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AvrPtoB: a bacterial type III effector that both elicits and suppresses programmed cell death associated with plant immunity.

Pseudomonas syringae pv. tomato DC3000 is a model pathogen for studying the molecular basis of plant immunity and disease susceptibility in tomato and Arabidopsis. DC3000 uses a type III secretion system to inject effector proteins into the plant cell. Type III effectors are thought to promote bacterial virulence by suppressing plant defenses and enhancing access to nutrients trapped in the plant cell. The AvrPtoB type III effector elicits immunity-associated programmed cell death (PCD) when expressed in tomato plants carrying the Pto resistance protein. However, in the absence of Pto, AvrPtoB functions to suppress PCD and immunity in tomato. Here, we review current research examining the molecular basis of AvrPtoB-mediated elicitation and suppression of plant PCD. In addition, the "trump model" is proposed to explain how resistance proteins successfully elicit immunity-associated PCD in response to effectors that suppress PCD.

Apoptosis↗

Assessing immunization data quality from routine reports in Mozambique.

BACKGROUND: Worldwide immunization coverage shows an increase in the past years but the validity of the official reports for measuring change over time has been questioned. Facing this problem, donor supported initiatives like the Global Alliance for Vaccine and Immunizations, have been putting a lot of effort into assessing the quality of data used, since accurate immunization information is essential for the Expanded Program on Immunization managers to track and improve program performance. The present article, discusses the practices on record keeping, reporting and the support mechanism to ensure data quality in Mozambique. METHODS: A process evaluation study was carried out in Mozambique in one district (Cuamba) in Niassa Province, between January and March 2003. The study was based on semi-structured interviews, participant observation and review of the data collection materials. RESULTS: Differences were found for all vaccine types when comparing facility reports with the tally sheets. The same applies when comparing facility reports with district reports. The study also showed that a routine practice during supervision visits was data quality assessment for the outpatient services but none related to data consistency between the tally sheets and the facility report. For the Expanded Program on Immunization, supervisors concentrated more on the consistency checks between data in the facility reports and the number of vaccines received during the same period. Meetings were based on criticism, for example, why health workers did not reach the target. Nothing in terms of data quality was addressed nor validation rules. CONCLUSION: In this paper we have argued that the quality of data, and consequently of the information system, must be seen in a broader perspective not focusing only on technicalities (data collection tools and the reporting system) but also on support mechanisms. Implications of a poor data quality system will be reflected in the efficiency of health services facing increased demands, with stagnant or decreasing resources.

Child↗

Hepatitis B infection in rural Vietnam and the implications for a national program of infant immunization.

To ascertain hepatitis B virus (HBV) infection rates for Vietnam, we surveyed HBV markers in two districts of Thanh Hoa province. We randomly selected 536 infants (9- < or = 18 months old), 228 children (4 to < or = 6 years old), 219 adolescents (14 to < or = 16 years old), and 596 adults (25 to < or = 40 years old). On questioning, none of those surveyed had received vaccine against HBV. Hepatitis B virus surface antigen (HBsAg) and total HBV core antibody (anti-HBc) were measured in all specimens, and HBV e antigen (HBeAg) in those positive for HBsAg, and HBV surface antibody (anti-HBs) were measured in all others. Current infection (HBsAg+) rates were infants = 12.5%, children = 18.4%, adolescents = 20.5%, and adults = 18.8%. Current or previous infection (HBsAg+, anti-HBc+, or anti-HBs+) increased with age (infants = 19.6%, children = 36.4%, adolescents = 55.3%, adults = 79.2%). Rates of HBeAg among those HBsAg+ were infants = 85.1%, children = 88.1%, adolescents = 71.1%, and adults = 30.4%. The epidemiology of HBV in Vietnam resembles that of many southeast Asian nations before introduction of vaccine. Immunization of newborns will have enormous impact on HBV-related morbidity and mortality there.

Adolescent↗

Immune activation in HIV-infected African individuals. Italian-Ugandan AIDS cooperation program.

OBJECTIVE: Immune activation induced by chronic infections, dietary limitations, and poor hygienic conditions is suggested to be present in African HIV infection and is at the basis of the hypothesis that HIV infection in Africa could be prevalently associated with immunopathogenetic mechanisms. Very limited data are nevertheless available supporting this theory, and in particular no data are reported on functional and phenotypic analyses performed on fresh peripheral blood mononuclear cells (PBMC) of African HIV-infected patients living in Africa. DESIGN: Immunological and virological parameters were analysed in fresh PBMC of HIV-infected African and Italian patients with advanced HIV disease and comparable CD4 and CD8 counts, sex, and age. Both functional (antigen- and mitogen-stimulated cytokine production) and phenotypic (activation markers; markers preferentially expressed by T helper (Th) type 2 cells or by memory and naive cells) analyses were performed. Results were compared with those of HIV-seronegative African and Italian controls. HIV plasma viraemia was analysed by competitive polymerase chain reaction (PCR) and branched DNA techniques. RESULTS: (1) The production of mitogen-stimulated IFN-gamma and TNF-alpha as well as the production of env peptide-stimulated IFN-gamma, TNF-alpha, and IL-10 are increased in African HIV infection; (2) the expression of activation and Th2-associated markers is augmented in African HIV infection as is the memory/naive ratio; (3) mitogen-stimulated IFN-gamma and IL-10 production, as well as the expression of activation and Th2-associated markers and the memory/naive ratio, are augmented in African compared with Italian controls; and (4) plasma viraemia is reduced in African compared with Italian HIV-infected individuals. CONCLUSIONS: These results, which are the first to be reported on fresh material from African HIV-infected patients living in Africa, indicate that HIV disease is associated with an abnormal immune hyperactivation and may be accompanied in these patients by lower loads of virus, and show that such activation is present even in HIV-seronegative controls.

Adult↗

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits.

Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, we perturbed all expressed genes across 22 million primary human CD4+ T cells from four donors and developed a probe-based perturb-seq platform to measure the transcriptome effects in cells at rest and after stimulation. These data allowed us to map genes regulating immune pathways, including previously uncharacterized regulators of cytokine production. Importantly, active regulators and the gene programs they control changed dramatically across stimulation conditions. Perturbation signatures enabled us to model T cell states observed in population-scale transcriptomic atlases, nominating regulators of T cell polarization and of age-related phenotypes. Finally, we leveraged perturb-seq to implicate context-specific gene regulatory pathways in autoimmune disease risk. Our study provides a foundational resource and new approaches to decode T cell function and human immune traits.

CD4(+) T cell polarization↗

Immunization requirements for childcare programs. Are they enough?

BACKGROUND: School immunization legislation has resulted in high vaccination coverage rates and low rates of vaccine-preventable disease among school children. Similar legislation has been directed toward children in licensed and regulated childcare programs. The purpose of this investigation was to compare immunization coverage among children in and not in childcare. METHODS: For 18 months during 2001 and 2002, the National Immunization Survey (NIS), a random-digit-dialing telephone survey, collected information on children aged 19 through 35 months, including data on enrollment in childcare. Data were analyzed retrospectively to determine coverage at 24 months and at the time of the survey. Children were considered up-to-date if they had received all recommended immunizations for their age. RESULTS: Of the eligible NIS respondents, about 41% had a child in childcare at the time of or before the survey. Retrospective analysis of children at 24 months showed no significant differences in coverage between those in and not in childcare (73.1% vs 71.9%). Likewise, analysis of coverage at the time of the survey revealed no significant differences (76.4% vs 72.6%). CONCLUSIONS: Immunization legislation and regulations have been successful in increasing coverage rates in the school population. Similar legislation for childcare facilities appears not to have been as effective. Given these findings, it seems that new strategies are needed to increase coverage in preschool children.

Child Day Care Centers↗

Programmed cell death (apoptosis) in immunity and haematological neoplasia.

Programmed cell death, also commonly referred to as apoptosis, is a genetically controlled sequence of events, often requiring protein synthesis, which results in cell death. Although initially described 20 years ago, it is only recently that its role as a mechanism in controlling cell population size and content has been fully realised. In this review the biochemical events of apoptosis are discussed briefly, followed by a more detailed look at the role of programmed cell death in the control of haemopoiesis and the maintenance of a balanced functional immune system. The role of proto-oncogenes and suppressor genes known to regulate programmed cell death is covered, and also their influence on the induction and maintenance of neoplastic disease. Finally, the potential role of apoptosis in the resistance of haematological malignancies to chemotherapy is commented on.

Animals↗

Immunization.

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Communicable Disease Control↗

Apoptosis and programmed cell death in immunity.

Death of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism of apoptosis is currently under active investigation.

Animals↗

What mothers in the Women, Infants, and Children (WIC) program feel about WIC and immunization linkage activities. A summary of focus groups in Wisconsin.

BACKGROUND: Although studies indicate that strategies to improve immunization coverage among preschool-age children enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) are effective, the attitudes of parents of children enrolled in WIC toward the linkage between WIC and immunization programs is unknown. OBJECTIVE: To gain a better understanding of how parents using WIC resources feel about the association of WIC and immunization services, their attitudes toward WIC immunization activities, factors that may cause clients to drop out of the program, and the effects of racial background on parent attitudes. PARTICIPANTS AND METHODS: We conducted 8 focus group sessions with mothers whose children receive WIC services in Milwaukee, Wis. Mothers were between 18 and 35 years old, with at least 1 child between 6 and 24 months of age. The 47 mothers participating were each assigned to 1 of 8 focus groups, including 2 groups each of Asian, white, African American, and Hispanic mothers. A systematic content analysis was conducted for themes and key points within and across ethnic groups. RESULTS: Socially disadvantaged mothers reported their overall experiences in WIC to be very positive. Lengthy waiting time during a WIC visit was identified as the most important barrier to participation. Mothers believed strongly that it was the responsibility of parents to get their children vaccinated, but that WIC staff and the primary care provider should work together to remind parents when vaccinations were due. Mothers expressed very positive attitudes toward the linking of WIC and immunization activities. Telephone reminders and education were mentioned as the best ways to encourage mothers to get their child vaccinated on time. Immunization linkage activities and the requirement that a parent report to a WIC center more frequently if the child was underimmunized were not mentioned as reasons for dropping out of the WIC program; indeed, more frequent visits to a WIC center were actually viewed as a potentially effective strategy by several mothers. Some mothers found obtaining immunizations and WIC services at the same time and place to be very convenient. There did not seem to be any significant differences among ethnic groups in attitudes toward immunization linkage activities being performed in WIC. CONCLUSIONS: Mothers with preschool-age children enrolled in WIC feel that the linkage of immunization activities with WIC services is a helpful way to improve the health of their children. This linkage was not identified as a contributing factor for leaving the WIC program.

Adolescent↗

Tropical disease vaccines.

Infectious diseases remain a key cause of morbidity and mortality in the Tropics. Many of these diseases are already preventable by effective vaccines. The Extended Program of Immunization provides protection against six serious infections. However, this program is still not optimally implemented in all developing countries. The Extended Program of Immunization could benefit from the addition of several vaccines, but unfortunately the cost is prohibitive in many areas of the Tropics. For some of the most important infections, such as malaria and HIV, vaccines are not yet available. Novel strategies for vaccine development and policy implementation offer the best hope to combat the infections targeted by the World Health Organization as causing the highest annual death toll worldwide.

AIDS Vaccines↗

A program of acquired immune deficiency syndrome education for nurses in Romania.

After the fall of the communist government in Romania, many children were found to be human immunodeficiency virus (HIV) infected. The majority of these children were abandoned and currently live in orphanages. The children have been cared for on a day-to-day basis by nurses with little general nursing education and even less HIV education. The Romanian-American Pediatric AIDS Education and Clinical Research Program was established at Texas Children's Hospital and Baylor College of Medicine in May, 1996 to aid in the education of Romanian nurses. Syllabi developed by the U.S. nursing team were initially piloted in three pediatric HIV centers in Romania in July, 1997. Since that time, two annual nursing symposia have been held offering topics on general pediatrics and HIV-related content. The purpose of this article is to describe a program of HIV education for nurses in Romania.

Child↗

Nonspecific cytotoxic cells and innate immunity: regulation by programmed cell death.

Although programmed cell death (PCD) and the cellular pathology of apoptosis have been extensively studied in mammals and invertebrates, little is known regarding these important regulatory processes in cold blooded vertebrates, especially teleost fish. In the present review, select immunoregulatory properties of PCD/apoptosis in nonspecific cytotoxic cells (NCC) from catfish and tilapia were identified. The techniques used to define the characteristics of PCD in NCC were DNA ploidy, Annexin-V binding and cellular morphology. Using these procedures, we determined that the biochemical/genetic changes that NCC undergo during PCD are similar to those described in mammalian cells. We hypothesize that one immediate response of NCC to acute stress in teleost fish is the release of apoptosis regulatory factors (ARF) or stress activated serum factors (SASF) into the peripheral blood. These cytokine-like factors activate NCC by protecting them from initiation of: "activation induced cell death" (AICD); from "receptor induced apoptosis"; and from initiation of dexamethasone induced DNA hypoploidy. We predict that the mechanism of these actions is enhanced NCC recycling capacity and initiation of migration of NCC into sites of inflammation. In this review, studies were also summarized regarding the expression and release of "death and survival proteins" by NCC. Although the survey was not exhaustive, we showed that tilapia NCC that were activated in vitro with SASF contained increased levels of two adaptor proteins (i.e. CAS, FADD) and soluble FasL. At present the relevance of expression of the adaptor proteins by NCC is not known, however, additional evidence for the role of FasL in NCC innate immune responses was presented. Interestingly, NCC contained constitutive cytosolic FasL, and activation with tumor cells caused a significant decrease in the cytoplasmic levels of this "death protein". This indicated that FasL in NCC may function as a secretory cytokine-like molecule. Unlike mammalian NK cells and T-cells, activated NCC do not express membrane FasL. A level of phosphatase regulation of NCC apoptosis was indicated by demonstrating a reduced camptothecin induce DNA hypoploidy by pretreatment of NCC with the tyrosine phosphatase inhibitor sodium orthovanadate. This review emphasized the important regulatory functions of PCD/apoptosis for NCC in innate immune responses.

Animals↗

Tools for immunization guideline knowledge maintenance. II. Automated Web-based generation of user-customized test cases.

IMM/Test is a prototype software tool built to generate test cases that can be used to help test and verify the internal logic of an immunization forecasting program. A forecasting program takes as input a child's immunization history and produces recommendations as to which vaccinations are due and which should be scheduled next. IMM/Test was developed to test a specific immunization forecasting program, IMM/Serve. In addition, IMM/Test has been incorporated into a broader Web-based tool, IMM/Web, which allows the user (e.g., a member of an immunization registry staff) to customize the parameters used for immunization forecasting (e.g., the minimum ages for each dose and the minimum wait intervals between doses) to reflect local practice. IMM/Web then generates a customized set of test cases that may be used to test the user's immunization forecasting program. The user may also request that the test cases be automatically passed to IMM/Serve to analyze using the newly defined parameters. The paper describes the internal design of IMM/Test and IMM/Web and discusses certain lessons learned in the implementation of the two programs.

Adolescent↗