPs with characteristics to mimic pathogen structure and function, and manipulate NPs for the generation of efficacious vaccine adjuvants.

  20. Critical role of SAP in progression and reactivation but not maintenance of T cell-dependent humoral immunity.

    PubMed

    Zhong, Ming-Chao; Veillette, André

    2013-03-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. SAP plays a critical role in the initiation of T cell-dependent B cell responses leading to germinal center reaction, the production of high-affinity antibodies, and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. It is important to address this matter not only for mechanistic reasons but also because blockade of the SAP pathway is being contemplated as a means to treat autoimmune diseases in humans. Using an inducibly SAP deficient mouse, we found that SAP was required not only for the initiation but also for the progression of primary T cell-driven B cell responses to haptens. It was also necessary for the reactivation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of the lineage commitment factor Bcl-6 in follicular T helper (T(FH)) cells. However, once memory B cells and long-lived antibody-secreting cells were established, SAP became dispensable for maintaining T cell-dependent B cell responses. Thus, SAP is pivotal for nearly all phases, but not for maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for the treatment of immune disorders by targeting the SAP pathway.

  1. Effects of fish protein hydrolysate on growth performance and humoral immune response in large yellow croaker (Pseudosciaena crocea R.)* §

    PubMed Central

    Tang, Hong-gang; Wu, Tian-xing; Zhao, Zhan-yu; Pan, Xiao-dong

    2008-01-01

    We investigated the effects of fish protein hydrolysate (FPH) on growth performance and humoral immune response of the large yellow croaker (Pseudosciaena crocea R.). One thousand and two hundred large yellow croakers [initial average weight: (162.75±23.85) g] were divided into four groups and reared in floating sea cages (3 m×3 m×3 m). The animals were fed with 4 diets: basal diet only (control) or diets supplemented with 5%, 10% and 15% (w/w) FPH. The results show that dietary FPH levels significantly influenced the growth and immunity of the large yellow croaker. Compared with the control group, total weight gain (TWG) in all treatment groups, relative weight gain (RWG) and specific growth rate (SGR) in fish fed with diets supplemented with 10% and 15% FPH were significantly increased (P<0.05). Similar results were observed in immune parameters [lysozyme activity, serum complements, immunoglobulin M (IgM)]. Lysozyme activity, complement C4 and IgM were also significantly increased (P<0.05) in fish fed with diets supplemented with 10% and 15% FPH, while complement C3 level was significantly increased (P<0.05) in all treatment groups. In general, with the supplementation of FPH, particularly at dose of 10%, the growth performance and immunity of the large yellow croaker can be improved effectively. PMID:18763300

  2. Effects of fish protein hydrolysate on growth performance and humoral immune response in large yellow croaker (Pseudosciaena crocea R.).

    PubMed

    Tang, Hong-gang; Wu, Tian-xing; Zhao, Zhan-yu; Pan, Xiao-dong

    2008-09-01

    We investigated the effects of fish protein hydrolysate (FPH) on growth performance and humoral immune response of the large yellow croaker (Pseudosciaena crocea R.). One thousand and two hundred large yellow croakers [initial average weight: (162.75+/-23.85) g] were divided into four groups and reared in floating sea cages (3 m x 3 m x 3 m). The animals were fed with 4 diets: basal diet only (control) or diets supplemented with 5%, 10% and 15% (w/w) FPH. The results show that dietary FPH levels significantly influenced the growth and immunity of the large yellow croaker. Compared with the control group, total weight gain (TWG) in all treatment groups, relative weight gain (RWG) and specific growth rate (SGR) in fish fed with diets supplemented with 10% and 15% FPH were significantly increased (P<0.05). Similar results were observed in immune parameters [lysozyme activity, serum complements, immunoglobulin M (IgM)]. Lysozyme activity, complement C4 and IgM were also significantly increased (P<0.05) in fish fed with diets supplemented with 10% and 15% FPH, while complement C3 level was significantly increased (P<0.05) in all treatment groups. In general, with the supplementation of FPH, particularly at dose of 10%, the growth performance and immunity of the large yellow croaker can be improved effectively.

  3. Acquired immune deficiency syndrome (AIDS) in Brazil. Necropsy findings.

    PubMed

    Michalany, J; Mattos, A L; Michalany, N S; Filie, A C; Montezzo, L C

    1987-01-01

    According to the 15 autopsies performed at the Department of Pathological Anatomy, Escola Paulista de Medicina, São Paulo, Brazil, it was confirmed that acquired immunodeficiency syndrome (AIDS) occurs preferably in young homosexual males, who die in a short period of time of the disease, which leads to a consumptive state verified by cachexia of the cadavers. The most affected organs of this series were the lungs and encephalum, exactly the ones responsible for the immediate cause of death. In this series of autopsies there were 9 types of microorganisms represented by virus, bacteria, fungi, protozoans and two types of tumors, Kaposi's sarcoma and lymphoma of the central nervous system. From the microorganisms, the most frequent was the Cytomegalovirus and, from the tumors, Kaposi's sarcoma. The various types of microorganisms were frequently associated, principally in the central nervous and digestive systems. There was also association of microorganisms with tumors. Besides the lesions produced by microorganisms there were other associated alterations as brown atrophy of neuronia, which was related to the infiltration of cerebral lymphoma, and the lymphocytic depletion of lymphoid organs due to immunological exhaustion. Cellular reaction to microorganisms was practically none, principally with Pneumocystis carinii and Cryptococcus neoformans, the first one behaving as an inert mould in the pulmonary alveoli and the second proliferating freely in tissues. In two cases there was no granulomatous reaction to Mycobacterium tuberculosis. The primary lymphoma of the central nervous system should be interpreted as a microglioma, i.e., a reticulosarcoma of this system according to Hortega's school.

  4. Acquired immunity and stochasticity in epidemic intervals impede the evolution of host disease resistance.

    PubMed

    Harding, Karin C; Hansen, B Johan L; Goodman, Simon J

    2005-12-01

    Disease can generate intense selection pressure on host populations, but here we show that acquired immunity in a population subject to repeated disease outbreaks can impede the evolution of genetic disease resistance by maintaining susceptible genotypes in the population. Interference between the life-history schedule of a species and periodicity of the disease has unintuitive effects on selection intensity, and stochasticity in outbreak period further reduces the rate of spread of disease-resistance alleles. A general age-structured population genetic model was developed and parameterized using empirical data for phocine distemper virus (PDV) epizootics in harbor seals. Scenarios with acquired immunity had lower levels of epizootic mortality compared with scenarios without acquired immunity for the first PDV outbreaks, but this pattern was reversed after about five disease cycles. Without acquired immunity, evolution of disease resistance was more rapid, and long-term population size variation is efficiently dampened. Acquired immunity has the potential to significantly influence rapid evolutionary dynamics of a host population in response to age-structured disease selection and to alter predicted selection intensities compared with epidemiological models that do not consider such feedback. This may have important implications for evolutionary population dynamics in a range of human, agricultural, and wildlife disease settings.

  5. Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses

    PubMed Central

    Moreno, Noelia; Mena, Ignacio; Angulo, Iván; Gómez, Yolanda; Crisci, Elisa; Montoya, María; Castón, José R.; Blanco, Esther; Bárcena, Juan

    2016-01-01

    Virus-like particles (VLPs), comprised of viral structural proteins devoid of genetic material, are tunable nanoparticles that can be chemically or genetically engineered, to be used as platforms for multimeric display of foreign antigens. Here, we report the engineering of chimeric VLPs, derived from rabbit hemorrhagic disease virus (RHDV) for presentation of foreign B-cell antigens to the immune system. The RHDV capsid comprises 180 copies of a single capsid subunit (VP60). To evaluate the ability of chimeric RHDV VLPs to elicit protective humoral responses against foreign antigens, we tested two B-cell epitopes: a novel neutralizing B-cell epitope, derived from feline calicivirus capsid protein, and a well characterized B-cell epitope from the extracellular domain of influenza A virus M2 protein (M2e). We generated sets of chimeric RHDV VLPs by insertion of the foreign B-cell epitopes at three different locations within VP60 protein (which involved different levels of surface accessibility) and in different copy numbers per site. The immunogenic potential of the chimeric VLPs was analyzed in the mouse model. The results presented here indicated that chimeric RHDV VLPs elicit potent protective humoral responses against displayed foreign B-cell epitopes, demonstrated by both, in vitro neutralization and in vivo protection against a lethal challenge. PMID:27549017

  6. Isolation, antiproliferation on tumor cell and immunomodulatory activity of BSP-I, a novel bursal peptide from chicken humoral immune system.

    PubMed

    Feng, Xiuli; Liu, Taoqing; Wang, Fangquan; Cao, Ruibing; Zhou, Bin; Zhang, Yu; Mao, Xiang; Chen, Puyan; Zhang, Hui

    2011-06-01

    The bursa of Fabricius (BF) is acknowledged as central humoral immune organ unique to birds. Our purpose was to identify the potential function of a novel bursal-derived bioactive peptide. A bursal septpeptide (BSP-I), EPASGMM, first isolated from BF, reduced MCF and Hela tumor cells proliferation, and enhanced antitumor factor p53 luciferase activity and protein expression. Further, we found the significantly immune inducing function of BSP-I on antigen-specific immune response in BALB/c mice intraperitoneally immunized with inactivated avian influence virus (AIV, H(9)N(2) subtype) vaccine, including of enhancing the antibody (IgG, the isotypes IgG1 and IgG2a) production, and stimulating cytokines IL-4 and IFN-γ level, and inducing T cell immunophenotyping and lymphocyte proliferation. These results suggested that as the bioactive peptide from avian humoral immune system, various biological function of BSP-I may have far-reaching implication on immune system significance, which might provide novel insight on linking between humoral immune system and development of effective immunotherapeutic strategies for treating human cancers diseases.

  7. Toward immunogenetic studies of amphibian chytridiomycosis: Linking innate and acquired immunity

    USGS Publications Warehouse

    Richmond, J.Q.; Savage, Anna E.; Zamudio, Kelly R.; Rosenblum, E.B.

    2009-01-01

    Recent declines in amphibian diversity and abundance have contributed significantly to the global loss of biodiversity. The fungal disease chytridiomycosis is widely considered to be a primary cause of these declines, yet the critical question of why amphibian species differ in susceptibility remains unanswered. Considerable evidence links environmental conditions and interspecific variability of the innate immune system to differential infection responses, but other sources of individual, population, or species-typical variation may also be important. In this article we review the preliminary evidence supporting a role for acquired immune defenses against chytridiomycosis, and advocate for targeted investigation of genes controlling acquired responses, as well as those that functionally bridge the innate and acquired immune systems. Immunogenetic data promise to answer key questions about chytridiomycosis susceptibility and host-pathogen coevolution, and will draw much needed attention to the importance of considering evolutionary processes in amphibian conservation management and practice. ?? 2009 by American Institute of Biological Sciences.

  8. Humoral Immune Responses of White-tailed Deer (Odocoileus virginianus) to Mycobacterium bovis BCG Vaccination and Experimental Challenge with M. bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Monitoring serum antibody production kinetics to multiple mycobacterial antigens can be useful as a diagnostic tool for the detection of Mycobacterium bovis infection as well as for the characterization of disease progression and efficacy of intervention strategies in several species. Humoral immun...

  9. [Changes of local resistance of oral cavity and humoral immunity among workers of metallurgical and chemical production during parodontitis].

    PubMed

    Kobakhidze, M V; Dzhashi, L M; Chelidze, L N; Gogebashvili, N V

    2005-01-01

    On the basis of the data of immunological investigations of 142 workers of metallurgical (melting shops of Zestaphoni's Farroalloy Plant) and chemical (electrolytic shops of manganese and dioxide manganese of Farroalloy Plant and "Azoti") production it was found that during parodontitis among studied contingent local resistance of mouth cavity and humoral immunity are changed, the compound of lysozyme and amylase in saliva is lowered, in the layers of saliva and blood is revealed the misbalance of immunoglobulin's system. First of all was established, that during parodontitis among the studied workers autoimmune processes are developed directed against the I-st type collagen and the tissue of gum. Changes of local and common homeostasis as well as the changes of intensity of autoimmune process are in direct correlation with the severity of parodontitis and the pollution of production environment with the spray of manganese dioxide.

  10. Prolonged suppression of chick humoral immune response by antigen specific maternal antibody.

    PubMed

    Elazab, Mohamed Fahmy Abou; Fukushima, Yuji; Horiuchi, Hiroyuki; Matsuda, Haruo; Furusawa, Shuichi

    2009-04-01

    Although the inhibitory effect of maternal antibodies on active immunization of neonates has been extensively documented, much less attention has been devoted on the exact level of these antibodies which can induce this effect and the extent of such effect. Firstly, laying hens were immunized with dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH).Then, maternal anti-DNP antibodies in chicks derived from these hens were measured by using enzyme-linked immunosorbent assay (ELISA). Chicks with high levels of maternal anti-DNP showed immune suppression, while chicks with low levels of maternal anti-DNP showed normal immune response when they immunized with the same antigen at 1 and 4 weeks of age. Then, different doses of purified maternal anti-DNP were transferred to fertile eggs at 16 days of embryogenesis by in ovo injection and all chicks were immunized with DNP-KLH at 1 and 4 weeks of age. Chicks received 1 mg of anti-DNP showed normal immune response, chicks received 3 mg of anti-DNP showed weak immune response, and chicks received 5 and 8 mg of anti-DNP showed immune suppression. Chicks received 8 mg of anti-DNP were immunized with DNP-KLH at 4 and 7 weeks of age. Their immune response was significantly lower than that of chicks of no-maternal anti-DNP. These results suggested that high levels of maternal antibodies interfere or suppress the immune response of active immunization not only at early period but also at the period in which the maternal antibodies at very low levels.

  11. Using Humor in Physical Education

    ERIC Educational Resources Information Center

    Barney, David; Christenson, Robert

    2013-01-01

    Humor can be extremely beneficial in everyday life, whether giving or receiving it. It can be used to lighten the mood, give encouragement, or make corrections. Humor in physical education is no exception. Physical educators can use humor as a teaching tool and to create an environment for students to acquire the knowledge to practice a lifetime…

  12. Assessment of selected biochemical parameters and humoral immune response of Nile crocodiles (Crocodylus niloticus) experimentally infected with Trichinella zimbabwensis.

    PubMed

    La Grange, Louis J; Mukaratirwa, Samson

    2014-08-21

    Fifteen crocodiles were randomly divided into three groups of five animals. They represented high-infection, medium-infection and low-infection groups of 642 larvae/kg, 414 larvae/kg and 134 larvae/kg bodyweight, respectively. The parameters assessed were blood glucose, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT). The humoral immune response to Trichinella zimbabwensis infection was evaluated in all three groups by an indirect ELISA method. The results showed deviations from normal parameters of blood glucose, CPK, LDH, AST and ALT when compared with reported levels in uninfected reptiles. Contrary to studies involving mammals, hypoglycaemia was not observed in the infected groups in this study. Peak values of blood glucose were reached on post-infection (PI) Day 49, Day 42 and Day 35 in the high-infection, medium-infection and low-infection groups, respectively. Peak values of LDH and AST were observed on PI Day 56, Day 49 and Day 42 in the high-infection, medium-infection and low-infection groups, respectively. Peak values of CPK were observed on Day 35 PI in all three groups. Peak ALT values were reached on Day 56 in the high-infection group and on Day 28 PI in both the medium-infection and low-infection groups. No correlations between the biochemical parameters and infection intensity were observed. Peak antibody titres were reached on Day 49 PI in the medium-infection group, and on Day 42 PI in both the high-infection and low-infection groups. Infection intensity could not be correlated with the magnitude of the humoral immune response or time to sero-conversion. Results from this study were in agreement with results reported in mammals infected with other Trichinella species and showed that antibody titres could not be detected indefinitely.

  13. Avian CD154 enhances humoral and cellular immune responses induced by an adenovirus vector-based vaccine in chickens.

    PubMed

    Sánchez Ramos, Oliberto; González Pose, Alain; Gómez-Puerta, Silvia; Noda Gomez, Julia; Vega Redondo, Armando; Águila Benites, Julio César; Suárez Amarán, Lester; Parra, Natalie C; Toledo Alonso, Jorge R

    2011-05-01

    Recombinant adenoviral vectors have emerged as an attractive system for veterinary vaccines development. However, for poultry vaccination a very important criterion for an ideal vaccine is its low cost. The objective of this study was to test the ability of chicken CD154 to enhance the immunogenicity of an adenoviral vector-based vaccine against avian influenza virus in order to reduce the amount of antigen required to induce an effective immune response in avian. Chickens were vaccinated with three different doses of adenoviral vectors encoding either HA (AdHA), or HA fused to extracellular domain chicken's CD154 (AdHACD). Hemagglutination inhibition (HI) assay and relative quantification of IFN-γ showed that the adenoviral vector encoding for the chimeric antigen is able to elicit an improved humoral and cellular immune response, which demonstrated that CD154 can be used as a molecular adjuvant allowing to reduce in about 50-fold the amount of adenoviral vector vaccine required to induce an effective immune response.

  14. Effect of different levels of dietary sweet orange (Citrus sinensis) peel extract on humoral immune system responses in broiler chickens.

    PubMed

    Pourhossein, Zohreh; Qotbi, Ali Ahmad Alaw; Seidavi, Alireza; Laudadio, Vito; Centoducati, Gerardo; Tufarelli, Vincenzo

    2015-01-01

    This experiment was conducted to evaluate the effects of different levels of sweet orange (Citrus sinensis) peel extract (SOPE) on humoral immune system responses in broiler chickens. Three hundred 1-day broilers (Ross-308) were randomly allocated to treatments varying in supplemental SOPE added in the drinking water. The experimental groups consisted of three treatments fed for 42 days as follows: a control treatment without feed extract, a treatment containing 1000 ppm of SOPE and a treatment containing 1250 ppm of SOPE. All treatments were isocaloric and isonitrogenous. Broilers were vaccinated with Newcastle disease virus (NDV), avian influenza (AI), infectious bursal disease (IBD) and infectious bronchitis virus (IBV) vaccines. Antibody titer response to sheep red blood cells (SRBC) was higher in the group fed 1250 ppm of SOPE (P < 0.05) as well as for immunoglobulin G (IgG) and IgM. Similarly, antibody titer responses to all vaccines were constantly elevated (P < 0.05) by SOPE enrichment in a dose-dependent manner. Relative weights of spleen and bursa of Fabricius were unaffected by treatments. Dietary SOPE supplementation may improve the immune response and diseases resistance, indicating that it can constitute a useful additive in broiler feeding. Thus, supplying SOPE in rations may help to improve relative immune response in broiler chickens.

  15. Drosophila immune priming against Pseudomonas aeruginosa is short-lasting and depends on cellular and humoral immunity

    PubMed Central

    Apidianakis, Yiorgos

    2013-01-01

    Immune responses are traditionally divided into the innate and the adaptive arm, both of which are present in vertebrates, while only the innate arm is found in invertebrates. Immune priming experiments in Drosophila melanogaster and other invertebrates during the last decade have challenged this dogma, questioning the boundaries between innate and adaptive immunity. Studies on repeated inoculation of Drosophila with microbes reveal a long-lasting cellular immunity adaptation against particular microorganisms. Here we study the lasting effect of immune priming against infection with Pseudomonas aeruginosa, an opportunistic human pathogen that is lethal to the common fruit fly. Drosophila priming with heat-killed or low in virulence P. aeruginosa extends fly survival during a secondary lethal infection with a virulent strain of the same species. The protective immune response can last for more than 10 days after exposure to a persistent low-in-virulence live infection, but it is eliminated 7 days after the host is primed with heat-killed bacteria. Moreover, not only the cellular, but also the systemic NF-κB-mediated immune responses contribute to immune priming. Thus each microbe might elicit different mechanisms of immune priming that may or may not last for long. PMID:24358857

  16. Evidence of a humoral immune response against the prokaryotic expressed N-terminal autoprotease (N(pro)) protein of bovine viral diarrhoea virus.

    PubMed

    Mishra, Niranjan; Rajukumar, Katherukamem; Pitale, Shruti Shrikant; Prakash, Anil; Nema, Ram Kumar; Behera, Sthita Pragnya; Dubey, Shiv Chandra

    2010-03-01

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle and sheep belonging to the genus Pestivirus of the family Flaviviridae. Although the BVDV non-structural N-terminal protease (N(pro)) acts as an interferon antagonist and subverts the host innate immunity, little is known about its immunogenicity. Hence, we expressed a recombinant BVDV N(pro)-His fusion protein (28 kDa) in E. coli and determined the humoral immune response generated by it in rabbits. The antigenicity of the N(pro) protein was confirmed by western blot using anti-BVDV hyperimmune cattle, sheep and goat serum, and anti-N(pro) rabbit serum. When rabbits were immunized with the N(pro) protein, a humoral immune response was evident by 4 weeks and persisted till 10 weeks post immunization as detected by ELISA and western blot. Despite N(pro)-specific antibodies remaining undetectable in 80 serum samples from BVDV-infected sheep and goats, BVDV hyperimmune sera along with some of the field cattle, sheep and goat sera with high BVDV neutralizing antibody titres were found positive for N(pro) antibodies. Our results provide evidence that despite the low immunogenicity of the BVDV N(pro) protein, a humoral immune response is induced in cattle, sheep and goats only with repeated BVDV exposure.

  17. Development of a lipopolysaccharide (LPS)-supplemented adjuvant and its effects on cell-mediated and humoral immune responses in male rats immunized against sperm

    PubMed Central

    NOGUCHI, Junko; WATANABE, Shinya; NGUYEN, Thanh Q. Dang; KIKUCHI, Kazuhiro; KANEKO, Hiroyuki

    2016-01-01

    Supplementation with lipopolysaccharide (LPS) from non-pathogenic Escherichia coli was found to enhance the adjuvant effects of a veterinary vaccine adjuvant (ISA 71VG®). Sperm immunization using 71VG as an adjuvant in the immature period induced infertility in 25% of male rats, whereas this increased to 62.5% after immunization with 71VG + LPS or Freund′s complete adjuvant (FCA). Mean testicular weight of non-sterile males in the 71VG + LPS group was significantly lower than that in the 71VG or FCA group. Histological examination of testicular tissue from sterile males demonstrated severe impairment of spermatogenesis due to experimental autoimmune orchitis, a cell-mediated autoimmune condition. The serum anti-sperm titer was elevated in the three sperm-immunized groups relative to male rats treated with adjuvant alone, but the titer was higher in the 71VG + LPS and FCA groups than in the 71VG group. We consider that this LPS-supplemented adjuvant stimulates both humoral and cell-mediated immune responses to an extent comparable to FCA. PMID:27890874

  18. Atopic manifestations in the acquired immune deficiency syndrome: response to recombinant interferon gamma.

    PubMed Central

    Parkin, J M; Eales, L J; Galazka, A R; Pinching, A J

    1987-01-01

    Six patients with the acquired immune deficiency syndrome (AIDS) had exacerbations or recurrences of previously quiescent atopic disease when they developed immunodeficiency. Four developed a different atopic illness from that suffered previously. Atopic symptoms developed within three months after the patients developed AIDS or during prodromal illness. Two of the patients were treated with recombinant interferon gamma: both showed a striking improvement in symptoms and cellular immunity. These results indicate that cellular immunity, through interferon gamma, may have a role in regulating atopic disease. PMID:3109572

  19. Disseminated varicella zoster virus in an immunized child as the acquired immunodeficiency syndrome-defining illness.

    PubMed

    Chilek, Katherine; Routhouska, Shannon; Tamburro, Joan

    2010-01-01

    Varicella zoster virus (VZV) immunization aids in the prevention of future VZV infections in immunocompetent patients; however, severely immunocompromised patients remain at increased risk of VZV infection. We report a case of a 10-year-old boy previously immunized to Varicella who presented with herpes zoster with hematogenous dissemination as the Acquired Immunodeficiency Syndrome-defining illness. Disseminated VZV is more commonly seen in human immunodeficiency virus (HIV)-infected individuals with more advanced disease, as was the case with our patient. Disseminated VZV infection in a previously immunized child should raise suspicion for underlying immunosuppression.

  20. Masking of antigenic epitopes by antibodies shapes the humoral immune response to influenza

    PubMed Central

    Zarnitsyna, Veronika I.; Ellebedy, Ali H.; Davis, Carl; Jacob, Joshy; Ahmed, Rafi; Antia, Rustom

    2015-01-01

    The immune responses to influenza, a virus that exhibits strain variation, show complex dynamics where prior immunity shapes the response to the subsequent infecting strains. Original antigenic sin (OAS) describes the observation that antibodies to the first encountered influenza strain, specifically antibodies to the epitopes on the head of influenza's main surface glycoprotein, haemagglutinin (HA), dominate following infection with new drifted strains. OAS suggests that responses to the original strain are preferentially boosted. Recent studies also show limited boosting of the antibodies to conserved epitopes on the stem of HA, which are attractive targets for a ‘universal vaccine’. We develop multi-epitope models to explore how pre-existing immunity modulates the immune response to new strains following immunization. Our models suggest that the masking of antigenic epitopes by antibodies may play an important role in describing the complex dynamics of OAS and limited boosting of antibodies to the stem of HA. Analysis of recently published data confirms model predictions for how pre-existing antibodies to an epitope on HA decrease the magnitude of boosting of the antibody response to this epitope following immunization. We explore strategies for boosting of antibodies to conserved epitopes and generating broadly protective immunity to multiple strains. PMID:26194761

  1. Humoral Immunity through Immunoglobulin M Protects Mice from an Experimental Actinomycetoma Infection by Nocardia brasiliensis

    PubMed Central

    Salinas-Carmona, Mario C.; Pérez-Rivera, Isabel

    2004-01-01

    An experimental model of infection with Nocardia brasiliensis, used as an example of a facultative intracellular pathogen, was tested. N. brasiliensis was injected into the rear foot pads of BALB/c mice to establish an infection. Within 30 days, infected animals developed a chronic actinomycetoma infection. Batch cultures of N. brasiliensis were used to purify P61, P38, and P24 antigens; P61 is a catalase, and P38 is a protease with strong caseinolytic activity. Active and passive immunizations of BALB/c mice with these three purified soluble antigens were studied. Protection was demonstrated for actively immunized mice. However, immunity lasted only 30 days. Other groups of immunized mice were bled at different times, and their sera were passively transferred to naive recipients that were then infected with N. brasiliensis. Sera collected 5, 6, and 7 days after donor immunization conferred complete, long-lasting protection. The protective effect of passive immunity decreased when sera were collected 2 weeks after donor immunization. However, neither the early sera (1-, 2-, and 3-day sera) nor the later sera (30- or 45-day sera) prevented the infection. Hyperimmune sera with the highest levels of immunoglobulin G (IgG) to N. brasiliensis antigens did not protect at all. The antigens tested induced two IgM peaks. The first peak was present 3 days after immunization but was not antigen specific and did not transfer protection. The second peak was evident 7 days after immunization, was an IgM response, was antigen specific, and conferred protection. This results clearly demonstrate that IgM antibodies protect the host against a facultative intracellular bacterium. PMID:15385456

  2. [Diagnosis and treatment of major protozoal infections among acquired immune deficiency syndrome patients].

    PubMed

    Shen, Yin-Zhong; Lu, Hong-Zhou

    2008-04-01

    Protozoal infection is one of the most important opportunistic infections among patients with acquired immune deficiency syndrome (AIDS). In order to enhance the knowledge of protozoal infections in AIDS, the current status of diagnosis and treatment of toxoplasmic encephalitis, cryptosporidiosis, microsporidiosis and isosporiasis was reviewed in this paper.

  3. Acquired Immune Deficiency Syndrome, AIDS: A Selected Bibliography of Federal Government Publications. Research Guide 90 104.

    ERIC Educational Resources Information Center

    Alexander, Margaret

    This research guide presents a selected bibliography of federal government publications about the Acquired Immune Deficiency Syndrome (AIDS). These documents are listed in five categories: (1) Bibliographies (7); (2) Congressional Publications (69 hearings and reports); (3) Executive Branch Publications (43 reports); (4) Federal Government…

  4. AIDS. Acquired Immune Deficiency Syndrome Curriculum Planning Guidelines: Elementary, Junior High, High School.

    ERIC Educational Resources Information Center

    Montana State Dept. of Public Instruction, Helena.

    The support materials in this guide provide background and content materials for school personnel and others to modify and use in their education programming on Acquired Immune Deficiency Syndrome (AIDS) for K-12 students. The following support materials are included: (1) the U.S. Surgeon General's report on AIDS; (2) digest and reference guide to…

  5. Acquired Immune Deficiency Syndrome: A Preliminary Examination of the Effects on Gay Couples and Coupling.

    ERIC Educational Resources Information Center

    Carl, Douglas

    1986-01-01

    The Acquired Immune Deficiency Syndrome (AIDS) epidemic significantly influences attitudes about life and lifestyles. Homosexuals have to give increased consideration to coupling, the nature of coupled relationships, sex and intimacy, and death long before the normal time. Discusses impact of AIDS on the early stages of gay coupling and on the…

  6. AIDS Instruction about Acquired Immune Deficiency Syndrome in Wisconsin Schools. Bulletin No. 8248.

    ERIC Educational Resources Information Center

    Taff, Laura

    This document provides a comprehensive framework for school districts to follow in developing instruction about Acquired Immune Deficiency Syndrome (AIDS) within kindergarten through 12th grade health education programs. A curriculum progression matrix about AIDS is included. It lists student outcome objectives by grade level in the areas of…

  7. Humoral immune responses and CD27+ B cells in children with DiGeorge syndrome (22q11.2 deletion syndrome).

    PubMed

    Finocchi, A; Di Cesare, S; Romiti, M L; Capponi, C; Rossi, P; Carsetti, R; Cancrini, C

    2006-08-01

    The spectrum of T-cell abnormalities in 22q11.2 syndrome is quite broad, ranging from profound and life threatening to non-existent defects. Humoral abnormalities have been described in some of these patients, although no data are currently available on their phenotypical and functional B cell subsets. The purpose of this study was to investigate humoral immune function in a cohort of 13 children with DiGeorge syndrome by immunophenotyping B and by analysing their functionality in vivo. Humoral immunity was assessed by serum immunoglobulin evaluation, IgG subclasses determination, and testing of specific antibody titers to recall antigens. B cells were analyzed by flow cytometry and the relevant percentage of membrane surface expression of CD27, IgM, IgD was evaluated. In our cohort, one of 13 children (7.7%) had a complete IgA deficiency, four of 13 (30.7%) had minor immunoglobulin abnormalities, and five (38%) had an impaired production of specific antibodies. Five of 13 children (38%) had recurrent infections. Interestingly, peripheral CD27+ B cells were reduced in our patients as compared with age-matched healthy controls, and this decrement was statistically significant for IgM+ IgD+ CD27+ B cells. Immunoglobulin abnormalities were associated with the occurrence of recurrent infections. We conclude that a significant proportion of patients with DiGeorge syndrome have defective humoral immunity, which may represent an additional pathogenic mechanism underlying the increased susceptibility to infections. Whether the decreased CD27+ B-cell subset might be one of the defects that contribute to impaired humoral immunity, and to susceptibility to infection remains to be elucidated.

  8. Effects of Space Radiation on Humoral and Cellular Immunity in Rhesus Monkeys.

    DTIC Science & Technology

    1992-12-01

    About 10% were antinuclear antibodies that are associated with renal disease, especially systemic lupus erythematosus (Schwartz, 1986). ASSAY OF T...possible late effects of ionizing radiations on parameters associated with B-cell and T-cell functions. Antibody -mediated immune (AMI) functior was...study were as follows: 1. To assess the possible effects of radiation on antibody - mediated immune (AMI) function by measuring immunoglobulin (Ig

  9. Induction of humoral immune response against Plasmodium falciparum sporozoites by immunization with a synthetic peptide mimotope whose sequence was derived from screening a filamentous phage epitope library.

    PubMed

    Stoute, J A; Ballou, W R; Kolodny, N; Deal, C D; Wirtz, R A; Lindler, L E

    1995-03-01

    The mouse monoclonal antibody 2A10 (immunoglobulin G), which recognizes the (NANP)n repeat of Plasmodium falciparum circumsporozoite surface protein, was used to screen a filamentous phage epitope library expressing random amino acid hexamers. The sequences obtained were TNRNPQ, SNRNPQ, NND-NPQ, SNYNPQ, and QNDNPQ (single-letter amino acid designation). These peptides showed 50% homology with the native epitope (PNANPN) and therefore were considered to mimic its structure (mimotopes). Two of these mimotopes (TNRNPQ and NNDNPQ) inhibited the binding of monoclonal antibody 2A10 to the recombinant protein R32LR, which contains the amino acid sequence [(NANP)15NVDP]2. Immunization of mice and rabbits using the peptide (TNRNPQ)4 induced a humoral response that recognized R32LR by an enzyme-linked immunosorbent assay and P. falciparum sporozoites by an immunofluorescence assay. These results suggest that phage epitope libraries can be exploited to screen for mimotopes in the design of subunit vaccines against infectious agents.

  10. Delivery of DNA HIV-1 Vaccine to the Liver Induces High and Long-lasting Humoral Immune Responses

    PubMed Central

    Raska, Milan; Moldoveanu, Zina; Novak, Jan; Hel, Zdenek; Bozja, Jadranka; Compans, Richard W.; Yang, Chinglai; Mestecky, Jiri

    2008-01-01

    The quality of immune responses induced by DNA vaccination depends on the site of DNA administration, the expression, and the properties of the encoded antigen. In the present study we demonstrate that intravenous hydrodynamic HIV-1 envelope DNA injection resulted in high levels of expression of HIV-1 envelope antigen in the liver. When compared to the administration of DNA by i.n., i.d., i.m., and i.splenic routes, hydrodynamic vaccination induced, upon DNA boosting, 40 times increase of HIV-1 envelope-specific antibodies over the preimmune levels. Hydrodynamic vaccination with 1 μg DNA induced higher humoral responses than 100 μg DNA given intramuscularly in the prime – boost regimen. High levels of envelope-specific IgG and IgA antibodies were induced in genital tract secretions after two doses of DNA followed by intranasal boosting with recombinant HIV-1 gp120 protein. Furthermore, two doses of 100 μg DNA generated interferon-gamma production in ~ 4.3 ± 1.7 % of CD8+ splenocytes after in vitro stimulation with HIV-1 envelope peptides. These results demonstrate that DNA vaccines targeted to tissues with high proteosynthetic activity, such as the liver, results in enhanced immune responses. PMID:18304708

  11. Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

    SciTech Connect

    Ribiero, Ruy M

    2009-01-01

    To investigate the impact of humoral immunity on SIV replication, 11 rhesus macaques (RMs) were inoculated with the neutralization-sensitive strain SIVsmmD215. Seven RMs were treated every three weeks, with 50 mglkg of an anti-CD20 antibody (Rituxan, gift from Genentech) starting from day -7 p.i., as follows: four RMs were treated for two months, and three were treated for five months. The remaining four RMs were used as controls. Three RMs were completely depleted of CD20 cells. Four RMs only partially depleted CD20 cells in the LNs and intestine. The efficacy of tissue CD20 depletion predicted the ablation of antibody production, with SIVsmm seroconversion being delayed in the animals with complete tissue CD20 depletion, and neutralizing antibody production being significantly delayed and at low levels in all CD20-depleted RMs. There was no significant difference in acute or chronic VLs between CD20-depleted RMs and control monkeys, with a tendency for lower set-point VLs in CD20-depleted RMs. At 6 weeks p.i., cellular immune responses were significantly stronger in CD20 depleted RMs than in controls. After two years p.i., there was no significant difference in survival between CD20-depleted and control RMs. We concluded that CD20 depletion plays no significant role in the control of SIV replication or disease progression in SIVsmmD215-infected RMs.

  12. Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity

    PubMed Central

    Lee, Won-Hee; Choi, Hyun-Il; Hong, Sung-Wook; Kim, Kwang-sun; Gho, Yong Song; Jeon, Seong Gyu

    2015-01-01

    The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections. PMID:26358222

  13. Tetanus toxoid-loaded cationic non-aggregated nanostructured lipid particles triggered strong humoral and cellular immune responses.

    PubMed

    Kaur, Amandeep; Jyoti, Kiran; Rai, Shweta; Sidhu, Rupinder; Pandey, Ravi Shankar; Jain, Upendra Kumar; Katyal, Anju; Madan, Jitender

    2016-05-01

    In the present investigation, non-aggregated cationic and unmodified nanoparticles (TT-C-NLPs4 and TT-NLPs1) were prepared of about 49.2 ± 6.8-nm and 40.8 ± 8.3-nm, respectively. In addition, spherical shape, crystalline architecture and cationic charge were also noticed. Furthermore, integrity and conformational stability of TT were maintained in both TT-C-NLPs4 and TT-NLPs1, as evidenced by symmetrical position of bands and superimposed spectra, respectively in SDS-PAGE and circular dichroism. Cellular uptake in RAW264.7 cells indicating the concentration-dependent internalisation of nanoparticles. Qualitatively, CLSM exhibited enhanced cellular uptake of non-aggregated TT-C-NLPs4 owing to interaction with negatively charged plasma membrane and clevaloe mediated/independent endocytosis. In last, in vivo immunisation with non-aggregated TT-C-NLPs4 elicited strong humoral (anti-TT IgG) and cellular (IFN-γ) immune responses at day 42, as compared to non-aggregated TT-NLPs1 and TT-Alum following booster immunisation at day 14 and 28. Thus, non-aggregated cationic lipid nanoparticles may be a potent immune-adjuvant for parenteral delivery of weak antigens.

  14. Small intestinal lymphoma in three patients with acquired immune deficiency syndrome.

    PubMed

    Steinberg, J J; Bridges, N; Feiner, H D; Valensi, Q

    1985-01-01

    Three cases of small bowel lymphoma in young homosexual men are presented. All three had acquired immune deficiency syndrome as demonstrated by demography, sexual history, cachexia, opportunistic infections by Cytomegalovirus, Pneumocystis carinii, atypical Mycobacterium, Candida, and/or evidence of immune deficiency, such as skin test anergy, lymphopenia, inversion of T-helper/T-suppressor ratio, and diminished lymphocyte response to either phytohemmaglutinin or pokeweed mitogen. All had peripheral and/or abdominal lymphadenopathy, and gastrointestinal symptoms, e.g., diarrhea, spasms, constipation, and oral candidiasis. The diagnosis of lymphoma was made at laparotomy in all cases. All three had complete removal of localized tumor (stage Ie or IIe), yet died within 6 months of surgery and/or chemotherapy. Thus gastrointestinal complaints may not always be related to "gay bowel" syndrome, or other infectious diseases in patients with acquired immune deficiency syndrome. Small intestinal lymphoma should be added to the list of neoplasms to which this group is susceptible.

  15. Evaluation of the humoral immune response and cross reactivity against Mycobacterium tuberculosis of mice immunized with liposomes containing glycolipids of Mycobacterium smegmatis

    PubMed Central

    2013-01-01

    Mycobacterium smegmatis (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis. PMID:23458474

  16. [Diagnostic and prognostic value of humoral immune status indices for alimentary system diseases].

    PubMed

    Tsaregorodtseva, T M; Serova, T I

    2007-01-01

    The paper describes the results of studying the immune status of 1,960 patients with stomach, pancreas, liver, gall bladder, small and large intestine disorders, who were treated in the Central Research Institute of Gastroenterology. The results of the study demonstrate that alimentary system diseases are concomitant with changes in the functional activity of the immune system and development of the systemic immune response aimed at the neutralization and elimination of pathogenic agents. Impaired regulatory and efferent lymphocyte capacities, increased synthesis of cytokines, immunoglobulins, heterologous (anti-viral, anti-bacterial or antigliadin), autologous (to parietal cells, microsome mitochondria, tissue transglutaminase) antibodies, formation of immune complexes, autoimmune reactions and secondary immunodeficiency are specific immune mechanisms of the pathological process development, its synchronization and progression in patients with alimentary system diseases. Changes in the immunological status indices are expressed in varying degree depending on the organ involved, etiological factor, clinical course and stage of the disease, as well as treatment used. The immunological status indices have maximal values in cases of chronic hepatitis, hepatic cirrhosis, peptic or duodenal ulcer, cholelithiasis, chronic pancreatitis, gluten-sensitive enteropathy and minimal values in cases of chronic gastritis, gastroesophageal disease, steatohepatitis and irritable bowel syndrome. These data are sufficient for developing an algorithm of immune diagnostics for a number of alimentary system diseases. The study of immune status indices is of great diagnostic and prognostic value as it defines the etiological factor, intensity of inflammatory, infectious and autoimmune processes as well as disease stage and activity, its forecast and the efficacy of treatment of alimentary system diseases.

  17. Clearance of Bordetella parapertussis from the Lower Respiratory Tract Requires Humoral and Cellular Immunity

    PubMed Central

    Wolfe, Daniel N.; Kirimanjeswara, Girish S.; Harvill, Eric T.

    2005-01-01

    Bordetella parapertussis and Bordetella pertussis are closely related species that cause whooping cough, an acute, immunizing disease. Their coexistence in the same host populations at the same time and vaccine studies showing that B. pertussis vaccines have little effect on B. parapertussis infection or disease suggest that the protective immunity induced by each does not efficiently cross protect against the other. Although the mechanisms of protective immunity to B. pertussis have been well studied, those of B. parapertussis have not. The present study explores the mechanism by which B. parapertussis is cleared from the lower respiratory tract by anamnestic immunity. Serum antibodies are necessary and sufficient for elimination of this bacterium, and CD4+ T cells, complement, and neutrophils are required for serum antibody-mediated clearance. Mice lacking immunoglobulin A had no defect in their ability to control or clear infection. Interestingly, serum antibody-mediated clearance of B. parapertussis did not require Fc receptors that are required for antibody-mediated clearance of B. pertussis. Together these data support a model for the mechanism of protective immunity to B. parapertussis that is similar but distinct from that of B. pertussis. PMID:16177324

  18. Development of a lavage procedure to collect lung secretions from chickens for evaluating respiratory humoral immunity.

    PubMed

    Holt, Peter S; Stone, Henry D; Moore, Randle W; Gast, Richard K

    2005-10-01

    Mucosal immunology research has been hampered by the difficulty and labour-intensiveness of collecting samples. This is especially true for sites such as the lung, and the present paper describes a simple method for obtaining samples from this organ in chickens. Following sacrifice, the bird was placed on its back and the trachea was cut and exteriorized. Narrow-diameter tubing, to which a 30 ml syringe was attached, was threaded down the trachea to the bronchi and air was evacuated from the lung. Warm buffer was administered and the lung sample then aspirated, processed and frozen. In the current experiment this sampling system was tested on hens that were challenged with Salmonella Enteritidis. Elevated anti-Salmonella Enteritidis antibody levels in lung from infected hens were observed in significantly more infected hens than non-infected control hens in two trials. The simplicity and utility of this sampling system will make it a useful tool for those laboratories wishing to expand their humoral mucosal immunology capabilities, even for study of non-respiratory pathogens.

  19. Humoral immunity to tetanus, measles and rubella in children with acute lymphoblastic leukemia after chemotherapy.

    PubMed

    Onorateli, Myriam; Botana, Claudia; Peralta, Laura; Rebollo, Magali; Ruvinsky, Silvina; Guitter, Myriam; Felice, Maria S; Posadas, Mercedes; Evangelista, Silvina; Villar, Maria V; Golluscio, Mariana; Molina, Agustina; Fraquelli, Lidia

    2016-12-01

    Chemotherapy regimens and clinical support advances have improved survival in children with acute lymphoblastic leukemia. The after-effects of treatment are a reason for concern, including damage to the immune system induced by immunosuppressive therapy which is reflected in the loss of antibody protection provided by prior immunizations. Our goal was to assess the presence of measles, rubella, and tetanus protective antibody titers among patients with acute lymphoblastic leukemia after completing chemotherapy. Sixty-one children with acute lymphoblastic leukemia seen at the Hospital Garrahan were included; patients had finished their chemotherapy at least 6 months earlier and had a complete immunization schedule before diagnosis. The rates of protective antibodies were 46% (CI: 32-59) for measles, 53% (CI 40-67) for tetanus, and 60% (CI 47-63) for rubella. These results strengthen the need to reconsider revaccination in this group of patients.

  20. Humoral immune response to the entire human immunodeficiency virus envelope glycoprotein made in insect cells

    SciTech Connect

    Rusche, J.R.; Lynn, D.L.; Robert-Guroff, M.; Langlois, A.J.; Lyerly, H.K.; Carson, H.; Krohn, K.; Ranki, A.; Gallo, R.C.; Bolognesi, D.P.; Putney, S.D.

    1987-10-01

    The human immunodeficiency virus envelope gene was expressed in insect cells by using a Baculovirus expression vector. The protein has an apparent molecular mass of 160 kDa, appears on the surface of infected insect cells, and does not appear to be cleaved to glycoproteins gp120 and gp41. Goats immunized with the 160-kDa protein have high titers of antibody that neutralizes virus infection as measured by viral gene expression or cell cytolysis. In addition, immune sera can block fusion of human immunodeficiency virus-infected cells in culture. Both neutralization and fusion-blocking activities are bound to and eluted from immobilized gp120.

  1. Effects of gestational and lactational exposure to organochlorine compounds on cellular, humoral, and innate immunity in swine.

    PubMed

    Bilrha, Houda; Roy, Raynald; Wagner, Eric; Belles-Isles, Marthe; Bailey, Janice L; Ayotte, Pierre

    2004-01-01

    Few studies have characterized the immunotoxic potential of complex mixtures of organochlorines (OCs) that bear environmental relevance. We monitored immune parameters in male piglets exposed in utero and through lactation to an OC mixture which was designed to approximate that found in the traditional diet of Arctic aboriginal populations. Prepubertal sows were administered orally either corn oil (control group) or the OC mixture in increasing doses (low, medium, and high). The sows were inseminated with the semen from an untreated boar and OC treatment was continued throughout gestation and lactation (21 days). Blood was collected from the sows at delivery and monthly from piglets until 8 months of age for the determination of plasma OC concentrations and parameters of innate, cellular, and humoral immunity. Treatment with the OC mixture had no dose-dependent effect on the proportion of CD4+ and CD8+ T-cell subsets, and did not modulate the functional activity of the complement component C2. The proportion of CD4+CD8+ cells, CD8+DR+ cells, and the mitogenic lymphoproliferative response increased in OC-treated, 4-month-old piglets. At 6 months, the lymphoproliferative response to mitogen and the proportion CD4+CD8+ cells were still elevated in the OC-treated piglets, but the proportion of CD8+DR+ cells was decreased as compared to the controls. Animals in the high-dose group also exhibited a slight increase in polymorphonuclear leukocyte phagocytic activity at 8 months of age. Furthermore, the high dose decreased the antibody response to Mycoplasma hyopneumoniae. Our results indicate that developmental exposure to an environmentally relevant OC mixture alters the immune function in swine.

  2. The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses

    PubMed Central

    Plana, Montserrat; Garcia, Felipe; Darwich, Laila; Romeu, Joan; López, Anna; Cabrera, Cecilia; Massanella, Marta; Canto, Esther; Ruiz-Hernandez, Raul; Blanco, Julià; Sánchez, Marcelo; Gatell, Josep M; Clotet, Bonaventura; Ruiz, Lidia; Bofill, Margarita

    2011-01-01

    Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses. PMID:21501161

  3. [Local and general humoral immunity in patients with migraine, Horton's syndrome and autonomic pain].

    PubMed

    Puzin, M N; Kulakov, A V; Balashov, K E; Sharov, M N; Vodop'ianov, N P

    1989-01-01

    Patients with migraines, Horton syndrome and autonomic pains were subjected to immunological investigation that revealed different degrees of local and general immunity disorders: increase in blood serum IfA and salival IgAc concentrations. These changes are believed to be capable of serving as diagnostic and prognostic indices.

  4. Effects of prolonged weightlessness on the humoral immune response of humans

    NASA Technical Reports Server (NTRS)

    Voss, E. W., Jr.

    1981-01-01

    An experiment to examine the possible interrelationship of various classes of immunoglobulins by utilizing the effect of weightlessness as a stress factor and subsequently measuring inhibitory, compensatory, or enhancing interrelationships. A second objective of the experiment is to investigate the state of immune competency under conditions of sustained weightlessness.

  5. C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus

    SciTech Connect

    Tong Tiezhu; Fan Huiying; Tan Yadi; Xiao Shaobo; Ling Jieyu; Chen Huanchun; Guo Aizhen . E-mail: aizhen@mail.hzau.edu.cn

    2006-09-08

    Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28{sub 4} were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d{sub 3} DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD{sub 5}) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d{sub 3} DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response.

  6. Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance

    PubMed Central

    Hugo, Willy; Shi, Hubing; Sun, Lu; Piva, Marco; Song, ChunYing; Kong, Xiangju; Moriceau, Gatien; Hong, Aayoung; Dahlman, Kimberly B.; Johnson, Douglas B.; Sosman, Jeffrey A.; Ribas, Antoni; Lo, Roger S.

    2015-01-01

    SUMMARY Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression, and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T-cell inflammation prior to MAPKi therapy preceded CD8 T-cell deficiency/exhaustion and loss of antigen-presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi-resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity. PMID:26359985

  7. Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance.

    PubMed

    Hugo, Willy; Shi, Hubing; Sun, Lu; Piva, Marco; Song, Chunying; Kong, Xiangju; Moriceau, Gatien; Hong, Aayoung; Dahlman, Kimberly B; Johnson, Douglas B; Sosman, Jeffrey A; Ribas, Antoni; Lo, Roger S

    2015-09-10

    Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T cell inflammation prior to MAPKi therapy preceded CD8 T cell deficiency/exhaustion and loss of antigen presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity.

  8. Humoral immune response against proteophosphoglycan surface antigens of Entamoeba histolytica elicited by immunization with synthetic mimotope peptides.

    PubMed

    Melzer, Helen; Baier, Karin; Felici, Franco; von Specht, Bernd Ulrich; Wiedermann, Gerhard; Kollaritsch, Herwig; Wiedermann, Ursula; Duchêne, Michael

    2003-07-15

    The protozoan parasite Entamoeba histolytica, which is responsible for intestinal amebiasis and amebic liver abscess, is causing significant morbidity and mortality worldwide. Proteophosphoglycans (PPGs, also known as lipophosphoglycans, LPGs, or lipopeptidophosphoglycans, LPPGs) are major surface components of E. histolytica. Passive immunization with a monoclonal antibody (EH5) directed against the PPGs protected severe combined immune-deficient mice from amebic liver abscess. The structure of the PPGs is very complex and only known in part. To find peptide mimics of E. histolytica PPG antigens, we had screened phage-displayed random peptide libraries with the antibody EH5. We identified various peptide mimics of E. histolytica PPGs, all sharing a consensus sequence Gly-Thr-His-Pro-X-Leu. Several of the phage clones induced a significant, specific IgG response against membrane antigens of E. histolytica after immunization of mice with whole phage particles. In the present work, in order to avoid the use of phage particles for immunization, we coupled two selected chemically synthesized peptides to keyhole limpet hemocyanin (KLH). The two KLH-conjugated peptides were immunogenic in mice and induced the production of high titers of anti-peptide antibodies, and one of the two peptides was also able to induce significant titers of antibodies against E. histolytica PPGs. Our results demonstrate that the KLH-conjugated peptides are able to mimic the EH5 epitope without the M13 phage sequences flanking the peptide inserts and independent of the structural framework of the phage.

  9. Analysis of humoral immune responses to LM1 ganglioside in guinea pigs.

    PubMed

    Gu, Yajuan; Chen, Zi-Wei; Siegel, Allan; Koshy, Ranie; Ramirez, Cristhian; Raabe, Timothy D; Devries, George H; Ilyas, Amjad A

    2012-05-15

    Guillain-Barré syndrome (GBS) is an autoimmune-mediated disease triggered by a preceding infection. A substantial body of evidence implicates antibodies to various gangliosides in subtypes of GBS. A significant proportion of patients with acute demyelinating subset of GBS have IgG antibodies against peripheral nervous system myelin specific neolactogangliosides such as LM1 and Hex-LM1. Although anti-neolactoganglioside antibodies in GBS were described more than two decades ago, their pathogenic role in neuropathy remains unknown due to the lack of suitable experimental models. In this study, we immunized ten guinea pigs with purified LM1 ganglioside mixed with keyhole limpet hemocyanin (KLH) and emulsified in complete Freund's adjuvant (CFA). Control guinea pigs were injected with KLH emulsified in CFA only. The animals were bled every four week intervals. The animals were boosted 3 times every four weeks. Experiments were terminated four months after initial immunization. Nine of 10 guinea pigs immunized with LM1 exhibited antibody responses to LM1. Anti-LM1 IgG titers in nine guinea pigs ranged from 1:400 to 1:12,800 at 16-weeks after initial immunization. Anti-LM1 antibodies were predominantly of IgG2 subclass. One guinea pig with the highest levels of IgG antibodies exhibited mild signs of neuropathy. There was no evidence of demyelination or inflammation in the sciatic nerves of LM1-immunized guinea pigs. Anti-LM1 antibodies bound to rat sciatic nerve myelin and to isolated rat Schwann cells. In summary, our findings suggest that relatively high levels of anti-LM1 IgG antibodies can be induced in guinea pigs and that LM1 is localized in peripheral nerve myelin and in Schwann cells. Further studies are needed to determine the pathogenic potential of anti-neolactoganglioside antibodies in neuropathy.

  10. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE

    PubMed Central

    LESCANO, Susana A. Zevallos; dos SANTOS, Sergio Vieira; ASSIS, Jesiel Maurício Lemos; CHIEFFI, Pedro Paulo

    2015-01-01

    SUMMARY The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ. PMID:26422159

  11. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE.

    PubMed

    Lescano, Susana A Zevallos; Santos, Sergio Vieira dos; Assis, Jesiel Maurício Lemos; Chieffi, Pedro Paulo

    2015-01-01

    The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canis and grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocara antibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- Toxocara IgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ.

  12. Cellular and humoral immunity in a wild mammal: Variation with age & sex and association with overwinter survival.

    PubMed

    Watson, Rebecca L; McNeilly, Tom N; Watt, Kathryn A; Pemberton, Josephine M; Pilkington, Jill G; Waterfall, Martin; Hopper, Phoebe R T; Cooney, Daniel; Zamoyska, Rose; Nussey, Daniel H

    2016-12-01

    Immune defenses are expected to be crucial for survival under the considerable parasite pressures experienced by wild animals. However, our understanding of the association between immunity and fitness in nature remains limited due to both the complexity of the vertebrate immune system and the often-limited availability of immune reagents in nonmodel organisms. Here, we use methods and reagents developed by veterinary researchers for domestic ungulates on blood samples collected from a wild Soay sheep population, to evaluate an unusually broad panel of immune parameters. Our evaluation included different innate and acquired immune cell types as well as nematode parasite-specific antibodies of different isotypes. We test how these markers correlate with one another, how they vary with age-group and sex, and, crucially, whether they predict overwinter survival either within or among demographic groups. We found anticipated patterns of variation in markers with age, associated with immune development, and once these age trends were accounted for, correlations among our 11 immune markers were generally weak. We found that females had higher proportions of naïve T cells and gamma-delta T cells than males, independent of age, while our other markers did not differ between sexes. Only one of our 11 markers predicted overwinter survival: sheep with higher plasma levels of anti-nematode IgG antibodies were significantly more likely to survive the subsequent high mortality winter, independent of age, sex, or weight. This supports a previous finding from this study system using a different set of samples and shows that circulating antibody levels against ecologically relevant parasites in natural systems represent an important parameter of immune function and may be under strong natural selection. Our data provide rare insights into patterns of variation among age- and sex groups in different T-cell subsets and antibody levels in the wild, and suggest that certain types of

  13. A reappraisal of humoral immunity based on mechanisms of antibody-mediated protection against intracellular pathogens.

    PubMed

    Casadevall, Arturo; Pirofski, Liise-anne

    2006-01-01

    Sometime in the mid to late twentieth century the study of antibody-mediated immunity (AMI) entered the doldrums, as many immunologists believed that the function of AMI was well understood, and was no longer deserving of intensive investigation. However, beginning in the 1990s studies using monoclonal antibodies (mAbs) revealed new functions for antibodies, including direct antimicrobial effects and their ability to modify host inflammatory and cellular responses. Furthermore, the demonstration that mAbs to several intracellular bacterial and fungal pathogens were protective issued a serious challenge to the paradigm that host defense against such microbes was strictly governed by cell-mediated immunity (CMI). Hence, a new view of AMI is emerging. This view is based on the concept that a major function of antibody (Ab) is to amplify or subdue the inflammatory response to a microbe. In this regard, the "damage-response framework" of microbial pathogenesis provides a new conceptual viewpoint for understanding mechanisms of AMI. According to this view, the ability of an Ab to affect the outcome of a host-microbe interaction is a function of its capacity to modify the damage ensuing from such an interaction. In fact, it is increasingly apparent that the efficacy of an Ab cannot be defined either by immunoglobulin or epitope characteristics alone, but rather by a complex function of Ab variables, such as specificity, isotype, and amount, host variables, such as genetic background and immune status, and microbial variables, such as inoculum, mechanisms of avoiding host immune surveillance and pathogenic strategy. Consequently, far from being understood, recent findings in AMI imply a system with unfathomable complexity and the field is poised for a long overdue renaissance.

  14. Analysis of humoral immune response of animals exposed to bacterial antigens

    PubMed Central

    Pugazhenthi, M.; Valivittan, K.

    2014-01-01

    From the Aeromonas hydrophila strain, five different types of antigens such as heat killed antigen, whole cell antigen, heat killed antigen with antiserum, whole cell antigen with antiserum and nucleotide antigens were prepared and injected into the experimental fish (Catla catla) groups for the study of immunomodulation. Analysis of immunogenicity of antigens against the fish Catla catla was estimated. The A. hydrophila produced β hemolytic pattern on the blood agar plate. B lymphocyte counts using rosette forming assay revealed a significant decrement in pathogens exposed fishes as compared to controls. Fishes exposed to pathogenic strains (1/10th sublethal concentration) for 3 weeks showed a reduction in PFC. The effect or pathogenic antigens in direct spleenic plaque forming cells (1 g M producing cells) showed a reduction in the secondary plaque forming cell in the first 3 weeks and a time- and dose-dependent decrease in primary and secondary PFC response. A remarkable observation enhancement in B cell production due to immune complex of antigens was noted in the present study. The enhancement of this type of immune responses confirms the potential of immune complexes to be used as vaccines. PMID:26155142

  15. Differential effect of pancreatectomy on humoral and cell-mediated immune responses.

    PubMed Central

    Fabris, N; Piantanelli, L

    1977-01-01

    Cell-mediated immune reactions, such as allogenic skin-graft rejection and PHA or MLC responses, and antibody synthesis against different antigens (sheep erythrocytes, Brucella antigen, bovine serum albumin) have been evaluated in rats suffering from experimentally-induced diabetes and in age-matched sham-treated controls. Cell-mediated immune reactions are strongly depressed diabetic rats. The cellularity of the thymus and of thymus-dependent areas and the number of peripheral blood lymphocytes is significantly reduced in pancreatectomized rats. Moreover, the immunological recovery from heavy cortisonization is also greatly impaired. Daily treatment with insulin may prevent these immunological alterations. By contrast, antibody responses in diabetic rats are not quantitatively altered in respect to either the number of antibody producing cells in the spleen or the circulating antibody titres. The discrepancy between the abnormality of cell-mediated immune reactions in diabetic rats and their physiological capacity to synthetize antibodies suggests that the sensitivity to an insulin-deprived environment is present only in a definite, although yet undefined, subpopulation of lymphoid cells rather than in the whole lymphoid system. Images Fig. 4 PMID:141353

  16. Acquired immune deficiency syndrome (AIDS)--complications in dental treatment. Report of a case.

    PubMed

    Hurlen, B; Gerner, N W

    1984-04-01

    Acquired immune deficiency syndrome (AIDS) is a new disease which has recently alerted the medical world. AIDS may also concern dental practitioners and oral surgeons who may be the first to suspect impairment of immunity in patients presenting opportunistic oral infections. Extraordinary resistance to treatment of dental infections, such as encountered in a 27-year-old man developing AIDS, could also be a sign of immunodepression. Epidemiological features of AIDS indicate transmissibility, and interim recommendations for prevention of spread correspond to the measures appropriate for hepatitis B.

  17. Genetic polymorphisms in host antiviral genes: associations with humoral and cellular immunity to measles vaccine.

    PubMed

    Haralambieva, Iana H; Ovsyannikova, Inna G; Umlauf, Benjamin J; Vierkant, Robert A; Shane Pankratz, V; Jacobson, Robert M; Poland, Gregory A

    2011-11-08

    Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella (MMR) vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction for FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and

  18. Impaired T Cell-dependent Humoral Immune Response Associated with Juvenile-onset Recurrent Respiratory Papillomatosis Progression

    PubMed Central

    Wu, Xunyao; Wang, Guoliang; Chen, Xi; Zhang, Jie; Zhao, Jing; Wang, Jun; Xiao, Yang; Tai, Jun; Wang, Shengcai; Wang, Guixiang; Wang, Hua; Bai, Lina; Gui, Jingang; Ni, Xin

    2016-01-01

    Whether humoral immunity plays a role in HPV type 6 or 11 virus-mediated Juvenile-onset Recurrent Respiratory Papillomatosis (JORRP) remains unknown. In the present study, serum total IgG level in 44 JORRP patients was significantly decreased compared with that in 40 healthy controls. Moreover, expanded CD3−CD19+ B cells with down-regulation of CD23, CD40, HLA-DR and up-regulation of CD86 expression were found in the peripheral blood of JORRP patients. Flow cytometry analysis of B-cell compartment showed that the frequency of both CD19+CD27hi plasma cells and CD19+CD27+ memory B cells were decreased in JORRP patients. Importantly, although the proportion of circulating CXCR5+PD1hi Tfh cells was not changed, the function of Tfh cells were greatly impaired with reduced ability of IL-21 secretion to promote B cell maturation. Association analysis by the Kaplan-Meier method revealed that IL-21 secreting Tfh cell was positively correlated to the CD27+ B cell subset frequency, the serum IgG level and the frequency of recurrence in JORRP patients, but negatively correlated to the percentage of IgD+CD27− B cell. We concluded that a reduced IL-21 secretion by Tfh cells may limit B cell maturation and antibody production in JORRP patients and Tfh cell-derived IL-21 might be associated with JORRP outcome in clinic. PMID:27821867

  19. Complement and Humoral Adaptive Immunity in the Human Choroid Plexus: Roles for Stromal Concretions, Basement Membranes, and Epithelium

    PubMed Central

    Laule, Cornelia; Leung, Esther; Pavlova, Vladimira; Morgan, B. Paul; Esiri, Margaret M.

    2016-01-01

    The choroid plexus (CP) provides a barrier to entry of toxic molecules from the blood into the brain and transports vital molecules into the cerebrospinal fluid. While a great deal is known about CP physiology, relatively little is known about its immunology. Here, we show immunohistochemical data that help define the role of the CP in innate and adaptive humoral immunity. The results show that complement, in the form of C1q, C3d, C9, or C9neo, is preferentially deposited in stromal concretions. In contrast, immunoglobulin (Ig) G (IgG) and IgA are more often found in CP epithelial cells, and IgM is found in either locale. C4d, IgD, and IgE are rarely, if ever, seen in the CP. In multiple sclerosis CP, basement membrane C9 or stromal IgA patterns were common but were not specific for the disease. These findings indicate that the CP may orchestrate the clearance of complement, particularly by deposition in its concretions, IgA and IgG preferentially via its epithelium, and IgM by either mechanism. PMID:26994633

  20. HIV--Leishmania infantum co-infection: humoral and cellular immune responses to the parasite after chemotherapy.

    PubMed

    Moreno, J; Cañavate, C; Chamizo, C; Laguna, F; Alvar, J

    2000-01-01

    Specific serum antibodies, peripheral blood T-cell subsets, cellular response in vitro to soluble Leishmania antigens, phenotype of stimulated cells, and serum levels of tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta 1 were studied in Spain in 17 patients co-infected with HIV and Leishmania infantum who had been previously treated with pentavalent antimony. Both humoral and cellular responses to Leishmania sp. appeared diminished, 8 out of 17 patients were positive by indirect immunofluorescence, and immunoblotting detected heterogeneous antibody-binding pattern in 11 out of 13 subjects. A blastogenesis test was positive in 4 cases; 2 of them presented proliferation of CD4+ cells while CD8+ cells proliferated in the other 2 patients. Serum levels of TNF-alpha were similar to those observed in patients infected with HIV only, while serum levels of TGF-beta 1 were significantly lower in the co-infected patients. The inability of antibody response to control the parasite and the absence of specific T-cell immunity to Leishmania sp. would explain the high frequency of relapses reported in these patients. The decreased levels of TGF-beta 1 could have an important role in the interaction between the 2 pathogens.

  1. Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity.

    PubMed

    Tenno, Mari; Ohtsubo, Kazuaki; Hagen, Fred K; Ditto, David; Zarbock, Alexander; Schaerli, Patrick; von Andrian, Ulrich H; Ley, Klaus; Le, Dzung; Tabak, Lawrence A; Marth, Jamey D

    2007-12-01

    Core-type protein O glycosylation is initiated by polypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease. We found that ppGalNAcT-1 plays key roles in cell and glycoprotein selective functions that modulate the hematopoietic system. Loss of ppGalNAcT-1 activity in the mouse results in a bleeding disorder which tracks with reduced plasma levels of blood coagulation factors V, VII, VIII, IX, X, and XII. ppGalNAcT-1 further supports leukocyte trafficking and residency in normal homeostatic physiology as well as during inflammatory responses, in part by providing a scaffold for the synthesis of selectin ligands expressed by neutrophils and endothelial cells of peripheral lymph nodes. Animals lacking ppGalNAcT-1 are also markedly impaired in immunoglobulin G production, coincident with increased germinal center B-cell apoptosis and reduced levels of plasma B cells. These findings reveal that the initiation of protein O glycosylation by ppGalNAcT-1 provides a distinctive repertoire of advantageous functions that support vascular responses and humoral immunity.

  2. Acquired immune deficiency in Haitians: opportunistic infections in previously healthy Haitian immigrants.

    PubMed

    Vieira, J; Frank, E; Spira, T J; Landesman, S H

    1983-01-20

    We describe acquired immune deficiency manifested by opportunistic infections in 10 previously healthy heterosexual Haitian men. The opportunistic pathogens included Toxoplasma gondii (in four patients), Cryptococcus neoformans (in one), Pneumocystis carinii (in four patients), and Candida albicans (in three). Six of the patients also had Mycobacterium tuberculosis. Immunologic studies of three patients showed a decrease in the numbers and activity of helper T cells, with normal or increased populations of suppressor T cells. Serologic markers for previous infections from hepatitis A, cytomegalovirus, and herpes simplex virus were detected in several patients. Six of the patients died despite specific antimicrobial therapy. The clinical and immunologic findings in these 10 Haitians are similar to those reported in drug addicts and homosexuals with the acquired immune-deficiency syndrome.

  3. Studies on acquired immunity to coccidiosis in bursaless and thymectomized fowls

    PubMed Central

    Pierce, A. E.; Long, P. L.

    1965-01-01

    Fowls hatched from embryos inoculated in ovo with testosterone between the sixth and ninth day of incubation hatched without a detectable bursa of Fabricius. These fowls failed to develop antibodies as the result of repeated infection with Eimeria tenella and levels of serum immune globulin were usually markedly reduced or undetectable. There were very few pyroninophilic cells in the caeca or spleen and secondary foci in the spleen and caecal lymphoid tissue were either not detected or were very reduced in number. The spleen and thymus weights were significantly reduced by testosterone treatment. Nevertheless, these fowls were successfully immunized, so that they resisted infection when challenged with viable oocysts of E. tenella. Active E. tenella infection of normal, susceptible, control fowls significantly reduced the thymus weight and increased the bursa weight. Severe haemorrhage into the caecal lumen of infected fowls resulted in lowered blood erythrocyte and lymphocyte counts and a reduction in the total serum protein. Antibodies, capable of lysing sporozoites, were detected in normal fowls after immunization and in normal susceptible fowls 5 days after initial infection. Complete surgical thymectomy was attempted within the first 1½ hours after hatching. However, this was only exceptionally complete and about 10 per cent of thymic tissue was detectable at subsequent post-mortem 56 days later. Thymectomized birds produced antibody, pyroninophilic cells and secondary spleen foci indistinguishable from normal control immunized chickens. However, there was a significant reduction in the number of small lymphocytes in the blood. Although thymectomized fowls were successfully immunized against E. tenella infection, there was an indication, shown by daily oocyst discharge determinations that thymectomized fowls were less resistant during immunization than normal fowls. However, both groups of fowls, when challenged, were fully immune. The significance of partial

  4. Hair-type sheep generate an accelerated and longer-lived humoral immune response to Haemonchus contortus infection.

    PubMed

    Bowdridge, Scott; MacKinnon, Kathryn; McCann, Joshua C; Zajac, Anne M; Notter, David R

    2013-09-01

    Antibody levels produced in response to gastro-intestinal nematode (GIN) parasite infection are typically higher in GIN-resistant breeds than susceptible breeds. Consequently, GIN-resistant ewes should generate greater parasite-specific antibody in colostrum and milk, potentially providing greater passive immunity to young lambs. To test this hypothesis, we monitored immunoglobulin levels in wool and hair-type sheep infected with Haemonchus contortus for 35 days following the end of a 45-day autumn breeding season and subsequently for 6 weeks around the time of parturition. Ten, first-parity ewes of each type were infected with 12,000 H. contortus L3 larvae following the end of breeding. In response to infection, hair ewes generated greater serum IgA (P<0.05), although the pattern of IgA production was similar between the types. Following experimental infection, wool ewes were incapable of clearing the parasite infection well in advance of parturition. Prior to parturition, hair ewes had lower FEC and greater circulating H. contortus-specific IgA. However, no difference was seen in total or antigen-specific IgA production in the colostrum and milk of either breed. These data further demonstrate that hair-type sheep can rapidly reduce fecal egg output and generate greater humoral immunity as evidenced by higher levels of circulating antigen-specific antibody, but there is no evidence to suggest GIN-resistant sheep preferentially mobilize antigen-specific IgA to colostrum or milk. Thus, no clear difference exists between types of sheep in ability to deliver parasite-specific IgA to their offspring.

  5. A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and Prevents Corneal Immunopathology via Humoral Immunity

    PubMed Central

    Royer, Derek J.; Gurung, Hem R.; Jinkins, Jeremy K.; Geltz, Joshua J.; Wu, Jennifer L.; Halford, William P.

    2016-01-01

    ABSTRACT Correlates of immunologic protection requisite for an efficacious herpes simplex virus 1 (HSV-1) vaccine remain unclear with respect to viral pathogenesis and clinical disease. In the present study, mice were vaccinated with a novel avirulent, live attenuated virus (0ΔNLS) or an adjuvanted glycoprotein D subunit (gD-2) similar to that used in several human clinical trials. Mice vaccinated with 0ΔNLS showed superior protection against early viral replication, neuroinvasion, latency, and mortality compared to that of gD-2-vaccinated or naive mice following ocular challenge with a neurovirulent clinical isolate of HSV-1. Moreover, 0ΔNLS-vaccinated mice exhibited protection against ocular immunopathology and maintained corneal mechanosensory function. Vaccinated mice also showed suppressed T cell activation in the draining lymph nodes following challenge. Vaccine efficacy correlated with serum neutralizing antibody titers. Humoral immunity was identified as the correlate of protection against corneal neovascularization, HSV-1 shedding, and latency through passive immunization. Overall, 0ΔNLS affords remarkable protection against HSV-1-associated ocular sequelae by impeding viral replication, dissemination, and establishment of latency. IMPORTANCE HSV-1 manifests in a variety of clinical presentations ranging from a rather benign “cold sore” to more severe forms of infection, including necrotizing stromal keratitis and herpes simplex encephalitis. The present study was undertaken to evaluate a novel vaccine to ocular HSV-1 infection not only for resistance to viral replication and spread but also for maintenance of the visual axis. The results underscore the necessity to reconsider strategies that utilize attenuated live virus as opposed to subunit vaccines against ocular HSV-1 infection. PMID:27030264

  6. B cell-specific deficiencies in mTOR limit humoral immune responses.

    PubMed

    Zhang, Shuling; Pruitt, Margaret; Tran, Dena; Du Bois, Wendy; Zhang, Ke; Patel, Rushi; Hoover, Shelley; Simpson, R Mark; Simmons, John; Gary, Joy; Snapper, Clifford M; Casellas, Rafael; Mock, Beverly A

    2013-08-15

    Generation of high-affinity Abs in response to Ags/infectious agents is essential for developing long-lasting immune responses. B cell maturation and Ab responses to Ag stimulation require Ig somatic hypermutation (SHM) and class-switch recombination (CSR) for high-affinity responses. Upon immunization with either the model Ag 4-hydroxy-3-nitrophenylacetyl hapten (NP) conjugated to chicken γ globulin lysine (NP-CGG) or heat-killed Streptococcus pneumoniae capsular type 14 protein (Pn14), knock-in (KI) mice hypomorphic for mTOR function had a decreased ability to form germinal centers, develop high-affinity anti-NP-specific or anti-Pn14-specific Abs, and perform SHM/CSR. Hypomorphic mTOR mice also had a high mortality (40%) compared with wild-type (WT) (0%) littermates and had lower pneumococcal surface protein A-specific Ab titers when immunized and challenged with live S. pneumoniae infection. Mice with mTOR deleted in their B cell lineage (knockout [KO]) also produced fewer splenic germinal centers and decreased high-affinity Ab responses to NP-CGG than did their WT littermates. CSR rates were lower in mTOR KI and KO mice, and pharmacologic inhibition of mTOR in WT B cells resulted in decreased rates of ex vivo CSR. RNA and protein levels of activation-induced cytidine deaminase (AID), a protein essential for SHM and CSR, were lower in B cells from both KI and B cell-specific KO mice, concomitant with increases in phosphorylated AKT and FOXO1. Rescue experiments increasing AID expression in KI B cells restored CSR levels to those in WT B cells. Thus, mTOR plays an important immunoregulatory role in the germinal center, at least partially through AID signaling, in generating high-affinity Abs.

  7. Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women.

    PubMed

    Huygen, Kris; Caboré, Raïssa Nadège; Maertens, Kirsten; Van Damme, Pierre; Leuridan, Elke

    2015-08-07

    Vaccination of pregnant women is recommended for some infectious diseases in order to protect both women and offspring through high titres of maternal IgG antibodies. Less is known on the triggering of cellular immune responses by vaccines administered during pregnancy. In an ongoing study on maternal pertussis vaccination (2012-2014) 18 pregnant women were vaccinated with a tetanus-diphtheria-acellular pertussis (Tdap) containing vaccine (Boostrix®) during the third pregnancy trimester. Sixteen age-matched nonpregnant women received the same vaccine in the same time period. A blood sample was taken at the moment of, but before vaccination and one month and one year after vaccination. Anti-Pertussis Toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxin (TT) and diphtheria toxin (DT) antibodies were measured by ELISA. Cellular immune responses were analyzed using a diluted whole blood assay, measuring proliferation, and cytokine release in response to vaccine antigens PT, FHA, TT, and to pokeweed mitogen (PWM) as polyclonal stimulus. Antibody levels to all five vaccine components increased significantly and to the same extent after vaccination in pregnant and nonpregnant women. One year after vaccination, antibody titres had decreased particularly to PT, but they were still significantly higher to all antigens than before vaccination. In contrast, proliferative and IFN-γ responses were increased to TT, PT, and FHA in nonpregnant women one month after vaccination, whereas in pregnant women only TT specific T cell responses were increased and to a lesser extent than in the control group. One year after vaccination, cellular responses equaled the baseline levels detected prior to vaccination in both groups. In conclusion, a Tdap vaccination can increase vaccine specific IgG antibodies to the same extent in pregnant and in nonpregnant women, whereas the stimulation of vaccine specific Th1 type cellular immune responses with this acellular vaccine

  8. B Cell-specific Deficiencies in mTOR Limit Humoral Immune Responses1

    PubMed Central

    Zhang, Shuling; Pruitt, Margaret; Tran, Dena; Bois, Wendy Du; Zhang, Ke; Patel, Rushi; Hoover, Shelley; Simpson, R. Mark; Simmons, John; Gary, Joy; Snapper, Clifford M.; Casellas, Rafael; Mock, Beverly A.

    2013-01-01

    Generation of high-affinity antibodies in response to antigens/infectious agents is essential for developing long-lasting immune responses. B cell maturation and antibody responses to antigen stimulation require immunoglobulin (Ig) somatic hypermutation (SHM) and class-switch recombination (CSR) for high-affinity responses. Upon immunization with either the model antigen NP-CGG or heat-killed Pn14 derived from Streptococcus pneumoniae, knock-in (KI) mice hypomorphic for mTOR function had decreased ability to form germinal centers, develop high-affinity anti-NP or –Pn14 specific antibodies, and perform SHM/CSR. Hypomorphic mTOR mice also had a high mortality rate (40%) compared to WT (0%) littermates and had lower PspA specific antibody titers when immunized and challenged with live S. pneumoniae infection. Mice with mTOR deleted in their B cell lineage (KO) also produced fewer splenic germinal centers and decreased high-affinity antibody responses to NP-CGG than their WT littermates. CSR rates were lower in mTOR KI and KO mice, and pharmacologic inhibition of mTOR in WT B cells resulted in decreased rates of ex vivo CSR. RNA and protein levels of activation-induced cytidine deaminase (AID), a protein essential for SHM and CSR, were lower in B cells from both KI and B-cell specific KO mice, concomitant with increases in phosphorylated AKT and FOXO1. Rescue experiments increasing AID expression in KI B cells restored CSR levels to those in wild-type B cells. Thus, mTOR plays an important immunoregulatory role in the germinal center, at least partially through AID signaling, in generating high affinity antibodies. PMID:23858034

  9. Humoral and cellular immune response generated by different vaccine programs before and after Salmonella Enteritidis challenge in chickens.

    PubMed

    Penha Filho, Rafael Antonio Casarin; Moura, Bruna Silva; de Almeida, Adriana Maria; Montassier, Hélio José; Barrow, Paul A; Berchieri Junior, Angelo

    2012-12-14

    The poultry industry has a high demand for Salmonella vaccines in order to generate safer Salmonella-free food for consumers around the world. Vaccination against S. Enteritidis (SE) is vastly undertaken in many countries, although the criteria for the use of live vaccine (LV) or killed vaccine (KV) should also depend on the immune mechanisms triggered by each. In this study, a commercial bacterin (KV) and an attenuated SG mutant (LV) were used in four different vaccine programs (LV; LV+LV; KV; LV+KV). At 1 day before (dbi) and 1, 6 and 9 days after SE challenge (dpi), humoral (IgM, IgG and secretory IgA) and cellular (CD8(+) T cells) immune responses were evaluated along with the production of IL-10, IL-12 and IFN-γ. Although after challenge, all birds from each group had an influx of CD8(+) T cells, birds which received KV had lower levels of these cells in organs and significantly higher levels of immunoglobulins. The expression of the cytokines was up-regulated in all groups post-vaccination, although, after challenge, cytokine expression decreased in the vaccinated groups, and increased in the unvaccinated group A. IL-10 levels were significantly higher at 1 day post-infection in the group that received KV, which may be involved in the weak cellular immune response observed within this group. In caecal tonsils, IFN-γ expression at 1 dbi was higher in birds which received two vaccine doses, and after challenge, the population of CD8(+) T cells constantly increased in birds that were only vaccinated with the LV. This study demonstrated that the development of a mature immune response by CD8(+) T cells, provided by the use of the LV, had better efficacy in comparison to the high antibody levels in the serum stimulated by the KV. However, high secretory IgA levels in the intestinal lumen associated with influx CD8(+) T cells may be indicative of protection as noticed in group E (LV+KV).

  10. Investigation of the Role of Immunoglobulin Classes and Subclasses in Humoral and Mucosal Immunity in Cetaceans

    DTIC Science & Technology

    2005-06-01

    interest was derived from mice immunized with IgG1 and produced monoclonal antibodies for the light chain (Tt Lc). The initial ELISA screening was for...specific for the light chains present in both IgG and IgA. After the specificity the three monoclonal antibodies had been determined, the isotype of...species) and another having a molecular weight of 29.5 kDa (consistent with the molecular weight of light chains from many species). Of interest was

  11. Inital observations of the effect of radiotherapy on epidemic Kaposi's sarcoma. [Acquired immune deficiency syndrome

    SciTech Connect

    Cooper, J.S.; Fried, P.R.; Laubenstein, L.J.

    1984-08-17

    Fifteen patients who had Kaposi's sarcoma in conjunction with the acquired immune deficiency syndrome (AIDS) received radiotherapy to a total of 17 selected lesions. All tumors exhibited at least partial regression, and the majority responded completely. The radiosensitivity of these lesions is similar to that observed in the classic form of the disease. The authors conclude that in appropriately selected cases radiotherapy should be considered the treatment of choice.

  12. Psychological support and counselling for patients with acquired immune deficiency syndrome (AIDS).

    PubMed Central

    Miller, D; Green, J

    1985-01-01

    The growing numbers of patients with the acquired immune deficiency syndrome (AIDS) in England had led to the development of a counselling service for patients, their sexual partners, contacts, and others. The nature of the counselling is described with reference to the primary qualitative issues arising from diagnosis. The necessity for preventative education for patients and those at risk is stressed, and guidelines for low risk sexual activities are outlined. PMID:2991121

  13. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy.

    PubMed

    Drane, W E; Tipler, B M

    1987-06-01

    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  14. Humoral and cell-mediated immunity to the Plasmodium falciparum ring-infected erythrocyte surface antigen in an adult population exposed to highly endemic malaria.

    PubMed Central

    Beck, H P; Felger, I; Genton, B; Alexander, N; al-Yaman, F; Anders, R F; Alpers, M

    1995-01-01

    A parasitological and immunological survey was carried out in an area in Papua New Guinea highly endemic for malaria. Two hundred fourteen adult individuals were selected for studies to assess their immune responses against the malaria vaccine candidate ring-infected erythrocyte surface antigen (RESA). Total immunoglobulin G (IgG) antibodies directed against RESA as well as specific IgG1, IgG2, and IgG3 antibodies were determined. Humoral responses directed against RESA were frequent in all IgG subclasses. Only IgG3 responses were found to be age dependent. Total anti-RESA IgG antibodies were not correlated with protection against malaria as measured by parasite prevalence, parasite density, or health center attendance. In contrast, cytophilic antibodies (IgG1 and IgG3) were associated with reduced Plasmodium falciparum prevalence and reduced health center attendance. T-cell proliferation in general was low and very infrequent. No correlation between humoral and cellular immune responses could be found. Parasite density, parasite prevalence, and health center visits tended to be reduced in individuals with good humoral and cell-mediated immune responses. PMID:7822028

  15. Bifidobacterium bifidum OLB6378 Simultaneously Enhances Systemic and Mucosal Humoral Immunity in Low Birth Weight Infants: A Non-Randomized Study

    PubMed Central

    Tanaka, Katsunori; Tsukahara, Takamitsu; Yanagi, Takahide; Nakahara, Sayuri; Furukawa, Ouki; Tsutsui, Hidemi; Koshida, Shigeki

    2017-01-01

    Probiotic supplementation has been part of the discussion on methods to enhance humoral immunity. Administration of Bifidobacterium bifidum OLB6378 (OLB6378) reduced the incidence of late-onset sepsis in infants. In this non-randomized study, we aimed to determine the effect of administration of live OLB6378 on infants’ humoral immunity. Secondly, we tried to elucidate whether similar effects would be observed with administration of non-live OLB6378. Low birth weight (LBW) infants weighing 1500–2500 g were divided into three groups: Group N (no intervention), Group L (administered live OLB6378 concentrate), and Group H (administered non-live OLB6378 concentrate). The interventions were started within 48 h after birth and continued until six months of age. Serum immunoglobulin G (IgG) levels (IgG at one month/IgG at birth) were significantly higher in Group L than in Group N (p < 0.01). Group H exhibited significantly higher serum IgG levels (p < 0.01) at one month of age and significantly higher intestinal secretory immunoglobulin A (SIgA) levels (p < 0.05) at one and two months of age than Group N. No difference was observed in the mortality or morbidity between groups. Thus, OLB6378 administration in LBW infants enhanced humoral immunity, and non-live OLB6378, which is more useful as a food ingredient, showed a more marked effect than the viable bacteria. PMID:28245626

  16. Comparative analyses of humoral and cell-mediated immune responses upon vaccination with different commercially available single-dose porcine circovirus type 2 vaccines.

    PubMed

    Seo, Hwi Won; Lee, Jeehoon; Han, Kiwon; Park, Changhoon; Chae, Chanhee

    2014-08-01

    The objective of this study was to compare the induction of humoral and cell-mediated immune responses by four commercially available single-dose porcine circovirus type 2 (PCV-2) vaccines. A total of 50 3-week-old piglets were assigned to five groups (10 pigs per group). Four commercial PCV-2 vaccines were administered according to the manufacturer's instructions and the piglets were observed for 154 days post vaccination (dpv). Inactivated chimeric PCV-1-2 vaccines induced higher levels of PCV-2-specific neutralizing antibodies (NA) and interferon-γ-secreting cells (IFN-γ-SC) in pigs than did the other three commercial PCV-2 vaccines. The proportions of CD4(+) cells were significantly higher in animals vaccinated with inactivated chimeric PCV-1-2 and PCV-2 vaccines than in animals vaccinated with the two subunit vaccines. To our knowledge, this is the first comparison of humoral and cell-mediated immunity induced by four commercial single-dose PCV-2 vaccines under the same conditions. The results of this study demonstrated quantitative differences in the induction of humoral and cell-mediated immunity following vaccination.

  17. Antibody-mediated immunity in CFW mice infected with Mycobacterium lepraemurium. Humoral immune response in murine leprosy.

    PubMed Central

    Rojas-Espinosa, O; Casoluengo-Méndez, M; Díaz, G V

    1976-01-01

    A depression in antibody-mediated immunity (AMI) measured both in terms of circulating antibody and plaque-forming cells in the spleen was observed in CFW mice infected with M. lepraemurium when sheep red blood cells (SRBC) and human gammaglobulin (HGG) were used as antigens. The impairment in AMI was evident only after 75 days of infection thereafter the antibody response to SRBC antigen progressively decreased until the last day of experimentation (135 days). Within the first 60 days of infection no alteration in AMI was observed with the HGG antigen while the response to the SRBC antigen was significantly higher in the infected animals than in uninfected controls. PMID:795574

  18. Assessment of Humoral Immune Responses to Blood-Stage Malaria Antigens following ChAd63-MVA Immunization, Controlled Human Malaria Infection and Natural Exposure

    PubMed Central

    Elias, Sean C.; Miura, Kazutoyo; Milne, Kathryn H.; de Cassan, Simone C.; Collins, Katharine A.; Halstead, Fenella D.; Bliss, Carly M.; Ewer, Katie J.; Osier, Faith H.; Hodgson, Susanne H.; Duncan, Christopher J. A.; O’Hara, Geraldine A.; Long, Carole A.; Hill, Adrian V. S.; Draper, Simon J.

    2014-01-01

    The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite – MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors – ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other

  19. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

    PubMed

    Biswas, Sumi; Choudhary, Prateek; Elias, Sean C; Miura, Kazutoyo; Milne, Kathryn H; de Cassan, Simone C; Collins, Katharine A; Halstead, Fenella D; Bliss, Carly M; Ewer, Katie J; Osier, Faith H; Hodgson, Susanne H; Duncan, Christopher J A; O'Hara, Geraldine A; Long, Carole A; Hill, Adrian V S; Draper, Simon J

    2014-01-01

    The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases

  20. Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired Immunity

    NASA Astrophysics Data System (ADS)

    Hirai, Toshiro; Yoshioka, Yasuo; Udaka, Asako; Uemura, Eiichiro; Ohe, Tomoyuki; Aoshima, Hisae; Gao, Jian-Qing; Kokubo, Ken; Oshima, Takumi; Nagano, Kazuya; Higashisaka, Kazuma; Mashino, Tadahiko; Tsutsumi, Yasuo

    2016-10-01

    The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific antibody production and ovalbumin-specific T cell responses in vivo, although T cell-independent antibodies responses were not affected by C60-P. Together, our data suggest that fullerene derivatives can suppress acquired immune responses that require T cells.

  1. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses

    PubMed Central

    Peng, K-W; Myers, R; Greenslade, A; Mader, E; Greiner, S; Federspiel, MJ; Dispenzieri, A; Russell, SJ

    2013-01-01

    Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. A single dose of cyclophosphamide (CPA) at 370 mg m−2 was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. We therefore tested clinically approved multidose CPA regimens, which are known to kill proliferating lymphocytes, to determine if more intensive CPA therapy can more effectively suppress antiviral antibody responses during virotherapy. In virus-susceptible mice, primary antibody responses to intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular stomatitis virus (VSV) were partially or completely suppressed, respectively, by oral (1 mg × 8 days) or systemic (3 mg × 4 days) CPA regimens initiated 1 day before virus. When MV- or VSV-immune mice were re-challenged with the respective viruses and concurrently treated with four daily systemic doses of CPA, their anamnestic antibody responses were completely suppressed and antiviral antibody titers fell significantly below pre-booster levels. We conclude that the CPA regimen of four daily doses at 370 mg m−2 should be evaluated clinically with i.v. virotherapy to control the antiviral antibody response and facilitate effective repeat dosing. PMID:22476202

  2. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses.

    PubMed

    Peng, K-W; Myers, R; Greenslade, A; Mader, E; Greiner, S; Federspiel, M J; Dispenzieri, A; Russell, S J

    2013-03-01

    Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. A single dose of cyclophosphamide (CPA) at 370 mg m(-2) was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. We therefore tested clinically approved multidose CPA regimens, which are known to kill proliferating lymphocytes, to determine if more intensive CPA therapy can more effectively suppress antiviral antibody responses during virotherapy. In virus-susceptible mice, primary antibody responses to intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular stomatitis virus (VSV) were partially or completely suppressed, respectively, by oral (1 mg × 8 days) or systemic (3 mg × 4 days) CPA regimens initiated 1 day before virus. When MV- or VSV-immune mice were re-challenged with the respective viruses and concurrently treated with four daily systemic doses of CPA, their anamnestic antibody responses were completely suppressed and antiviral antibody titers fell significantly below pre-booster levels. We conclude that the CPA regimen of four daily doses at 370 mg m(-2) should be evaluated clinically with i.v. virotherapy to control the antiviral antibody response and facilitate effective repeat dosing.

  3. Humoral immune response of mice injected with tocopherol after exposure to X-radiation

    SciTech Connect

    Roy, R.M.; Petrella, M.

    1987-01-01

    Serum haemagglutination (HA) titers have been determined for irradiated and non-irradiated mice responding to injection of two different concentrations of sheep red blood cells (SRBC) 24 to 48 hours after irradiation and immediate intraperitoneal injection of 2.5 mg DL alpha-tocopherol, the emulsifying vehicle, or saline. Mice maintained on tocopherol-deficient diets for 8 weeks post-weaning and those on regular diets exhibited increased IgG titers during peak response when injected with vitamin E. This partially alleviated the radiation-depression of the primary immune response induced by the smaller SRBC injection. This stimulatory effect was most significant in mice maintained on vitamin E-deficient diets. The HA titers of irradiated and non-irradiated mice maintained on normal rations were determined following a 10-fold increase in the SRBC inoculation. Antibody titer was greater following injection of the higher concentration of SRBC but post-irradiation injection of tocopherol immediately or 24 hours after irradiation did not enhance immune response. At the higher SRBC concentration maximum observed HA titers decreased with increasing dose of radiation; however, tocopherol had no significant dose-reducing effect. Tocopherol toxicity as manifested by depressed HA titers was observed occasionally in non-irradiated mice challenged with the higher concentration of SRBC.

  4. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine

    PubMed Central

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-01-01

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways. PMID:23453730

  5. Humoral immune response in dogs and cats vaccinated against rabies in southeastern Brazil

    PubMed Central

    2013-01-01

    Background Brazil holds annual nationwide public campaigns to vaccinate dogs and cats against rabies. The presence of rabies antibodies in these animals, which are among the main transmitters of rabies to humans, is a good indicator that they are immunized and protected. Methods In the present study we analyzed 834 serum samples from dogs and cats from the Southeast of Brazil (Presidente Prudente and Dracena cities), 12 months after the 2009 vaccination campaign. We used the technique known as rapid fluorescent focus inhibition test (RFFIT) and considered reactant those sera with values higher 0.5 IU/mL. Results and discussion Reactant sample results in Presidente Prudente were 153 (51.0%) for dogs and 59 (32.6%) for cats, and in Dracena 110 (52.1%) for dogs and 71 (50.0%) for cats. We discussed vaccine coverage of animals involved in this experiment, and observed low titers < 0.5 IU/mL, especially in cats from Presidente Prudente. Conclusion According to the results presented in our experiment, we suggest that titers below 0.5 IU/mL are worrisome and that, for multiple reasons, animals should be immunized against rabies in the period between public vaccination campaigns. Hence, the desired vaccine coverage was not accomplished, especially among cats from Presidente Prudente. PMID:23899101

  6. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine.

    PubMed

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-04-08

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways.

  7. Innate humoral immune parameters in Tilapia zillii under acute stress by low temperature and crowding.

    PubMed

    Chebaani, Nadjoua; Guardiola, Francisco A; Sihem, Merbah; Nabil, Adjajdi; Oumouna, Mustapha; Meseguer, José; Esteban, María A; Cuesta, Alberto

    2014-06-01

    Redbelly tilapia (Tilapia zillii; Gervais, 1848) is one of the most valuable freshwater species in North Africa representing an important part of the continental production, especially in brackish lakes. In Algeria, T. zillii is distributed in several lakes and tributaries of some rivers in the south. Though some attempts are in progress to culture this species, many investigations covering its biology and farm management are still needed. In this sense, this is the first study attempting to evaluate some of the T. zillii immune parameters and valuable data to assess their health and well-being status. Thus, we have determined the levels of serum peroxidases as well as the alternative complement, antiprotease and bactericidal activities. Furthermore, we have also evaluated the potential impact of two acute stress factors, commonly found in fish farms, in these parameters. Although it was assessed that fish exposed to low temperatures or crowding were stressed, as indicated by their increased serum levels of cortisol and glucose, both acute stressors failed to significantly affect serum peroxidases as well as antiprotease and complement activities. However, the bactericidal activity was reduced in general but only in those exposed to crowding reached statistical significance. Further studies are needed to characterise the immune response in T. zillii as well as the effects that farming stresses may produce.

  8. Contributions of humoral and cellular immunity to vaccine-induced protection in humans

    PubMed Central

    Amanna, Ian J.; Slifka, Mark K.

    2011-01-01

    Vaccines play a vital role in protecting the host against infectious disease. The most effective licensed vaccines elicit long-term antigen-specific antibody responses by plasma cells in addition to the development of persisting T cell and B cell memory. The relative contributions of these different immune cell subsets is context-dependent and varies depending on the attributes of the vaccine (i.e., live/attenuated, inactivated, subunit) as well as the biology of the pathogen in question. For relatively simple vaccines against bacterial antigens (e.g., tetanus toxin) or invariant viruses, the immunological correlates of protection are well-characterized. For more complex vaccines against viruses, especially ones that mutate or cause latent infections, it is more difficult to define the specific correlates of immunity. This often requires observational/natural history studies, clinical trials, or experimental evaluation in relevant animal models in order for immunological correlates to be determined or extrapolated. In this review, we will discuss the relative contributions of virus-specific T cell and B cell responses to vaccine-mediated protection against disease. PMID:21216425

  9. Antigen-specific acquired immunity in human brucellosis: implications for diagnosis, prognosis, and vaccine development.

    PubMed

    Cannella, Anthony P; Tsolis, Renee M; Liang, Li; Felgner, Philip L; Saito, Mayuko; Sette, Alessandro; Gotuzzo, Eduardo; Vinetz, Joseph M

    2012-01-01

    Brucella spp., are Gram negative bacteria that cause disease by growing within monocyte/macrophage lineage cells. Clinical manifestations of brucellosis are immune mediated, not due to bacterial virulence factors. Acquired immunity to brucellosis has been studied through observations of naturally infected hosts (cattle, goats), mouse models (mice), and human infection. Even though Brucella spp. are known for producing mechanisms that evade the immune system, cell-mediated immune responses drive the clinical manifestations of human disease after exposure to Brucella species, as high antibody responses are not associated with protective immunity. The precise mechanisms by which cell-mediated immune responses confer protection or lead to disease manifestations remain undefined. Descriptive studies of immune responses in human brucellosis show that TH(1) (interferon-γ-producing T cells) are associated with dominant immune responses, findings consistent with animal studies. Whether these T cell responses are protective, or determine the different clinical responses associated with brucellosis is unknown, especially with regard to undulant fever manifestations, relapsing disease, or are associated with responses to distinct sets of Brucella spp. antigens are unknown. Few data regarding T cell responses in terms of specific recognition of Brucella spp. protein antigens and peptidic epitopes, either by CD4+ or CD8+ T cells, have been identified in human brucellosis patients. Additionally because current attenuated Brucella vaccines used in animals cause human disease, there is a true need for a recombinant protein subunit vaccine for human brucellosis, as well as for improved diagnostics in terms of prognosis and identification of unusual forms of brucellosis. This review will focus on current understandings of antigen-specific immune responses induced Brucella peptidic epitopes that has promise for yielding new insights into vaccine and diagnostics development, and for

  10. Obtaining hyperimmune anti-Cryptosporidium parvum ovine colostrum. A study of the humoral immune response in immunized sheep.

    PubMed

    Martín-Gómez, S; Alvarez-Sánchez, M A; Rojo-Vázquez, F A

    2006-01-01

    Three ewes were immunized five times over a 2-month period prior to giving birth by intramuscular injection, oral administration and intramammary infusion of antigen and viable or freeze-dried Cryptosporidium parvum oocyst solution emulsified with Freund's complete and incomplete adjuvant. Two animals served as controls and another two as adjuvant controls. Serum was collected at first immunization and thereafter every 2 to 4 weeks. Colostrum and milk were collected as well. All samples were assayed for C. parvum-specific antibodies using an enzyme-linked immunosorbent assay methodology, and Western blotting was used to recognize the C. parvum antigens. Hyperimmunization resulted in a progressive and significant increase in specific anti-C. parvum serum IgG, IgA and IgM titres, with the highest values noted at the point of lambing. Titres decreased slightly in milk, although they were in all cases higher than those in the control animals. Moreover, some 30 bands of C. parvum were recognized.

  11. Humor's healing potential.

    PubMed

    Seaward, B L

    1992-04-01

    In the past three decades the medical world has begun to take more serious notice of the healing power of humor and the positive emotions associated with it. Humor and laughter are currently being employed by psychotherapists and other care givers as tools to promote and maintain health, as well as intervention and rehabilitation tools for a host of maladies and illnesses related to stress and life-style. Although this empirical medical approach is relatively new, the study of humor has revealed a complex psychological phenomenon. Senses of humor have been categorized in types associated with personality. Humor has many styles and can be found in almost any situation, on any occasion. Theories of humor include the superiority theory, the incongruity theory, the release/relief theory, and the divinity theory. Laughter has many clinical benefits, promoting beneficial physiological changes and an overall sense of well-being. Humor even has long-term effects that strengthen the effectiveness of the immune system. In healthcare, humor therapy can help relieve stress associated with disease and illness. It serves as a diversionary tactic, a therapeutic tool for disorders such as depression, and a coping mechanism. It also is a natural healing component for care givers trying to cope with the stress and personal demands of their occupations.

  12. Patterns in age-seroprevalence consistent with acquired immunity against Trypanosoma brucei in Serengeti lions.

    PubMed

    Welburn, Sue; Picozzi, Kim; Coleman, Paul G; Packer, Craig

    2008-01-01

    Trypanosomes cause disease in humans and livestock throughout sub-Saharan Africa. Although various species show evidence of clinical tolerance to trypanosomes, until now there has been no evidence of acquired immunity to natural infections. We discovered a distinct peak and decrease in age prevalence of T. brucei s.l. infection in wild African lions that is consistent with being driven by an exposure-dependent increase in cross-immunity following infections with the more genetically diverse species, T. congolense sensu latu. The causative agent of human sleeping sickness, T. brucei rhodesiense, disappears by 6 years of age apparently in response to cross-immunity from other trypanosomes, including the non-pathogenic subspecies, T. brucei brucei. These findings may suggest novel pathways for vaccinations against trypanosomiasis despite the notoriously complex antigenic surface proteins in these parasites.

  13. Impairment of humoral immune responses in mice exposed to nitrogen dioxide and ozone mixtures

    SciTech Connect

    Fujimaki, H.

    1989-04-01

    The relationship between immune defense mechanisms and environmental pollutants remains unknown because of uncertainty about the effects of combined or mixed pollutants. To investigate whether exposure to toxic gas mixtures change the effect of a single gas exposure on immune function, BALB/c mice were continuously exposed to 4.0 ppm nitrogen dioxide (NO/sub 2/), 0.8 ppm ozone (O/sub 3/), or the mixture of NO/sub 2/ plus O/sub 3/ for 3, 7, 14, and 56 days. Organ weights (lung, thymus, and spleen) and antibody responses to sheep red blood cells (SRBC), and to DNP-Ficoll were measured immediately after the exposure. Lung weights in mice exposed to O/sub 3/ or the mixture were increased significantly in all exposure periods. The weights of thymus and spleen in mice exposed for 3, 7, and 14 days to the mixture were decreased. O/sub 3/ exposure for 56 days showed significant decreases of the weights of both organs. Antibody response to SRBC in mice exposed for 3, 7, and 14 days to O/sub 3/ or the mixture was markedly suppressed, but exposure to the mixture for 56 days did not show the suppression of anti-SRBC antibody response. No differences in anti-DNP antibody response between exposed and control mice were observed, except those exposed to O/sub 3/ or the mixture for 14 days. These results suggest that mixed gas exposures variously modify the effects of a single gas exposure on antibody production in mice.

  14. 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.

  15. Antibodies to Lytic Infection Proteins in Lymphocryptovirus-Infected Rhesus Macaques: a Model for Humoral Immune Responses to Epstein-Barr Virus Infection ▿

    PubMed Central

    Orlova, Nina; Fogg, Mark H.; Carville, Angela; Wang, Fred

    2011-01-01

    Humoral immune responses to rhesus lymphocryptovirus (rhLCV) lytic infection proteins were evaluated in the rhesus macaque animal model for Epstein-Barr virus (EBV) infection. We found a hierarchy of humoral responses to 14 rhLCV lytic infection proteins in naturally infected rhesus macaques, with (i) widespread and robust responses to four glycoproteins expressed as late proteins, (ii) frequent but less robust responses to a subset of early proteins, and (iii) low-level responses to immediate-early proteins. This hierarchy of humoral responses was similar to that reported for EBV-infected humans, with the notable exception of the response to rhBARF1. Serum antibodies to rhBARF1 were frequently detected in healthy rhLCV-infected macaques, but in humans, anti-BARF1 antibodies have been reported primarily in patients with EBV-positive nasopharyngeal carcinoma (NPC). The macaque data accurately predicted that serum antibodies against BARF1 are a normal response to EBV infection when human serum samples are analyzed. The rhesus macaque animal provides a unique perspective on humoral responses to EBV infection in humans and can be a valuable model for EBV vaccine development. PMID:21734064

  16. TRAF3 regulates the effector function of regulatory T cells and humoral immune responses

    PubMed Central

    Chang, Jae-Hoon; Hu, Hongbo; Jin, Jin; Puebla-Osorio, Nahum; Xiao, Yichuan; Gilbert, Brian E.; Brink, Robert; Ullrich, Stephen E.

    2014-01-01

    Regulatory T cells (Treg cells) control different aspects of immune responses, but how the effector functions of Treg cells are regulated is incompletely understood. Here we identified TNF receptor–associated factor 3 (TRAF3) as a regulator of Treg cell function. Treg cell–specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by an increase in the Th1 type of effector/memory T cells. Moreover, the ablation of TRAF3 in Treg cells resulted in increased antigen-stimulated activation of follicular T helper cells (TFH cells), coupled with heightened formation of germinal centers and production of high-affinity IgG antibodies. Although the loss of TRAF3 did not reduce the overall frequency of Treg cells, it attenuated the antigen-stimulated production of follicular Treg cells (TFR cells). TRAF3 signaling in Treg cells was required to maintain high level expression of inducible co-stimulator (ICOS), which in turn was required for TFR cell generation and inhibition of antibody responses. These findings establish TRAF3 as a mediator of Treg cell function in the regulation of antibody responses and suggest a role for TRAF3 in mediating ICOS expression in Treg cells. PMID:24378539

  17. The goldfish immune response. I. Characterization of the humoral response to particulate antigens.

    PubMed Central

    Desvaux, F X; Charlemagne, J

    1981-01-01

    Anti-red blood cells (RBC) and anti-hapten antibody synthesis were studied in the goldfish, Carassius auratus. Spontaneous haemagglutination titres were found against all the antigens tested. A weak secondary response was observed in RBC-primed fish boosted during the end-phase of the primary antibody production. However, when the second antigenic challenge was performed during the early exponential phase of a primary stimulation, an important amplified response was obtained. The antibody production and immunological memory can be dissociated: no antibody synthesis occurred in glutaraldehyde-fixed RBC (F-RBC) primed was obtained when untreated or F-RBC were given to F-RBC primed animals. The amplified response to sheep red blood cells (SRBC) was significantly inhibited when fish were primed with a mixture of SRBC and Xenopus red blood cells (XRBC), demonstrating an antigenic competition phenomenon. Studies on anti-trinitrobenzene responses confirm the efficiency of E. coli lipopolysaccharide as a carrier for fish anti-hapten immunization. The kinetics and regulation of antibody synthesis in fish are discussed in relation to the described results. PMID:7275178

  18. A study of the localized humoral immune response to implicated microorganisms in juvenile periodontitis

    SciTech Connect

    Hall, E.R.

    1988-01-01

    A study was undertaken using an in vitro explant culture system to determine the presence of immunoglobulins (IgG, IgA, and IgM) in the supernatant fluids (SF) of disease gingival tissue explant cultures. Studies were also undertaken to determine if the de novo biosynthesis of {sup 14}C-immunoglobulins could be observed in the explant cultures of diseased tissues from juvenile periodontitis (JP) patients. Radiolabeled proteins were detected in the SF and immunodiffusion studies using goat antihuman gamma, alpha or mu chain serum revealed the presence of IgG and IgA but no IgM present in the SF of the JP gingival tissue explant cultures. Immunodiffusion studies using goat anti-human gamma chain serum with Staph protein A isolated IgG fractions of the SF, followed by autoradiography of the IgG precipitation lines demonstrated the biosynthesis of IgG by the JP gingival tissue explant cultures. The serological studies suggested that local immune response in JP was to a polymicrobic infection. The SF of JP showed significantly higher levels of antibody reactivity to B. intermedius, C. ochracea, E. nodatum and P. micros as compared to healthy tissues. The local antibody response to the microorganisms tested differed from that observed in the sera of the patients.

  19. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses

    NASA Astrophysics Data System (ADS)

    Moon, James J.; Suh, Heikyung; Bershteyn, Anna; Stephan, Matthias T.; Liu, Haipeng; Huang, Bonnie; Sohail, Mashaal; Luo, Samantha; Ho Um, Soong; Khant, Htet; Goodwin, Jessica T.; Ramos, Jenelyn; Chiu, Wah; Irvine, Darrell J.

    2011-03-01

    Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.

  20. Substituting Threonine 187 with Alanine in p27Kip1 Prevents Pituitary Tumorigenesis by Two-Hit Loss of Rb1 and Enhances Humoral Immunity in Old Age*

    PubMed Central

    Zhao, Hongling; Bauzon, Frederick; Bi, Enguang; Yu, J. Jessica; Fu, Hao; Lu, Zhonglei; Cui, Jinhua; Jeon, Hyungjun; Zang, Xingxing; Ye, B. Hilda; Zhu, Liang

    2015-01-01

    p27Kip1 (p27) is an inhibitor of cyclin-dependent kinases. Inhibiting p27 protein degradation is an actively developing cancer therapy strategy. One focus has been to identify small molecule inhibitors to block recruitment of Thr-187-phosphorylated p27 (p27T187p) to SCFSkp2/Cks1 ubiquitin ligase. Since phosphorylation of Thr-187 is required for this recruitment, p27T187A knockin (KI) mice were generated to determine the effects of systemically blocking interaction between p27 and Skp2/Cks1 on tumor susceptibility and other proliferation related mouse physiology. Rb1+/− mice develop pituitary tumors with full penetrance and the tumors are invariably Rb1−/−, modeling tumorigenesis by two-hit loss of RB1 in humans. Immunization induced humoral immunity depends on rapid B cell proliferation and clonal selection in germinal centers (GCs) and declines with age in mice and humans. Here, we show that p27T187A KI prevented pituitary tumorigenesis in Rb1+/− mice and corrected decline in humoral immunity in older mice following immunization with sheep red blood cells (SRBC). These findings reveal physiological contexts that depend on p27 ubiquitination by SCFSkp2-Cks1 ubiquitin ligase and therefore help forecast clinical potentials of Skp2/Cks1-p27T187p interaction inhibitors. We further show that GC B cells and T cells use different mechanisms to regulate their p27 protein levels, and propose a T helper cell exhaustion model resembling that of stem cell exhaustion to understand decline in T cell-dependent humoral immunity in older age. PMID:25583987

  1. Substituting threonine 187 with alanine in p27Kip1 prevents pituitary tumorigenesis by two-hit loss of Rb1 and enhances humoral immunity in old age.

    PubMed

    Zhao, Hongling; Bauzon, Frederick; Bi, Enguang; Yu, J Jessica; Fu, Hao; Lu, Zhonglei; Cui, Jinhua; Jeon, Hyungjun; Zang, Xingxing; Ye, B Hilda; Zhu, Liang

    2015-02-27

    p27Kip1 (p27) is an inhibitor of cyclin-dependent kinases. Inhibiting p27 protein degradation is an actively developing cancer therapy strategy. One focus has been to identify small molecule inhibitors to block recruitment of Thr-187-phosphorylated p27 (p27T187p) to SCF(Skp2/Cks1) ubiquitin ligase. Since phosphorylation of Thr-187 is required for this recruitment, p27T187A knockin (KI) mice were generated to determine the effects of systemically blocking interaction between p27 and Skp2/Cks1 on tumor susceptibility and other proliferation related mouse physiology. Rb1(+/-) mice develop pituitary tumors with full penetrance and the tumors are invariably Rb1(-/-), modeling tumorigenesis by two-hit loss of RB1 in humans. Immunization induced humoral immunity depends on rapid B cell proliferation and clonal selection in germinal centers (GCs) and declines with age in mice and humans. Here, we show that p27T187A KI prevented pituitary tumorigenesis in Rb1(+/-) mice and corrected decline in humoral immunity in older mice following immunization with sheep red blood cells (SRBC). These findings reveal physiological contexts that depend on p27 ubiquitination by SCF(Skp2-Cks1) ubiquitin ligase and therefore help forecast clinical potentials of Skp2/Cks1-p27T187p interaction inhibitors. We further show that GC B cells and T cells use different mechanisms to regulate their p27 protein levels, and propose a T helper cell exhaustion model resembling that of stem cell exhaustion to understand decline in T cell-dependent humoral immunity in older age.

  2. Human immunodeficiency virus/acquired immune deficiency syndrome: Using drug from mathematical perceptive.

    PubMed

    Chatterjee, Amar Nath; Saha, Shubhankar; Roy, Priti Kumar

    2015-11-12

    Entry of acquired immune deficiency syndrome virus into the host immune cell involves the participation of various components of host and viral cell unit. These components may be categorized as attachment of the viral surface envelope protein subunit, gp120, to the CD4(+) receptor and chemokine coreceptors, CCR5 and CXCR4, present on T cell surface. The viral fusion protein, gp41, the second cleaved subunit of Env undergoes reconfiguration and the membrane fusion reaction itself. Since the CD4(+) T cell population is actively involved; the ultimate outcome of human immunodeficiency virus infection is total collapse of the host immune system. Mathematical modeling of the stages in viral membrane protein-host cell receptor-coreceptor interaction and the effect of antibody vaccine on the viral entry into the susceptible host cell has been carried out using as impulsive differential equations. We have studied the effect of antibody vaccination and determined analytically the threshold value of drug dosage and dosing interval for optimum levels of infection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that systematic drug dosage of the immune cells leads to longer and improved lives.

  3. Mucosal humoral immune response to SIVmac239Δnef vaccination and vaginal challenge

    PubMed Central

    Zeng, Ming; Smith, Anthony J.; Shang, Liang; Wietgrefe, Stephen W.; Voss, James E.; Carlis, John V.; Li, Qingsheng; Piatak, Michael; Lifson, Jeffrey D.; Johnson, R. Paul; Haase, Ashley T.

    2016-01-01

    Live attenuated vaccines such as SIV with a deleted nef gene (SIVmac239Δnef) have provided the most robust protection against subsequent vaginal challenge with wild type (WT) SIV in the SIV-rhesus macaque (RM) model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such pre-challenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG antibodies reacting with the viral envelope glycoprotein, trimeric gp41 (gp41t); 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal Fc receptor in the overlying epithelium. We now examine the mucosal production of antibody component of this system post-vaginal challenge. We show that vaginal challenge immediately elicits striking increases in plasma cells not only in the female reproductive tract but also at other mucosal sites, and that these increases correlate with low but persistent replication at mucosal sites. We describe vaginal ectopic follicles that are structurally and functionally organized like follicles in secondary lymphoid organs, and provide inferential evidence for a key role of the female reproductive tract epithelium in facilitating antibody production, affinity maturation and class switch recombination. Vaccination thus accesses an epithelial-immune system axis in the female reproductive tract to respond to exposure to mucosal pathogens. Designing strategies to mimic this system could advance development of an effective HIV-1 vaccine. PMID:26864031

  4. Enhanced humoral and cellular immune responses after sublingual immunization against human papillomavirus 16 L1 protein with adjuvants.

    PubMed

    Cho, Hee-Jeong; Kim, Ji-Yeon; Lee, Young; Kim, Jung Mogg; Kim, Young Bong; Chun, Taehoon; Oh, Yu-Kyoung

    2010-03-19

    Needle-free nonparenteral vaccines offer a number of practical advantages, especially in developing countries. To address the effects of vaccine administration route, we tested mucosal and systemic immune responses against human papillomavirus 16 L1(HPV16L1) protein using intranasal, intravaginal, transdermal, sublingual (SL) and intramuscular routes. The SL route provided the most effective mucosal secretory IgA (sIgA) and serum IgG responses. After a 150 microg antigen dose via the SL route, saliva sIgA levels were 7.2- and 5.8-fold higher than those achieved via intravaginal and transdermal routes, respectively. Notably, SL administration even produced 4.6-fold higher levels of vaginal sIgA levels than did intravaginal delivery of 150 microg antigen. To enhance the immunogenicity of SL vaccines, we tested the adjuvanticity of nine molecules: three toll-like receptor agonists, three nucleotide-binding oligomerization-domain agonists, vitamin D3, poly-gamma-glutamic acid and cholera toxin subunit B (CTB). Among the molecules tested, CTB provided the most enhanced mucosal sIgA and systemic IgG induction. SL-applied CTB enhanced the production of interleukin-4 and interferon-gamma from stimulated CD4+ T cells. Moreover, interferon-gamma-producing CD8+ T cell responses were increased 1.7-fold after co-treatment with SL CTB and HPV16L1. These results suggest the potential of the SL route for delivery of HPV16L1 vaccines using CTB as an adjuvant.

  5. Epitope-based vaccines with the Anaplasma marginale MSP1a functional motif induce a balanced humoral and cellular immune response in mice.

    PubMed

    Santos, Paula S; Sena, Angela A S; Nascimento, Rafael; Araújo, Thaise G; Mendes, Mirian M; Martins, João R S; Mineo, Tiago W P; Mineo, José R; Goulart, Luiz R

    2013-01-01

    Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based approach in mice. Mice infection with bovine anaplasmosis was demonstrated by qPCR analysis of erythrocytes after 15-day exposure. A proof-of-concept was obtained in this murine model, in which peptides conjugated to bovine serum albumin were used for immunization in three 15-day intervals by intraperitoneal injections before challenging with live bacteria. Blood samples were analyzed for the presence of specific IgG2a and IgG1 antibodies, as well as for the rickettsemia analysis. A panel containing the cytokines' transcriptional profile for innate and adaptive immune responses was carried out through qPCR. Immunized BALB/c mice challenged with A. marginale presented stable body weight, reduced number of infected erythrocytes, and no mortality; and among control groups mortality rates ranged from 15% to 29%. Additionally, vaccines have significantly induced higher IgG2a than IgG1 response, followed by increased expression of pro-inflammatory cytokines. This is a successful demonstration of epitope-based vaccines, and protection against anaplasmosis may be associated with elicitation of effector functions of humoral and cellular immune responses in murine model.

  6. Chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine is safe and expands humoral and cellular immunity in adults

    PubMed Central

    Green, CA; Scarselli, E; Sande, CJ; Thompson, AJ; de Lara, CM; Taylor, K; Haworth, K; Del Sorbo, M; Angus, B; Siani, L; Di Marco, S; Traboni, C; Folgori, A; Colloca, S; Capone, S; Vitelli, A; Cortese, R; Klenerman, P; Nicosia, A; Pollard, AJ

    2015-01-01

    Respiratory syncytial virus (RSV) causes respiratory infection in annual epidemics, with infants and the elderly at particular risk of developing severe disease and death. However, despite its importance, no vaccine exists. The chimpanzee adenovirus, PanAd3-RSV, and modified vaccinia virus Ankara, MVA-RSV, are replication defective viral vectors encoding the RSV proteins F, N and M2-1 for the induction of humoral and cellular responses. We performed an open-label, dose-escalation, phase 1 clinical trial in 42 healthy adults in which four different combinations of prime/boost vaccinations were investigated for safety and immunogenicity, including both intra-muscular and intra-nasal administration of the adenoviral vectored vaccine. The vaccines were safe and well tolerated, with the most common reported adverse events being mild injection site reactions. No vaccine-related serious adverse events occurred. RSV neutralising antibody titres rose in response to intramuscular (IM) prime with PanAd3-RSV, and after IM boost for individuals primed by the intra-nasal (IN) route. Circulating anti-F IgG and IgA antibody secreting cells (ASCs) were observed after IM prime and IM boost. RSV-specific T-cell responses were increased after IM PanAd3-RSV prime and were most efficiently boosted by IM MVA-RSV. IFNγ secretion after boost was from both CD4+ and CD8+ T-cells, without detectable Th2 cytokines that have been previously associated with immune pathogenesis following exposure to RSV after formalin inactivated RSV vaccine. In conclusion, PanAd3-RSV and MVA-RSV are safe and immunogenic in healthy adults. These vaccine candidates warrant further clinical evaluation of efficacy to assess their potential to reduce the burden of RSV disease. PMID:26268313

  7. Differential humoral immune response against hepatitis C virus antigenic synthetic peptides in infected patients with and without mixed cryoglobulinaemia

    PubMed Central

    GABRIELLI, A; ZHANG, Z-X; CHERUBINI, G; CANDELA, M; SAVOLDI, S; MANZIN, A; CLEMENTI, M; AMOROSO, A; SALLBERG, M

    1996-01-01

    In this study we have evaluated the prevalence of antibodies against core region peptides (residues 1–28, 21–38 and 51–68), the envelope 1, the non-structural (NS) 4 and 5 proteins of hepatitis C virus (HCV) in sera from 65 chronically HCV-infected patients, 47 with mixed cryoglobulinaemia (MC+) and 18 without (MC−). The major binding sites were located within the core region. Regions 1–28 and 51–68 were recognized by a similar proportion of MC+ and MC− patients, while peptide 21–38 was less frequently detected by samples from MC+ patients (65.5% versus 100%; P = 0.011). The patterns of the reactions showed a minimum of three binding sites: one, located within region 51–68, was shared by both groups; a second determinant was identified at residues 1–21 for MC+ patients and at residues 28–38 for MC− patients; a third, not exactly localized, lay between residues 1 and 38. Recognition of NS5 peptides was not significantly different between MC+ and MC− patients, but while the former mostly reacted either with peptide 1 (residues 2294–2309) (five of 15 sera) or with peptide 2 (residues 2304–2319) (nine of 15 sera), the latter group showed a more scattered reaction. Antibodies to HCV peptides prevalently belonged to IgG1 subclass. However, whereas IgG1 antibodies against peptide 21–38 and peptide 1 of NS5 were more frequently found in MC− rather than in MC+ patients (100% versus 63.8%, P = 0.003, and 22.2% versus 4.2%, P = 0.025, respectively), IgG3 antibodies against region 1–28 were more frequent in MC+ patients (53.19% versus 16.6%, P = 0.0078). Overall, the data suggest that a differential humoral immune response to HCV antigens occurs in patients with and without cryoglobulinaemia. PMID:8697636

  8. Cross-reactive acquired immunity influences transmission success of the Lyme disease pathogen, Borrelia afzelii.

    PubMed

    Jacquet, Maxime; Durand, Jonas; Rais, Olivier; Voordouw, Maarten J

    2015-12-01

    Cross-reactive acquired immunity in the vertebrate host induces indirect competition between strains of a given pathogen species and is critical for understanding the ecology of mixed infections. In vector-borne diseases, cross-reactive antibodies can reduce pathogen transmission at the vector-to-host and the host-to-vector lifecycle transition. The highly polymorphic, immunodominant, outer surface protein C (OspC) of the tick-borne spirochete bacterium Borrelia afzelii induces a strong antibody response in the vertebrate host. To test how cross-immunity in the vertebrate host influences tick-to-host and host-to-tick transmission, mice were immunized with one of two strain-specific recombinant OspC proteins (A3, A10), challenged via tick bite with one of the two B. afzelii ospC strains (A3, A10), and infested with xenodiagnostic ticks. Immunization with a given rOspC antigen protected mice against homologous strains carrying the same major ospC group allele but provided little or no cross-protection against heterologous strains carrying a different major ospC group allele. There were cross-immunity effects on the tick spirochete load but not on the probability of host-to-tick transmission. The spirochete load in ticks that had fed on mice with cross-immune experience was reduced by a factor of two compared to ticks that had fed on naive control mice. In addition, strain-specific differences in mouse spirochete load, host-to-tick transmission, tick spirochete load, and the OspC-specific IgG response revealed the mechanisms that determine variation in transmission success between strains of B. afzelii. This study shows that cross-immunity in infected vertebrate hosts can reduce pathogen load in the arthropod vector with potential consequences for vector-to-host pathogen transmission.

  9. Gambiense human african trypanosomiasis and immunological memory: effect on phenotypic lymphocyte profiles and humoral immunity.

    PubMed

    Lejon, Veerle; Mumba Ngoyi, Dieudonné; Kestens, Luc; Boel, Luc; Barbé, Barbara; Kande Betu, Victor; van Griensven, Johan; Bottieau, Emmanuel; Muyembe Tamfum, Jean-Jacques; Jacobs, Jan; Büscher, Philippe

    2014-03-01

    In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and

  10. Abnormal humoral immune response to mucosal antigenic stimulation in patients with lung cancer.

    PubMed

    Michils, A; Yernault, J C; Noel, E; Gossart, B; Servais, G; Duchateau, J

    1992-05-01

    difference in the prevalence of atopy between the three groups. They document a selective, rather than general, defect in the immune response initiated at the mucosal level in patients with lung cancer, the most frequent mucosal cancer in man.

  11. Production and function of cytokines in natural and acquired immunity to Candida albicans infection.

    PubMed Central

    Ashman, R B; Papadimitriou, J M

    1995-01-01

    Host resistance against infections caused by the yeast Candida albicans is mediated predominantly by polymorphonuclear leukocytes and macrophages. Antigens of Candida stimulate lymphocyte proliferation and cytokine synthesis, and in both humans and mice, these cytokines enhance the candidacidal functions of the phagocytic cells. In systemic candidiasis in mice, cytokine production has been found to be a function of the CD4+ T helper (Th) cells. The Th1 subset of these cells, characterized by the production of gamma interferon and interleukin-2, is associated with macrophage activation and enhanced resistance against reinfection, whereas the Th2 subset, which produces interleukins-4, -6, and -10, is linked to the development of chronic disease. However, other models have generated divergent data. Mucosal infection generally elicits Th1-type cytokine responses and protection from systemic challenge, and identification of cytokine mRNA present in infected tissues of mice that develop mild or severe lesions does not show pure Th1- or Th2-type responses. Furthermore, antigens of C. albicans, mannan in particular, can induce suppressor cells that modulate both specific and nonspecific cellular and humoral immune responses, and there is an emerging body of evidence that molecular mimicry may affect the efficiency of anti-Candida responses within defined genetic contexts. PMID:8531890

  12. Physiological and proteomic responses to single and repeated hypoxia in juvenile Eurasian perch under domestication--clues to physiological acclimation and humoral immune modulations.

    PubMed

    Douxfils, Jessica; Deprez, Mélissa; Mandiki, S N M; Milla, Sylvain; Henrotte, Emilie; Mathieu, Cédric; Silvestre, Frédéric; Vandecan, Michaël; Rougeot, Carole; Mélard, Charles; Dieu, Marc; Raes, Martine; Kestemont, Patrick

    2012-11-01

    We evaluated the physiological and humoral immune responses of Eurasian perch submitted to 4-h hypoxia in either single or repeated way. Two generations (F1 and F5) were tested to study the potential changes in these responses with domestication. In both generations, single and repeated hypoxia resulted in hyperglycemia and spleen somatic index reduction. Glucose elevation and lysozyme activity decreased following repeated hypoxia. Complement hemolytic activity was unchanged regardless of hypoxic stress or domestication level. A 2D-DIGE proteomic analysis showed that some C3 components were positively modulated by single hypoxia while C3 up- and down-regulations and over-expression of transferrin were observed following repeated hypoxia. Domestication was associated with a low divergence in stress and immune responses to hypoxia but was accompanied by various changes in the abundance of serum proteins related to innate/specific immunity and acute phase response. Thus, it appeared that the humoral immune system was modulated following single and repeated hypoxia (independently of generational level) or during domestication and that Eurasian perch may display physiological acclimation to frequent hypoxic disturbances.

  13. Effects of the endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae) parasitism, venom, and calyx fluid on cellular and humoral immunity of its host Chilo suppressalis (Lepidoptera: Crambidae) larvae.

    PubMed

    Teng, Zi-Wen; Xu, Gang; Gan, Shi-Yu; Chen, Xuan; Fang, Qi; Ye, Gong-Yin

    2016-02-01

    The larval endoparasitoid Cotesia chilonis injects venom and bracoviruses into its host Chilo suppressalis during oviposition. Here we study the effects of the polydnavirus (PDV)-carrying endoparasitoid C. chilonis (Hymenoptera: Braconidae) parasitism, venom and calyx fluid on host cellular and humoral immunity, specifically hemocyte composition, cellular spreading, encapsulation and melanization. Total hemocyte counts (THCs) were higher in parasitized larvae than in unparasitized larvae in the late stages following parasitization. While both plasmatocyte and granulocyte fractions and hemocyte mortality did not differ between parasitized and unparasitized hosts, in vitro spreading behavior of hemocytes was inhibited significantly by parasitism throughout the course of parasitoid development. C. chilonis parasitism suppressed the encapsulation response and melanization in the early stages. Venom alone did not alter cellular immune responses, including effects on THCs, mortality, hemocyte composition, cell spreading and encapsulation, but venom did inhibit humoral immunity by reducing melanization within 6h after injection. In contrast to venom, calyx fluid had a significant effect on cell spreading, encapsulation and melanization from 6h after injection. Dose-response injection studies indicated the effects of venom and calyx fluid synergized, showing a stronger and more persistent reduction in immune system responses than the effect of either injected alone.

  14. Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100

    PubMed Central

    Morrow, Matthew P; Kraynyak, Kimberly A; Sylvester, Albert J; Shen, Xuefei; Amante, Dinah; Sakata, Lindsay; Parker, Lamar; Yan, Jian; Boyer, Jean; Roh, Christian; Humeau, Laurent; Khan, Amir S; Broderick, Kate; Marcozzi-Pierce, Kathleen; Giffear, Mary; Lee, Jessica; Trimble, Cornelia L; Kim, J Joseph; Sardesai, Niranjan Y; Weiner, David B; Bagarazzi, Mark L

    2016-01-01

    We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV)16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFN)γ production, tumor necrosis factor (TNF)α production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR) sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth “booster” dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100. PMID:28054033

  15. Molecular characteristics of Illicium verum extractives to activate acquired immune response

    PubMed Central

    Peng, Wanxi; Lin, Zhi; Wang, Lansheng; Chang, Junbo; Gu, Fangliang; Zhu, Xiangwei

    2015-01-01

    Illicium verum, whose extractives can activate the demic acquired immune response, is an expensive medicinal plant. However, the rich extractives in I. verum biomass were seriously wasted for the inefficient extraction and separation processes. In order to further utilize the biomedical resources for the good acquired immune response, the four extractives were obtained by SJYB extraction, and then the immunology moleculars of SJYB extractives were identified and analyzed by GC–MS. The result showed that the first-stage extractives contained 108 components including anethole (40.27%), 4-methoxy-benzaldehyde (4.25%), etc.; the second-stage extractives had 5 components including anethole (84.82%), 2-hydroxy-2-(4-methoxy-phenyl)-n-methyl-acetamide (7.11%), etc.; the third-stage extractives contained one component namely anethole (100%); and the fourth-stage extractives contained 5 components including cyclohexyl-benzene (64.64%), 1-(1-methylethenyl)-3-(1-methylethyl)-benzene (17.17%), etc. The SJYB extractives of I. verum biomass had a main retention time between 10 and 20 min what’s more, the SJYB extractives contained many biomedical moleculars, such as anethole, eucalyptol, [1S-(1α,4aα,10aβ)]-1,2,3,4,4a,9,10,10a-octahydro-1,4a-dimethyl-7-(1-methylethyl)-1-phenanthrenecarboxylic acid, stigmast-4-en-3-one, γ-sitosterol, and so on. So the functional analytical results suggested that the SJYB extractives of I. verum had a function in activating the acquired immune response and a huge potential in biomedicine. PMID:27081359

  16. Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.

    PubMed

    Edgar, Contessa E; Terrell, Deirdra R; Vesely, Sara K; Wren, Jonathan D; Dozmorov, Igor M; Niewold, Timothy B; Brown, Michael; Zhou, Fang; Frank, Mark Barton; Merrill, Joan T; Kremer Hovinga, Johanna A; Lämmle, Bernhard; James, Judith A; George, James N; Farris, A Darise

    2015-01-01

    Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and

  17. Kaposi's sarcoma of the head and neck in the acquired immune deficiency syndrome.

    PubMed

    Patow, C A; Steis, R; Longo, D L; Reichert, C M; Findlay, P A; Potter, D; Masur, H; Lane, H C; Fauci, A S; Macher, A M

    1984-06-01

    Since 1981 a new syndrome of acquired immune deficiency (AIDS) has been recognized. Male homosexuals, male and female intravenous drug abusers, and recipients of blood products (i.e., hemophiliacs) appear to be the populations at risk. The syndrome has been manifested by community-acquired opportunistic infections and/or Kaposi's sarcoma (KS). Otolaryngologic manifestations of AIDS are not infrequent. Thirteen AIDS patients at the National Institutes of Health with KS of the head and neck region are presented. All 13 patients were homosexual or bisexual males. Nine initially presented with KS, five with KS of the head or neck. As a group the patients demonstrated lesions involving the oropharyngeal, tracheobronchial, and gastrointestinal regions. Their clinical course and complications are presented in detail. The mortality rate in this subgroup of AIDS patients is extraordinarily high (62%), with an average longevity of 11 months following initial diagnosis.

  18. Immunologic studies in asymptomatic hemophilia patients. Relationship to acquired immune deficiency syndrome (AIDS).

    PubMed

    Landay, A; Poon, M C; Abo, T; Stagno, S; Lurie, A; Cooper, M D

    1983-05-01

    Asymptomatic hemophilia patients receiving Factor VIII concentrate were found to have normal natural killer (NK) cells and B cells, and an inverted T helper/suppressor ratio due to an increase in cells of T suppressor phenotype. In contrast, a hemophilia patient with acquired immune deficiency syndrome (AIDS) exhibited nonfunctional NK cells, low B cells, and an inverted T helper/suppressor ratio due to very low numbers of T helper cells. Hemophilia patients on cryoprecipitate therapy exhibited normal immune parameters. A high percentage of hemophilia patients on both treatments had antibody to hepatitis B virus. The isolated finding of elevated levels of T suppressor cells in hemophilia patients receiving Factor VIII concentrate has not been recognized as an early indicator of impending AIDS, and longitudinal studies will be required to determine its clinical significance.

  19. Human Immune Responses to HTLV-III Virus Infections in the Acquired Immunodeficiency Syndrome

    DTIC Science & Technology

    1988-11-10

    in western blots in the antibodies to HIV-1 structural antigens between this serum and the other sera which neutralize HIV at low dilutions but enhance...n3est AvailabCe AD N T== HUMAN IMMUNE RESPONSE TO HTLV -III VIRUS INFECTION IN ACQUIRED IMMUNODEFICIENCY SYNDROME N ANNUAL REPORT FRANCIS A. ENNIS D...Stimulation of HIV-1 specific T cells. We have stimulated the PBL of 20 HIV antibody-positive donors with live HIV-1 ( HTLV -IIIB) virus, and only 30% respond

  20. Acquired immune deficiency syndrome: recommendations of a working party of the Hospital Infection Society.

    PubMed

    1985-12-01

    Unified procedures to control those infections that are transmitted by inoculation of blood are recommended. These should be applied to patients with overt acquired immune deficiency syndrome, persistent generalized lymphadenopathy or hepatitis B, those with serological evidence of infection by HTLV III or hepatitis B virus, and those in medical and social categories with a higher than average prevalence of such infections. Rational infection control measures, based on the known modes of spread, permit efficient management of infected patients, with satisfactory protection of staff and other patients.

  1. Acquired immune response to oncogenic human papillomavirus associated with prophylactic cervical cancer vaccines.

    PubMed

    Einstein, Mark H

    2008-04-01

    Human papillomavirus (HPV) is a common infection among women and a necessary cause of cervical cancer. Oncogenic HPV types infecting the anogenital tract have the potential to induce natural immunity, but at present we do not clearly understand the natural history of infection in humans and the mechanisms by which the virus can evade the host immune response. Natural acquired immune responses against HPV may be involved in the clearance of infection, but persistent infection with oncogenic virus types leads to the development of precancerous lesions and cancer. B cell responses are important for viral neutralization, but antibody responses in patients with cervical cancer are poor. Prophylactic vaccines targeting oncogenic virus types associated with cervical cancer have the potential to prevent up to 80% of cervical cancers by targeting HPV types 16 and 18. Clinical data show that prophylactic vaccines are effective in inducing antibody responses and in preventing persistent infection with HPV, as well as the subsequent development of high-grade cervical intraepithelial neoplasia. This article reviews the known data regarding natural immune responses to HPV and those developed by prophylactic vaccination.

  2. The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

    PubMed Central

    Haralambieva, Iana H.; Painter, Scott D.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Goergen, Krista M.; Oberg, Ann L.; Poland, Gregory A.

    2015-01-01

    Background Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly. Methods We assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles – TREC content, peripheral white blood cell telomerase – TERT expression and CD28 expression on T cells) and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination. Results TERT activity (TERT mRNA expression) was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025). TREC levels were positively correlated with the baseline and early (Day 3) influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively). The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28) was negatively associated with age, the percentage of CD8+CD28low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively). Conclusion Our data suggest that influenza-specific humoral immunity

  3. Comparative evaluation of immunization with recombinant protein and plasmid DNA vaccines of fusion antigen ROP2 and SAG1 from Toxoplasma gondii in mice: cellular and humoral immune responses.

    PubMed

    Li, Wen-Shu; Chen, Qing-Xin; Ye, Ju-Xiu; Xie, Zi-Xin; Chen, Jun; Zhang, Li-Fang

    2011-09-01

    The aim of this work was to evaluate immune responses in BALB/c mice vaccinated subcutaneously by recombinant protein, or intramuscularly by plasmid DNA with fusion antigen of rhoptry protein 2 (ROP2) and major surface protein 1 (SAG1) from Toxoplasma gondii (T. gondii). BALB/c mice were immunized with one of three different antigen formulations respectively, which were rROP2-SAG1, pcROP2-SAG1, and pcROP2-SAG1 boosted with rROP2-SAG1. The production of IgG, IgG subclasses, lymphoproliferation, and level of gamma interferon (IFN-γ) were detected after vaccination. The animals vaccinated with rROP2-SAG1 quickly developed specific anti-TLA (T. gondii lysate antigen) antibodies, which continued to rise after immunization. However, production of IgG against TLA in mice vaccinated with pcROP2-SAG1 was relatively slow and maintained a high level after reaching plateau. There are more vigorous specific lymphoproliferative responses observed in mice of group rROP2-SAG1 than in pcROP2-SAG1. Immune responses in mice of group pcROP2-SAG1 boosted with rROP2-SAG1 were similar to the protein immunization group. Three immunization procedures resulted in a similar level of IFN-γ production. Our results indicate that BALB/c mice vaccinated by three immunization procedures induce similar humoral and cellular immunity against infection of T. gondii. Mice immunized with recombinant protein rROP2-SAG1 produce more humoral immune responses than mice immunized with other antigen formulations.

  4. [Effect of radiation-induced bystander chemosignals of mice on the humoral immune response in spleen and lymph nodes of intact recipients].

    PubMed

    Sharetskiĭ, A N; Kharlamov, V A; Surinov, B P

    2012-01-01

    The ability of post-radiation (4 Gy) bystander chemosignals (the volatile components of mouse urine) to distantly modulate the humoral immune response to the sheep red blood cells in the spleen and popliteal lymph nodes of intact recipients has been investigated. It was shown that the exposure of animals to chemosignals before antigen injection resulted in the decrease and increase of the immune response in the spleen and lymph nodes, respectively. When animals were exposed to chemosignals after the antigenic stimulus, an increased immune response was observed in both spleen and lymph nodes. The contribution of radiation-induced bystander signaling in the response of socially organized animals to the effect of ionizing irradiation is discussed.

  5. Naloxone/alum mixture a potent adjuvant for HIV-1 vaccine: induction of cellular and poly-isotypic humoral immune responses.

    PubMed

    Velashjerdi Farahani, Sima; Reza Aghasadeghi, Mohammad; Memarnejadian, Arash; Faezi, Sobhan; Shahosseini, Zahra; Mahdavi, Mehdi

    2016-03-01

    In the present study we used a fusion peptide from HIV-1 p24 and Nef as vaccine model and adjuvant activity of Naloxone/alum mixture was evaluated in a peptide vaccine model. HIV-1 p24-Nef fusion peptide was synthesized. Female BALB/c mice were divided into five groups. The first group immunized subcutaneously with the p24-Nef fusion peptide adjuvanted with Naloxone/alum mixture and boosted with same protocol. The second was immunized with fusion peptide adjuvanted in alum. The control groups were injected with NLX (Group 3), Alum (Group 4), or PBS (Groups 5) under the same conditions. To determine the type of induced immune response, sera and splenocytes were analyzed by commercial ELISA method for total IgG and isotypes and cytokine secretion (IL-4 & IFN-γ), respectively. We have also used the ELISPOT assay to monitor changes in the frequency of IFN-γ-producing T cells. The proliferation of T cells was assessed using Brdu method and T-cell cytotoxicity was assessed with CFSE method. Immunization of mice with HIV-1 p24-Nef fusion peptide formulated in Naloxone/alum mixture significantly increased lymphocyte proliferation and shifted cytokine responses toward Th1 profile compared to all other groups. Analysis of humoral immune responses revealed that administration of HIV-1 p24-Nef fusion peptide with Naloxone/alum mixture significantly increased specific IgG responses and also increased IgG1,IgG2a, IgG2b, IgG3, and IgM vs. alum-adjuvanted vaccine groups. Naloxone/alum mixture as an adjuvant could improve cellular and humoral immune response for HIV vaccine model and this adjuvant maybe useful for HIV vaccine model in human clinical trial.

  6. Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens

    PubMed Central

    Reglinski, Mark; Jose, Ricardo J.; Marshall, Helina; de Vogel, Corné; Gordon, Stephen; Petersen, Fernanda C.; Baxendale, Helen

    2017-01-01

    Naturally acquired immunity against invasive pneumococcal disease (IPD) is thought to be dependent on anti-capsular antibody. However nasopharyngeal colonisation by Streptococcus pneumoniae also induces antibody to protein antigens that could be protective. We have used human intravenous immunoglobulin preparation (IVIG), representing natural IgG responses to S. pneumoniae, to identify the classes of antigens that are functionally relevant for immunity to IPD. IgG in IVIG recognised capsular antigen and multiple S. pneumoniae protein antigens, with highly conserved patterns between different geographical sources of pooled human IgG. Incubation of S. pneumoniae in IVIG resulted in IgG binding to the bacteria, formation of bacterial aggregates, and enhanced phagocytosis even for unencapsulated S. pneumoniae strains, demonstrating the capsule was unlikely to be the dominant protective antigen. IgG binding to S. pneumoniae incubated in IVIG was reduced after partial chemical or genetic removal of bacterial surface proteins, and increased against a Streptococcus mitis strain expressing the S. pneumoniae protein PspC. In contrast, depletion of type-specific capsular antibody from IVIG did not affect IgG binding, opsonophagocytosis, or protection by passive vaccination against IPD in murine models. These results demonstrate that naturally acquired protection against IPD largely depends on antibody to protein antigens rather than the capsule. PMID:28135322

  7. Speculations on the viral etiology of acquired immune deficiency syndrome and Kaposi's sarcoma.

    PubMed

    Conant, M A

    1984-07-01

    The acquired immune deficiency syndrome (AIDS) appeared in the United States in late 1978 and has spread at an epidemic rate through the four major coastal cities of this country. The disease appears to show the same epidemiologic distribution as hepatitis B virus infection, and for this reason, most investigators feel that this new disease is caused by a blood-borne sexually transmitted virus. A number of viral agents have been suggested as the cause of AIDS, but to date, no virus has been consistently isolated. The most likely candidate is a retrovirus that has recently been introduced into the human population and has found its way into two extremely high-risk groups, namely, promiscuous male homosexuals and intravenous drug abusers. The relationship between Kaposi's sarcoma and cytomegalovirus is still unclear, but evidence is mounting that cytomegalovirus may be the agent that initiates this multifocal malignancy. Multiple factors must be involved in this process. It is known that some immunosuppressed individuals develop Kaposi's sarcoma, which completely resolves when the immunosuppression is reversed; however, in individuals with classical Kaposi's sarcoma, the profound degree of helper T-cell depression that characterizes the acquired immune deficiency syndrome is not seen.

  8. Associations between Single Nucleotide Polymorphisms in Cellular Viral Receptors and Attachment Factor-Related Genes and Humoral Immunity to Rubella Vaccination

    PubMed Central

    Haralambieva, Iana H.; Lambert, Nathaniel D.; Ovsyannikova, Inna G.; Kennedy, Richard B.; Larrabee, Beth R.; Pankratz, V. Shane; Poland, Gregory A.

    2014-01-01

    Background Viral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity. Methods Using a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts. Results Our analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05). Conclusion Our results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination. PMID:24945853

  9. Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes

    PubMed Central

    Lee, Andrew C. Y.; Zhu, Houshun; Zhang, Anna J. X.; Li, Can; Wang, Pui; Li, Chuangen; Chen, Honglin; Hung, Ivan F. N.; To, Kelvin K. W.

    2015-01-01

    Influenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. In this study, we compared serum hemagglutination inhibition (HI) and microneutralization (MN) antibody titers of mice challenged with wild-type A(H7N9) viruses [H7N9(Anhui) and H7N9(Zhejiang)], an A(H1N1)pdm09 virus [pH1N1(2009)], and a recombinant A(H7N9) virus with PR8/H1N1 internal genes (rg-PR8-H7-N9). All mice infected by H7N9(Anhui) and H7N9(Zhejiang) developed serum HI antibodies at 14 days postinfection (dpi) but no detectable MN antibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)- and H7N9(Zhejiang)-infected mice using fluorescent focus MN assay, but convalescent-phase serum samples obtained from H7N9(Anhui)-infected mice did not reduce the mortality of naive mice after homologous virus challenge. Reinfection with homologous A(H7N9) virus induced higher HI and MN titers than first infection. In contrast, pH1N1(2009) virus infection induced robust HI and MN antibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI and MN antibody titers than H7N9(Zhejiang). In conclusion, the internal genes of A(H7N9) virus can affect the humoral immune response against homologous viral surface proteins, which may also contribute to the virulence of A(H7N9) virus. PMID:26446420

  10. Silicate antibodies in women with silicone breast implants: development of an assay for detection of humoral immunity.

    PubMed Central

    Shen, G Q; Ojo-Amaize, E A; Agopian, M S; Peter, J B

    1996-01-01

    Silicon, in the form of sodium silicate (Na2SiO3), adsorbed onto bovine serum albumin (BSA)-precoated plates served as the solid-phase antigen in an enzyme immunoassay to detect silicate-reactive antibodies in the plasma of 40 symptomatic women with silicone breast implants, 91 asymptomatic women with silicone breast implants, 50 healthy control women, and 52 women with rheumatic diseases and without silicone breast implants, Silicate-reactive antibodies of immunoglobulin G (IgG) or IgM isotypes were detected in the plasma of 30% (12 of 40) of the symptomatic women with silicone breast implants; 9% (8 of 91) of the asymptomatic women with silicone breast implants; 5% (1 of 20) of the women without implants who had systemic lupus erythematosus; and 0% (0 of 32) of the women without implants who had either Sjögren syndrome, scleroderma, or rheumatoid arthritis. Only 2% (1 of 50) of the sera from the healthy control women contained silicate-reactive antibodies. Preincubation of sera with silicate and eight other metal compounds (including SiO2) demonstrated that the IgG and IgM antibodies bound specifically to silicate, because preincubation with Na2SiO3 inhibited more than 90% of the activity, whereas CrO3, Li2SO4, MgSO4, NiSO4, HgCl2, ZrOCl2, BeSO4, and SiO2 failed to inhibit the IgG or IgM antibody binding to the silicate-BSA plates. Furthermore, the F(ab')2 portion and not the Fc portion of the silicate-reactive IgG was reactive with BSA-bound silicate in the enzyme immunoassay. The assay for silicate-reactive antibodies was quantified by assigning arbitrary units to a standard curve composed of serial twofold dilutions of high-positive (ten times higher than the cutoff) silicate antibody sera. This novel assay is a useful method for detecting and quantifying humoral immune response to silicate. PMID:8991630

  11. Norovirus Infection and Acquired Immunity in 8 Countries: Results From the MAL-ED Study

    PubMed Central

    Rouhani, Saba; Peñataro Yori, Pablo; Paredes Olortegui, Maribel; Siguas Salas, Mery; Rengifo Trigoso, Dixner; Mondal, Dinesh; Bodhidatta, Ladaporn; Platts-Mills, James; Samie, Amidou; Kabir, Furqan; Lima, Aldo; Babji, Sudhir; Mason, Carl J.; Kalam, Adil; Bessong, Pascal; Ahmed, Tahmeed; Mduma, Estomih; Bhutta, Zulfiqar A.; Lima, Ila; Ramdass, Rakhi; Lang, Dennis; George, Ajila; Zaidi, Anita K. M.; Kang, Gagandeep; Houpt, Eric; Kosek, Margaret N.

    2016-01-01

    Background. Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life. Methods. A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity. Results. Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was comparable to other enteropathogens, with the exception of rotavirus. Incidence of genogroup II (GII) infection was higher than genogroup I and peaked at 6–11 months across sites. Undernutrition was a risk factor for symptomatic norovirus infection, with an increase in 1 standard deviation of length-for-age z score associated with a 17% reduction (odds ratio, 0.83 [95% confidence interval, .72–.97]; P = .011) in the odds of experiencing diarrhea when norovirus was present, after accounting for genogroup, rotavirus vaccine, and age. Evidence of acquired immunity was observed among GII infections only: Children with prior GII infection were found to have a 27% reduction in the hazard of subsequent infection (hazard ratio, 0.727; P = .010). Conclusions. The high prevalence of norovirus across 8 sites in highly variable epidemiologic settings and demonstration of protective immunity for GII infections provide support for investment in vaccine development. PMID:27013692

  12. Acquired transmission-blocking immunity to Plasmodium vivax in a population of southern coastal Mexico.

    PubMed

    Ramsey, J M; Salinas, E; Rodríguez, M H

    1996-05-01

    Naturally acquired transmission-blocking immunity to Plasmodium vivax was studied in three groups of patients from the southern coast of Mexico: primary cases (Group A, 61% of the study population), secondary cases with the prior infection seven or more months earlier (Group B, 23%), and secondary cases with the previous malaria experience within six months of the present study (Group C, 16%). Anopheles albimanus mosquitoes were fed with patients' infected blood cells in the presence of autologous or control serum, with or without heat-inactivation. Patients from all three groups had transmission-blocking immunity, although the quality and quantity of this blocking activity was significantly higher in the two secondary patient groups (B and C). Only primary malaria cases produced transmission-enhancing activity (23% of the cases), which was dependent on heat-labile serum components. The levels of patient group transmission-blocking immunity and mosquito infectivity were used to calculate the probabilities of a mosquito becoming infective after taking a blood meal from a P. vivax-infected patient from any one of the three groups. This probability was 0.025, with Group A patients providing the major source of these infections (92% risk from Group A and 4% risk for Groups B and C).

  13. Persistence of Immunity Acquired after a Single Dose of Rubella Vaccine in Japan.

    PubMed

    Okafuji, Takao; Okafuji, Teruo; Nakayama, Tetsuo

    2016-05-20

    To date, Takahashi, Matsuura, and TO-336 strains of live-attenuated rubella vaccine have been used in Japan. Japan implemented a single-dose rubella vaccination program until 2006. However, few reports are available on the persistence of immunity after this vaccination program. We collected 276 serum samples from January 2009 to December 2011 at Okafuji Pediatric Clinic and assessed the immune status of these samples against rubella virus during 1-10 years after vaccination with a single dose of Takahashi rubella vaccine. Regional outbreak of rubella did not occur during 1999-2011. The collected serum samples were tested for antibodies against the rubella virus by performing a standard hemagglutination inhibition (HAI) test. Our results showed that all the tested serum samples contained antibodies against the rubella virus 10 years after the vaccination. Geometric mean titer of HAI antibodies was 1:180 and decreased to 1:68 at 10 years after the vaccination. The levels of HAI antibodies decreased logarithmically with time after the vaccination. In conclusion, vaccine-acquired immunity after vaccination with a single dose of live-attenuated Takahashi rubella vaccine was retained for at least 10 years when rubella was under regional control.

  14. Salivary Defense Proteins: Their Network and Role in Innate and Acquired Oral Immunity

    PubMed Central

    Fábián, Tibor Károly; Hermann, Péter; Beck, Anita; Fejérdy, Pál; Fábián, Gábor

    2012-01-01

    There are numerous defense proteins present in the saliva. Although some of these molecules are present in rather low concentrations, their effects are additive and/or synergistic, resulting in an efficient molecular defense network of the oral cavity. Moreover, local concentrations of these proteins near the mucosal surfaces (mucosal transudate), periodontal sulcus (gingival crevicular fluid) and oral wounds and ulcers (transudate) may be much greater, and in many cases reinforced by immune and/or inflammatory reactions of the oral mucosa. Some defense proteins, like salivary immunoglobulins and salivary chaperokine HSP70/HSPAs (70 kDa heat shock proteins), are involved in both innate and acquired immunity. Cationic peptides and other defense proteins like lysozyme, bactericidal/permeability increasing protein (BPI), BPI-like proteins, PLUNC (palate lung and nasal epithelial clone) proteins, salivary amylase, cystatins, prolin-rich proteins, mucins, peroxidases, statherin and others are primarily responsible for innate immunity. In this paper, this complex system and function of the salivary defense proteins will be reviewed. PMID:22605979

  15. Chronic beryllium disease: an updated model interaction between innate and acquired immunity

    PubMed Central

    Sawyer, Richard T.; Maier, Lisa A.

    2011-01-01

    During the last decade, there have been concerted efforts to reduce beryllium (Be) exposure in the workplace and thereby reduce potential cases of this occupational lung disorder. Despite these efforts, it is estimated that there are at least one million Be-exposed individuals in the U.S. who are potentially at risk for developing chronic beryllium disease (CBD). Previously, we reviewed the current CBD literature and proposed that CBD represents a model interaction between innate and acquired immunity (Sawyer et al., Int Immunopharmacol 2:249–261, 2002). We closed this review with a section on “future directions” that identified key gaps in our understanding of the pathogenesis of CBD. In the intervening period, progress has been made to fill in some of these gaps, and the current review will provide an update on that progress. Based on recent findings, we provide a new hypothesis to explain how Be drives sustained chronic inflammation and granuloma formation in CBD leading to progressive compromised lung function in CBD patients. This paradigm has direct implications for our understanding of the development of an immune response to Be, but is also likely applicable to other immune-mediated lung diseases of known and unknown etiology. PMID:20981472

  16. [A novel immunization strategy to induce strong humoral responses against HIV-1 using combined DNA, recombinant vaccinia virus and protein vaccines].

    PubMed

    Liu, Chang; Wang, Shu-hui; Ren, Li; Hao, Yan-ling; Zhang, Qi-cheng; Liu, Ying

    2014-11-01

    To optimize the immunization strategy against HIV-1, a DNA vaccine was combined with a recombinant vaccinia virus (rTV) vaccine and a protein vaccine. Immune responses against HIV-1 were detected in 30 female guinea pigs divided into six groups. Three groups of guinea pigs were primed with HIV-1 DNA vaccine three times, boosted with rTV at week 14, and then boosted with gp140 protein at intervals of 4, 8 or 12 weeks. Simultaneously, the other three groups of animals were primed with rTV vaccine once, and then boosted with gp140 after 4, 8 or 12 weeks. The HIV-1 specific binding antibody and neutralizing antibody, in addition to the relative affinity of these antibodies, were detected at different time points after the final administration of vaccine in each group. The DNA-rTV-gp140 immune regimen induced higher titers and affinity levels of HIV-1 gp120/gp140 antibodies and stronger V1V2-gp70 antibodies than the rTV-gp140 regimen. In the guinea pigs that underwent the DNA-rTV-gp140 regimen, the highest V1V2-gp70 antibody was induced in the 12-week-interval group. However, the avidity of antibodies was improved in the 4-week-interval group. Using the rTV-gp140 immunization strategy, guinea pigs boosted at 8 or 12 weeks after rTV priming elicited stronger humoral responses than those boosted at 4 weeks after priming. In conclusion, this study shows that the immunization strategy of HIV-1 DNA vaccine priming, followed by rTV and protein vaccine boosting, could strengthen the humoral response against HIV-1. Longer intervals were better to induce V1V2-gp70-specific antibodies, while shorter intervals were more beneficial to enhance the avidity of antibodies.

  17. Vaccination with gp120-depleted HIV-1 plus immunostimulatory CpG oligodeoxynucleotides in incomplete Freund's adjuvant stimulates cellular and humoral immunity in rhesus macaques.

    PubMed

    Silvera, Peter; Savary, Jay R; Livingston, Virginia; White, Jessica; Manson, Kelledy H; Wyand, Michael H; Salk, Peter L; Moss, Ronald B; Lewis, Mark G

    2004-12-21

    Whole killed human immunodeficiency virus type 1 (HIV-1) immunogens contain the more conserved epitopes of HIV-1 and therefore may provide some utility as potential HIV-1 vaccine candidates. Previous studies have shown that synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine-guanine (CpG) dinucleotides trigger rapid stimulation of both CD4+ and CD8+ T cells. Here, we investigated whether immunization of rhesus macaques with an inactivated gp120-depleted HIV-1 immunogen, emulsified in incomplete Freund's adjuvant (IFA) together with immunostimulatory CpG-containing ODN (ODN 2006), would elicit HIV-specific cellular and humoral immune responses. High titer anti-p24 antibody levels were induced in all four immunized animals that were sustained 6 weeks after the fifth and final boost at 23 months. These anti-gag antibodies mapped to linear B-cell epitopes within the matrix (MA), capsid (CA), p2, nucleocapsid (NC) and p6 proteins of HIV-1 gag. HIV-specific interferon-gamma-producing CD4+ and CD8+ T-cell responses were measured before and after the fourth and fifth immunizations by both intracellular cytokine (ICC) and ELISPOT techniques; responses were detected in three of the four immunized animals. CD4+ T-cell epitopes appear to map within amino acids 261-290 and 291-320 of p24 CA protein. Immunizations were well tolerated both locally and systemically. Based on these results, further studies of this approach are warranted.

  18. A pilot study of surrogate tests to prevent transmission of acquired immune deficiency syndrome by transfusion.

    PubMed

    Simon, T L; Bankhurst, A D

    1984-01-01

    Because of reports that acquired immune deficiency syndrome (AIDS) might be transmissible by blood transfusion, we studied potential surrogate tests that could be used for screening donors. Male donors at one volunteer blood center and two plasma centers were screened for total lymphocyte count, OKT3, OKT4, OKT8, OKT11, LEU-7, LEU-M2, antibodies to hepatitis B core (anti-HBc), cytomegalovirus (CMV), and herpes and circulating immune complexes. Total lymphocyte counts and the OKT11 were significantly lower in one plasma center. No significant differences were found for the other lymphocyte or monocyte tests. Low T4/T8 ratios, found in 20 percent of donors, did not correlate with other abnormalities. A small percentage (3.3%) of volunteer donors, 15.4 percent at one plasma center and 20.8 percent at a second plasma center, and 38.5 percent of the male homosexual donors were positive for anti-HBc (significant when comparing the male homosexuals to the volunteers at p = 0.032). Positive CMV and herpes titers were similar in the groups. Circulating immune complex levels greater than two standard deviations above the mean were found in 20 percent of the volunteer donors, 7.7 percent at one plasma center and 8.3 percent at the second plasma center, and none in the male homosexual population. Pearson product moment correlations showed reasonably good agreement among the lymphocyte tests. However, the anti-HBc, CMV, and herpes antibodies and circulating immune complex levels did not correlate with any of the other tests. Surrogate tests for AIDS are nonspecific and unlikely to be helpful in screening blood donor units.

  19. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses

    PubMed Central

    Dzharullaeva, Alina S.; Tukhvatulina, Natalia M.; Shcheblyakov, Dmitry V.; Shmarov, Maxim M.; Dolzhikova, Inna V.; Stanhope-Baker, Patricia; Naroditsky, Boris S.; Gudkov, Andrei V.; Logunov, Denis Y.; Gintsburg, Alexander L.

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  20. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses.

    PubMed

    Tukhvatulin, Amir I; Dzharullaeva, Alina S; Tukhvatulina, Natalia M; Shcheblyakov, Dmitry V; Shmarov, Maxim M; Dolzhikova, Inna V; Stanhope-Baker, Patricia; Naroditsky, Boris S; Gudkov, Andrei V; Logunov, Denis Y; Gintsburg, Alexander L

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  1. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection

    SciTech Connect

    Correa-Oliveira, R.; Sher, A.; James, S.L.

    1984-03-01

    Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model.

  2. Active viral B hepatitis in parenteral drug abusers with acquired immune deficiency syndrome (AIDS).

    PubMed

    Leevy, C B; Nurse, H; Kapila, R

    1989-01-01

    Eighty-percent of 47 parenteral drug abusers with hepatomegaly and acquired immunodeficiency syndrome had HBV DNA in serum, although only 27% were HBsAg or "e" antigen-positive by polyclonal radioimmunoassay. Liver biopsies from each of 37 HBV DNA seropositive patients showed HBV DNA and were HBcAg-positive. The absence of positive HBsAg and "e" antigen in HBV DNA-positive patients was attributable to the presence of immune complexes; after in vitro dissociation of these complexes there was an increase in HBsAg from 24% to 86%, and of "e" antigen from 19% to 62%. These data indicate that actively replicating hepatitis B virus is common in patients with AIDS, and that precautions should be taken to prevent its dissemination. Therapy in these patients should address both human immunodeficiency and hepatitis B virus infections.

  3. Pathologic features of the liver in acquired immune deficiency syndrome (AIDS).

    PubMed

    Nakanuma, Y; Liew, C T; Peters, R L; Govindarajan, S

    1986-06-01

    The livers of 26 adult males with acquired immune deficiency syndrome (AIDS) were reviewed. The occurrence of portal tracts with diminished lymphocytes, probably reflecting generalized exhaustion of the lymphoid system, was a characteristic morphologic change, and was found in all cases. Kupffer cell hyperplasia was also a frequent finding and probably reflected generalized infection(s). Punched-out clusters of foamy histiocytes filled with acid-fast bacilli, typical for infection with Mycobacterium avium intracellulare (MAC), were found in three patients. In addition, MAC was cultured from two livers without the foamy histiocytic changes. Chronic viral hepatitis (three cases) and deposition of polarizable materials (one case) in the liver might be related to unusual habits of patients with AIDS. In conclusion, livers from patients with AIDS disclosed several kinds of lesions reflecting underlying or associated conditions in AIDS, but these did not contribute to the cause of death in our patients.

  4. Histopathologic features of the liver in pediatric acquired immune deficiency syndrome.

    PubMed

    Jonas, M M; Roldan, E O; Lyons, H J; Fojaco, R M; Reddy, R K

    1989-07-01

    Autopsy and liver biopsy specimens from 30 pediatric patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were retrospectively reviewed. Of 28 cases with histologic abnormalities, the following findings were noted singly or in combination: giant-cell transformation, cytomegalovirus inclusions, Kaposi's sarcoma, diffuse lymphoplasmocytic infiltrate, granulomatous hepatitis, mild portal inflammation, necrosis around central veins, steatosis, and cholestasis. For the most part, abnormalities in the liver were not predictive of those in other organs, but the two children with the diffuse parenchymal lymphoplasmocytic infiltrate also had lymphoid interstitial pneumonitis (LIP). Liver histopathology in pediatric patients with AIDS shares some features with that in adults, but appreciable differences are noted. In particular, these differences include the higher frequency of giant-cell transformation and the lower frequency of granulomas in children and the observation of diffuse lymphoplasmocytic infiltrate associated with LIP.

  5. Hepatitis B virus (HBV) DNA in leucocytes in acquired immune deficiency syndrome (AIDS).

    PubMed

    Lie-Injo, L E; Volberding, P; Golden, J A; Herrera, A R

    1985-01-01

    Earlier reported findings of hepatitis B virus (HBV) DNA in white blood cells of patients with hepatoma, and in a patient with autoimmune haemolytic anaemia, led to the examination of HBV DNA in a series of twenty three patients with acquired immune deficiency syndrome (AIDS), including nine with opportunistic infections and fourteen with Kaposi's sarcoma, by Southern blot hybridization method, using 32P labelled HBV DNA specific probe obtained by nick translation of HBV DNA cloned into plasmid pBR325. Four of the patients were found to be positive for HBV DNA or HBV related DNA in their leucocytes. The HBV DNA was found free or integrated in the leucocytes of the patients.

  6. Acquired immune deficiency syndrome: recommendations of a Working Party of the Hospital Infection Society.

    PubMed

    Speller, D C; Shanson, D C; Ayliffe, G A; Cooke, E M

    1990-01-01

    Unified procedures to control those infections that are transmitted by inoculation of blood are recommended. These should be applied to patients with acquired immune-deficiency syndrome (AIDS), AIDS-related complex, persistent generalized lymphadenopathy or hepatitis B, those with serological evidence of infection by human immunodeficiency virus or hepatitis B virus, and those in medical and social categories with a higher than average prevalence of such infections. When the identification of these categories of patient would be particularly difficult, the precautions should be applied to all patients, in situations of high risk for inoculation incidents. Rational infection-control measures, based on the known mode of spread, permit efficient management of infected patients, with satisfactory protection of staff and other patients.

  7. Social capital of Iranian patients living with acquired immune deficiency syndrome and associated factors.

    PubMed

    Ansari, S K; Nedjat, S; Jabbari, H; Saiepour, N; Heris, M J

    2015-12-13

    This study investigated the social capital of Iranian patients living with acquired immune deficiency syndrome (AIDS) and the associated factors. In a cross-sectional study the Integrated Social Capital Questionnaire was filled by a sequential sample of 300 patients visiting a referral counselling centre in Tehran. The patients' social capital scores were around 50% in the trust, social cohesion, collective action and cooperation and political empowerment domains. The groups and networks membership domain scored the lowest (27.1%). In regression analysis, employment status was significantly associated with groups and networks membership; age, marital status and financial status were associated with collective action and cooperation; period of disease awareness and marital status affected social cohesion and inclusion; and having risky behaviour affected empowerment and political action. Efforts are needed to enhance the social capital of those patients living with AIDS who are younger, unemployed, divorced/widowed, with risky behaviours and shorter disease awareness.

  8. Findings in psychiatric consultations with patients with acquired immune deficiency syndrome.

    PubMed

    Dilley, J W; Ochitill, H N; Perl, M; Volberding, P A

    1985-01-01

    Thirteen of 40 patients with acquired immune deficiency syndrome (AIDS) admitted to the wards of a large city hospital were seen by the staff of a psychiatric consultation service. Eleven were gay men and two were bisexual men. "Depression" was the stated reason for referral of 10 patients; of these, two met DSM-III criteria for major depression, one had dysthymic disorder, and seven had adjustment disorder with depressed mood. Recurrent psychological themes of the 13 patients were: dealing with a life-threatening illness, uncertainty about the implications of an AIDS diagnosis, social isolation, and guilt over their previous life style. The role of the primary physician and of the mental health professional in the psychological care of AIDS patients is discussed.

  9. Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques

    PubMed Central

    Negri, Donatella; Blasi, Maria; LaBranche, Celia; Parks, Robert; Balachandran, Harikrishnan; Lifton, Michelle; Shen, Xiaoying; Denny, Thomas; Ferrari, Guido; Vescio, Maria Fenicia; Andersen, Hanne; Montefiori, David C; Tomaras, Georgia D; Liao, Hua-Xin; Santra, Sampa; Haynes, Barton F; Klotman, Mary E; Cara, Andrea

    2016-01-01

    The design of an effective HIV-1 vaccine remains a major challenge. Several vaccine strategies based on viral vectors have been evaluated in preclinical and clinical trials, with largely disappointing results. Integrase defective lentiviral vectors (IDLV) represent a promising vaccine candidate given their ability to induce durable and protective immune responses in mice after a single immunization. Here, we evaluated the immunogenicity of a SIV-based IDLV in nonhuman primates. Six rhesus monkeys were primed intramuscularly with IDLV-Env and boosted with the same vector after 1 year. A single immunization with IDLV-Env induced broad humoral and cellular immune responses that waned over time but were still detectable at 1 year postprime. The boost with IDLV-Env performed at 1 year from the prime induced a remarkable increase in both antibodies and T-cell responses. Antibody binding specificity showed a predominant cross-clade gp120-directed response. Monkeys' sera efficiently blocked anti-V2 and anti-CD4 binding site antibodies, neutralized the tier 1 MW965.26 pseudovirus and mediated antibody-dependent cellular cytotoxicity (ADCC). Durable polyfunctional Env-specific T-cell responses were also elicited. Our study demonstrates that an IDLV-Env-based vaccine induces functional, comprehensive, and durable immune responses in Rhesus macaques. These results support further evaluation of IDLV as a new HIV-1 vaccine delivery platform. PMID:27455880

  10. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

    1987-11-01

    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

  11. Anterior segment manifestations of human immunodeficiency virus/acquired immune deficiency syndrome

    PubMed Central

    Sudharshan, S

    2008-01-01

    Ocular complications are known to occur as a result of human immunodeficiency virus (HIV) disease. They can be severe leading to ocular morbidity and visual handicap. Cytomegalovirus (CMV) retinitis is the commonest ocular opportunistic infection seen in acquired immune deficiency syndrome (AIDS). Though posterior segment lesions can be more vision-threatening, there are varied anterior segment manifestations which can also lead to ocular morbidity and more so can affect the quality of life of a HIV-positive person. Effective antiretroviral therapy and improved prophylaxis and treatment of opportunistic infections have led to an increase in the survival of an individual afflicted with AIDS. This in turn has led to an increase in the prevalence of anterior segment and adnexal disorders. Common lesions include relatively benign conditions such as blepharitis and dry eye, to infections such as herpes zoster ophthalmicus and molluscum contagiosum and malignancies such as squamous cell carcinoma and Kaposi′s sarcoma. With the advent of highly active antiretroviral therapy, a new phenomenon known as immune recovery uveitis which presents with increased inflammation, has been noted to be on the rise. Several drugs used in the management of AIDS such as nevirapine or indinavir can themselves lead to severe inflammation in the anterior segment and adnexa of the eye. This article is a comprehensive update of the important anterior segment and adnexal manifestations in HIV-positive patients with special reference to their prevalence in the Indian population. PMID:18711264

  12. Effectiveness and safety of traditional Chinese medicine in treating acquired immune deficiency syndrome: 2004-2014.

    PubMed

    Liu, Zhi-Bin; Yang, Ji-Ping; Xu, Li-Ran

    2015-12-23

    Substantial progress has been made in China in using traditional Chinese medicine (TCM) to treat acquired immune deficiency syndrome (AIDS). Our objective was to review the latest developments in TCM treatment of AIDS in China between 2004 and 2014. We reviewed the content of original articles investigating the efficacy and safety of TCM for treating AIDS published in Chinese and English language journals. Relevant references from 2004 to 2014 were found using PubMed and the China National Knowledge Infrastructure Database. We found that TCM has been widely used for treating AIDS and its complications in China. The number of TCM studies has increased, which indicates efficacy and safety. Measures of efficacy in the reviewed articles included the alleviation of human immunodeficiency virus (HIV)-related signs and symptoms, improvements in quality of life, improvements in long-term survival, counteraction of the adverse side effects of antiviral drugs, promotion of immune reconstitution, and improvement of laboratory results. In sum, the literature indicates that TCM is safe. TCM plays an important role in the treatment of AIDS. Some studies have attempted to measure the efficacy and safety of TCM for treating AIDS, but more evidence is needed. Therefore, more research on this topic is required in the future.

  13. Herd immunity acquired indirectly from interactions between the ecology of infectious diseases, demography and economics.

    PubMed

    Bonds, Matthew H; Rohani, Pejman

    2010-03-06

    Patterns of morbidity and mortality around the globe are determined by interactions between infectious diseases and systematic human socioeconomic processes. The most obvious of these patterns is that the greatest burdens of infectious diseases are found among the poor, who lack the basic resources for disease prevention and treatment. Yet, it is becoming increasingly clear that many infectious diseases are themselves causes of poverty owing to their effects on labour productivity. A particularly subtle phenomenon that receives little attention in the epidemiology literature and is especially important for poor communities is the role of the birth rate as an important direct cause of high disease burdens. Because of their high rates of transmission and life-long immunity, the persistence of many child diseases such as measles relies on high rates of reproduction as their source of susceptible individuals. Thus, there are significant direct health benefits of lower fertility rates, which are further enhanced by interactions with economic processes. Indeed, fertility, poverty and disease all interact with each other in important and predictable ways that can be built into traditional disease ecology models. We present such a model here that provides insights into the long-term effect of policy interventions. For example, because of indirect income effects, herd immunity may be acquired with lower vaccine coverage than previously thought. Reductions in the disease burden can also occur through lower fertility. Our model thus provides a disease ecology framework that is useful for the analysis of demographic transitions.

  14. Effect of nutrient density on production performance, egg quality and humoral immune response of brown laying (Dahlem Red) hens in the tropics.

    PubMed

    Panda, Arun Kumar; Rao, Savaram Venkata Rama; Raju, Mantena Venkata Lakshmi Narasimha; Niranjan, Matam; Reddy, Maddula Ramkoti

    2012-02-01

    A study was conducted to evaluate the effect of various concentrations of metabolizable energy (ME) with graded incremental levels of crude protein (CP) and essential amino acids (lysine and methionine) on production performance, egg quality and humoral immune response of Dahlem Red laying hens. Four experimental diets based on maize-soybean meal-deoiled rice bran were prepared. Diet 1 was fed as a control diet containing 2,600 kcal ME/kg, 15% CP, 0.75% Lys and 0.36% Met, and in the other three diets (D2, D3 and D4), concentrations of the above nutrients were increased by 2.5%, 5.0% and 7.5%, respectively. The levels of Ca (3.5%) and available P (0.32) were constant in all the diets. Each diet was offered ad libitum from 28 to 40 weeks of age to eight replicates containing six birds in each replicate. The egg production, egg weight and egg mass (in grams of egg per hen per day) were not affected by increasing the nutrient density up to 7.5% (2,795 kcal ME/kg diet) compared to the control group (2,600 ME/kg diet). However, feed consumption and feed efficiency (in grams of egg per gram of feed) were influenced by the variation in the nutrient density of diets. As the nutrient density increased by 5% (2,730 ME/kg diet), birds consumed significantly (P < 0.001) less feed. The birds in the 7.5% higher density group produced significantly (P < 0.05) higher egg mass per unit feed consumption compared to the control diet. Increasing nutrient density up to 7.5% had no effect on relative weight of albumen, yolk or shell. The Haugh unit, yolk colour and shell thickness were also not affected due to variation in the nutrient density. The humoral immune response measured at 34 and 40 weeks was progressively improved by increasing the nutrient density up to 5%. Increasing the nutrient density beyond 5% in the diet had no further influence on the humoral immune response. Based on the results of the present study, it can be concluded that Dahlem Red laying hens required 2,795 kcal

  15. Immunogenicity of HIV-1 IIIB and SHIV 89.6P Tat and Tat toxoids in rhesus macaques: induction of humoral and cellular immune responses.

    PubMed

    Richardson, Max W; Mirchandani, Jyotika; Silvera, Peter; Régulier, Emmanuel G; Capini, Christelle; Bojczuk, Paul M; Hu, Jason; Gracely, Edward J; Boyer, Jean D; Khalili, Kamel; Zagury, Jean-François; Lewis, Mark G; Rappaport, Jay

    2002-09-01

    This study compared immune responses in rhesus macaques immunized with unmodified HIV-1 IIIB Tat, SHIV89.6P Tat, and carboxymethylated IIIB and 89.6P Tat toxoids. Immunization with either IIIB or 89.6P preparation induced high titer and broadly crossreactive serum anti-Tat IgG that recognized HIV-1 subtype-E and SIVmac251 Tat. However, the response was delayed, and titers were lower in 89.6P vaccination groups. Serum anti-Tat IgG recognized peptides corresponding to the amino-terminus, basic domain, and carboxy-terminal region. Cellular proliferative responses to Tat toxoids corresponding to the immunogen were evident in vitro in both IIIB and 89.6P groups. Crossreactive proliferative responses were observed in IIIB groups in response to stimulation with 89.6P or SIVmac251 Tat toxoids, but were much less prevalent in 89.6P groups. The truncated 86 amino acid IIIB Tat appears to be more immunogenic than the 102 amino acid 89.6P Tat with respect to both humoral and cellular immune responses, and may be a better vaccine component. Despite induction of robust humoral and cellular immune responses (including both CD4+ and CD8+ T-cell responses) to Tat, all animals were infected upon intravenous challenge with 30 MID(50) of SHIV89.6P and outcome of vaccine groups was not different from controls. Sequencing both Tat exons from serum viral RNA revealed no evidence of escape mutants. These results suggest that with intravenous SHIV89.6P challenge in rhesus macaques, precipitous CD4+ T-cell decline overwhelms potentially protective immune responses. Alternatively, Tat specific CD8+ T-cell responses may not appropriately recognize infected cells in vivo in this model. In view of evidence demonstrating Tat specific CTLs in the SIV model and in humans infected with HIV-1, results in this pathogenic SHIV model may not apparently predict the efficacy of this approach in human studies. The potency and cross-reactivity of these immune responses confirm Tat toxoid as an excellent

  16. Cooperation between CD4+ T Cells and Humoral Immunity Is Critical for Protection against Dengue Using a DNA Vaccine Based on the NS1 Antigen

    PubMed Central

    Gonçalves, Antônio J. S.; Oliveira, Edson R. A.; Costa, Simone M.; Paes, Marciano V.; Silva, Juliana F. A.; Azevedo, Adriana S.; Mantuano-Barradas, Marcio; Nogueira, Ana Cristina M. A.; Almeida, Cecília J.; Alves, Ada M. B.

    2015-01-01

    Dengue virus (DENV) is spread through most tropical and subtropical areas of the world and represents a serious public health problem. At present, the control of dengue disease is mainly hampered by the absence of antivirals or a vaccine, which results in an estimated half worldwide population at risk of infection. The immune response against DENV is not yet fully understood and a better knowledge of it is now recognized as one of the main challenge for vaccine development. In previous studies, we reported that a DNA vaccine containing the signal peptide sequence from the human tissue plasminogen activator (t-PA) fused to the DENV2 NS1 gene (pcTPANS1) induced protection against dengue in mice. In the present work, we aimed to elucidate the contribution of cellular and humoral responses elicited by this vaccine candidate for protective immunity. We observed that pcTPANS1 exerts a robust protection against dengue, inducing considerable levels of anti-NS1 antibodies and T cell responses. Passive immunization with anti-NS1 antibodies conferred partial protection in mice infected with low virus load (4 LD50), which was abrogated with the increase of viral dose (40 LD50). The pcTPANS1 also induced activation of CD4+ and CD8+ T cells. We detected production of IFN-γ and a cytotoxic activity by CD8+ T lymphocytes induced by this vaccine, although its contribution in the protection was not so evident when compared to CD4+ cells. Depletion of CD4+ cells in immunized mice completely abolished protection. Furthermore, transfer experiments revealed that animals receiving CD4+ T cells combined with anti-NS1 antiserum, both obtained from vaccinated mice, survived virus infection with survival rates not significantly different from pcTPANS1-immunized animals. Taken together, results showed that the protective immune response induced by the expression of NS1 antigen mediated by the pcTPANS1 requires a cooperation between CD4+ T cells and the humoral immunity. PMID:26650916

  17. Cooperation between CD4+ T Cells and Humoral Immunity Is Critical for Protection against Dengue Using a DNA Vaccine Based on the NS1 Antigen.

    PubMed

    Gonçalves, Antônio J S; Oliveira, Edson R A; Costa, Simone M; Paes, Marciano V; Silva, Juliana F A; Azevedo, Adriana S; Mantuano-Barradas, Marcio; Nogueira, Ana Cristina M A; Almeida, Cecília J; Alves, Ada M B

    2015-12-01

    Dengue virus (DENV) is spread through most tropical and subtropical areas of the world and represents a serious public health problem. At present, the control of dengue disease is mainly hampered by the absence of antivirals or a vaccine, which results in an estimated half worldwide population at risk of infection. The immune response against DENV is not yet fully understood and a better knowledge of it is now recognized as one of the main challenge for vaccine development. In previous studies, we reported that a DNA vaccine containing the signal peptide sequence from the human tissue plasminogen activator (t-PA) fused to the DENV2 NS1 gene (pcTPANS1) induced protection against dengue in mice. In the present work, we aimed to elucidate the contribution of cellular and humoral responses elicited by this vaccine candidate for protective immunity. We observed that pcTPANS1 exerts a robust protection against dengue, inducing considerable levels of anti-NS1 antibodies and T cell responses. Passive immunization with anti-NS1 antibodies conferred partial protection in mice infected with low virus load (4 LD50), which was abrogated with the increase of viral dose (40 LD50). The pcTPANS1 also induced activation of CD4+ and CD8+ T cells. We detected production of IFN-γ and a cytotoxic activity by CD8+ T lymphocytes induced by this vaccine, although its contribution in the protection was not so evident when compared to CD4+ cells. Depletion of CD4+ cells in immunized mice completely abolished protection. Furthermore, transfer experiments revealed that animals receiving CD4+ T cells combined with anti-NS1 antiserum, both obtained from vaccinated mice, survived virus infection with survival rates not significantly different from pcTPANS1-immunized animals. Taken together, results showed that the protective immune response induced by the expression of NS1 antigen mediated by the pcTPANS1 requires a cooperation between CD4+ T cells and the humoral immunity.

  18. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

    PubMed

    Rivat, Christine; Booth, Claire; Alonso-Ferrero, Maria; Blundell, Michael; Sebire, Neil J; Thrasher, Adrian J; Gaspar, H Bobby

    2013-02-14

    X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice.We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1.

  19. An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular, and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge.

    PubMed Central

    Buge, S L; Richardson, E; Alipanah, S; Markham, P; Cheng, S; Kalyan, N; Miller, C J; Lubeck, M; Udem, S; Eldridge, J; Robert-Guroff, M

    1997-01-01

    Six female rhesus macaques were immunized orally and intranasally at 0 weeks and intratracheally at 12 weeks with an adenovirus type 5 host range mutant (Ad5hr)-simian immunodeficiency virus SIVsm env recombinant and at 24 and 36 weeks with native SIVmac251 gp120 in Syntex adjuvant. Four macaques received the Ad5hr vector and adjuvant alone; two additional controls were naive. In vivo replication of the Ad5hr wild-type and recombinant vectors occurred with detection of Ad5 DNA in stool samples and/or nasal secretions in all macaques and increases in Ad5 neutralizing antibody in 9 of 10 macaques following Ad administrations. SIV-specific neutralizing antibodies appeared after the second recombinant immunization and rose to titers > 10,000 following the second subunit boost. Immunoglobulin G (IgG) and IgA antibodies able to bind gp120 developed in nasal and rectal secretions, and SIV-specific IgGs were also observed in vaginal secretions and saliva. T-cell proliferative responses to SIV gp140 and T-helper epitopes were sporadically detected in all immunized macaques. Following vaginal challenge with SIVmac251, transient or persistent infection resulted in both immunized and control monkeys. The mean viral burden in persistently infected immunized macaques was significantly decreased in the primary infection period compared to that of control macaques. These results establish in vivo use of the Ad5hr vector, which overcomes the host range restriction of human Ads for rhesus macaques, thereby providing a new model for evaluation of Ad-based vaccines. In addition, they show that a vaccine regimen using the Ad5hr-SIV env recombinant and gp120 subunit induces strong humoral, cellular, and mucosal immunity in rhesus macaques. The reduced viral burden achieved solely with an env-based vaccine supports further development of Ad-based vaccines comprising additional viral components for immune therapy and AIDS vaccine development. PMID:9343211

  20. Acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response.

    PubMed

    Tambo, Ernest; Xiao-Nong, Zhou

    2014-01-01

    The number of surveillance networks for infectious disease diagnosis and response has been growing. In 2000, the World Health Organization (WHO) established the Global Outbreak Alert and Response Network, which has been endorsed by each of the 46 WHO African members since then. Yet, taming the dynamics and plague of the vicious Ebola virus disease (EVD) in African countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. Despite the widespread acceptance of syndromic surveillance (SS) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. Information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. Indeed, little is known about the role and the interactions between the Ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and Ebola seroconversion. Can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? In most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. The frontline and airport Ebola SS systems in West Africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into Ebola, and proactive actions, are needed. The quest for effective early indicators (EEE) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective

  1. Adenoviral vectors elicit humoral immunity against variable loop 2 of clade C HIV-1 gp120 via “Antigen Capsid-Incorporation” strategy

    PubMed Central

    Gu, Linlin; Krendelchtchikova, Valentina; Krendelchtchikov, Alexandre; Farrow, Anitra L.; Derdeyn, Cynthia A.; Matthews, Qiana L.

    2016-01-01

    Adenoviral (Ad) vectors in combination with the “Antigen Capsid-Incorporation” strategy have been applied in developing HIV-1 vaccines, due to the vectors’ abilities in incorporating and inducing immunity of capsid-incorporated antigens. Variable loop 2 (V2)-specific antibodies were suggested in the RV144 trial to correlate with reduced HIV-1 acquisition, which highlights the importance of developing novel HIV-1 vaccines by targeting the V2 loop. Therefore, the V2 loop of HIV-1 has been incorporated into the Ad capsid protein. We generated adenovirus serotype 5 (Ad5) vectors displaying variable loop 2 (V2) of HIV-1 gp120, with the “Antigen Capsid-Incorporation” strategy. To assess the incorporation capabilities on hexon hypervariable region1 (HVR1) and protein IX (pIX), 20aa or full length (43aa) of V2 and V1V2 (67aa) were incorporated, respectively. Immunizations with the recombinant vectors significantly generated antibodies against both linear and discontinuous V2 epitopes. The immunizations generated durable humoral immunity against V2. This study will lead to more stringent development of various serotypes of adenovirus-vectored V2 vaccine candidates, based on breakthroughs regarding the immunogenicity of V2. PMID:26499044

  2. Model for In Vivo Assessment of Humoral Protection against Malaria Sporozoite Challenge by Passive Transfer of Monoclonal Antibodies and Immune Serum

    PubMed Central

    Sack, Brandon K.; Miller, Jessica L.; Vaughan, Ashley M.; Douglass, Alyse; Kaushansky, Alexis; Mikolajczak, Sebastian; Coppi, Alida; Gonzalez-Aseguinolaza, Gloria; Tsuji, Moriya; Zavala, Fidel; Sinnis, Photini

    2014-01-01

    Evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. Novel pre-erythrocytic antibody (Ab) targets could be key to improving vaccine formulations, which are currently based on targeting antigens such as the circumsporozoite protein (CSP). However, methods to assess the effects of sporozoite-specific Abs on pre-erythrocytic infection in vivo remain underdeveloped. Here, we combined passive transfer of monoclonal Abs (MAbs) or immune serum with a luciferase-expressing Plasmodium yoelii sporozoite challenge to assess Ab-mediated inhibition of liver infection in mice. Passive transfer of a P. yoelii CSP MAb showed inhibition of liver infection when mice were challenged with sporozoites either intravenously or by infectious mosquito bite. However, inhibition was most potent for the mosquito bite challenge, leading to a more significant reduction of liver-stage burden and even a lack of progression to blood-stage parasitemia. This suggests that Abs provide effective protection against a natural infection. Inhibition of liver infection was also achieved by passive transfer of immune serum from whole-parasite-immunized mice. Furthermore, we demonstrated that passive transfer of a MAb against P. falciparum CSP inhibited liver-stage infection in a humanized mouse/P. falciparum challenge model. Together, these models constitute unique and sensitive in vivo methods to assess serum-transferable protection against Plasmodium sporozoite challenge. PMID:24478094

  3. A novel dendritic-cell-targeting DNA vaccine for hepatitis B induces T cell and humoral immune responses and potentiates the antivirus activity in HBV transgenic mice.

    PubMed

    Yu, Debin; Liu, Hong; Shi, Shuai; Dong, Liwei; Wang, Hongge; Wu, Nuoting; Gao, Hui; Cheng, Zhaojun; Zheng, Qun; Cai, Jiaojiao; Zou, Libo; Zou, Zhihua

    2015-12-01

    Strategies for inducing an effective immune response following vaccination have focused on targeting antigens to dendritic cells (DCs) through the DC-specific surface molecule DEC-205. The immunogenicity and efficacy of DNA vaccination can also be enhanced by fusing the encoded antigen to single-chain antibodies directed against DEC-205. Here, we investigated this promising approach for its enhancement of hepatitis B virus (HBV)-specific cellular and humoral immune responses and its antiviral effects in HBV transgenic mice. A plasmid DNA vaccine encoding mouse DEC-205 single-chain fragment variable (mDEC-205-scFv) linked with the hepatitis B surface antigen (HBsAg) was constructed. Vaccination with this fusion DNA vaccine in HBV transgenic mice induced robust antiviral T cell and antibody immunity against HBsAg. The levels of serum-circulating HBsAg and the HBV DNA copy number were downregulated by the induction of a higher HBsAg-specific response. Thus, in this study, we demonstrated the therapeutic efficacy of the novel mDEC-205-scFv-fused DNA vaccine in a mouse model of immune-tolerant, chronic HBV infection.

  4. Gene discovery and differential expression analysis of humoral immune response elements in female Culicoides sonorensis (Diptera: Ceratopogonidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Female Culicoides sonorensis midges (Diptera: Ceratopogonidae) are vectors of pathogens that impact livestock and wildlife in the United States. Little is known about their molecular functioning, including components of their immune system. Because the insect immune response is involved ...

  5. Morph-specific genetic and environmental variation in innate and acquired immune response in a color polymorphic raptor.

    PubMed

    Gangoso, Laura; Roulin, Alexandre; Ducrest, Anne-Lyse; Grande, Juan Manuel; Figuerola, Jordi

    2015-08-01

    Genetic color polymorphism is widespread in nature. There is an increasing interest in understanding the adaptive value of heritable color variation and trade-off resolution by differently colored individuals. Melanin-based pigmentation is often associated with variation in many different life history traits. These associations have recently been suggested to be the outcome of pleiotropic effects of the melanocortin system. Although pharmacological research supports that MC1R, a gene with a major role in vertebrate pigmentation, has important immunomodulatory effects, evidence regarding pleiotropy at MC1R in natural populations is still under debate. We experimentally assessed whether MC1R-based pigmentation covaries with both inflammatory and humoral immune responses in the color polymorphic Eleonora's falcon. By means of a cross-fostering experiment, we disentangled potential genetic effects from environmental effects on the covariation between coloration and immunity. Variation in both immune responses was primarily due to genetic factors via the nestlings' MC1R-related color genotype/phenotype, although environmental effects via the color morph of the foster father also had an influence. Overall, dark nestlings had lower immune responses than pale ones. The effect of the color morph of the foster father was also high, but in the opposite direction, and nestlings raised by dark eumelanic foster fathers had higher immune responses than those raised by pale foster fathers. Although we cannot completely discard alternative explanations, our results suggest that MC1R might influence immunity in this species. Morph-specific variation in immunity as well as pathogen pressure may therefore contribute to the long-term maintenance of genetic color polymorphism in natural populations.

  6. Can we find a solution to the human immunodeficiency virus/acquired immune deficiency syndrome controversy? Is acquired immune deficiency syndrome the consequence of continuous excessive stressing of the body?

    PubMed

    Hässig, A; Wen-Xi, L; Stampfli, K

    1996-04-01

    The time of re-evaluation of the role of human immunodeficiency viruses in the pathogenesis of acquired immune deficiency syndrome has now come, now that methods are available for the direct detection of human immunodeficiency viruses and for the detection of cellular anti-human immunodeficiency virus immune reactions. It has been shown that human immunodeficiency virus infections are common among anti-human immunodeficiency virus antibody negative high-risk individuals. The disease is brought under control by cellular immune reactions and the anti-human immunodeficiency virus antibody test remains negative. Apart from proof that infection with human immunodeficiency viruses has occurred, a positive result in an anti-human immunodeficiency virus-antibody test is also an indication of an independent immunosuppression state. According to the definition of the Centers of Disease Control classical acquired immune deficiency syndrome is the consequence of infection with human immunodeficiency virus in association with continuous excessive stress, such as observed in the known risk groups. At the center of the pathogenetic process is hypercortisolism-determined damage of T lymphocytes, in which insufficiency of thymus is prominent. For this reason, in our view, there are indications for shifting efforts from the prophylaxis of infection with human immunodeficiency viruses to the prophylaxis of acquired immune deficiency syndrome by reducing stress factors.

  7. Identification of a prostate-specific membrane antigen-derived peptide capable of eliciting both cellular and humoral immune responses in HLA-A24+ prostate cancer patients.

    PubMed

    Kobayashi, Kazuhiko; Noguchi, Masanori; Itoh, Kyogo; Harada, Mamoru

    2003-07-01

    We tried to identify prostate-specific membrane antigen (PSMA)-derived peptides capable of eliciting both cellular and humoral immune responses in peripheral blood mononuclear cells (PBMCs) and plasma of HLA-A24(+) prostate cancer patients, respectively. For cellular response, peptide-specific and prostate cancer-reactive responses of in vitro-stimulated PBMCs were examined with regard to interferon (IFN)-gamma production and cytotoxicity against both a parental HLA-A24(-) prostate cancer cell line (PC-93) and an HLA-A24-expressing transfectant cell line (PC93-A24). For humoral response, patients' plasma was tested for reactivity to the peptides by means of an enzyme-linked immunosorbent assay (ELISA). Among 13 PSMA peptides, PSMA 624-632 peptide induced peptide-specific and tumor-reactive cytotoxic T lymphocytes (CTLs) most effectively. The PSMA 624-632 peptide-stimulated PBMCs from either healthy donors or prostate cancer patients produced a significant level of IFN-gamma in response to prostate cancer cells in an HLA-A24-restricted manner, and also showed a higher level of cytotoxicity against PC93-A24 than against PC93. Antibodies to the PSMA 624-632 peptide, but not to any others, were detected in prostate cancer patients. These results demonstrate that the PSMA 624-632 peptide could be an appropriate molecule for use in specific immunotherapy of HLA-A24(+) patients with prostate cancer.

  8. Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine.

    PubMed

    McIntosh, J H; Cochrane, M; Cobbold, S; Waldmann, H; Nathwani, S A; Davidoff, A M; Nathwani, A C

    2012-01-01

    The ability of transient immunosuppression with a combination of a non-depleting anti-CD4 (NDCD4) antibody and cyclosporine (CyA) to abrogate immune reactivity to both adeno-associated viral vector (AAV) and its transgene product was evaluated. This combination of immunosuppressants resulted in a 20-fold reduction in the resulting anti-AAV8 antibody titres, to levels in naïve mice, following intravenous administration of 2 × 10(12) AAV8 vector particles per kg to immunocompetent mice. This allowed efficient transduction upon secondary challenge with vector pseudotyped with the same capsid. Persistent tolerance did not result, however, as an anti-AAV8 antibody response was elicited upon rechallenge with AAV8 without immunosuppression. The route of vector administration, vector dose, AAV serotype or the concomitant administration of adenoviral vector appeared to have little impact on the ability of the NDCD4 antibody and CyA combination to moderate the primary humoral response to AAV capsid proteins. The combination of NDCD4 and CyA also abrogated the humoral response to the transgene product, that otherwise invariably would occur, following intramuscular injection of AAV5, leading to stable transgene expression. These observations could significantly improve the prospects of using rAAV vectors for chronic disorders by allowing for repeated vector administration and avoiding the development of antibodies to the transgene product.

  9. Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy.

    PubMed

    Montoya, Carlos J; Toro, Maria F; Aguirre, Carlos; Bustamante, Alberto; Hernandez, Mariluz; Arango, Liliana P; Echeverry, Marta; Arango, Ana E; Prada, Maria C; Alarcon, Herminia del P; Rojas, Mauricio

    2007-06-01

    Given that highly active antiretroviral therapy (HAART) has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1)-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI) antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40) against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

  10. AIDS: Acquired Immune Deficiency Syndrome, Information and Procedural Guidelines for Providing Services to Persons with AIDS/HTLV-III.

    ERIC Educational Resources Information Center

    Montana State Dept. of Health and Environmental Sciences, Helena.

    This manual presents information about the disease, Acquired Immune Deficiency Syndrome (AIDS), and guidelines for service delivery to Montana residents who have been diagnosed with AIDS or related disorders. The first section describes the disease's causes, symptoms, and transmission; risk factors; high-risk populations; prevention suggestions;…

  11. AIDS: Acquired Immune Deficiency Syndrome; Information and Procedural Guidelines for Providing Services to Persons with AIDS/HIV. Revised.

    ERIC Educational Resources Information Center

    Montana State Dept. of Health and Environmental Sciences, Helena. Health Education Bureau.

    This volume consists of updated information to be inserted into a Montana AIDS Project manual on providing services to persons with acquired immune deficiency syndrome/human immunodeficiency virus (AIDS/HIV), originally published in December 1985. The updates are mainly statistics and terminology, along with the addition of several new sections.…

  12. Coping Strategies of Patients with Haemophilia as a Risk Group for AIDS (Acquired Immune Deficiency Syndrome). Brief Research Report.

    ERIC Educational Resources Information Center

    Naji, Simon; And Others

    1986-01-01

    Plans are described for a 2-year project whose major focus is the identification of ways in which patients with hemophilia and their families assimilate, interpret, and act on information about Acquired Immune Deficiency Syndrome (AIDS). Findings will be related to perceived risk, anxiety levels, and the development of coping strategies.…

  13. Select Personality Characteristic Differences between Caregivers for Persons with Acquired Immune Deficiency Syndrome and Caregivers for Other Types of Illness.

    ERIC Educational Resources Information Center

    Angel, Daniel Scott; Heritage, Jeannette

    The purpose of this study was to analyze select personality characteristics of individuals working within the Acquired Immune Deficiency Syndrome (AIDS) population in comparison to non-AIDS caregivers by using two personality assessment instruments. Subjects were from two health care provider populations. Two hundred research packets were…

  14. Primary central nervous system lymphoma in acquired immune deficiency syndrome mimicking toxoplasmosis.

    PubMed

    Utsuki, Satoshi; Oka, Hidehiro; Abe, Katsutoshi; Osawa, Shigeyuki; Yamazaki, Tomoya; Yasui, Yoshie; Fujii, Kiyotaka

    2011-02-01

    A 37-year-old man, a hepatitis B virus carrier due to mother-to-child transmission, had a medical examination in September 2008 in nearby hospitals due to anorexia and weight loss. He was transported to our hospital because computed tomography (CT) detected intracranial lesions, and he had a positive human immunodeficiency virus (HIV) antibody test. Head computed tomography (CT) revealed multiple hemorrhagic lesions and enhancement effect, suggesting a thin wall. Also, an enhancement effect was present in the ventricle walls and the subarachnoid space. No accumulation was found in the thallium-201 scintigraphy. The enhancement effect of the ventricle walls and the subarachnoid space disappeared after oral administration of pyrimethamine, sulfadiazine, and calcium folinate, contributing to the diagnosis of an abscess and meningitis due to toxoplasma. However, mass lesions did not reduce. A biopsy was performed on 30 October, and the pathological diagnosis was malignant lymphoma. He died from respiratory function deterioration on 8 November. Lymphoma cells were found in ventricle wall tissue and the subarachnoid space at the autopsy. Toxoplasmosis will typically occur as a brain lesion most commonly in acquired immune deficiency syndrome (AIDS), whereas malignant lymphoma commonly manifests as a brain neoplastic lesion. However, differentiating between images of these lesions is difficult, so diagnosis by early biopsy is recommended.

  15. The acquired immune deficiency syndrome: an international health problem of increasing importance.

    PubMed

    Wofsy, C B; Mills, J

    1984-06-01

    The Acquired Immune Deficiency Syndrome (AIDS) is a new disease which first appeared in human populations about 1979. The disease is defined by the development of unusual types of cancer (e.g. Kaposi's sarcoma), or severe cellular immunodeficiency manifested by opportunistic infections (e.g. Pneumocystis carinii infection), or both. Although the etiology of AIDS is unknown, the epidemiologic evidence is consistent with an infectious agent transmitted by blood (e.g. transfusion, needle sharing) or sexual intercourse. Over three-quarters of the cases have been in homosexual or bisexual males and in intravenous drug abusers; about 5% of cases do not have recognized risk factors. A small number of cases have resulted from transfusion of blood or blood products. The early clinical manifestations are non-specific, and may include asymptomatic skin lesions, dyspnea and dry cough, weight loss, chronic diarrhea, and focal and non-focal central nervous system findings. Treatment for the associated cancers and opportunistic infections may be successful in individual instances, but the underlying immunosuppression of AIDS appears to progress inexorably and the fatality rate approaches 100% within a few years from diagnosis. Although nosocomial transmission has not been documented, infection control guidelines have been developed by analogy with hepatitis B infection.

  16. Liver biopsies in the acquired immune deficiency syndrome: influence of endemic disease and drug abuse.

    PubMed

    Comer, G M; Mukherjee, S; Scholes, J V; Holness, L G; Clain, D J

    1989-12-01

    A retrospective review of 48 liver biopsies in 34 patients with acquired immune deficiency syndrome (AIDS) and 10 patients with AIDS-related complex (ARC) was performed at Harlem Hospital Center to assess the diagnostic yield of liver biopsies in this distinct patient population. Among the patients, 93.2% were black and 32 were males, with a mean age of 36.7 yr. Intravenous drug abuse was a risk factor for AIDS in 81.8% of patients. Liver biopsies were particularly useful in patients with fever of unclear origin, which was positively correlated with the presence of granulomas (p = 0.01). Granulomas due to mycobacteria were present in 16 (33.3%) of the biopsies. Liver biopsy proved to be clinically significant in 14 of 17 patients (82.3%) with mycobacterial disease, or 29.3% of the liver biopsies. Chronic active hepatitis was present in 12 (29.2%) of the biopsies, and in all but one was due to non-A non-B hepatitis viruses. All patients with chronic active hepatitis were intravenous drug abusers or the sexual partners of intravenous drug abusers. Liver biopsy can provide important diagnostic information in AIDS patients. The pathological findings in this series reflect the high risk of exposure to tuberculosis and hepatitis in the intravenous drug abusers in Harlem.

  17. Clinical and pathologic findings of the liver in the acquired immune deficiency syndrome (AIDS).

    PubMed

    Glasgow, B J; Anders, K; Layfield, L J; Steinsapir, K D; Gitnick, G L; Lewin, K J

    1985-05-01

    Clinical data and histologic sections of the liver, including immunohistochemical studies for hepatitis B surface and core antigens, were reviewed in 42 autopsy cases of the acquired immune deficiency syndrome (AIDS). Hepatomegaly, elevation of serum transaminases, and mild elevation of alkaline phosphatase were commonly observed clinical and biochemical abnormalities. Mildly elevated alkaline phosphatase and normal bilirubin levels were present in patients with Mycobacterium avium-intracellulare (MAI) infection, cytomegalovirus (CMV) infection, and Kaposi's sarcoma (KS). Histologic sections demonstrated liver involvement by MAI in eight cases; KS in six cases; cryptococcus in three cases; and CMV in two cases. One case of MAI infection was associated with marked central vein sclerosis, a finding previously unreported. Thirty-two (76%) of 42 cases had serologic or pathologic evidence of hepatitis exposure. Two patients had histologic evidence of chronic active hepatitis. The pathologic processes involving the liver appeared to be secondary to the infections and neoplasms for which this population is susceptible and did not significantly contribute to morbidity or mortality. No findings specific or pathognomic for AIDS were identified in the liver.

  18. Predictive factors for the Nursing Diagnoses in people living with Acquired Immune Deficiency Syndrome 1

    PubMed Central

    da Silva, Richardson Augusto Rosendo; Costa, Romanniny Hévillyn Silva; Nelson, Ana Raquel Cortês; Duarte, Fernando Hiago da Silva; Prado, Nanete Caroline da Costa; Rodrigues, Eduardo Henrique Fagundes

    2016-01-01

    Abstract Objective: to identify the predictive factors for the nursing diagnoses in people living with Acquired Immune Deficiency Syndrome. Method: a cross-sectional study, undertaken with 113 people living with AIDS. The data were collected using an interview script and physical examination. Logistic regression was used for the data analysis, considering a level of significance of 10%. Results: the predictive factors identified were: for the nursing diagnosis of knowledge deficit-inadequate following of instructions and verbalization of the problem; for the nursing diagnosis of failure to adhere - years of study, behavior indicative of failure to adhere, participation in the treatment and forgetfulness; for the nursing diagnosis of sexual dysfunction - family income, reduced frequency of sexual practice, perceived deficit in sexual desire, perceived limitations imposed by the disease and altered body function. Conclusion: the predictive factors for these nursing diagnoses involved sociodemographic and clinical characteristics, defining characteristics, and related factors, which must be taken into consideration during the assistance provided by the nurse. PMID:27384466

  19. Invasive fungal infections among inpatients with acquired immune deficiency syndrome at a Chinese university hospital.

    PubMed

    Shen, Yin Zhong; Qi, Tang Kai; Ma, Jian Xin; Jiang, Xue Yan; Wang, Jiang Rong; Xu, Qing Nian; Huang, Qin; Liu, Xi Nian; Sun, Hong Qing; Lu, Hong Zhou

    2007-11-01

    Invasive fungal infections (IFIs) have become a major cause of morbidity and mortality among people with acquired immune deficiency syndrome (AIDS), however, little is known about the clinical features and prognosis of IFI in AIDS in China. This study aimed to characterise the clinical features and prognosis of IFI in AIDS patients in China. We retrospectively reviewed the records of all HIV-infected patients at a Chinese university hospital between December 2004 and May 2006. We identified 35 patients with IFI. IFIs included thrush, oesophageal candidiasis, fungal pneumonia, cryptococcosis, penicilliosis and fungaemia, 44.4% of IFIs occurred in the digestive tract, 71.8% of IFIs occurred in patients with CD4(+)T-lymphocyte counts <100 cells mm(-3). Candida albicans accounted for 57.4% of fungal pathogens isolated. All the patients received both antiretroviral and antifungal therapy; 27 patients were cured and eight died. IFI is one of the most common opportunistic infections in AIDS patients in China. IFIs mainly occur in patients with low CD4(+)T-lymphocyte counts. The majority of IFIs occur in the digestive tract. The most common pathogen causing IFI is C. albicans. The mortality rate remains high although antiretroviral therapy and many newer antifungals are available in China.

  20. Serum immunoglobulin G subclass dysbalances in the lymphadenopathy syndrome and acquired immune deficiency syndrome.

    PubMed Central

    Aucouturier, P; Couderc, L J; Gouet, D; Danon, F; Gombert, J; Matheron, S; Saimot, A G; Clauvel, J P; Preud'homme, J L

    1986-01-01

    Serum IgG subclass levels were measured by an indirect competitive immunoenzymatic assay with monoclonal antibodies in 61 adult patients of different geographic origins affected either with the lymphoadenopathy syndrome (LAS, 46 cases) or with the acquired immune deficiency syndrome (AIDS, 15 cases). In spite of considerable variations from patient to patient, IgG-1 and IgG-3 levels were higher than in normal Caucasians, with IgG-1 levels much more elevated in LAS than in AIDS patients. In Caucasians with AIDS or LAS, IgG-4 levels were low. IgG-2 levels tended to be low and correlated negatively with IgG-1 levels. IgG subclass imbalances were especially striking in patients with lymphoid interstitial pneumonitis. The results suggest that the IgG increase predominantly affects the less T-dependent subclasses. The low levels of the more T-dependent isotypes do not appear to play a clear role in the occurrence of pyogenic infections in certain patients. PMID:3955884

  1. The humoral immune response and protective efficacy of vaccination with inactivated split and whole influenza virus vaccines in BALB/c mice.

    PubMed

    Cox, Rebecca Jane; Hovden, Arnt-Ove; Brokstad, Karl Albert; Szyszko, Ewa; Madhun, Abdullah Sami; Haaheim, Lars Reinhardt

    2006-11-10

    Recently the urgency of developing a pandemic influenza vaccine has lead to the re-evaluation of the use of whole virus vaccine. We have compared the humoral immune response and the protective efficacy of whole and split influenza virus vaccines in mice. Whole virus vaccine was more immunogenic particularly after the first dose of vaccine, generally eliciting higher numbers of systemic antibody secreting cells and an earlier and higher neutralising antibody response. Immunisation with one dose of whole virus vaccine more effectively reduced viral shedding upon non-lethal homologous viral challenge, but two doses of split virus vaccine was most effective at limiting viral replication and this was correlated with high influenza specific serum IgG concentrations. The two vaccine formulations induced different T helper profiles particularly after one dose of vaccine; split virus vaccine induced a type 2 bias response, whereas whole virus vaccine elicited a dominant type 1 response.

  2. Quantification of the humoral immune response and hemoplasma blood and tissue loads in cats coinfected with 'Candidatus Mycoplasma haemominutum' and feline leukemia virus.

    PubMed

    Wolf-Jäckel, Godelind A; Cattori, Valentino; Geret, Catrina P; Novacco, Marilisa; Meli, Marina L; Riond, Barbara; Boretti, Felicitas S; Lutz, Hans; Hofmann-Lehmann, Regina

    2012-08-01

    'Candidatus Mycoplasma haemominutum' (CMhm) is a hemotropic mycoplasma (aka hemoplasma) of domestic cats and wild felids. In a transmission study, we exposed eight specified pathogen-free cats to blood from Iberian lynxes (Lynx pardinus) infected with CMhm. The cats were coinfected with feline leukemia virus (FeLV) from an Iberian lynx or with a prototype FeLV. The goal of the present study was to quantify the humoral immune response to CMhm and to identify potential target tissues and sequestration sites. Antibodies were measured by a recombinant antigen-based enzyme-linked immunosorbent assay, and blood and tissue loads were quantified using real-time PCR. Seven out of eight cats became CMhm-infected; all of these cats seroconverted between 3 and 13 weeks after inoculation. Antibody levels correlated with the CMhm blood loads. The peak CMhm blood loads were inversely correlated with the incubation period. PCR-positive results were found in all 24 tissues tested but not for all samples. Although all tissues were PCR-positive in one cat euthanized ten weeks after infection, many tissues tested negative in six cats euthanized at week 20 after infection. In several cats, the spleen, lung, liver, heart and aorta contained more copies than expected given the tissue's blood supply, but most tissues contained fewer copies than expected. In conclusion, this is the first study to quantify the humoral immune response and tissue loads in CMhm-FeLV-coinfected cats. The tissue loads appeared to correlate with the duration of infection and with the blood loads, but no evidence of significant CMhm tissue sequestration was found.

  3. Assessment of yeast cell wall as replacements for antibiotic growth promoters in broiler diets: effects on performance, intestinal histo-morphology and humoral immune responses.

    PubMed

    Ghosh, T K; Haldar, S; Bedford, M R; Muthusami, N; Samanta, I

    2012-04-01

    The study compared the effects of an antibiotic growth promoter (AGP), yeast (Saccharomyces cerevisiae) and yeast cell wall (YCW) on performance, microbiology and histo-morphology of the small intestine and humoral immune responses in Ross 308 broilers. The treatments (eight replicates/treatment, n = 12/replicate) were negative control (NC, without AGP), positive control (PC, supplemented with bacitracin methylene disalicylate, 400 mg/kg), Y and YCW (supplemented with yeast and YCW, respectively, 1000 mg/kg). Live weight at 42 days improved (p = 0.086) in the PC, Y and YCW groups. Feed conversion ratio was better (p = 0.039) in the YCW group compared with the other groups. Antibiotic growth promoter in the PC group shortened the villi in duodenum (p = 0.044). Mucosal Escherichia coli number was higher in the PC group (p < 0.001), whereas in the digesta E. coli number was lower (p = 0.001) in the PC, Y and YCW groups in relation to the NC. Mucosal Salmonella populations increased (p = 0.0001) in the PC group, whereas in the digesta, all treatments reduced the Salmonella (p = 0.0001). Following oral challenge with Salmonella pullorum, YCW increased E. coli numbers on the mucosa (p < 0.001) whereas in the digesta the Y group had lower (p < 0.0001) number of E. coli. In the digesta, Salmonella count was lower in the YCW group compared with the other treatments (p < 0.01). Yeast cell wall -treated birds exhibited better (p < 0.05) humoral immune response against Newcastle disease which was far more persistent over time than in any other treatments. It was concluded that the yeast and the yeast cell wall may have effects identical to BMD on performance of broilers and thus may constitute an effective replacement strategy in the dietary regimens for broiler chickens.

  4. Robust antigen-specific humoral immune responses to sublingually delivered adenoviral vectors encoding HIV-1 Env: association with mucoadhesion and efficient penetration of the sublingual barrier.

    PubMed

    Domm, William; Brooks, Lauren; Chung, Hung Li; Feng, Changyong; Bowers, William J; Watson, Gene; McGrath, James L; Dewhurst, Stephen

    2011-09-16

    The efficient induction of virus-specific mucosal antibodies is an important unmet objective in Human Immunodeficiency Virus Type-1 (HIV-1) vaccine research. One promising approach is sublingual (SL) immunization. We examined the effectiveness of SL delivery of two different viral vectors: (i) a recombinant adenovirus (rAd5), and (ii) a Herpes Simplex Virus Type-1 amplicon vector (HSV-1). Initial in vitro videomicroscopy experiments showed that rAd5 particles were trapped in saliva (i.e., that Ad5 was mucoadhesive) - unlike HSV-1 virions, which migrated freely in both saliva and water. In vivo imaging studies in mice revealed that only the rAd5 vector efficiently transduced the SL epithelium. Consistent with this, SL delivery of an rAd5 encoding HIV-1 envelope glycoprotein (Env) resulted in robust antigen-specific antibody responses in plasma and in vaginal washes, whereas SL delivery of a HSV-1 amplicon vector encoding HIV-1 Env failed to elicit Env-specific antibodies. In contrast, both vectors elicited equivalent humoral responses following intramuscular (IM) delivery. Finally, SL delivery of the rAd5:Env vector resulted in elevated levels of Env-specific serum IgA, and vaginal IgA and IgG, when compared to IM delivery of the same vector. These results findings shed light on vector properties (mucoadhesion, penetration of the sublingual barrier) which may be important for the induction of potent humoral immune responses following sublingual vector administration. Our data also show that SL delivery of an Env-encoding rAd5 vector can elicit a potent antigen-specific mucosal antibody response in the absence of adjuvant. Overall, these findings support the further exploration of the SL delivery route for HIV-1 vaccine delivery.

  5. Characterization of Humoral Immune Responses against Capsid Protein p24 and Transmembrane Glycoprotein gp41 of Human Immunodeficiency Virus Type 1 in China.

    PubMed

    Li, Xiufen; Wu, Yue; Ren, Xuqi; Deng, Shuyun; Hu, Guifang; Yu, Shouyi; Tang, Shixing

    2016-01-01

    The objective of this study was to extend our previous research and to further characterize the humoral immune responses against HIV-1 p24, gp41 and the specific peptides carrying the immunodominant epitopes (IDEs) that react with human serum samples from HIV-1-infected individuals in China. We found that the majority (90.45%, 180/199) of the samples did not react with any of the three HIV-1 p24 peptides carrying IDEs, but did react with the recombinant full-length p24, suggesting that these samples tested in China were primarily directed against the conformational epitopes of HIV-1 p24. In contrast, 84.54% (164/194) of the samples reacted with at least one HIV-1 linear gp41 peptide, in particular the gp41-p1 peptide (amino acids 560-616). Both recently and long-term HIV-1-infected individuals displayed similar humoral immune responses against the recombinant gp41. However, samples from long-term HIV-1-infected subjects but not from recently infected subjects, showed a very strong reaction against the gp41-p1 peptide. The different response patterns observed for the two groups against the gp41 and the peptide gp41-p1 were statistically significant (P<0.01, Chi-square test). These results have direct relevance and importance for design of improved HIV-1 p24 detection assays and the gp41- based immunoassay that can be used to reliably distinguish recent and long-term HIV-1 infection.

  6. Humoral immunity of dTap-IPV vaccine (REPEVAX®) administered one month after dT-IPV vaccine (REVAXIS®) in adults with unknown vaccination history.

    PubMed

    Larnaudie, Sylvie; Guiso, Nicole; Baptiste, Charles; Desaint, Corinne; Desforges, Lionel; Lebon, Pierre; Soubeyrand, Benoit; Launay, Odile

    2010-10-01

    This study was to assess the humoral immune response induced by a vaccination schedule routinely used in France in 18-50 year old adults with unknown vaccination history. In this monocentric, prospective study, subjects received one dose of REVAXIS® (dT-IPV, diphtheria, tetanus and poliomyelitis (inactivated) vaccine (adsorbed, reduced antigen(s) content)) (Visit 1) followed by one dose of REPEVAX® (dTap-IPV, diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed, reduced antigen(s) content)) one month later (Visit 2). Antibodies against diphtheria, tetanus, poliomyelitis types 1, 2 and 3, and pertussis toxin (PT) were measured one month after the administration of REPEVAX® (Visit 3). A total of 136 subjects were included in the study, but blood samples were available for only 73 subjects. Their mean age at inclusion was 33.2 ± 7.3 years. 49.3% of the 73 subjects originated from the WHO African Region, 6.8% from the WHO Western Pacific Region and 5.5% from the WHO European Region. One month after REPEVAX® administration, all subjects had seroprotective antibody titers against diphtheria and tetanus (≥0.1 IU/mL), poliomyelitis types 2 and 3 (≥ 8 1/dil); one subject (1.4%) did not have antibodies against poliomyelitis type 1. The rate of anti-PT seropositivity (≥8 EU/mL) was 94.4%. One dose of REPEVAX® administered one month after a dose of REVAXIS® in subjects with unknown vaccination history induced a high humoral response. These results validate a vaccination schedule routinely used for years that rapidly elicits effective immunization against diphtheria, tetanus, poliomyelitis and pertussis.

  7. Robust Antigen-Specific Humoral Immune Responses to Sublingually Delivered Adenoviral Vectors Encoding HIV-1 Env: Association with Mucoadhesion and Efficient Penetration of the Sublingual Barrier

    PubMed Central

    Domm, William; Brooks, Lauren; Chung, Hung Li; Feng, Changyong; Bowers, William J.; Watson, Gene; McGrath, James L.; Dewhurst, Stephen

    2011-01-01

    The efficient induction of virus-specific mucosal antibodies is an important unmet objective in Human Immunodeficiency Virus Type-1 (HIV-1) vaccine research. One promising approach is sublingual (SL) immunization. We examined the effectiveness of SL delivery of two different viral vectors: (i) a recombinant adenovirus (rAd5), and (ii) a Herpes Simplex Virus Type-1 amplicon vector (HSV-1). Initial in vitro videomicroscopy experiments showed that rAd5 particles were trapped in saliva (i.e., that Ad5 was mucoadhesive) - unlike HSV-1 virions, which migrated freely in both saliva and water. In vivo imaging studies in mice revealed that only the rAd5 vector efficiently transduced the SL epithelium. Consistent with this, SL delivery of an rAd5 encoding HIV-1 envelope glycoprotein (Env) resulted in robust antigen-specific antibody responses in plasma and in vaginal washes, whereas SL delivery of a HSV-1 amplicon vector encoding HIV-1 Env failed to elicit Env-specific antibodies. In contrast, both vectors elicited equivalent humoral responses following intramuscular (IM) delivery. Finally, SL delivery of the rAd5:Env vector resulted in elevated levels of Env-specific serum IgA, and vaginal IgA and IgG, when compared to IM delivery of the same vector. These results findings shed light on vector properties (mucoadhesion, penetration of the sublingual barrier) which may be important for the induction of potent humoral immune responses following sublingual vector administration. Our data also show that SL delivery of an Env-encoding rAd5 vector can elicit a potent antigen-specific mucosal antibody response in the absence of adjuvant. Overall, these findings support the further exploration of the SL delivery route for HIV-1 vaccine delivery. PMID:21801777

  8. Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo

    NASA Technical Reports Server (NTRS)

    Fitzgerald, Wendy; Sylwester, Andrew W.; Grivel, Jean-Charles; Lifson, Jeffrey D.; Margolis, Leonid B.

    2004-01-01

    Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4(+) T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4(+) T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.

  9. Cellular and humoral immune responses in sheep vaccinated with candidate antigens MAP2698c and MAP3567 from Mycobacterium avium subspecies paratuberculosis

    PubMed Central

    Gurung, Ratna B.; Purdie, Auriol C.; Whittington, Richard J.; Begg, Douglas J.

    2014-01-01

    Control of Johne's disease, caused by Mycobacterium avium subspecies paratuberculosis (MAP) in ruminants using commercially available vaccine reduces production losses, mortality, fecal shedding and histopathological lesions but does not provide complete protection from infection and interferes with serological diagnosis of Johne's disease and bovine tuberculosis. At this time no recombinant antigens have been found to provide superior protection compared to whole killed or live-attenuated MAP vaccines. Therefore, there is a need to evaluate more candidate MAP antigens. In this study recombinant MAP antigens MAP2698c and MAP3567 were formulated with four different MONTANIDE™ (ISA 50V2, 61VG, 71VG, and 201VG) adjuvants and evaluated for their ability to produce specific immune responses in vaccinated sheep. The cellular immune response was measured with an interferon-gamma (IFN-γ) release assay and the humoral immune response was measured by antibody detection enzyme linked immunosorbent assay. Recombinant vaccine formulation with the antigen MAP2698c and MONTANIDE™ ISA 201VG adjuvant produced strong whole-MAP as well as MAP2698c-specific IFN-γ responses in a high proportion of the vaccinated sheep. The formulation caused less severe injection site lesions in comparison to other formulations. The findings from this study suggest that the MAP2698c + 201VG should be evaluated in a challenge trial to determine the efficacy of this vaccine candidate. PMID:25077074

  10. Cellular and humoral immune responses in sheep vaccinated with candidate antigens MAP2698c and MAP3567 from Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Gurung, Ratna B; Purdie, Auriol C; Whittington, Richard J; Begg, Douglas J

    2014-01-01

    Control of Johne's disease, caused by Mycobacterium avium subspecies paratuberculosis (MAP) in ruminants using commercially available vaccine reduces production losses, mortality, fecal shedding and histopathological lesions but does not provide complete protection from infection and interferes with serological diagnosis of Johne's disease and bovine tuberculosis. At this time no recombinant antigens have been found to provide superior protection compared to whole killed or live-attenuated MAP vaccines. Therefore, there is a need to evaluate more candidate MAP antigens. In this study recombinant MAP antigens MAP2698c and MAP3567 were formulated with four different MONTANIDE™ (ISA 50V2, 61VG, 71VG, and 201VG) adjuvants and evaluated for their ability to produce specific immune responses in vaccinated sheep. The cellular immune response was measured with an interferon-gamma (IFN-γ) release assay and the humoral immune response was measured by antibody detection enzyme linked immunosorbent assay. Recombinant vaccine formulation with the antigen MAP2698c and MONTANIDE™ ISA 201VG adjuvant produced strong whole-MAP as well as MAP2698c-specific IFN-γ responses in a high proportion of the vaccinated sheep. The formulation caused less severe injection site lesions in comparison to other formulations. The findings from this study suggest that the MAP2698c + 201VG should be evaluated in a challenge trial to determine the efficacy of this vaccine candidate.

  11. Improved uptake of plant-derived LTB-linked proteins in carp gut and induction of specific humoral immune responses upon infeed delivery.

    PubMed

    Companjen, A R; Florack, D E A; Slootweg, T; Borst, J W; Rombout, J H W M

    2006-09-01

    Oral vaccination of fish is an effortless and stress free immunisation method which can be used for almost any age. However, vaccination via the mucosal route does have disadvantages. For example, the vaccine may induce tolerance and has to be protected to escape digestion. Also the vaccine should be efficiently delivered to immune-competent cells in the gut or other lymphoid organs. In addition, it should be cost effective. Here we present a novel fish vaccination model using potato tubers as vaccine production and delivery system. The model vaccines discussed here include fusion proteins consisting of a gut adhesion molecule (LTB) and a viral peptide or green fluorescent protein (GFP) expressed in potato tubers. The adhesion molecule mediates binding to and uptake from the gut, whereas the viral peptide or GFP functions as model vaccine antigen provoking the induction of an immune response. We demonstrate that fusion to LTB facilitates an elevated uptake of the model vaccines in carp gut mucosa. The plant-derived fusion proteins also elicit a specific systemic humoral immune response upon oral application of crude tuber material incorporated into a standard dietary feed pellet. The data presented here show the promising potentials of the plant as a production system for oral vaccines in aquaculture and feed mediated immunisation of fish.

  12. Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice.

    PubMed

    Wang, Chong; Zheng, Xuexing; Gai, Weiwei; Wong, Gary; Wang, Hualei; Jin, Hongli; Feng, Na; Zhao, Yongkun; Zhang, Weijiao; Li, Nan; Zhao, Guoxing; Li, Junfu; Yan, Jinghua; Gao, Yuwei; Hu, Guixue; Yang, Songtao; Xia, Xianzhu

    2017-04-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation.

  13. Comparative immunotoxicity of 2,2`-dichlorodiethyl sulfide and cyclophosphamide: Evaluation of L1210 tumor cell resistance, cell-mediated immunity, and humoral immunity. (Reannouncement with new availability information)

    SciTech Connect

    Blank, J.A.; Joiner, R.L.; Houchens, D.P.; Dill, G.S.; Hobson, D.W.

    1991-12-31

    The immunotoxicity of 2,2`-dichlorodiethyl sulfide (sulfur mustard, SM),on humoral and cell-mediated immunity was compared with that of the nitrogen mustard 2-(bis(2-chloroethyl) amino)tetrahydro- 2H-1,3,2-oxazophosphorine 2-oxide (cyclophosphamide, CP). SM and CP had similar effects on thymic and splenic weights, spleen cell number, and the formation of antibody producing cells to sheep red blood cells (sRBC) when examined 5 days after exposure, but differed in their effects on body weights. Although there were no differences in the delayed hypersensitivity response to keyhole limpet hemocyanin, CP and SM had different effects in the L1210 tumor cell allograft rejection assay. CP, but not SM, decreased the 28 day survival rate of allogeneic mice exposed to a sublethal L1210 tumor challenge. The differing effects on survival to the L1210 tumor challenge could not be attributed to a direct cytotoxic effect of SM on the L1210 tumor cells as SM did not increase the survival rate or mediansurvival time of syngeneic mice exposed to a lethal L1210 tumor cell challenge. In summary, SM and CP had immunosuppressive effects in the humoral immune assay. Although neither compound suppressed the delayed hypersensitivity response, CP was found to suppress host resistance to L1210 tumor cells.

  14. Single and mixed-species trypanosome and microsporidia infections elicit distinct, ephemeral cellular and humoral immune responses in honey bees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Frequently encountered parasite species impart strong selective pressures on host immune system evolution and are more apt to concurrently infect the same host, yet molecular impacts in light of this are often overlooked. We have contrasted immune responses in honey bees to two common eukaryotic en...

  15. IL-33 Enhances Humoral Immunity Against Chronic HBV Infection Through Activating CD4(+)CXCR5(+) TFH Cells.

    PubMed

    Zhao, Ping-Wei; Shi, Xu; Li, Cong; Ayana, Desalegn Admassu; Niu, Jun-Qi; Feng, Jun-Yan; Wang, Juan; Jiang, Yan-Fang

    2015-06-01

    This study aimed to investigate the potential effect of interleukin 33 (IL-33) on humoral responses to hepatitis B virus (HBV) and the possible mechanisms underlying the action of IL-33 in regulating follicular helper T (TFH) cells. The impact of IL-33 treatment on the levels of serum HBV DNA, HBsAg, HBeAg, HBsAb, and HBeAb, as well as the frequencies of CD4(+)CXCR5(+) TFH cells in wild-type HBV transgenic (HBV-Tg) mice and in a transwell coculture of HepG2.2.15 with IL-33-treated peripheral blood mononuclear cells (PBMCs) were determined. Furthermore, the gene transcription profiles in IL-33-treated TFH cells were determined by microarrays. IL-33 treatment significantly reduced the levels of serum HBV DNA, HBsAg, and HBeAg, but increased the levels of HBsAb and HBeAb in HBV-Tg mice, accompanied by increased frequency of splenic infiltrating CD4(+)CXCR5(+) TFH cells in HBV-Tg. Similarly, coculture of HepG2.2.15 cells with IL-33-treated PBMCs reduced the levels of HBV DNA, HBsAg, and HBeAg, but increased the levels of HBsAb and HBeAb. Microarray analyses indicated that IL-33 significantly modulated the transcription of many genes involved in regulating TFH activation and differentiation. Our findings suggest that IL-33 may activate TFH cells, promoting humoral responses to HBV during the pathogenic process.

  16. Blood donors at high risk of transmitting the acquired immune deficiency syndrome.

    PubMed

    Contreras, M; Hewitt, P E; Barbara, J A; Mochnaty, P Z

    1985-03-09

    The acquired immune deficiency syndrome (AIDS) occurs most commonly in homosexual men. This group carries the greatest risk of transmitting AIDS by blood transfusion. Both promiscuous and nonpromiscuous male homosexuals should refrain from giving blood. A leaflet stating this advice was prepared by the Department of Health and Social Security, United Kingdom. In July 1984 a questionnaire was given to all donors attending a blood donor clinic in the west end of London, England. 53% were male. Donors were given a leaflet on AIDS and a questionnaire to complete in private. Those who considered themselves to be in a high risk group were asked to designate their blood for research purposes only. Serum samples from donors who confirmed that they were in the high risk category were tested for antihepatitis B core antigen and anti-human T lymphotropic virus type III (anti-HTLV-III) in addition to the routine screening of donors for hepatitis B surface antigen and syphilis. All high risk donors were men. Homosexuality was the only high risk factor. Of 5000 questionnaires administered between July and October, 614 were not completed or had ambiguous answers. 38 donors who completed the questionnaire beonged to a high risk group. Of these, 7 were positive for antihepatitis B core antigen; none were positive for anti-HTLV-III, T pallidum hemagglatination, or hepatits B surface antigen. Although the homosexual donors had a much lower incidence of sexually transmitted disease than those attending special clinics, this should not encourage complacency. All possible measures must be taken to prevent homosexuals from donating blood.

  17. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet

    PubMed Central

    Mabuchi, Yuko; Frankel, Theresa L.

    2016-01-01

    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons. PMID:27069640

  18. Humoral and cell-mediated immune mechanisms in the production of pathology in avirulent Semliki Forest virus encephalitis.

    PubMed Central

    Berger, M L

    1980-01-01

    Seven days after peripheral inoculation with an avirulent strain of Semliki Forest virus, the brains of CBA and nude mice exhibited a mononuclear inflammation and spongiform degeneration. Mice that had received cyclophosphamide (150 mg/kg) 24 h after infection showed no pathology until day 11. However, immunofluorescence studies of the brains of immunosuppressed, infected mice demonstrated viral antigen within the soma and processes of neurons at earlier periods. The brain lesions could be reconstituted on day 7 in immunosuppressed, infected recipients with 6-day immune spleen cells. Immune spleen cells depleted of T lymphocytes, the non-immunoglobulin-bearing population deficient in B lymphocytes, or immune sera plus nonimmune bone marrow cells could also reconstitute the lesions. However, inflammation and spongiform changes were reduced when donor immune cells were depleted of either T or B lymphocytes. When both T and B lymphocytes were removed from the donor immune population, recipient brains did not show pathology. The results demonstrate that either antibody or immune T cells can trigger pathology, but there is also participation of nonimmune bone marrow-derived mononuclear cells, probably of the monocyte-macrophage lineage. Images Fig. 2 Fig. 3 Fig. 4 PMID:6254882

  19. Broad humoral and cellular immunity elicited by a bivalent DNA vaccine encoding HA and NP genes from an H5N1 virus.

    PubMed

    Xu, Ke; Ling, Zhi-Yang; Sun, Liang; Xu, Ying; Bian, Chao; He, Yuan; Lu, Wei; Chen, Ze; Sun, Bing

    2011-02-01

    Influenza A virus is highly variable and a major viral respiratory pathogen that can cause severe illness in humans. Therefore it is important to induce a sufficient immune response specific to current strains and to heterosubtypic viruses with vaccines. In this study, we developed a dual-promoter-based bivalent DNA vaccine that encodes both hemagglutinin (HA) and nucleoprotein (NP) proteins from a highly pathogenic A/Chicken/Henan/12/2004 (H5N1) virus. Our results show that the expression levels of HA and NP genes from the dual-promoter plasmid are similar to those seen when they are expressed individually in independent plasmids. When the bivalent DNA vaccine was inoculated via intramuscular injection and in vivo electroporation, high levels of both humoral and cellular immune responses were elicited against homologous H5N1 virus and heterosubtypic H9N2 virus. Furthermore, no obvious antigenic competition was observed between HA and NP proteins in the dual-promoter-based bivalent vaccine compared to monovalent vaccines. Our data suggest that a combination of influenza surface and internal viral genes in a dual-promoter-expressing plasmid may provide a new approach for developing a DNA vaccine that may protect not only specifically against a currently circulating strain, but also may cross-protect broadly against new heterosubtypic viruses.

  20. Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity.

    PubMed

    Wu, Zeguang; Sinzger, Christian; Frascaroli, Giada; Reichel, Johanna; Bayer, Carina; Wang, Li; Schirmbeck, Reinhold; Mertens, Thomas

    2013-07-01

    Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2C(hi) CD57(hi) NK cells gated on CD3(neg) CD56(dim) cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2C(hi) CD57(hi) NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2C(hi) CD57(hi) NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2C(hi) CD57(hi) NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.

  1. Mexican Trypanosoma cruzi T. cruzi I strains with different degrees of virulence induce diverse humoral and cellular immune responses in a murine experimental infection model.

    PubMed

    Espinoza, B; Rico, T; Sosa, S; Oaxaca, E; Vizcaino-Castillo, A; Caballero, M L; Martínez, I

    2010-01-01

    It is has been shown that the majority of T. cruzi strains isolated from Mexico belong to the T. cruzi I (TCI). The immune response produced in response to Mexican T. cruzi I strains has not been well characterized. In this study, two Mexican T. cruzi I strains were used to infect Balb/c mice. The Queretaro (TBAR/MX/0000/Queretaro)(Qro) strain resulted in 100% mortality. In contrast, no mortality was observed in mice infected with the Ninoa (MHOM/MX/1994/Ninoa) strain. Both strains produced extended lymphocyte infiltrates in cardiac tissue. Ninoa infection induced a diverse humoral response with a higher variety of immunoglobulin isotypes than were found in Qro-infected mice. Also, a stronger inflammatory TH1 response, represented by IL-12p40, IFNgamma, RANTES, MIG, MIP-1beta, and MCP-1 production was observed in Qro-infected mice when compared with Ninoa-infected mice. We propose that an exacerbated TH1 immune response is a likely cause of pathological damage observed in cardiac tissue and the primary cause of death in Qro-infected mice.

  2. Immunoblot detection of class-specific humoral immune response to outer membrane proteins isolated from Salmonella typhi in humans with typhoid fever.

    PubMed Central

    Ortiz, V; Isibasi, A; García-Ortigoza, E; Kumate, J

    1989-01-01

    The studies reported here were undertaken to assess the ability of the outer membrane proteins (OMPs) of Salmonella typhi to induce a humoral immune response in humans with typhoid fever. OMPs were isolated with the nonionic detergent Triton X-100 and were found to be contaminated with approximately 4% lipopolysaccharide. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns showed protein bands with molecular size ranges from 17 to 70 kilodaltons; the major groups of proteins were those that correspond to the porins and OmpA of gram-negative bacteria. Rabbit antiserum to OMPs or to S. typhi recognized OMPs after absorption with lipopolysaccharide. Sera from patients with typhoid fever contained immunoglobulin M antibodies which reacted with a protein of 28 kilodaltons and immunoglobulin G antibodies which reacted mainly with the porins, as determined by immunoblotting. These results indicate that the porins are the major immunogenic OMPs from S. typhi and that the immune response induced in the infection could be related to the protective status. Images PMID:2768450

  3. Immunoblot detection of class-specific humoral immune response to outer membrane proteins isolated from Salmonella typhi in humans with typhoid fever.

    PubMed

    Ortiz, V; Isibasi, A; García-Ortigoza, E; Kumate, J

    1989-07-01

    The studies reported here were undertaken to assess the ability of the outer membrane proteins (OMPs) of Salmonella typhi to induce a humoral immune response in humans with typhoid fever. OMPs were isolated with the nonionic detergent Triton X-100 and were found to be contaminated with approximately 4% lipopolysaccharide. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns showed protein bands with molecular size ranges from 17 to 70 kilodaltons; the major groups of proteins were those that correspond to the porins and OmpA of gram-negative bacteria. Rabbit antiserum to OMPs or to S. typhi recognized OMPs after absorption with lipopolysaccharide. Sera from patients with typhoid fever contained immunoglobulin M antibodies which reacted with a protein of 28 kilodaltons and immunoglobulin G antibodies which reacted mainly with the porins, as determined by immunoblotting. These results indicate that the porins are the major immunogenic OMPs from S. typhi and that the immune response induced in the infection could be related to the protective status.

  4. Mexican Trypanosoma cruzi T. cruzi I Strains with Different Degrees of Virulence Induce Diverse Humoral and Cellular Immune Responses in a Murine Experimental Infection Model

    PubMed Central

    Espinoza, B.; Rico, T.; Sosa, S.; Oaxaca, E.; Vizcaino-Castillo, A.; Caballero, M. L.; Martínez, I.

    2010-01-01

    It is has been shown that the majority of T. cruzi strains isolated from Mexico belong to the T. cruzi I (TCI). The immune response produced in response to Mexican T. cruzi I strains has not been well characterized. In this study, two Mexican T. cruzi I strains were used to infect Balb/c mice. The Queretaro (TBAR/MX/0000/Queretaro)(Qro) strain resulted in 100% mortality. In contrast, no mortality was observed in mice infected with the Ninoa (MHOM/MX/1994/Ninoa) strain. Both strains produced extended lymphocyte infiltrates in cardiac tissue. Ninoa infection induced a diverse humoral response with a higher variety of immunoglobulin isotypes than were found in Qro-infected mice. Also, a stronger inflammatory TH1 response, represented by IL-12p40, IFNγ, RANTES, MIG, MIP-1β, and MCP-1 production was observed in Qro-infected mice when compared with Ninoa-infected mice. We propose that an exacerbated TH1 immune response is a likely cause of pathological damage observed in cardiac tissue and the primary cause of death in Qro-infected mice. PMID:20396398

  5. Adenovirus-based vaccination against Clostridium difficile toxin A allows for rapid humoral immunity and complete protection from toxin A lethal challenge in mice.

    PubMed

    Seregin, Sergey S; Aldhamen, Yasser A; Rastall, David P W; Godbehere, Sarah; Amalfitano, Andrea

    2012-02-14

    Clostridium difficile associated diarrhea (CDAD) is a critical public health problem worldwide with over 300,000 cases every year in the United States alone. Clearly, a potent vaccine preventing the morbidity and mortality caused by this detrimental pathogen is urgently required. However, vaccine efforts to combat C. difficile infections have been limited both in scope as well as to efficacy, as such there is not a vaccine approved for use against C. difficile to date. In this study, we have used a highly potent Adenovirus (Ad) based platform to create a vaccine against C. difficile. The Ad-based vaccine was able to generate rapid and robust humoral as well as cellular (T-cell) immune responses in mice that correlated with provision of 100% protection from lethal challenge with C. difficile toxin A. Most relevant to the clinical utility of this vaccine formulation was our result that toxin A specific IgGs were readily detected in plasma of Ad immunized mice as early as 3 days post vaccination. In addition, we found that several major immuno-dominant T cell epitopes were identified in toxin A, suggesting that the role of the cellular arm in protection from C. difficile infections may be more significant than previously appreciated. Therefore, our studies confirm that an Adenovirus based-C. difficile vaccine could be a promising candidate for prophylactic vaccination both for use in high risk patients and in high-risk environments.

  6. Schistosoma mansoni: is acquired immunity induced by highly x-irradiated cercariae dependent on the size of the challenging dose

    SciTech Connect

    Hsue, S.Y.; Hsue, H.F.; Osborne, J.W.; Johnson, S.C.

    1982-04-01

    A high degree of immunity, as shown by a 91% reduction of the number of worms recovered was found in five groups of mice that were immunized five times with highly X-irradiated cercariae and then challenged with 10, 20, 50, 100, or 500 normal Schistosoma mansoni cercariae. The results indicated that there were no significant differences in worm reduction in immunized mice challenged with different numbers of cercariae; consequently the immunity induced by this immunization method did not appear to be challenge-dose-dependent. However, the results also showed that when immunized mice were challenged with 500, 100, 50, 20, and 10 cercariae, 0, 13, 26, 56, and 68%, respectively, of the experimental animals were free of worms. Thus, the percentage of worm-negative cases increased as the number of challenge cercariae decreased. When viewed in this manner, the acquired immunity may be considered challenge-dose-dependent as well. If this method of vaccination is used for schistosomiasis control, we may anticipate that in both hypo- and hyperendemic areas, the intensity of infection and the severity of the disease will be reduced owing to a reduction in worms burdens, and in hypoendemic areas, there will be a number of worm-free cases.

  7. Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.

    PubMed

    Azuma, Koichi; Komatsu, Nobukazu; Hattori, Satoshi; Matsueda, Satoko; Kawahara, Akihiko; Sasada, Tetsuro; Itoh, Kyogo; Hoshino, Tomoaki

    2014-01-01

    Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with clinical response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, in patients with non-small cell lung cancer (NSCLC). However, humoral immune responses to EGFR in NSCLC patients have not been well studied. In this study, we investigated the clinical significance of immunoglobulin G (IgG) responses to EGFR-derived peptides in NSCLC patients receiving gefitinib. Plasma IgG titers to each of 60 different EGFR-derived 20-mer peptides were measured by the Luminex system in 42 NSCLC patients receiving gefitinib therapy. The relationships between the peptide-specific IgG titers and presence of EGFR mutations or patient survival were evaluated statistically. IgG titers against the egfr_481-500, egfr_721-740, and egfr_741-760 peptides were significantly higher in patients with exon 21 mutation than in those without it. On the other hand, IgG titers against the egfr_841-860 and egfr_1001-1020 peptides were significantly lower and higher, respectively, in patients with deletion in exon 19. Multivariate Cox regression analysis showed that IgG responses to egfr_41_ 60, egfr_61_80 and egfr_481_500 were significantly prognostic for progression-free survival independent of other clinicopathological characteristics, whereas those to the egfr_41_60 and egfr_481_500 peptides were significantly prognostic for overall survival. Detection of IgG responses to EGFR-derived peptides may be a promising method for prognostication of NSCLC patients receiving gefitinib. Our results may provide new insight for better understanding of humoral responses to EGFR in NSCLC patients.

  8. Evidence for induction of humoral and cytotoxic immune responses against devil facial tumor disease cells in Tasmanian devils (Sarcophilus harrisii) immunized with killed cell preparations.

    PubMed

    Kreiss, A; Brown, G K; Tovar, C; Lyons, A B; Woods, G M

    2015-06-12

    Tasmanian devils (Sarcophilus harrisii) risk extinction from a contagious cancer, devil facial tumour disease (DFTD) in which the infectious agent is the tumor cell itself. Because devils are unable to produce an immune response against the tumor cells no devil has survived 'infection'. To promote an immune response we immunized healthy devils with killed DFTD tumor cells in the presence of adjuvants. Immune responses, including cytotoxicity and antibody production, were detected in five of the six devils. The incorporation of adjuvants that act via toll like receptors may provide additional signals to break 'immunological ignorance'. One of these devils was protected against a challenge with viable DFTD cells. This was a short-term protection as re-challenge one year later resulted in tumor growth. These results suggest that Tasmanian devils can generate immune responses against DFTD cells. With further optimization of immune stimulation it should be possible to protect Tasmanian devils against DFTD with an injectable vaccine.

  9. Humoral immune response of a pneumococcal conjugate vaccine: capsular polysaccharide serotype 14-Lysine modified PspA.

    PubMed

    Santamaria, Raquel; Goulart, Cibelly; Perciani, Catia T; Barazzone, Giovana C; Carvalho, Rimenys; Gonçalves, Viviane M; Leite, Luciana C C; Tanizaki, Martha M

    2011-11-03

    Polysaccharide-protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the specificity of the reaction between protein and polysaccharide, inhibiting polymerization and the gel formation reaction. In the synthesis process, the currently used activator, 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) was substituted for 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). BALB/c mice were immunized with either the PS14-mPspA conjugate or the co-administered components in a three dose regimen and sera from the immunized animals were assayed for immunity induced against both antigens: PS14 and mPspA. Modification of more than 70% of lysine residues from PspA (mPspA) did not interfere in the immune response as evaluated by the anti-PspA titer and C3 complement deposition assay. Sera of mice immunized with conjugated PS14-mPspA showed similar IgG titers, avidity and isotype profile as compared to controls immunized with PspA or mPspA alone. The complement deposition was higher in the sera of mice immunized with the conjugate vaccine and the opsonophagocytic activity was similar for both sera. Conjugation improved the immune response against PS14. The anti PS14 IgG titer was higher in sera of mice immunized with the conjugate than with co-administered antigens and presented an increased avidity index, induction of a predominant IgG1 isotype and increased complement deposition on a bacteria with a surface serotype 14. These results strongly support the use of PspA as carrier in a conjugate vaccine where both components act as antigens.

  10. Intradermal DNA Electroporation Induces Cellular and Humoral Immune Response and Confers Protection against HER2/neu Tumor

    PubMed Central

    Lamolinara, Alessia; Stramucci, Lorenzo; Hysi, Albana; Iezzi, Manuela; Marchini, Cristina; Mariotti, Marianna; Amici, Augusto; Curcio, Claudia

    2015-01-01

    Skin represents an attractive target for DNA vaccine delivery because of its natural richness in APCs, whose targeting may potentiate the effect of vaccination. Nevertheless, intramuscular electroporation is the most common delivery method for ECTM vaccination. In this study we assessed whether intradermal administration could deliver the vaccine into different cell types and we analyzed the evolution of tissue infiltrate elicited by the vaccination protocol. Intradermal electroporation (EP) vaccination resulted in transfection of different skin layers, as well as mononuclear cells. Additionally, we observed a marked recruitment of reactive infiltrates mainly 6–24 hours after treatment and inflammatory cells included CD11c+. Moreover, we tested the efficacy of intradermal vaccination against Her2/neu antigen in cellular and humoral response induction and consequent protection from a Her2/neu tumor challenge in Her2/neu nontolerant and tolerant mice. A significant delay in transplantable tumor onset was observed in both BALB/c (p ≤ 0,0003) and BALB-neuT mice (p = 0,003). Moreover, BALB-neuT mice displayed slow tumor growth as compared to control group (p < 0,0016). In addition, while in vivo cytotoxic response was observed only in BALB/c mice, a significant antibody response was achieved in both mouse models. Our results identify intradermal EP vaccination as a promising method for delivering Her2/neu DNA vaccine. PMID:26247038

  11. GENE SIGNATURES ASSOCIATED WITH ADAPTIVE HUMORAL IMMUNITY FOLLOWING SEASONAL INFLUENZA A/H1N1 VACCINATION

    PubMed Central

    Ovsyannikova, Inna G.; Salk, Hannah M.; Kennedy, Richard B.; Haralambieva, Iana H.; Zimmermann, Michael T.; Grill, Diane E.; Oberg, Ann L.; Poland, Gregory A.

    2016-01-01

    This study aimed to identify gene expression markers shared between both influenza hemagglutination-inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010–2011 trivalent inactivated influenza vaccine (TIV). Influenza-specific HAI and VNA titers, and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post-vaccination. For antibody response at Day 28 vs Day 0, several genesets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses. Five genesets (comprising the genes MAZ, TTF, GSTM, RABGGTA, SMS, CA, IFNG, and DOPEY) were in common for both HAI and VNA. For response at Day 28 vs Day 3, many genesets were identified in predictive models for HAI (n=13) and VNA (n=41). Ten genesets (comprising biologically related genes, such as MAN1B1, POLL, CEBPG, FOXP3, IL12A, TLR3, TLR7, and others) were shared between HAI and VNA. These identified genesets demonstrated a high degree of network interactions and likelihood for functional relationships. Influenza-specific HAI and VNA responses demonstrated a remarkable degree of similarity. Although unique geneset signatures were identified for each humoral outcome, several genesets were determined to be in common with both HAI and VNA response to influenza vaccine. PMID:27534615

  12. The liver in acquired immune deficiency syndrome: emphasis on patients with intravenous drug abuse.

    PubMed

    Dworkin, B M; Stahl, R E; Giardina, M A; Wormser, G P; Weiss, L; Jankowski, R; Rosenthal, W S

    1987-03-01

    To assess the spectrum of hepatic abnormalities in acquired immune deficiency syndrome (AIDS), we reviewed clinical, biochemical, and pathological material in 32 patients with AIDS. Eight-four percent of AIDS cases had a history of intravenous drug abuse. Ninety percent of AIDS patients has some liver biochemical abnormality at the first presentation of illness. During the course of AIDS, significant (p less than 0.05, paired Student's t test) rises in alkaline phosphatase and bilirubin occurred, without rises in aminotransferases. Mean abnormalities were mild, reflecting approximately 2-fold increases over baseline. Liver failure was not believed to contribute to the death of any AIDS patient. Pathological findings in AIDS included specific infectious diagnosis in 26%, granulomas in 16%, hemosiderosis in 26%, nonspecific abnormalities in 39%, cirrhosis in 23%, and chronic active hepatitis in 3%. AIDS cases were also compared to 10 selected age, sex, and epidemiologically similar non-AIDS patients. Although granulomas or infections were not seen in our comparison group, only the incidence of chronic active hepatitis was significantly different between the groups. If only those with intravenous drug abuse were studied, then none of 24 AIDS patients versus four of eight non-AIDS cases (p less than 0.005) had chronic active hepatitis. AIDS patients with specific hepatic infections tended to have a higher alkaline phosphatase and aspartate aminotransferase (p less than 0.05) than noninfected cases. However, substantial overlap existed, and no difference in hepatomegaly was noted. Ninety percent of AIDS patients were ingesting at least one potentially hepatotoxic drug. We conclude that AIDS patients have a high incidence of underlying hepatic abnormalities. However, clinical and biochemical abnormalities are similar in our selected liver biopsy patients with intravenous drug abuse with or without AIDS. As expected, AIDS patients have a higher incidence of hepatic

  13. Selected prfA* mutations in recombinant attenuated Listeria monocytogenes strains augment expression of foreign immunogens and enhance vaccine-elicited humoral and cellular immune responses.

    PubMed

    Yan, Lin; Qiu, Jin; Chen, Jianbo; Ryan-Payseur, Bridgett; Huang, Dan; Wang, Yunqi; Rong, Lijun; Melton-Witt, Jody A; Freitag, Nancy E; Chen, Zheng W

    2008-08-01

    While recombinant Listeria monocytogenes strains can be explored as vaccine candidates, it is important to develop attenuated but highly immunogenic L. monocytogenes vaccine vectors. Here, prfA* mutations selected on the basis of upregulated expression of L. monocytogenes PrfA-dependent genes and proteins were assessed to determine their abilities to augment expression of foreign immunogens in recombinant L. monocytogenes vectors and therefore enhance vaccine-elicited immune responses (a prfA* mutation is a mutation that results in constitutive overexpression of PrfA and PrfA-dependent virulence genes; the asterisk distinguishes the mutation from inactivation or stop mutations). A total of 63 recombinant L. monocytogenes vaccine vectors expressing seven individual viral or bacterial immunogens each in nine different L. monocytogenes strains carrying wild-type prfA or having prfA* mutations were constructed and investigated. Mutations selected on the basis of increased PrfA activation in recombinant L. monocytogenes prfA* vaccine vectors augmented expression of seven individual protein immunogens remarkably. Consistently, prime and boost vaccination studies with mice indicated that the prfA(G155S) mutation in recombinant L. monocytogenes DeltaactA prfA* strains enhanced vaccine-elicited cellular immune responses. Surprisingly, the prfA(G155S) mutation was found to enhance vaccine-elicited humoral immune responses as well. The highly immunogenic recombinant L. monocytogenes DeltaactA prfA* vaccine strains were as attenuated as the recombinant parent L. monocytogenes DeltaactA vaccine vector. Thus, recombinant attenuated L. monocytogenes DeltaactA prfA* vaccine vectors potentially are better antimicrobial and anticancer vaccines.

  14. Whole inactivated equine influenza vaccine: Efficacy against a representative clade 2 equine influenza virus, IFNgamma synthesis and duration of humoral immunity.

    PubMed

    Paillot, R; Prowse, L; Montesso, F; Huang, C M; Barnes, H; Escala, J

    2013-03-23

    Equine influenza (EI) is a serious respiratory disease of horses induced by the equine influenza virus (EIV). Surveillance, quarantine procedures and vaccination are widely used to prevent or to contain the disease. This study aimed to further characterise the immune response induced by a non-updated inactivated EI and tetanus vaccine, including protection against a representative EIV isolate of the Florida clade 2 sublineage. Seven ponies were vaccinated twice with Duvaxyn IE-T Plus at an interval of four weeks. Five ponies remained unvaccinated. All ponies were experimentally infected with the EIV strain A/eq/Richmond/1/07 two weeks after the second vaccination. Clinical signs of disease were recorded and virus shedding was measured after experimental infection. Antibody response and EIV-specific IFNgamma synthesis, a marker of cell-mediated immunity, were measured at different time points of the study. Vaccination resulted in significant protection against clinical signs of disease induced by A/eq/Richmond/1/07 and reduced virus shedding when challenged at the peak of immunity. Antigenic drift has been shown to reduce protection against EIV infection. Inclusion of a more recent and representative EIV vaccine strain, as recommended by the OIE expert surveillance panel on equine influenza vaccine, may maximise field protection. In addition, significant levels of EIV-specific IFNgamma synthesis by peripheral blood lymphocytes were detected in immunised ponies, which provided a first evidence of CMI stimulation after vaccination with a whole inactivated EIV. Duration of humoral response was also retrospectively investigated in 14 horses vaccinated under field condition and following the appropriate immunisation schedule, up to 599 days after first immunisation. This study revealed that most immunised horses maintained significant levels of cross-reactive SRH antibody for a prolonged period of time, but individual monitoring may be beneficial to identify poor vaccine

  15. Role of lipid structure in the humoral immune response in mice to covalent lipid-peptides from the membrane proximal region of HIV-1 gp41

    PubMed Central

    Watson, Douglas S.; Szoka, Francis C.

    2009-01-01

    The membrane proximal region (MPR) of HIV-1 gp41 is a desirable target for development of a vaccine that elicits neutralizing antibodies since the patient-derived monoclonal antibodies, 2F5 and 4E10, bind to the MPR and neutralize primary HIV isolates. The 2F5 and 4E10 antibodies cross-react with lipids and structural studies suggest that MPR immunogens may be presented in a membrane environment. We hypothesized that covalent attachment of lipid anchors would enhance the humoral immune response to MPR-derived peptides presented in liposomal bilayers. In a comparison of eight lipids conjugated to an extended 2F5 epitope peptide, a sterol, cholesterol hemisuccinate (CHEMS), was found to promote the strongest anti-peptide IgG titers (6.4 × 104) in sera of BALB/C mice. Two lipid anchors, palmitic acid and phosphatidylcholine, failed to elicit a detectable serum anti-peptide IgG response. Association with the liposomal vehicle contributed to the ability of a lipopeptide to elicit anti-peptide antibodies, but no other single factor, such as position of the lipid anchor, peptide helical content, lipopeptide partition coefficient, or presence of phosphate on the anchor clearly determined lipopeptide potency. Conjugation to CHEMS also rendered a 4E10 epitope peptide immunogenic (5.6 × 102 IgG titer in serum). Finally, attachment of CHEMS to a peptide spanning both the 2F5 and 4E10 epitopes elicited serum IgG antibodies that bound to each of the individual epitopes as well as to recombinant gp140. Further research into the mechanism of how structure influences the immune response to the MPR may lead to immunogens that could be useful in prime-boost regimens for focusing the immune response in an HIV vaccine. PMID:19520200

  16. Coimmunization with an optimized IL15 plasmid adjuvant enhances humoral immunity via stimulating B cells induced by genetically engineered DNA vaccines expressing consensus JEV and WNV E DIII.

    PubMed

    Ramanathan, Mathura P; Kutzler, Michele A; Kuo, Yuan-Chia; Yan, Jian; Liu, Harrison; Shah, Vidhi; Bawa, Amrit; Selling, Bernard; Sardesai, Niranjan Y; Kim, J Joseph; Weiner, David B

    2009-07-09

    The Japanese encephalitis virus (JEV) and West Nile virus (WNV) are responsible for a large proportion of viral encephalitis in humans. Currently, there is no FDA approved specific treatment for either, though there are attempts to develop vaccines against both viruses. In this study, we proposed novel genetically engineered DNA vaccines against these two neurotrophic flaviviruses. The structural domain III (DIII) of E protein from these viruses is reported to carry dominant epitopes that induce neutralizing antibodies. Therefore we created consensus sequence of DIII domain across numerous strains of JEV and WNV. Based on the consensus amino acid sequence, synthetic codon and RNA optimized DIII-expressing DNA vaccine constructs with an efficient leader sequence were synthesized for immunization studies. In addition, we also constructed a genetically engineered IL15 DNA vaccine molecular adjuvant for co-stimulating the immune response against DIII clones. Vaccine constructs were delivered into BALB/C mice intramuscularly followed by electroporation using the CELLECTRA in vivo electroporator. We have observed that the combined delivery of both WNV DIII and IL15-ECRO DNA vaccine constructs resulted in not only the highest level of antibody against DIII, but also enhanced cross reactivity with two other antigens tested. Also, coimmunization with IL15 plasmid further increased the immune response by four- to five-fold. Importantly, we have shown that IL15 coimmunization adjuvanted humoral responses against DIII antigens by elevating the level of antibody secreting B cells. Such a DNA vaccine approach may better help to control potential travel related infectious agents such as JEV.

  17. Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity

    PubMed Central

    Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

    2016-01-01

    Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed. PMID:26819512

  18. I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection.

    PubMed

    Mancino, Alessandra; Habbeddine, Mohamed; Johnson, Ella; Luron, Lionel; Bebien, Magali; Memet, Sylvie; Fong, Carol; Bajenoff, Marc; Wu, Xuefeng; Karin, Michael; Caamano, Jorge; Chi, Hongbo; Seed, Michael; Lawrence, Toby

    2013-03-20

    Dendritic cells (DC) are required for priming antigen-specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, inappropriate priming of auto-reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen-specific T cells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases.

  19. Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity.

    PubMed

    Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

    2016-01-28

    Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

  20. Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and acquired immune responses to venoms.

    PubMed

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

    2015-10-01

    Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell's viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic type 2 (Th2) immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality.

  1. Testing the "toxin hypothesis of allergy": Mast cells, IgE, and innate and acquired immune responses to venoms*

    PubMed Central

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J.

    2015-01-01

    Summary Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell’s viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic Th2 immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. PMID:26210895

  2. Distinct Types of T-cell Help for the Induction of a Humoral Immune Response to Streptococcus pneumoniae

    DTIC Science & Technology

    2001-06-01

    cell-wall protein pneumococcal surface protein A (PspA) and the phosphorylcholine (PC) determinant of the cell-wall teichoic acid, was determined by...the cell- wall C-polysaccharide (teichoic acid). Phosphorylcholine (PC) residues are covalently linked to the teichoic acid and bind several...Clonal nature of the immune response to phosphorylcholine . I. Specificity, class, and idiotype of phosphorylcholine -binding receptors on lymphoid cells. J

  3. Nasally administered Lactobacillus rhamnosus accelerate the recovery of humoral immunity in B lymphocyte-deficient malnourished mice.

    PubMed

    Barbieri, Natalia; Villena, Julio; Herrera, Matias; Salva, Susana; Alvarez, Susana

    2013-02-01

    The ability of nasally administered Lactobacillus rhamnosus CRL1505 to accelerate the recovery of respiratory B cell-mediated immunity against pneumococcal infection in replete malnourished mice was evaluated. Weaned mice were malnourished after consumption of a protein-free diet for 21 d. Malnourished mice were fed a balanced conventional diet (BCD) for 7 d (BCD group) or a BCD for 7 d with supplemental L. rhamnosus CRL1505 by the nasal route during the last 2 d (BCD+Lr group). Nonreplete malnourished and normal mice were used as the malnourished (MNC) and the well-nourished (WNC) control groups, respectively. Mice were challenged with Streptococcus pneumoniae at the end of each dietary treatment. The immune response was studied before the challenge and at different times postinfection. The MNC mice had less resistance to pneumococcal infection, fewer mature and immature B cells in lung and spleen, and a reduced production of specific antibodies compared with WNC mice. The BCD treatment did not induce a complete normalization of the number B cell populations and antibody amounts. However, the BCD+Lr group had normal numbers of spleen and lung B cells. Moreover, the BCD+Lr mice had a significantly lower susceptibility to S. pneumoniae infection and higher amounts of anti-pneumococcal antibodies. Although further studies are necessary to clarify the effect of malnutrition and nasally administered lactobacilli in other immune cell populations involved in the protection against respiratory pathogens, this work gives evidence of the importance of using nasal priming with probiotics to accelerate the recovery of respiratory immunity in immunocompromised malnourished hosts.

  4. Oxidative damage of hepatopancreas induced by pollution depresses humoral immunity response in the freshwater crayfish Procambarus clarkii.

    PubMed

    Wei, Keqiang; Yang, Junxian

    2015-04-01

    Previous studies provide evidences for the possible oxidative damage of toxic environmental pollutants to tissue protein in fish and amphibian, but little information is available about their effects on immunity response in crustacean. In the present study, we evaluated the relationship between oxidative damage and immune response induced by both typical pollutants (viz. copper and beta-cypermethrin), by exposing the freshwater Procambarus clarkii to sub-lethal concentrations (1/40, 1/20, 1/10 and 1/5 of the 96 h LC50) up to 96 h. Five biomarkers of oxidative stress, i.e. reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and protein carbonyl in hepatopancreas, and two immune factors, i.e. phenoloxidase (PO) and hemocyanin in haemolymph were determined. The results indicated that there was a significant increase (P < 0.05) in the contents of ROS, MDA and protein carbonyl accompanied by markedly decreased (P < 0.05) PO and hemocyanin levels in a dose and time dependent manner. The significant and positive correlation (P < 0.01) between protein carbonyls induction and MDA formation was observed in crayfish hepatopancreas at 96 h. The production of these protein carbonyls could significantly depress (P < 0.01) the levels of phenoloxidase and hemocyanin in hemolymph. Higher contents of ROS enhanced the risk of lipid peroxidation, protein carbonylation and immunosuppression of crayfish, and hepatopancreas might play an important role in immune system of crustaceans. Protein oxidation may be one of the main mechanisms for pollution-induced immunotoxicity in P. clarkii.

  5. Canine distemper virus DNA vaccination induces humoral and cellular immunity and protects against a lethal intracerebral challenge.

    PubMed

    Sixt, N; Cardoso, A; Vallier, A; Fayolle, J; Buckland, R; Wild, T F

    1998-11-01

    We have studied the immune responses to the two glycoproteins of the Morbillivirus canine distemper virus (CDV) after DNA vaccination of BALB/c mice. The plasmids coding for both CDV hemagglutinin (H) and fusion protein (F) induce high levels of antibodies which persist for more than 6 months. Intramuscular inoculation of the CDV DNA induces a predominantly immunoglobulin G2a (IgG2a) response (Th1 response), whereas gene gun immunization with CDV H evokes exclusively an IgG1 response (Th2 response). In contrast, the CDV F gene elicited a mixed, IgG1 and IgG2a response. Mice vaccinated (by gene gun) with either the CDV H or F DNA showed a class I-restricted cytotoxic lymphocyte response. Immunized mice challenged intracerebrally with a lethal dose of a neurovirulent strain of CDV were protected. However, approximately 30% of the mice vaccinated with the CDV F DNA became obese in the first 2 months following the challenge. This was not correlated with the serum antibody levels.

  6. Cationic micelle based vaccine induced potent humoral immune response through enhancing antigen uptake and formation of germinal center.

    PubMed

    Luo, Zichao; Shi, Shuai; Jin, Ling; Xu, Lu; Yu, Jing; Chen, Hao; Li, Xingyi

    2015-11-01

    Nanoparticles have been proven to be an effective vaccine delivery system that can boost immune responses to subunit vaccines. Herein, we developed and characterized a cationic polymeric polyethylene glycol2000-poly ϵ-caprolactone2000-polyethylenimine2000 (mPEG2000-PCL2000-g-PEI2000) micelle as a potent vaccine delivery system to boost the immune response in vivo. The micelles that we developed exhibited great antigen-loading capability and minimal cytotoxicity in vitro. Meanwhile, micelles facilitated OVA antigen uptake by dendritic cells both in vitro and in vivo. More importantly, a micelle-formulated OVA vaccine could significantly promote anti-OVA antibody production by 190-fold and potently enhance T cell proliferation and the secretion of IL-5 and IFN-γ. We attributed these effects to its ability to promote antigen uptake, antigen deposition, and germinal center formation. In conclusion, the mPEG2000-PCL2000-PEI2000 micelle that we developed has potential as potent vaccine delivery system to induce Th2 immune response.

  7. The effect of Beauveria bassiana infection on cell mediated and humoral immune response in house fly, Musca domestica L.

    PubMed

    Mishra, Sapna; Kumar, Peeyush; Malik, Anushree

    2015-10-01

    Entomopathogenic fungi that manifest infections by overcoming insect's immune response could be a successful control agent for the house fly, Musca domestica L. which is a major domestic, medical, and veterinary pest. In this study, the immune response of house fly to Beauveria bassiana infection was investigated to reveal fundamental aspects of house fly hemocyte biology, such as hemocyte numbers and size, which is poorly understood. The total hemocyte counts (THCs) in B. bassiana-infected house fly showed an initial increase (from 6 to 9 h), followed by subsequent decrease (9 to 12 h) with increase in time of infection. The THCs was slightly greater in infected flies than the non-infected ones. Insight into relative hemocyte counts depicted a significant increase in prohemocyte (PR) and decrease in granulocyte (GR) in infected house flies compared to non-infected ones. The relative cell area of hemocyte cells showed a noticeable increase in PR and intermediate cells (ICs), while a considerable reduction was observed for plasmatocyte (PL) and GR. The considerable variation in relative cell number and cell area in the B. bassiana-infected house flies indicated stress development during infection. The present study highlights changes occurring during B. bassiana invasion to house fly leading to establishment of infection along with facilitation in understanding of basic hemocyte biology. The results of the study is expected to help in better understanding of house fly immune response during fungal infection, so as to assist production of more efficient mycoinsecticides for house fly control using B. bassiana.

  8. Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens

    PubMed Central

    Rodrigues, Anderson Messias; Fernandes, Geisa Ferreira; Araujo, Leticia Mendes; Della Terra, Paula Portella; dos Santos, Priscila Oliveira; Pereira, Sandro Antonio; Schubach, Tânia Maria Pacheco; Burger, Eva; Lopes-Bezerra, Leila Maria; de Camargo, Zoilo Pires

    2015-01-01

    Background Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans. Methodology We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20). Principal Findings Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis. Conclusions A convergent IgG-response in various hosts (mice, cats, and

  9. Alpha-tocopherol transfer protein gene inhibition enhances the acquired immune response during malaria infection in mice.

    PubMed

    Herbas, Maria Shirley; Natama, Magloire Hamtandi; Suzuki, Hiroshi

    2014-03-01

    Immune response to malaria infection is complex and seems to be regulated by innate and adaptive immune response as well as environmental factors such as host genetics and nutritional status. Previously, we have reported that α-tocopherol transfer protein knockout (α-ttp(Δ)) mice, showing low concentrations of α-tocopherol in circulation, infected with Plasmodium berghei NK65 survived significantly longer as compared with the wild-type mice. In addition, Plasmodium yoelii XL-17, a lethal strain, showed non-lethal virulence in α-ttp(Δ) mice. Thus, we hypothesized that the ability of the α-ttp(Δ) mice to control P. yoelli XL-17 proliferation may allow them to build an efficient immune response against murine malaria infection. On 15 days after infection with P. yoelli XL-17, α-ttp(Δ) mice were challenged to infection with P. berghei NK65. Results indicated that α-ttp(Δ) mice infected with P. yoelli XL-17 built a protective immunity against P. berghei NK65 associated to extremely low levels of parasitemia, a controlled inflammatory response, and a robust antibody response. Moreover, the importance of α-tocopherol for parasite proliferation was remarkable. The results suggest that inhibition of α-tocopherol transfer protein activity is effective for the enhancement of acquired immunity in murine malaria infection.

  10. Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection.

    PubMed

    Fouts, Timothy R; Bagley, Kenneth; Prado, Ilia J; Bobb, Kathryn L; Schwartz, Jennifer A; Xu, Rong; Zagursky, Robert J; Egan, Michael A; Eldridge, John H; LaBranche, Celia C; Montefiori, David C; Le Buanec, Hélène; Zagury, Daniel; Pal, Ranajit; Pavlakis, George N; Felber, Barbara K; Franchini, Genoveffa; Gordon, Shari; Vaccari, Monica; Lewis, George K; DeVico, Anthony L; Gallo, Robert C

    2015-03-03

    A guiding principle for HIV vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. However, three efficacy trials of Ad5-vectored HIV vaccines showed no protection. Transmission was increased in two of the trials, suggesting that this vaccine strategy elicited CD4+ T-cell responses that provide more targets for infection, attenuating protection or increasing transmission. The degree to which this problem extends to other HIV vaccine candidates is not known. Here, we show that a gp120-CD4 chimeric subunit protein vaccine (full-length single chain) elicits heterologous protection against simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) acquisition in three independent rhesus macaque repeated low-dose rectal challenge studies with SHIV162P3 or SIVmac251. Protection against acquisition was observed with multiple formulations and challenges. In each study, protection correlated with antibody-dependent cellular cytotoxicity specific for CD4-induced epitopes, provided that the concurrent antivaccine T-cell responses were minimal. Protection was lost in instances when T-cell responses were high or when the requisite antibody titers had declined. Our studies suggest that balance between a protective antibody response and antigen-specific T-cell activation is the critical element to vaccine-mediated protection against HIV. Achieving and sustaining such a balance, while enhancing antibody durability, is the major challenge for HIV vaccine development, regardless of the immunogen or vaccine formulation.

  11. The characterization of the repertoire of wheat antigens and peptides involved in the humoral immune responses in patients with gluten sensitivity and Crohn's disease.

    PubMed

    Vojdani, Aristo

    2011-01-01

    Intestinal T cells from gluten sensitivity/celiac disease patients respond to a heterogeneous array of peptides. Our study extended this heterogeneity to humoral immune response to various wheat proteins and peptides in patients with gluten sensitivity or Crohn's disease. IgG and IgA antibodies in sera from those patients and healthy control subjects were measured against an array of wheat antigens and peptides. In gluten-sensitive patients, IgG reacted most against transglutaminase, prodynorphin, wheat extract, and α-, γ-, and ω-gliadin; IgA reacted most against wheat then transglutaminase, glutenin, and other peptides. In the sera of Crohn's disease patients, IgG reacted most against wheat and wheat germ agglutinin then transglutaminase, prodynorphin, α-, and γ-gliadin; IgA reacted foremost against prodynorphin then transglutaminase and α-gliadin. These results showed a substantial heterogeneity in the magnitude of IgG and IgA response against various wheat antigens and peptides. Measurements of IgG and IgA antibodies against such an array of wheat peptides and antigens can enhance the sensitivity and specificity of serological assays for gluten sensitivity and celiac disease and may also detect silent celiac disease or its overlap with inflammatory bowel disease.

  12. Immunization with the Haemophilus ducreyi trimeric autotransporter adhesin DsrA with alum, CpG or imiquimod generates a persistent humoral immune response that recognizes the bacterial surface.

    PubMed

    Samo, Melissa; Choudhary, Neelima R; Riebe, Kristina J; Shterev, Ivo; Staats, Herman F; Sempowski, Gregory D; Leduc, Isabelle

    2016-02-24

    The Ducreyi serum resistance A (DsrA) protein of Haemophilus ducreyi belongs to a large family of multifunctional outer membrane proteins termed trimeric autotransporter adhesins responsible for resistance to the bactericidal activity of human complement (serum resistance), agglutination and adhesion. The ability of DsrA to confer serum resistance and bind extracellular matrix proteins lies in its N-terminal passenger domain. We have previously reported that immunization with a recombinant form of the passenger domain of DsrA, rNT-DsrA, in complete/incomplete Freund's adjuvant, protects against a homologous challenge in swine. We present herein the results of an immunogenicity study in mice aimed at investigating the persistence, type of immune response, and the effect of immunization route and adjuvants on surrogates of protection. Our results indicate that a 20 μg dose of rNT-DsrA administered with alum elicited antisera with comparable bacterial surface reactivity to that obtained with complete/incomplete Freund's adjuvant. At that dose, high titers and bacterial surface reactivity persisted for 211 days after the first immunization. Administration of rNT-DsrA with CpG or imiquimod as adjuvants elicited a humoral response with similar quantity and quality of antibodies (Abs) as seen with Freund's adjuvant. Furthermore, intramuscular administration of rNT-DsrA elicited high-titer Abs with significantly higher reactivity to the bacterial surface than those obtained with subcutaneous immunization. All rNT-DsrA/adjuvant combinations tested, save CpG, elicited a Th2-type response. Taken together, these findings show that a 20 μg dose of rNT-DsrA administered with the adjuvants alum, CpG or imiquimod elicits high-quality Abs with reactivity to the bacterial surface that could protect against an H. ducreyi infection.

  13. Evaluation of humoral and cellular immune responses to BP26 and OMP31 epitopes in the attenuated Brucella melitensis vaccinated sheep.

    PubMed

    Wang, Wenjing; Wu, Jingbo; Qiao, Jun; Weng, Yunceng; Zhang, Hui; Liao, Qingyu; Qiu, Jinlang; Chen, Chuangfu; Allain, Jean-Pierre; Li, Chengyao

    2014-02-07

    In recent years, the number of cases of human brucellosis has been increasing by approximately 10% per year in China. Most cases were caused by Brucella melitensis through contacts with infected sheep, goats or their products. An attenuated B. melitensis vaccine M5-90 is currently used to vaccinate both animals in China. This vaccine has not been investigated for critical parameters such as immune response and its association with protective efficacy. In this study, humoral and cellular immune response to the periplasmic protein BP26 and the outer membrane protein OMP31 were evaluated in M5-90 vaccinated Chinese merino and Kazak sheep. Antibodies to BP26 or OMP31 were detected at low levels, and specific IFN-γ response was quantified. Strongly reactive peptides derived from BP26 and OMP31 identified five T-cell epitopes (BP26-6, -8, -11, -12 and OMP31-23) common to both sheep species, five species-specific epitopes (BP26-10, -18, -21 and -22 and OMP31-12) and four animal-specific epitopes (BP26-15, -23, OMP31-6 and -21), which stimulated specific IFN-γ response in vaccinated sheep. Among those T-cell epitopes, reactivity to BP26-18 and -21 epitopes was significantly associated with MHC-I B allele (P=0.024). However, a specific T-cell response induced by the M5-90 vaccine was relatively week and did not sustain long enough, which might be suppressed by rapid activation of T-regulatory (Treg) cells following vaccination. These findings provide an insight in designing a safer and more effective vaccine for use in animals and in humans.

  14. Subnormal expression of cell-mediated and humoral immune responses in progeny disposed toward a high incidence of tumors after in utero exposure to benzo(a)pyrene

    SciTech Connect

    Urso, P.; Gengozian, N.

    1984-01-01

    Pregnant mice were exposed to 150 ..mu..g benzol(a)pyrene (BaP) per gram of body weight during fetogenesis (d 11-17 of gestation) and the progeny were assayed for humoral and cell mediated immune responses at different time intervals after birth. Immature offspring (1-4 wk) were severely suppressed in their ability to produce antibody (plaque-) forming cells (PFC) against sheep red blood cells (SRBC) and in the ability of their lymphocytes to undergo a mixed lymphocyte response (MLR). Lymphocytes from these progeny showed a moderate to weak capacity to inhabit production of colony-forming units (CFU) in host spleens following transfer with semiallogeneic bone marrow (BM) cells into lethally x-irradiated recipients syngeneic to the BM (in vivo graft-versus-host response, GVHR). A severe and sustained suppression in the MLR and the PFC response occurred from the fifth month up to 18 mo. The in vivo GVHR, also subnormal later in life, was not as severely suppressed as the other two parameters. Tumor incidence in the BP-exposed progeny was 8- to 10-fold higher than in those encountering corn oil alone from 18 to 24 mo of age. These data show that in utero exposure to the chemical carcinogen BaP alters development of components needed for establishing competent hemoral and cell-mediated functions of the immune apparatus and leads to severe and sustained postnatal suppression of the defense mechanism. The immunodeficiency exhibited, particularly in the T-cell compartment (MLR, GVHR), before and during the increase in tumor frequency, may provide a favorable environment for the growth of nascent neoplasms induced by BaP. 30 references, 4 figures, 2 tables.

  15. Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice

    PubMed Central

    Song, Li; Xiong, Dan; Hu, Maozhi; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2016-01-01

    In spring 2013, human infections with a novel avian influenza A (H7N9) virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC) and polyethyleneimine (PEI), through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza. PMID:26930068

  16. Development of an ELISA to detect the humoral immune response to Trichinella zimbabwensis in Nile crocodiles (Crocodylus niloticus).

    PubMed

    Ludovisi, Alessandra; La Grange, Louis Jacobus; Gómez Morales, Maria Angeles; Pozio, Edoardo

    2013-05-20

    Crocodiles are known reservoir hosts of Trichinella papuae and Trichinella zimbabwensis, two zoonotic parasites that also infect mammals. Since commercial crocodile farming represents a key source of income in several countries, it is important to monitor this nematode infection in both farmed crocodiles and in breeding stocks which are frequently introduced from the wild. For this purpose, an indirect ELISA was developed to detect the anti-Trichinella immune response in crocodile sera. New Zealand rabbits were immunized with pooled sera from non-infected farmed crocodiles in the presence of Freund's complete adjuvant. The anti-crocodile serum was then conjugated with horseradish peroxidase. Serum samples from four Nile crocodiles (Crocodylus niloticus) experimentally infected with T. zimbabwensis and from four uninfected crocodiles were used to set up the ELISA. The larval burden per gram of muscle tissue was determined by muscle biopsy. The test was performed on serum samples from an additional 15 experimentally infected crocodiles as well as eight wild Nile crocodiles. Among the 19 experimentally infected crocodiles, seroconversion was observed in 11 animals. The highest antibody response was observed six weeks post infection (p.i.), but in most of these animals, antibodies were not detectable after six weeks p.i. even though live larvae were present in the muscles up to six months p.i.

  17. The age-related resistance of rats to Plasmodium berghei infection is associated with differential cellular and humoral immune responses.

    PubMed

    Adam, Estelle; Pierrot, Christine; Lafitte, Sophia; Godin, Claude; Saoudi, Abdelhadi; Capron, Monique; Khalife, Jamal

    2003-09-15

    In this study, we investigated how the age of rats would affect the course of infection of and the immune response to Plasmodium berghei. Both young (4-week-old) and adult rats (8-week-old) can be infected with P. berghei ANKA strain, with significantly higher levels of infected red blood cells in young rats. While 100% of young rats succumbed to infection, adult rats were able to clear blood parasites and no mortality was observed. Analysis of cellular distribution and circulating cytokines demonstrated the persistence of CD4+/CD25+ T cells and high expression of circulating interleukin-10 (IL-10) during the progression of infection in young-susceptible rats, whereas high levels of CD8+ T cells and natural killer T cells are detected in adult-resistant rats. Analysis of antibody isotypes showed that adult rats produced significantly higher levels of interferon-gamma (IFN-gamma)-dependent IgG2c antibodies than young rats during infection. Further evaluation of the role of IL-10, IFN-gamma and of immune cells showed that only the adoptive transfer of spleen cells from adult-resistant rats was able to convert susceptibility of young-susceptible rats to a resistant phenotype. These observations suggest that cell-mediated mechanisms are crucial for the control of a primary infection with P. berghei in young rats.

  18. A novel dengue virus serotype-2 nanovaccine induces robust humoral and cell-mediated immunity in mice.

    PubMed

    Hunsawong, Taweewun; Sunintaboon, Panya; Warit, Saradee; Thaisomboonsuk, Butsaya; Jarman, Richard G; Yoon, In-Kyu; Ubol, Sukathida; Fernandez, Stefan

    2015-03-30

    Dengue virus (DENV), a member of the Flaviviridae family, can be transmitted to humans through the bite of infected Aedes mosquitoes. The incidence of dengue has increased worldwide over the past few decades. Inadequate vector control, changing global ecology, increased urbanization, and faster global travel are factors enhancing the rapid spread of the virus and its vector. In the absence of specific antiviral treatments, the search for a safe and effective vaccine grows more imperative. Many strategies have been utilized to develop dengue vaccines. Here, we demonstrate the immunogenic properties of a novel dengue nanovaccine (DNV), composed of ultraviolet radiation (UV)-inactivated DENV-2, which has been loaded into the nanoparticles containing chitosan/Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (CS/BCG-NPs). We investigated the immunogenicity of DNV in a Swiss albino mouse model. Inoculation with various concentrations of vaccine (0.3, 1, 3 and 10μg/dose) with three doses, 15-day apart, induced strong anti-dengue IgM and IgG antibodies in the mouse serum along with neutralizing antibody against DENV-2 reference strain (16681), a clinical-isolate strain (00745/10) and the mouse-adapted New Guinea-C (NGC) strain. Cytokine and chemokine secretion in the serum of DNV-immunized mice showed elevated levels of IFN-γ, IL-2, IL-5, IL-12p40, IL-12p70, IL-17, eotaxin and RANTES, all of which have varying immune functions. Furthermore, we observed a DNV dose-dependent increase in the frequencies of IFN-γ-producing CD4(+) and CD8(+) T cells after in vitro stimulation of nucleated cells. Based on these findings, DNV has the potential to become a candidate dengue vaccine.

  19. Do IgA antibodies to Chlamydia trachomatis have protective role in humoral immunity: a study in reactive arthritis patients.

    PubMed

    Kumar, Praveen; Bhakuni, Darshan Singh; Rastogi, Sangita

    2015-01-01

    Chlamydia trachomatis-induced genitourinary Reactive Arthritis (ReA) can serve as good model for host-pathogen interaction. However, due to poor antigen presentation, cell-mediated immunity does not contribute as anticipated. Present study aims to evaluate protective role of anti-C. trachomatis antibodies vis-a-vis inflammatory chlamydial Major Outer Membrane Protein (MOMP). Prospective study was undertaken in 30 patients with genitourinary ReA. 30 Rheumatoid Arthritis (RA) and 30 osteoarthritis patients constituted controls. Subjects found to be PCR-positive for C. trachomatis were investigated for presence of MOMP in Synovial Fluid (SF) by fluorescence assay while anti-C. trachomatis IgA/IgM antibodies were estimated in SF/venous blood by ELISA. C. trachomatis MOMP was evident by the presence of elementary bodies in SF of 9 ReA PCR-positive patients (30%; p < 0.05 versus controls). Local secretory IgA antibodies were detected in 12 (40%) patients with ReA (p < 0.0001 versus controls); among 12 patients with anti-chlamydial IgA antibodies, 9 showed the presence of both MOMP and IgA antibodies in SF. 58.3% ReA patients (7/12) with secretory IgA antibodies were also positive for circulatory IgA antibodies (p < 0.01 versus controls). Serum IgM antibodies were present in 4 ReA (13.3%) and in 1 RA (3.3%) patient, respectively. In conclusion, the present study suggests that in ReA patients with chronic, persistent C. trachomatis infection in synovium, the chlamydial MOMP is triggering factor for generating a protective immune response by inducing anti-C. trachomatis IgA antibodies in the SF of large number of patients.

  20. Purinergic signaling and human immunodeficiency virus/acquired immune deficiency syndrome: From viral entry to therapy.

    PubMed

    Passos, Daniela F; Schetinger, Maria Rosa C; Leal, Daniela Br

    2015-08-12

    Human immunodeficiency virus (HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper.

  1. Plasmodesmata localizing proteins regulate transport and signaling during systemic acquired immunity in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Systemic acquired resistance (SAR) in plants is mediated by the signaling molecules azelaic acid (AzA),glycerol-3-phosphate (G3P), and salicylic acid (SA).Here, we show that AzA and G3P transport occurs via the symplastic route, which is regulated by channels known as plasmodesmata (PD). In contrast...

  2. Rhodoccocus Equi Pneumonia and Paradoxical Immune Reconstitution Inflammatory Syndrome in a Patient with Acquired Immune Deficiency Syndrome (AIDS)

    PubMed Central

    Zijoo, Ritika; Dirweesh, Ahmed; Karabulut, Nigahus

    2017-01-01

    Patient: Male, 47 Final Diagnosis: Rhodococcus equi pneumonia • paradoxical immune reconstitution inflammatory syndrome Symptoms: Cough • fever • shorthness of breath Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare co-existance of disease or pathology Background: Pulmonary infections are a major cause of mortality and morbidity in patients infected with human immunodeficiency virus (HIV) and can progress rapidly to respiratory failure and death without appropriate therapy. Herein, we present a rare case of an advanced HIV infection and Rhodoccocus equi (R. equi) pneumonia in a young male who had severe paradoxical immune reconstitution inflammatory syndrome (IRIS). Case Report: A 47-year-old nonsmoking Hispanic man with advanced HIV infection presented with severe acute necrotizing pneumonia secondary to R. equi. Although his initial response to antimicrobial therapy was optimal, he became symptomatic again in spite of continuation of antibiotics as he developed severe paradoxical IRIS 3 weeks after starting a new highly active anti-retroviral therapy (HAART). Conclusions: The diagnosis of IRIS remains challenging because of the wide variations in the clinical presentation and etiologies. In spite of its rarity as an opportunistic pathogen, we recommend that R. equi, an intracellular pathogen, be included in the differential list of pathogens associated with IRIS. PMID:28100903

  3. Enhancement of natural and acquired immunity by Lactobacillus rhamnosus (HN001), Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019).

    PubMed

    Gill, H S; Rutherfurd, K J; Prasad, J; Gopal, P K

    2000-02-01

    Consumption of lactic acid bacteria (LAB) has been suggested to confer a range of health benefits including stimulation of the immune system and increased resistance to malignancy and infectious illness. In the present study, the effects of feeding Lactobacillus rhamnosus (HN001, DR20), Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019, DR10) on in vivo and in vitro indices of natural and acquired immunity in healthy mice were examined. Mice were fed daily with L. rhamnosus, L. acidophilus or B. lactis (10(9) colony forming units) and their immune function was assessed on day 10 or day 28. Supplementation with L. rhamnosus, L. acidophilus or B. lactis resulted in a significant increase in the phagocytic activity of peripheral blood leucocytes and peritoneal macrophages compared with the control mice. The proliferative responses of spleen cells to concanavalin A (a T-cell mitogen) and lipopolysaccharide (a B-cell mitogen) were also significantly enhanced in mice given different LAB. Spleen cells from mice given L. rhamnosus, L. acidophilus or B. lactis also produced significantly higher amounts of interferon-gamma in response to stimulation with concanavalin A than cells from the control mice. LAB feeding had no significant effect on interleukin-4 production by spleen cells or on the percentages of CD4+, CD8+ and CD40+ cells in the blood. The serum antibody responses to orally and systemically administered antigens were also significantly enhanced by supplementation with L. rhamnosus, L. acidophilus or B. lactis. Together, these results suggest that supplementation of the diet with L. rhamnosus (HN001), L. acidophilus (HN017) or B. lactis (HN019) is able to enhance several indices of natural and acquired immunity in healthy mice.

  4. Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism.

    PubMed

    Kaminski, N E; Koh, W S; Yang, K H; Lee, M; Kessler, F K

    1994-11-16

    Cannabinoid compounds, including the major psychoactive component of marihuana, delta 9-tetrahydrocannabinol (delta 9-THC), have been widely established as being inhibitory on a broad array of humoral and cell-mediated immune responses. The presence of cannabinoid receptors has been identified recently on mouse spleen cells, which possess structural and functional characteristics similar to those of the G-protein coupled cannabinoid receptor originally identified in rat brain. These findings, together with those demonstrating that delta 9-THC inhibits adenylate cyclase in splenocytes, strongly suggest that certain aspects of immune inhibition by cannabinoids may be mediated through a cannabinoid receptor-associated mechanism. The objective of the present studies was to determine whether inhibition of adenylate cyclase is relevant to mouse spleen cell immune function and, if so, whether this inhibition is mediated through a Gi-protein coupled mechanism as previously described in neuronal tissue. Spleen cell activation by the phorbol ester phorbol-12-myristate-13-acetate (PMA), plus the calcium ionophore ionomycin, produced a rapid but transient increase in cytosolic cAMP, which was inhibited completely by immunosuppressive concentrations of delta 9-THC (22 microM) and the synthetic bicyclic cannabinoid CP-55940 (5.2 microM), which produced no effect on cell viability. Inhibition by cannabinoids of lymphocyte proliferative responses to PMA plus ionomycin and sheep erythrocyte (sRBC) IgM antibody-forming cell (AFC) response, was abrogated completely by low concentrations of dibutyryl-cAMP (10-100 microM). Inhibition of the sRBC AFC response by both delta 9-THC (22 microM) and CP-55940 (5.2 microM) was also abrogated by preincubation of splenocytes for 24 hr with pertussis toxin (0.1-100 ng/mL). Pertussis toxin pretreatment of spleen cells was also found to directly abrogate cannabinoid inhibition of adenylate cyclase, as measured by forskolin-stimulated accumulation

  5. Evaluation of specific humoral immune response and cross reactivity against Mycobacterium tuberculosis antigens induced in mice immunized with liposomes composed of total lipids extracted from Mycobacterium smegmatis

    PubMed Central

    2013-01-01

    The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate. PMID:23458421

  6. Dataset of aqueous humor cytokine profile in HIV patients with Cytomegalovirus (CMV) retinitis.

    PubMed

    Iyer, Jayant Venkatramani; Agrawal, Rupesh; Yeo, Tun Kuan; Gunasekeran, Dinesh V; Balne, Praveen Kumar; Lee, Bernett; Au, Veonice Bijin; Connolly, John; Teoh, Stephen C B

    2016-09-01

    The data shows the aqueous humor cytokine profiling results acquired in a small cohort of 17 HIV patients clinically diagnosed with Cytomegalovirus retinitis using the FlexMAP 3D (Luminex®) platform using the Milliplex Human Cytokine® kit. Aqueous humor samples were collected from these patients at different time points (pre-treatment and at 4-weekly intervals through the 12-week course of intravitreal ganciclovir treatment) and 41 cytokine levels were analyzed at each time point. CMV DNA viral load was assessed in 8 patients at different time points throughout the course of ganciclovir treatment. The data described herein is related to the research article entitled "Aqueous humor immune factors and cytomegalovirus (CMV) levels in CMV retinitis through treatment - The CRIGSS study" (Iyer et al., 2016) [1]. Cytokine levels against the different time points which indicate the response to the given treatment and against the CMV viral load were analyzed.

  7. Both Innate Immunity and Type 1 Humoral Immunity to Streptococcus pneumoniae Are Mediated by MyD88 but Differ in Their Relative Levels of Dependence on Toll-Like Receptor 2

    DTIC Science & Technology

    2005-01-01

    normal pathogen- specific IgG isotype response to Borrelia burgdorferi was ob- served in TLR2/ mice, although this was associated with a higher... Borrelia burgdorferi -infected mice. Infect. Immun. 72:3195–3203. 28. Lund, J., A. Sato, S. Akira, R. Medzhitov, and A. Iwasaki. 2003. Toll-like...Zachary, C. J. Kirschning, and J. J. Weis. 2002. Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi

  8. A two year BTV-8 vaccination follow up: molecular diagnostics and assessment of humoral and cellular immune reactions.

    PubMed

    Hund, Alexandra; Gollnick, Nicole; Sauter-Louis, Carola; Neubauer-Juric, Antonie; Lahm, Harald; Büttner, Mathias

    2012-01-27

    The compulsory vaccination campaign against Bluetongue virus serotype eight (BTV-8) in Germany was exercised in the state of Bavaria using three commercial monovalent inactivated vaccines given provisional marketing authorisation for emergency use. In eleven Bavarian farms representing a cross sectional area of the state the immune reactions of sheep and cattle were followed over a two year period (2008-2009) using cELISA, a serum neutralisation test (SNT) and interferon gamma (IFN-γ) ELISPOT. For molecular diagnostics of BTV genome presence two recommended real time quantitative RT-PCR protocols were applied. The recommended vaccination scheme led to low or even undetectable antibody titers (ELISA) in serum samples of both cattle and sheep. A fourfold increase of the vaccine dose in cattle, however, induced higher ELISA titers and virus neutralising antibodies. Accordingly, repeated vaccination in sheep caused an increase in ELISA-antibody titers. BTV-8 neutralising antibodies occurred in most animals only after multiple vaccinations in the second year of the campaign. The secretion of interferon gamma (IFN-γ) in ELISPOT after in vitro re-stimulation of PBMC of BTV-8 vaccinated animals with BTV was evaluated in the field for the first time. Sera of BTV-8 infected or vaccinated animals neutralising BTV-8 could also neutralise an Italian BTV serotype 1 cell culture adapted strain and PBMC of such animals secreted IFN-γ when stimulated with BTV-1.

  9. Intranasal Vaccination with Murabutide Enhances Humoral and Mucosal Immune Responses to a Virus-Like Particle Vaccine

    PubMed Central

    Jackson, Erin M.; Herbst-Kralovetz, Melissa M.

    2012-01-01

    Murabutide (MB) is a synthetic immunomodulator recognized by the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptor on mammalian cells. MB has previously been approved for testing in multiple human clinical trials to determine its value as an antiviral therapeutic, and as an adjuvant for injected vaccines. We have found a new use for this immunomodulator; it functions as a mucosal adjuvant that enhances immunogenicity of virus-like particles (VLP) administered intranasally. MB enhanced Norwalk virus (NV) VLP-specific IgG systemically and IgA production at distal mucosal sites following intranasal (IN) vaccination. A dose escalation study identified 100 µg as the optimal MB dosage in mice, based on the magnitude of VLP-specific IgG, IgG1, IgG2a and IgA production in serum and VLP-specific IgA production at distal mucosal sites. IN vaccination using VLP with MB was compared to IN delivery VLP with cholera toxin (CT) or gardiquimod (GARD) and to parenteral VLP delivery with alum; the MB groups were equivalent to CT and GARD and superior to alum in inducing mucosal immune responses and stimulated equivalent systemic VLP-specific antibodies. These data support the further testing of MB as a potent mucosal adjuvant for inducing robust and durable antibody responses to non-replicating subunit vaccines. PMID:22855691

  10. Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity

    PubMed Central

    Wan, Feng; Hu, Chong-bin; Ma, Jun-xia; Gao, Ke; Xiang, Li-xin; Shao, Jian-zhong

    2017-01-01

    γδ T cells represent an evolutionarily primitive T cell subset characterized by distinct T cell receptors (TCRs) and innate and adaptive immune functions. However, the presence of this T cell subset in ancient vertebrates remains unclear. In this study, γδ T cells from a zebrafish (Danio rerio) model were subjected to molecular and cellular characterizations. The constant regions of zebrafish TCR-γ (DrTRGC) and δ (DrTRDC) were initially identified. Zebrafish γδ T cells accounted for 7.7–20.5% of the total lymphocytes in spleen, head kidney, peripheral blood, skin, gill, and intestine tissues. They possess typical morphological features of lymphocytes with a surface phenotype of γ+δ+CD4−CD8+. Zebrafish γδ T cells functionally showed a potent phagocytic ability to both soluble and particulate antigens. They can also act as an antigen-presenting cell to initiate antigen (KLH)-specific CD4+ TKLH cell activation and to induce B cell proliferation and IgM production. Particularly, zebrafish γδ T cells also play a critical role in antigen-specific IgZ production in intestinal mucus. These findings demonstrated that γδ T cells had been originated as early as teleost fish, which providing valuable insights into the evolutionary history of T cell subset. It is anticipated that this study would be used as a guide to develop a zebrafish model for the cross-species investigation of γδ T cell biology. PMID:28119690

  11. Role of B Cells and Antibodies in Acquired Immunity against Mycobacterium tuberculosis

    PubMed Central

    Achkar, Jacqueline M.; Chan, John; Casadevall, Arturo

    2015-01-01

    Accumulating evidence has documented a role for B cells and antibodies (Abs) in the immunity against Mycobacterium tuberculosis (Mtb). Passive transfer studies with monoclonal antibodies (mAbs) against mycobacterial antigens have shown protection against the tubercle bacillus. B cells and Abs are believed to contribute to an enhanced immune response against Mtb by modulating various immunological components in the infected host including the T-cell compartment. Nevertheless, the extent and contribution of B cells and Abs to protection against Mtb remains uncertain. In this article we summarize the most relevant findings supporting the role of B cells and Abs in the defense against Mtb and discuss the potential mechanisms of protection. PMID:25301934

  12. Increasing the metabolizable protein supply enhanced growth performance and led to variable results on innate and humoral immune response of preconditioning beef steers.

    PubMed

    Moriel, P; Artioli, L F A; Poore, M H; Confer, A W; Marques, R S; Cooke, R F

    2015-09-01

    We evaluated the effects of MP supply on growth performance before and after preconditioning and measurements of innate and humoral immune response of beef steers following vaccination. Angus steers ( = 36; BW = 231 ± 21 kg; age = 184 ± 18 d) were weaned on d -6, stratified by BW and age on d 0, and randomly assigned to 1 of 18 drylot pens (2 steers/pen). Treatments were assigned to pens (6 pens/treatment) and consisted of corn silage-based diets formulated to provide 85%, 100%, or 115% of the daily MP requirements of a beef steer gaining 1.1 kg/d from d 0 to 42. Steers were vaccinated against infectious bovine rhinotracheitis virus, bovine viral diarrhea (BVDV) types 1 and 2 viruses, and clostridium on d 14 and 28. Blood samples were collected on d 0, 14, 15, 17, 21, 28, 29, 30, 35, and 42. Body weight did not differ ( ≥ 0.17) among treatments from d 0 to 28. On d 42, 115% MP steers were heaviest, 100% MP steers were intermediate, and 85% MP steers were lightest ( = 0.05; 297, 290, and 278 ± 7 kg, respectively). Overall, ADG and G:F did not differ ( ≥ 0.13) between 100% and 115% MP steers and were least ( < 0.01) for 85% MP steers (1.2, 1.4, and 0.8 ± 0.07 kg/d and 0.23, 0.24, and 0.19 ± 0.008, respectively). Plasma haptoglobin (Hp) concentrations did not differ among treatments ( ≥ 0.46), whereas plasma ceruloplasmin (Cp) concentrations were greatest ( ≤ 0.04) for 85% MP steers, intermediate for 100% MP steers, and least for 115% MP steers on d 30, 35, and 42. Plasma cortisol concentrations were greater ( ≤ 0.03) for 85% vs. 100% and 115% MP steers on d 14 and 28. Liver mRNA expression of Cp and Hp and muscle mRNA expression of m-calpain, mammalian target of rapamycin, and ubiquitin did not differ among treatments ( ≥ 0.17). Serum neutralization titers to BVDV-1b titers were greater ( ≤ 0.02) for 115% vs. 85% and 100% MP steers on d 42 (5.8, 3.0, and 3.7 ± 0.60 log, respectively), whereas mean serum leukotoxin titers were greater for 85% vs

  13. Altered erythrocyte C3b receptor expression, immune complexes, and complement activation in homosexual men in varying risk groups for acquired immune deficiency syndrome.

    PubMed Central

    Tausk, F A; McCutchan, A; Spechko, P; Schreiber, R D; Gigli, I

    1986-01-01

    We studied levels of erythrocyte C3b receptors (E-CR1) and correlated them to the level of circulating immune complexes (CIC) and complement activation in patients with or at risk for acquired immunodeficiency syndrome (AIDS). A significant reduction was found in patients with AIDS (185 +/- 93 CR1/cell), AIDS-related complex, and generalized lymphadenopathy, whereas healthy male homosexuals or normal controls had 434 +/- 193 and 509 +/- 140 CR1/cell, respectively (P less than 0.001). Family studies indicate that this defect is acquired. Reduction in E-CR1 was associated with increased levels of CIC when assayed by binding to Raji cells, but not when tested by C1q binding. Complement activation was assessed by levels of C3bi/C3d-g in plasma, measured with a monoclonal antibody specific for a neoantigen in C3d. AIDS patients had increased C3 activation (2.68 +/- 1.67%) when compared with normal controls (0.9 +/- 0.22%) (P less than 0.01). The decreased E-CR1, the pres