Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection

Regulatory T cell responses to infectious organisms influence not only immunity and immunopathology, but also responses to bystander antigens. Mice infected with the gastrointestinal nematode parasite Heligmosomoides polygyrus show an early Th2-dominated immune response (days 7–14), but by day 28 a strongly regulatory profile is evident with antigen-specific IL-10 release and elevated frequency of CD4+ T cells bearing surface TGF-β. CD4+CD25+ T cells from infected mice show enhanced capacity to block in vitro effector T cell proliferation. CD4+CD25+ cell numbers expand dramatically during infection, with parallel growth of both CD25+Foxp3+ and CD25+Foxp3– subsets. CTLA-4 and glucocorticoid-induced tolerance-associated receptor, also associated with regulatory T cell function, become more prominent, due to both expanded CD25+ cell numbers and increased expression among the CD25– population. Both intensity and frequency of CD103 expression by CD4+ T cells rise significantly, with greatest expansion among CD25+Foxp3+ cells. While TGF-β expression is observed among both CD25+Foxp3+ and CD25+Foxp3– subsets, it is the latter population which shows higher TGF-β staining following infection. These data demonstrate in a chronic helminth infection that Foxp3+ regulatory T cells are stimulated, increasing CD103 expression in particular, but that significant changes occur to other populations including expansion of CD25+TGF-β+Foxp3– cells, and induction of CTLA-4 on CD25– non-regulatory lymphocytes

TGF-β in tolerance, development and regulation of immunity

AbstractThe TGF-β superfamily is an ancient metazoan protein class which cuts across cell and tissue differentiation, developmental biology and immunology. Its many members are regulated at multiple levels from intricate control of gene transcription, post-translational processing and activation, and signaling through overlapping receptor structures and downstream intracellular messengers. We have been interested in TGF-β homologues firstly as key players in the induction of immunological tolerance, the topic so closely associated with Ray Owen. Secondly, our interests in how parasites may manipulate the immune system of their host has also brought us to study the TGF-β pathway in infections with longlived, essentially tolerogenic, helminth parasites. Finally, within the spectrum of mammalian TGF-β proteins is an exquisitely tightly-regulated gene, anti-Müllerian hormone (AMH), whose role in sex determination underpins the phenotype of freemartin calves that formed the focus of Ray’s seminal work on immunological tolerance

The hunters of nature treasures. The Nobel prize in physiology or medicine 2015

W 2015 r. Nagrodę Nobla w dziedzinie fizjologii i medycyny przyznano za opracowanie terapii przeciw chorobom tropikalnym, malarii i filariozom. Youyou Tu z Chin, specjalistka w dziedzinie farmakologii naturalnej, została nagrodzona za wskazanie artemizyniny w roślinie Artemisia annuata, jako leku hamującego namnażanie się zarodźca malarycznego w krwi człowieka. Satoshi Omura, mikrobiolog z Japonii i William Campbell amerykański biochemik i parazytolog, pochodzący z Irlandii, zostali nagrodzeni za zidentyfikowanie i wyizolowanie awermektyny ze szczepu bakterii Stretomyces avermicilis produkującego związek o silnej aktywności przeciwnicieniowej. Zastosowanie artemizyniny i iwermektyny ocaliło życie milionów dzieci w Afryce oraz zahamowało szerzenie się filarioz, groźnych chorób przyczyniających się do utraty wzroku i deformujących ciało ludzkie. W artykule omówiono historię odkrycia i mechanizm działania leków. Wprowadzenie globalnych programów leczenia w krajach tropikalnych przyczynia się do poprawy sytuacji ekonomicznej i społecznej na obszarach, na których choroby te dzięki lekom są coraz rzadziej notowane.The Nobel Prize in Physiology or Medicine 2015 was awarded to Youyou Tu "for her discoveries concerning a novel therapy against Malaria", and William C. Campbell and Satoshi Ōmura "for their discoveries concerning a novel therapy against infections caused by roundworm parasites". Chinese pharmacologist - Tu, identified artemisinin isolated from Artemisia annuata for inhibition of malaria development in the blood of man. Omura, microbiologist from Japan and William C. Campbell, biochemist and parasitologist from USA discovered anti-nematode activity of awermectin, extracted from bacteria Streptomyces avermicilis. Administration of drugs against malaria and filariasis salvaged millions lives, and reduced transmission of pathogens responsible for the lost vision and disability in Africa, Asia and Latin America. The history of the discoveries and mechanisms of drugs action are presented. International programs for the health introduced at the global scale have improved economic and social conditions in countries where diseases due to the treatment develop less frequently

The problem of using new technologies in museology, with particular emphasis on VR and AR technologies.

W pracy magisterskiej podjęta zostaje problematyka wykorzystania nowych technologii we współczesnym muzealnictwie. Poprzez analizę różnych projektów, powstałych w ostatniej dekadzie, wykorzystujących technologie wirtualnej oraz rozszerzonej rzeczywistości przedstawiam aktualne sposoby muzeów na urozmaicenie swojej oferty dla zwiedzających. Oprócz przedstawienia konkretnych rozwiązań praca zawiera również części dotyczące rozważań na temat konieczności wprowadzania takich rozwiązań do współczesnych muzeów, ich zalet oraz wad, w tym możliwość zastąpienia sztuki rzeczywistej poprzez jej cyfrowe odpowiedniki.The master thesis deals with the use of new technologies in contemporary museology. Through the analysis of various projects developed in the last decade, using virtual and augmented reality technologies, I present the current methods of museums to diversify their offer for visitors. In addition to presenting specific solutions, the work also contains parts concerning the need to introduce such solutions to contemporary museums, their advantages and disadvantages, including the possibility of replacing real art with its digital equivalents

Genetyczne aspekty odporności owiec na inwazje nicieni żołądkowo-jelitowych

The current control of parasitic diseases has been based on anthelmintic drug treatment. In the light of increasing occurrence of anthelmintic-resistant strains of parasites and lack of effective vaccines against gastrointestinal nematodes, the genetic selection of resistant animals seems to be very promising. Taking into account the fact that the immune response is under genetic control, an understanding of the processes involved in the development of adaptive immunity to infections will contribute to better understanding of variabilities in susceptibility and pathology of helminth infection

EFFECT OF KETOTIFEN ON THE IMMUNE RESPONSE IN BALB/C MICE INFECTED WITH TRICHINELLA SPIRALIS

Infection with Trichinella spiralis in mice generates Th-2 mediated response, which controls effector mechanism operating in the intestine. It is associated with a pronounced intestinal mastocytosis, eosinophilia and destruction of intestinal epithelial layer during expulsion of parasite from the gut. It is believed that protection is dependent on non-specific inflammatory reaction mediated by mast cells. Furthermore, the higher serum levels of parasite specific IgG1 and IgG2a and also mucosal IgA response were related to the course of infection. Inhibition of humoral and cellular immune responses using ketotifen as anti-allergic compound, resulted in the greater worm burden and worm size, but not in the significant prolongation of intestinal phase. Moreover, in treated mice epithelial layer of the gut was protected from destruction provoked by the nematode. As interaction between effector leukocytes and antibodies were not effective it was proposed that other mechanisms, not related to hypersensitivity or conventional inflammatory response regulated the level of infection. The immunological and physiological phenomenons are discussed in terms of events associated with protection to the parasite. Possibly, immunoregulatory capasity of the nematode is involved in the induction of multiple mechanisms operated during infection