Pertussis: infection, vaccination and gene polymorphisms

Pertussis or whooping cough is a human respiratory tract infection and a vaccine-preventable disease that is caused by Bordetella pertussis bacteria. Pertussis vaccination has been part of the Finnish national vaccine program since 1952. Despite extensive vaccinations, the incidence of pertussis has increased in many countries during the last decades. Large epidemics have been observed also in countries with high vaccine coverage. Inter-individual variation in immune responses is always encountered after vaccination. Low vaccine responses may cause vulnerability to pertussis even straight after vaccination. Reasons for low responses are not fully understood. The innate immune system is responsible for the initial recognition of pathogens and vaccine antigens. The role of innate immunity on pertussis immunity has not been thoroughly investigated. Mannose-binding lectin (MBL) and toll-like receptor 4 (TLR4) are important molecules of the innate immune system and in the recognition of pathogens. Cytokines form a signaling network that have a notable role in immune responses after infections as well as after vaccinations. Single nucleotide polymorphism (SNP) is common in genes encoding these molecules and the polymorphisms have been reported to affect vaccine response after viral and bacterial vaccines. This study investigated the gene polymorphisms of MBL2, TLR4 and interleukin (IL)-10 promoter and their association with vaccine responses after acellular pertussis (aP) vaccination in Finnish adolescents and infants. Cell-mediated immune responses were investigated ten years after the previous pertussis vaccinations in young adults. In addition, the role of MBL deficiency in pertussis infection susceptibility was evaluated. The results of this study show that subjects with TLR4 polymorphism had lower antibody production and persistence after aP vaccination compared with normal allele. A specific SNP in the TLR4 gene was associated with decreased antibody responses and persistence in adolescents after aP booster vaccination. Cell-mediated immune responses were partly detected ten years after the previous vaccination; booster vaccine clearly enhanced the responses. In addition, subjects with IL-10 polymorphism had altered cell-mediated immune responses. MBL deficiency was found to be more frequent in pertussis patients than healthy controls but the polymorphism of MBL2 was not associated with antibody responses after acellular pertussis vaccination. The novel finding of this study was that genetic variation in the innate immune system seems to play a role in altered pertussis vaccine responses as well as in pertussis infection. These new findings enlighten the mechanisms behind the low responses after pertussis vaccination and help to predict risk factors related to this phenomenon.

Occurrence of common scab in potato tubers following foliar treatment with glycinebetaine under glasshouse conditions

Selostus: Glysiinibetaiinilla suoritetun lehvästöruiskutuken vaikutus perunan rupisuuteen

Reforms of the Common Agricultural Policy and agriculture in Finland

Selostus: Euroopan unionin yhteisen maatalouspolitiikan uudistaminen ja Suomen maatalous

Contrasting tree-ring data with fire record in a pine-dominated landscape in the Komi Republic (Eastern European Russia) : recovering a common climate signal

Abstract

Defoliation by the common pine sawfly (Diprion pini) and subsequent growth reduction in Scots pine : a retrospective approach

Abstract

Immunopathogenesis of Asthma and Atopic Diseases – The specific Role of a selected Panel of Genes in human T helper Cell Differentiation

T helper cell (Th) functions are crucial for proper immune defence against various intra- and extracellular pathogens. According to the specific immune responses, Th cells can be classified into subtypes, Th1 and Th2 cells being the most frequently characterized classes. Th1 and Th2 cells interact with other immune cells by regulating their functions with specific cytokine production. IFN, IL-2 and TNF- are the cytokines predominantly produced by Th1 cells whereas Th2 cells produce Th2-type cytokines, such as IL-4, IL-5 and IL-13. Upon TCR activation and in the presence of polarizing cytokines, Th cells differentiate into effector subtypes from a common precursor cell. IFN and IL-12 are the predominant Th1 polarizing cytokines whereas IL-4 directs Th2 polarization. The cytokines mediate their effects through specific receptor signalling. The differentiation process is complex, involving various signalling molecules and routes, as well as functions of the specific transcription factors. The functions of the Th1/Th2 cells are tightly regulated; however, knowledge on human Th cell differentiation is, as yet, fairly poor. The susceptibility for many immune-mediated disorders often originates from disturbed Th cell responses. Thus, research is needed for defining the molecular mechanisms involved in the differentiation and balanced functions of the Th cells. Importantly, the new information obtained will be crucial for a better understanding of the pathogenesis of immune-mediated disorders, such as asthma or autoimmune diseases. In the first subproject of this thesis, the role of genetic polymorphisms in the human STAT6, GATA3 and STAT4 genes were investigated for asthma or atopy susceptibility in Finnish asthma families by association analysis. These genes code for key transcription factors regulating Th cell differentiation. The study resulted in the identification of a GATA3 haplotype that associated with asthma and related traits (high serum IgE level). In the second subproject, an optimized method for human primary T cell transfection and enrichment was established. The method can be utilized for functional studies for the selected genes of interest. The method was also utilized in the third subproject, which aimed at the identification of novel genes involved in early human Th cell polarization (0-48h) using genome-wide oligonucleotide arrays. As a result, numerous genes and ESTs with known or unknown functions were identified in the study. Using an shRNA knockdown approach, a panel of novel IL-4/STAT6 regulated genes were identified in the functional studies of the genes. Moreover, one of the genes, NDFIP2, with a previously uncharacterized role in the human Th differentiation, was observed to promote IFN production of the differentiated Th1 cells. Taken together, the results obtained have revealed potential new relevant candidate genes serving as a basis for further studies characterizing the detailed networks involved in the human Th cell differentiation as well as in the genetic susceptibility of Th-mediated immune disorders.

Effects of polymorphisms in beta1-adrenoceptor and alpha-subunit of G protein on heart rate and blood pressure during exercise test. The finnish cardiovascular study.

J Appl Physiol vol 100, no 2, pp 507-511, 2006