Xenotransplantation is the final frontier of using vascularised organs or cellular grafts to treat end-organ disease and offers a potential solution to the worldwide shortage of human tissue available for transplantation. The main immunological barrier to xenografting from pig-to-primate is the antigen, Galactose-α1,3-Galactose (Gal) which is found in all species except humans and other higher primates. Even with the major advancement of deleting Gal from the potential pig donor species with the aid of cloning technology, complete elimination may be elusive as alternative genes yet to be fully characterised, may still produce Gal at low levels. Thus, the human immune response against Gal may continue to be a barrier to successful xenotransplantation. The aim of this project was to develop small animal models of the important components of xenograft rejection that largely relate to the anti-Gal immune response. These include models of hyperacute, acute vascular and chronic xenograft-like rejection that in turn, provide new insights in the immune mechanisms of the rejection processes. The role of antibody and both innate and cognate cellular immunity are explored. Both vascularised heart grafts and non-vascularised skin graft models are examined as rejection of solid organs may differ from cellular transplantation. The project also provides a platform for future studies in testing genetic and pharmacotherapeutic strategies to overcome the rejection processes uncovered.

Xenotransplantation is the final frontier of using vascularised organs or cellular grafts to treat end-organ disease and offers a potential solution to the worldwide shortage of human tissue available for transplantation. The main immunological barrier to xenografting from pig-to-primate is the antigen, Galactose-α1,3-Galactose (Gal) which is found in all species except humans and other higher primates. Even with the major advancement of deleting Gal from the potential pig donor species with the aid of cloning technology, complete elimination may be elusive as alternative genes yet to be fully characterised, may still produce Gal at low levels. Thus, the human immune response against Gal may continue to be a barrier to successful xenotransplantation. The aim of this project was to develop small animal models of the important components of xenograft rejection that largely relate to the anti-Gal immune response. These include models of hyperacute, acute vascular and chronic xenograft-like rejection that in turn, provide new insights in the immune mechanisms of the rejection processes. The role of antibody and both innate and cognate cellular immunity are explored. Both vascularised heart grafts and non-vascularised skin graft models are examined as rejection of solid organs may differ from cellular transplantation. The project also provides a platform for future studies in testing genetic and pharmacotherapeutic strategies to overcome the rejection processes uncovered.

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Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met samenvatting in het Nederlands.

The aim of this essay is examine how the Moderate party ideas and values have changed over time in relation to the so-called GAL-TAN dimension. The dimension theorizes values regarding green, alternative and libertarianism against traditional, authoritarian and nationalism. The dimension has recently become relevant for the Swedish political party system and political culture. The source material we use are documents of the Moderate party from 1904 to 2013. We have examine the Moderate party ideas using qualitative and comparative method, the results are presented in the form of a “codified text analysis”. Also, to find a deeper understanding, the results is evaluated in an idea analysis. Finally, we offer an understanding of values and ideas from a cultural and social perspective. The results show that the dimension existed from the very beginning in the Moderate party and that it is most prominent today. The study compared over time, making possible comparisons of cultural positions over time.

Högerpopulismen har vuxit sig stark i Europa och västvärlden på senaste tiden. Fenomen som Trump, Brexit och Sverigedemokraterna är exempel på detta. Sverigedemokraterna har störst stöd bland män och samma mönster återfinns i stora delar av Europa. Könsgapet i partisympati till högerpopulistiska partier är ett omdebatterat ämne men relativt få studier har gjorts kring ämnet. De studier som har försökt förklara könsgapet har ännu inte lycktas – det är därför puzzlet fortfarande återstår. Sveriges politiska konfliktdimension har länge bestått av ekonomiska klasskillnader men det nuvarande politiska klimatet tycks kännetecknas av nya konfliktytor. Dessa ytor består av sakpolitiska frågor som rör kring bland annat; invandring, lag och ordning, miljö och jämställdhet. Vissa forskare hävdar att den traditionella höger/vänster-skalan bör kompletteras med en kulturell dimension. Den dimensionen går ibland under namnet GAL-TAN. För att förstå Sverigedemokraternas framgång och varför partiet lockar till sig fler män har denna studie som avsikt, att med hjälp av GAL-TAN-skalan, försöka förklara könsgapet utifrån eventuella värderingsskillnader mellan män och kvinnor. Värderingsperspektivet underbyggs av andra teorier som förklarar könsgapet mellan män och kvinnor till följd av olika socioekonomiska och sociokulturella positioner i samhället. Studien utförs genom enkätdata från SOM-institutet. Resultatet visar att det inte finns några särskilda könsskillnader i värderingar men att värderingar däremot spelar roll gällande stödet för Sverigedemokraterna, i synnerhet för män.

Den svenska väljarstrukturen har genomgått ett politiskt värderingsskifte, från att enbart präglas av en ekonomisk och materiell höger/- vänsterskala till att utmanas av en postmateriell kulturell dimension som fångar upp grundläggande motsättningar i frågor om nationalstatens gränser och globaliseringens konsekvenser. Den kulturella dimensionen brukar delas in två polariserade riktningar. Gröna, alternativa, och liberala värderingar, även kallade GAL, ställs emot värderingar som är traditionella, auktoritära, och nationalistiska, även kallade TAN. Som ett bidrag till den statsvetenskapliga debatten om postmaterialism och GAL/TAN- skalan syftar denna uppsats till att analysera vad den kulturella dimensionen innebär för det politiska klimatet i Sverige. Med grund i Ronald Ingleharts postmateriella teori undersöker studien hur den svenska väljarskarans syn på postmateriella frågor utvecklats mellan 2010 och 2018. Undersökningen appliceras på valundersökningar i väljarbeteende inom ramen för den valda tidsperioden. Resultaten visar en värderingsökning i postmateriella frågor mellan 2010- 2018, samt en värderingsminskning av materiella fördelningspolitiska frågor under samma period.

HCV is remarkable at disrupting human immunity to establish chronic infection. The accumulation of Treg cells at the site of infection and upregulation of inhibitory signaling pathways (such as T-cell Ig and mucin domain protein-3 (Tim-3) and galectin-9 (Gal-9)) play pivotal roles in suppressing antiviral effector T (Teff) cells that are essential for viral clearance. While Tim-3/Gal-9 interactions have been shown to negatively regulate Teff cells, their role in regulating Treg cells is poorly understood. To explore how Tim-3/Gal-9 interactions regulate HCV-mediated Treg-cell development, here we provide pilot data showing that HCV-infected human hepatocytes express higher levels of Gal-9 and TGF-β, and upregulate Tim-3 expression and regulatory cytokines TGF-β/IL-10 in co-cultured human CD4+ T cells, driving conventional CD4+ T cells into CD25+Foxp3+ Treg cells. Additionally, recombinant Gal-9 protein can transform TCR-activated CD4+ T cells into Foxp3+ Treg cells in a dose-dependent manner. Importantly, blocking Tim-3/Gal-9 ligations abrogates HCV-mediated Treg-cell induction by HCV-infected hepatocytes, suggesting that Tim-3/Gal-9 interactions may regulate human Foxp3+ Treg-cell development and function during HCV infection.

HCV is remarkable at disrupting human immunity to establish chronic infection. The accumulation of Treg cells at the site of infection and upregulation of inhibitory signaling pathways (such as T-cell Ig and mucin domain protein-3 (Tim-3) and galectin-9 (Gal-9)) play pivotal roles in suppressing antiviral effector T (Teff) cells that are essential for viral clearance. While Tim-3/Gal-9 interactions have been shown to negatively regulate Teff cells, their role in regulating Treg cells is poorly understood. To explore how Tim-3/Gal-9 interactions regulate HCV-mediated Treg-cell development, here we provide pilot data showing that HCV-infected human hepatocytes express higher levels of Gal-9 and TGF-β, and upregulate Tim-3 expression and regulatory cytokines TGF-β/IL-10 in co-cultured human CD4+ T cells, driving conventional CD4+ T cells into CD25+Foxp3+ Treg cells. Additionally, recombinant Gal-9 protein can transform TCR-activated CD4+ T cells into Foxp3+ Treg cells in a dose-dependent manner. Importantly, blocking Tim-3/Gal-9 ligations abrogates HCV-mediated Treg-cell induction by HCV-infected hepatocytes, suggesting that Tim-3/Gal-9 interactions may regulate human Foxp3+ Treg-cell development and function during HCV infection.

Amebiasis, also defined as invasive intestinal and extra intestinal amebiasis, is caused by Entameoba histolytica, an invasive protozoan parasite. World Health Organization (WHO) has reported that approximately 50 million people are infected each year causing an estimated 40 to 100 thousand deaths annually. Entameoba histolytica ranks only second to malaria as a protozoan cause of death. Amebiasis occurs world wide but people living in Central and South America, Africa and Asia are the majority to suffer from morbidity and mortality. The enteric parasite has no zoonotic reservoirs and insect vectors for its transmission and infects humans and non-human primates. Therefore, anti-amebic vaccine could completely eradicate the disease. Entamoeba histolytica invades tissue and causes the disease in series of events. The disease is caused when the cyst form of the parasite is ingested with contaminated food or water. After excysting in the small intestine to form the trophozoite, the parasite adheres to the colonic mucus and epithelial cells through interaction of Gal/GalNAc lectin, an amebic surface adhesin with the host glycoconjugates. The parasite then secrets the proteolytic enzymes that disrupt the intestinal mucus and epithelial barrier facilitating tissue penetration. The trophozoite then kills the host epithelial and immune cells. Also, it resists the host's immune response causing the prolonged infection called the invasive amebiasis and causes colon or liver abscess. The symptoms include gradual onset of abdominal pain, diarrhea and bloody stools. Also, it can form cysts that are excreted with stools to start new cycle. The parasite recognition of the host glycoconjugates plays an important role in the pathogenesis. Therefore, the Gal/GalNAc lectin could be a possible vaccine candidate. The Gal/GalNAc lectin is composed of a 260-kDa heterodimer of disulfide-linked heavy (170 kDa) and light (35 kDa) subunits, which is non-covalently associated with an intermediate sub-unit of 150 kDa. The only recognized Carbohydrate recognition domain (CRD) was found in the heavy sub-unit. The CRD of the lectin is the potential target for colonization blocking vaccines and drugs. Preliminary studies have shown that the recombinant fragments of cysteine-rich region of LecA (lectin) containing the CRD (carbohydrate recognition domain) of the GalNAc lectin conferred protection against amebiasis. Therefore, production of LecA in plants using chloroplast genetic engineering would result in low cost vaccine because of high expression levels of vaccine antigens, and elimination of the cold-chain (low temperature, storage & transportation), hospitals and health professionals for their delivery. The LecA protein was expressed in transgenic chloroplasts of Nicotiana tabacum var. Petit havana by transforming the chloroplast genome using the LecA gene (1755 bp) by homologous recombination. The pLD-CtV has trnI and trnA genes that are used as flanking sequences for homologous recombination and the constitutive 16s rRNA promoter to regulate transcription. The aadA gene conferring spectinomycin resistance has been used for selection and gene10 regulatory sequence from T7 bacteriophage to enhance translation. The chloroplast integration of LecA was confirmed by PCR and Southern blot analysis. The expression of LecA protein in transgenic chloroplasts was analyzed by immunoblot analysis using anti-LecA antibodies. Maximum expression levels of LecA up to 6.3 % of the total soluble protein were observed in the old leaves. The evaluation of the immune response in animal model is underway. This is the first report of expression of LecA in a plant system.