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

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

Genetyczne aspekty odpornosci owiec na inwazje nicieni zoladkowo-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

Regulacja reakcji obronnej i alergicznej w inwazjach pasozytow

Cytokines regulate development, differentiation and expression of effector function of the immune system. The profile of immune reactions depends on cytokine contents at the recognition of parasite. However, parasites themselves can modify immunological events and favourite these, which allow them to survive. The host immune defence can be transformed into the chronic reaction. Inflammatory reactions result from the recruitment of different cells, to the site where worms are localised. The eosinophil and mast cell migration preferentially is induced. These cells play also a major role in immediate allergic responses. Mast cells can bind allergenspecific IgE to their RcεRI, the high affinity receptor for IgE. Eosinophils, through their receptors for IgGl, IgG2, IgA and IgE are mainly involved in the cytotoxic reaction directed against parasites. Crosslinking of these receptors by antigen binding will lead to subsequent release of stored mediators and cytokines. Granular materials released from mast cell accelerate inflammatory reaction and in the case of intestinal worm parasites may be involved in the expulsion phenomenon. However these cells may also induce Th2 related immunological response because they produce and release of IL-4. Eosinophils are required into the tissue and release cytotoxic and stress proteins including reactive oxygen species. Parasites are destroyed but accelerated reaction results in the destruction of host proteins and cells. Antibodies, cytokines, chemokines and adhesion molecules are essential for elevation of defence against parasites. The role of cytokines, emphasizing IL-5, and function of eosinophils, mast cells and IgE are discussed in terms of induction and effector mechanisms during parasite infections