The ectonucleotidases CD39 and CD73 degrade immune stimulatory ATP to adenosine that inhibits T and NK cell responses via the A(2A) adenosine receptor (ADORA2A). This mechanism is used by regulatory T cells (T(reg)) that are associated with increased mortality in OvCA. Immunohistochemical staining of human OvCA tissue specimens revealed further aberrant expression of CD39 in 29/36 OvCA samples, whereas only 1/9 benign ovaries showed weak stromal CD39 expression. CD73 could be detected on 31/34 OvCA samples. While 8/9 benign ovaries also showed CD73 immunoreactivity, expression levels were lower than in tumour specimens. Infiltration by CD4(+) and CD8(+) T cells was enhanced in tumour specimens and significantly correlated with CD39 and CD73 levels on stromal, but not on tumour cells. In vitro, human OvCA cell lines SK-OV-3 and OaW42 as well as 11/15 ascites-derived primary OvCA cell cultures expressed both functional CD39 and CD73 leading to more efficient depletion of extracellular ATP and enhanced generation of adenosine as compared to activated T(reg). Functional assays using siRNAs against CD39 and CD73 or pharmacological inhibitors of CD39, CD73 and ADORA2A revealed that tumour-derived adenosine inhibits the proliferation of allogeneic human CD4(+) T cells in co-culture with OvCA cells as well as cytotoxic T cell priming and NK cell cytotoxicity against SK-OV3 or OAW42 cells. Thus, both the ectonucleotidases CD39 and CD73 and ADORA2A appear as possible targets for novel treatments in OvCA, which may not only affect the function of T(reg) but also relieve intrinsic immunosuppressive properties of tumour and stromal cells.

In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food allergy. Subcutaneous, epicutaneous, intralymphatic, oral and sublingual protocols of AIT exist. In animals, most data are available in dogs where subcutaneous AIT is an accepted treatment for atopic dermatitis. Initiating a regulatory response and a production of "blocking" IgG antibodies with AIT are similar mechanisms in human beings and dogs with allergic diseases. Although subcutaneous immunotherapy is used for atopic dermatitis in cats, data for its efficacy are sparse. There is some evidence for successful treatment of feline asthma with AIT. In horses, most studies evaluate the effect of AIT on insect hypersensitivity with conflicting results although promising pilot studies have demonstrated the prophylaxis of insect hypersensitivity with recombinant antigens of biting midges (Culicoides spp.). Optimizing AIT using allergoids, peptide immunotherapy, recombinant allergens and new adjuvants with the different administration types of allergen extracts will further improve compliance and efficacy of this proven treatment modality.

Cytokine secretion and degranulation represent key components of CD8(+) T-cell cytotoxicity. While transcriptional blockade of IFN-γ and inhibition of degranulation by TGF-β are well established, we wondered whether TGF-β could also induce immune-regulatory miRNAs in human CD8(+) T cells. We used miRNA microarrays and high-throughput sequencing in combination with qRT-PCR and found that TGF-β promotes expression of the miR-23a cluster in human CD8(+) T cells. Likewise, TGF-β up-regulated expression of the cluster in CD8(+) T cells from wild-type mice, but not in cells from mice with tissue-specific expression of a dominant-negative TGF-β type II receptor. Reporter gene assays including site mutations confirmed that miR-23a specifically targets the 3'UTR of CD107a/LAMP1 mRNA, whereas the further miRNAs expressed in this cluster-namely, miR-27a and -24-target the 3'UTR of IFN-γ mRNA. Upon modulation of the miR-23a cluster by the respective miRNA antagomirs and mimics, we observed significant changes in IFN-γ expression, but only slight effects on CD107a/LAMP1 expression. Still, overexpression of the cluster attenuated the cytotoxic activity of antigen-specific CD8(+) T cells. These functional data thus reveal that the miR-23a cluster not only is induced by TGF-β, but also exerts a suppressive effect on CD8(+) T-cell effector functions, even in the absence of TGF-β signaling.

Emergence of multidrug resistant bacteria has made the search for novel bioactive compounds from natural and unexplored habitats a necessity. have important bioactive substances. The present study investigated antimicrobial activity of isolated from soil samples of Egypt. One hundred samples were collected from agricultural farming soil of different governorates. Twelve isolates have produced activity against the tested microorganisms (, ,, ,, Typhi,, and). By VITEK 2 system version: 07.01 the 12 isolates were identified as ,, , and . Using ethyl acetate extraction method the isolates culture's supernatants were tested by diffusion method against indicator microorganisms. These results indicate that isolated from Egypt farms could be sources of antimicrobial bioactive substances.

Adverse reactions to insects occur in both human and veterinary patients. Systematic comparison may lead to improved recommendations for prevention and treatment in all species. In this position paper, we summarize the current knowledge on insect allergy induced via stings, bites, inhalation or ingestion, and compare reactions in companion animals to those in people. With few exceptions, the situation in human insect allergy is better documented than in animals. We focus on a review of recent literature and give overviews of the epidemiology and clinical signs.We discuss allergen sources and allergenic molecules to the extent described, and aspects of diagnosis, prophylaxis, management and therapy. K E Y W O R D S allergenic molecules in insects, comparative, insect bite hypersensitivity, insect food allergy, insect venom allergy Abbreviations: BAT, basophil activation test; CCD, cross-reactive carbohydrate determinant; CRD, component-resolved diagnosis; DBPCFC, double-blind placebo-controlled food challenge; FBH, flea bite hypersensitivity; HDM, house dust mite; IBH, insect bite hypersensitivity; IGR, insect growth regulator; LLR, large local reaction; MBH, mosquito bite hypersensitivity; RAST, radioallergosorbent test; VIT, venom immunotherapy.