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PubMed1980

Natural and immune cytolysis of canine distemper virus-infected target cells.

Natural and immune cytolysis of canine distemper virus (CDV)-infected target cells in vitro is described. Lymphocytes expressing natural cytotoxicity were found in specific-pathogen-free beagle dogs and in beagle-coonhound crosses before vaccination with CDV and indefinitely after vaccination, when the ephemeral immune lymphocyte-mediated cytotoxicity (ILMC) had declined. In contrast to the natural lymphocyte-mediated cytotoxicity, the ILMC was genetically restricted, could not be blocked by CDV-specific antibody, and was effective against measles virus-infected as well as CDV-infectd target cells. Lymphocyte populations were depleted of Fc receptor and surface immunoglobulin-bearing cells by rosetting techniques and tested in comparison. An antibody-dependent cell-mediated cytotoxicity was demostrated against CDV-infected target cells that were preincubated with CDV antibody when Fc receptor-bearing lymphocytes were not removed. The ILMC was measurable for approximately 10 days beginning at 6 days post-vaccination. In contrast, CDV antibody measured by virus neutralization and humoral cytotoxicity was detectable by 6 days postvaccination and persisted at peak levels for at least 5 months.

Animals↗
PubMed2005

Viral modulation of NK cell immunity.

Natural killer (NK) cells have been implicated in innate immune responses against viruses such as herpesviruses, which cause persistent infections in the host. In response to the selective pressure that is exerted by NK cells, many viruses have evolved strategies either to evade detection by NK cells or to modulate the activity of NK cells. Here, we review the unique relationship that exists between NK cells and viruses, with a focus on herpesviruses.

Animals↗
PubMed2002

CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity.

Natural killer (NK) cells are innate lymphocytes that provide cytokines critical for early host defense against pathogens. One subset of human NK cells (CD56(bright)) constitutively expresses the high-affinity interleukin 2 (IL-2) receptor and produces immunoregulatory cytokines. Here, we demonstrate that CD56(bright) NK cells are present in human lymph nodes and that endogenous T cell-derived IL-2, acting through the NK high-affinity IL-2 receptor, costimulates CD56(bright) NK cells to secrete IFN-gamma. Thus, adaptive immunoregulators influence innate cytokine production, which in turn may influence the developing antigen-specific immune response. These data show a dynamic interaction between innate and adaptive human lymphocytes and emphasize the importance of studying interactions between immune components to understand the immune response as a whole.

Adult↗
PubMed1994

Measles antibody: comparison of long-term vaccination titres, early vaccination titres and naturally acquired immunity to and booster effects on the measles virus.

A two-dose vaccination programme, using a combined measles, mumps and rubella vaccine (MMR) and administration at the ages of 18 months and 12 years, was introduced into Sweden in 1982. Since the combined MMR vaccine was introduced, a yearly evaluation of the immunity patterns and seroconversion rates in 12-year-old children has been carried out. This study includes three study groups. All groups consisted of pre- and postvaccination samples from 12-year-old children taken in connection with the MMR immunization. There were 332 paired samples from children who 8-10 years previously had received live measles vaccine. Prevaccination sera from these children represent late postvaccination titres. The postvaccination sera of 49 children seronegative to measles before vaccination, obtained 2 months after vaccination, represent early postvaccination immunity. Ninety-five children who had not been vaccinated earlier and who were seropositive to measles represent naturally acquired immunity. All samples were studied by an enzyme-linked immunosorbent assay (ELISA). Sera from children with late postvaccination immunity had significantly lower titres than children in group 2, who represented early postvaccination sera (p < 0.001). Children with naturally acquired immunity had significantly higher titres than children with vaccine-induced immunity titres (p < 0.001). After revaccination of the previously vaccinated children, a significant booster rise was seen (p < 0.001). After revaccination of children with naturally acquired immunity, no significant booster effect was observed. Sixty-five children of the 332 (20%) previously vaccinated children had no or borderline measles titres prior to the booster. The study suggests that the vaccine-induced measles antibodies decline with time and may fall under the protective level.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1989

Postpartum immunization with rubella virus vaccine and antibody response in breast-feeding infants.

Women who were susceptible to rubella, whether they had elected to breast-feed or formula-feed their infants, received immunization with subcutaneously administered rubella antibody 27/3 live, attenuated rubella virus vaccine in the postpartum period. The breast-fed or formula-fed infants of these mothers who had been immunized subsequently received active immunization with the rubella antibody 27/3 vaccine at 15 to 18 months of age. A second group of naturally immune women who were seropositive for rubella did not receive immunization after childbirth. However, infants of naturally immune mothers who did not receive immunization received immunization with the rubella vaccine and served as controls. Seroconversion for rubella antibody developed in over 94% of susceptible women who were seronegative for rubella after postpartum immunization. The infants of these mothers had no rubella antibody activity in the cord blood; however, 13% of such infants exhibited rubella antibody in serum at 6 months of age. On the other hand, 44% of breast-fed infants of naturally immune mothers (controls) demonstrated rubella antibody activity at 6 months of age. Subsequent immunization with rubella vaccine in breast-fed infants whose mothers had received postpartum immunization resulted in a serum antibody response that was similar to the response observed in the formula-fed infants or the infants of naturally immune mothers who had not received immunization. These data suggest that early neonatal exposure to the rubella virus in breast milk does not enhance or suppress subsequent responses to current programs of rubella vaccination in early childhood.

Antibodies, Viral↗
PubMed2001

Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity.

Natural killer (NK) cells attack many tumour cell lines, and are thought to have a critical role in anti-tumour immunity; however, the interaction between NK cells and tumour targets is poorly understood. The stimulatory lectin-like NKG2D receptor is expressed by NK cells, activated CD8+ T cells and by activated macrophages in mice. Several distinct cell-surface ligands that are related to class I major histocompatibility complex molecules have been identified, some of which are expressed at high levels by tumour cells but not by normal cells in adults. However, no direct evidence links the expression of these 'induced self' ligands with tumour cell rejection. Here we demonstrate that ectopic expression of the murine NKG2D ligands Rae1beta or H60 in several tumour cell lines results in potent rejection of the tumour cells by syngeneic mice. Rejection is mediated by NK cells and/or CD8+ T cells. The ligand-expressing tumour cells induce potent priming of cytotoxic T cells and sensitization of NK cells in vivo. Mice that are exposed to live or irradiated tumour cells expressing Rae1 or H60 are specifically immune to subsequent challenge with tumour cells that lack NKG2D ligands, suggesting application of the ligands in the design of tumour vaccines.

Animals↗
PubMed1993

The changes of some immunological parameters in subjects exposed to asbestos in dependence on age, duration of exposure, radiological findings and smoking habits.

We followed the changes in some parameters in men exposed to asbestos (to chrysotile and in part to crocidolite). The studied group consisted of exposed workers and retired workers who had been exposed to asbestos in the past. The results were compared with those in the control group of unexposed adults and analysed according to age, duration of exposure, smoking habits and radiological findings. Investigated were: the levels of immunoglobulins IgA, IgG, IgM, complement components C3, C4, alpha-1-antitrypsin and transferrin (humoral immunity) as well as the phagocytic activity of the leukocytes in peripheral blood (natural immunity). The comparison of the results with those in the control group showed that asbestos exposure stimulated markedly IgG and C4 production and to a lesser extent also IgA, IgM, C3 and transferrin production and it suppressed natural immunity. Comparison of the results of the same age categories--control (40.8), with the subgroup of active workers (44.4), showed significantly increased levels of IgA, IgG, IgM, C4 and decreased values of natural immunity in asbestos exposed group. Comparison of different age categories (pensioners--63.2: workers--44.4) showed, that from five parameters in which statistically significant differences were found, four had decreased values in pensioners. Radiological findings suggested, that changes in immunological parameters probably preceded pathologic processes. There were statistically significant differences in the levels of IgM in smokers compared with nonsmokers in the subgroup of workers exposed to asbestos and in the levels of IgG and C4 in the group of workers + pensioners together. It follows from the present study that asbestos exposure modulates the immune response and leads to significant changes of humoral and natural immunity.

Adult↗
PubMed1989

An observational study of naturally acquired immunity to rotaviral diarrhea in a cohort of 363 Egyptian children. Calculation of risk for second episodes using age-specific person-years of observation.

A cohort of 363 rural children in Bilbeis, Egypt, were followed from birth from 1981 to 1983, with twice-weekly home visits made to detect diarrheal illness. Enzyme-linked immunosorbent assay was used for detection of rotavirus in stools collected during episodes of diarrhea. Rotavirus-associated diarrhea was detected once in 74 children and twice in 12 children. Using a technique not previously described, the authors calculated the age-specific incidence rates for initial episodes and second episodes of rotavirus-associated diarrhea to estimate the effectiveness of naturally acquired immunity. Assuming that the risk of exposure was the same before and after the first episode, the observed and expected numbers of second episodes of rotaviral diarrhea were equal (age-adjusted rate ratio = 1.01; 95 percent confidence interval 0.55-1.86), given the age-specific person-years at risk. The assumption of equal risk for reexposure to rotavirus appears to be invalid, however, since the children with one and two rotavirus-positive episodes appeared to be at greater risk for diarrheal illness of all causes (rate ratios of 1.42 and 1.78, respectively). The clinical illness may have been less severe in second episodes; emesis was reported more often with first rotavirus episodes than with second rotavirus episodes, and the only fatal case was in an initial episode. These data are compatible with the existence of partial immunity, since it appears that the risk of reexposure may be greater in children who experienced rotaviral gastroenteritis earlier in life. In four of seven children, rotavirus isolates from first and second episodes were of identical serotypes, indicating that even serotype-specific immunity for rotaviral diarrhea was incomplete.

Age Factors↗
PubMed1995

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

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.

Journal Article↗
PubMed2006

Immunology of O-glycosylated proteins: approaches to the design of a MUC1 glycopeptide-based tumor vaccine.

Until about 1990 there was general consent about the assumption that only protein and peptide antigens have the capacity of CD4(+) or CD8(+) T-cell stimulation. Since about ten years evidence is now accumulating that carbohydrate-peptide epitopes do play a role in classical MHC-mediated immune responses. This holds true for glycopeptides, where the glycan chain is short and not located at an "anchor residue" needed for MHC interaction. T-cell recognition of O-glycosylated peptides is potentially of high biomedical significance, because it can mediate the immune protection against microorganisms, the vaccination in anti-tumor therapies, but also some aspects of autoimmunity. The epithelial type 1 transmembrane mucin MUC1 is established as a marker for monitoring recurrence of breast cancer and is a promising target for immunotherapeutic strategies to treat cancer by active specific immunization. Natural human immune responses to the tumor-associated glycoforms of the mucin indicate that antibody reactivities are more directed to glycopeptide than to non-glycosylated peptide epitopes. To overcome the weak immunogenicity of the natural target, heavily O-glycosylated MUC1, the question was addressed whether O-linked glycans remain intact during processing in the MHC class II pathway and interfere with endosomal processing and peptide presentation. Attempts were made to define on a biochemical level the structural requirements for an efficient endosomal proteolysis catalyzed by cathepsin L in antigen-presenting cells. Evidence based on work with CD4(+) T-hybridomas confirms that O-glycopeptides can be effectively presented to T-cells and that glycans can form integral parts of the TCR defined epitopes. Similar approaches are currently followed in the MHC class I pathway which aim at the identification of immunogenic glycopeptides generated by immunoproteasomes.

Amino Acid Sequence↗
PubMed2006

Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity.

Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses. We describe here a third DC lineage, termed interferon-producing killer DCs (IKDCs), distinct from conventional DCs and plasmacytoid DCs and with the molecular expression profile of both NK cells and DCs. They produce substantial amounts of type I interferons (IFN) and interleukin (IL)-12 or IFN-gamma, depending on activation stimuli. Upon stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)-9, IKDCs kill typical NK target cells using NK-activating receptors. Their cytolytic capacity subsequently diminishes, associated with the loss of NKG2D receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity is lost, DC-like antigen-presenting activity is gained, associated with upregulation of surface major histocompatibility complex class II (MHC II) and costimulatory molecules, which formally distinguish them from classical NK cells. In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity. By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity.

Adaptation, Physiological↗
PubMed2002

Current status of defensins and their role in innate and adaptive immunity.

Naturally occurring antimicrobial cationic polypeptides play a major role in innate and adaptive immunity. These polypeptides are found to be either linear and unstructured or structured through disulfide bonds. Among the structured antimicrobial polypeptides, defensins comprise a family of cysteine-rich cationic polypeptides that contribute significantly to host defense against the invasion of microorganisms in animals, humans, insects and plants. Their wide-spread occurrence in various tissues of these diverse organisms, and their importance in innate and adaptive immunity have led to their identification, isolation and characterization. A large volume of literature is available on defensins' occurrence, structural characterization, gene expression and regulation under normal and pathological conditions. Much has also been published regarding their antimicrobial, antiviral and chemoattractive properties, and their molecular and cellular interactions. In this review, we describe the current status of our knowledge of defensins with respect to their molecular, cellular and structural biology, their role in host defense, future research paradigms and the possibility of their utilization as a new class of non-toxic antimicrobial agents and immuno-modulators.

Amino Acid Sequence↗
PubMed2000

Natural HPV immunity and vaccination strategies.

BACKGROUND: the task of preventing premature death in women may be delivered by vaccinating against the high-risk papillomaviruses associated with various malignancies. OBJECTIVES: we will discuss the immune mechanisms likely to be relevant to the control of an HPV infection in the cervix and assess the limited evidence for such immune recognition in the natural history of infection. CONCLUSION: the next generation of vaccination strategies should include the use of HPV 16 early (E2 and/or E6 and/or E7) and late gene targets (L1 and L2) expressed as VLPs with their clinical and immunological evaluation aimed at therapy as well as prophylaxis. Important clinical efficacy assessment may be deliverable in relatively short-term studies by targeting patients with HPV 16 associated vulval intraepithelial neoplasia.

Female↗
PubMed2004

Role of gammadelta T lymphocytes in tumor defense.

The effectors of mucosal and natural immunity (i.e. natural killer, NK, cells and NKT lymphocytes) are known to play an important role in host defence against tumors. Gammadelta T lymphocytes are the most represented cell populations in mucosal associated lymphoid tissue and share several characteristics of T and NK cells. Two main subsets of gammadelta T cells are known: one, expressing the Vdelta2 T cell receptor (TCR), is found in the peripheral blood, while T cells expressing Vdelta1 TCR are resident in epithelial tissues. The former subset is capable of killing myeloma and Burkitt lymphoma cells, while the latter has been implied in the defence against epithelial cancers. Furthermore, there is increasing evidence that alphabeta and gammadelta T lymphocytes make distinct contributions to anticancer surveillance. Indeed, unlike alphabeta T cells, gammadelta T lymphocytes are involved in the recognition of antigens that do not undergo the conventional major histocompatibility complex (MHC)-driven antigen presentation. Down-regulation of expression of MHC alleles as well as tumor-specific antigens is observed frequently during tumor progression, resulting in an impairment of MHC-restricted, alphabeta-T-cell-mediated tumor-specific immunity. Given the unique set of antigens recognized and the lack of requirement for classical antigen-presenting molecules, gammadelta T lymphocytes might, therefore, represent a useful and potent system in anti-cancer surveillance, as proposed for the immune response against pathogens. Evidence that gammadelta and alphabeta cells make distinct contribution to anti-cancer surveillance have been recently provided in mice. Here, we discuss the potential role played by resident Vdelta1+ and circulating Vdelta2+ T lymphocytes in the defense against solid tumors and hematological malignancies.

Alleles↗
PubMed1986

Antibody response to the rubella virus structural proteins in infants with the congenital rubella syndrome.

Forty-five serum samples from 31 newborns and infants with the congenital rubella syndrome (CRS) were tested by immunoprecipitation to determine their antibody spectra to each of the structural proteins of rubella virus. Most sera (37/45) contained little or no E2 protein-specific antibody, but some (6/45) precipitated a greater amount of the E2 glycoprotein than the E1 glycoprotein. The relative E1/E2 ratio was found to decrease with time when serial serum samples from the same patient were tested. No correlation between the IgG class hemagglutination inhibition antibody titers and the E1/E2 ratio could be demonstrated. However, in some serum specimens relatively high neutralizing antibody titers were correlated with immunoprecipitation of the E2 glycopolypeptide. None of the CRS sera reacted well with the C protein. The immunoprecipitation patterns found in CRS sera were qualitatively different from those observed in a series of 25 sera from young adults with conventional serologic evidence of rubella immunity following natural infection. All of the natural immune sera recognized each of the three structural polypeptides of rubella virus.

Age Factors↗
PubMed1999

Compliance with recommended infection control procedures among Canadian dentists: results of a national survey.

OBJECTIVES: The objective of this study was to investigate compliance with recommended infection control (IC) practices by dentists in Canada in 1995. DESIGN: A mailed survey of a stratified random sample of dentists (N = 6444), with 3 follow-up attempts. Weighted analyses included multiple logistic regression to identify the best predictors of "excellent" compliance (18 items). RESULTS: The adjusted response rate was 66.4%. Respondents reported use of an IC manual (52%); postexposure protocol (41%); biologic monitoring of heat-sterilizers (71%); hepatitis B immunization of dentists (91%: of these 72% had post-immunization screening; natural immunity 3%) all hygienists (78%), and all other clinical staff (70%); handwashing (before treating patients 76%, after degloving 63%); always wearing gloves (95%); changing gloves after each patient (97%); masks (82%); protective eyewear (82%); protective uniform (48%); puncture-proof container for sharps (94%); recapping needles with scoop technique/device (60%); flushing waterlines (55%); heat-sterilizing handpieces (94%; after each patient 77%); high-volume suction (92%) and "excellent" compliance (6%). Significant predictors of "excellent compliance" included attending continuing education about IC (>/=10 hours, odds ratio [OR] = 6.3; 6-10 hours, OR = 3.3), treating 20 to 29 patients per day (OR = 2.8), being women (OR = 2.7), and population of city in which practice is located (>500,000, OR = 2.5). CONCLUSION: Improvements in IC are necessary in dental practice. The introduction of mandatory continuing education about IC may improve compliance with recommended IC procedures, which is important because of concerns related to transmission of bloodborne pathogens and drug-resistant microorganisms.

Adult↗
PubMed1995

Measles vaccination of infants in a well-vaccinated population.

During outbreaks of measles, measles vaccine is recommended for infants considered to be at risk who are 6 months of age and older. In a prospective trial the serologic response to early measles immunization has been evaluated in 125 infants given monovalent measles vaccine at 6 to 8.5 months of age and measles-mumps-rubella at 15 months. The response to vaccination was measured by plaque reduction neutralization (PRN) assay and enzyme immunoassay. Infants were grouped by the mother's immunization history: natural immunity (n = 60, Group 1); killed followed by live, further attenuated vaccine (n = 22, Group 2); and live, further attenuated vaccine only (n = 43, Group 3). The prevaccination geometric mean titer (GMT) by PRN for Group 1 (GMT = 69) was significantly higher than that of Group 2 (GMT = 18) or 3 (GMT = 13). Seroconversion (4-fold increase in PRN titer) rates after monovalent vaccine were 31, 71 and 76% for Groups 1, 2 and 3, respectively. Seroconversion percentages were higher when measured 6 to 8 weeks after vaccination compared with 4 to 5 weeks. After measles-mumps-rubella > or = 97% of all infants had PRN titers > 120 and were measles IgG-positive by enzyme immunoassay. These data show that as demographics shift to a well-vaccinated maternal population and susceptibility in younger infants, measles vaccination before the currently recommended age will be effective.

Age Factors↗
PubMed2006

Correlation between the nature of immunity induced by different immunogens and the establishment of latent infection by wild-type pseudorabies virus.

To assess the correlation between the nature of immunity induced by different types of immunogens and the establishment of latent infection by wild-type pseudorabies virus (PrV), we used a murine model immunized with different immunogens, the PrV modified live vaccine (MLV), inactivated vaccine (IAV), and commercial oil-adjuvant subunit vaccine (OSV), via either intranasal (i.n.) or intramuscular (i.m.) route. Both MLV and IAV induced a different nature of immunity biased to Th1- and Th2-type, respectively, as judged by the ratio of PrV-specific IgG isotypes (IgG2a/IgG1) and the profile of cytokine IL-2, IL-4, and IFN-gamma production. In contrast, the OSV induced a lower isotype IgG2a to IgG1 ratio and higher level of IL-2 production. The MLV (inducing Th1-type) provided more effective protection against a virulent wild-type PrV challenge than IAV and OSV (inducing Th2- and mixed type, respectively). In addition, the MLV impeded the establishment of a latent infection with wild-type PrV, and the decrease in the PrV latency load by immunization with the MLV appeared to be mediated by the immune T-cells. These results demonstrate the substantial role of the immune responses driven by preceding vaccination in modulating the establishment of PrV latency caused by the post-infection of a field virus.

Animals↗