Multivalency Beats Complexity: A Study on the Cell Uptake of Carbohydrate Functionalized Nanocarriers to Dendritic Cells.

Herein, we report the synthesis of carbohydrate and glycodendron structures for dendritic cell targeting, which were subsequently bound to hydroxyethyl starch (HES) nanocapsules prepared by the inverse miniemulsion technique. The uptake of the carbohydrate-functionalized HES nanocapsules into immature human dendritic cells (hDCs) revealed a strong dependence on the used carbohydrate. A multivalent mannose-terminated dendron was found to be far superior in uptake compared to the structurally more complex oligosaccharides used.

Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention.

Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy-protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy-protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins.

A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles through in Situ-Generated Acylazirines.

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced in situ formation of acylazirines combined with a subsequent cobalt(II)-catalyzed ring expansion with 1,3-diketones.

An attempt to estimate the minimal number of Poles infected and treated for malaria in Poland and abroad.

Background: Malaria is one of the three most dangerous infectious diseases in the world. According to official statistics, there are a few dozen cases in Poland annually while the number of Poles treated abroad or self-treating remains unknown. Poland has been declared to be malaria-free since 1963 and nowadays all cases are imported.

Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins.

Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections.

[Immune tolerance mechanisms--brief review].

The purpose of the immune system is not only to fight off pathogens but also to keep a tolerance to self-antigens. In central tolerance, major mechanisms include apoptosis (for T cells) and receptor editing (for B cells). Regulatory T cells appear to be the most important in peripheral tolerance.

Chemoenzymatic synthesis of functional sialyl Lewis(x) mimetics with a heteroaromatic core.

Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide.

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

Background: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected.

[Primary selective IgM deficiency--forgotten primary immunodeficiency?].

Immunoglobulin M is a pentamer found in the intravascular compartment and on the surface of B lymphocytes. It is the antibody isotype produced initially in the immune response, and the first immunoglobulin class to be synthesized by a fetus or newborn. IgM antibodies do not cross the placenta.

T lymphocytes and NK cells in X-linked agammaglobulinemia.

Seven boys with diagnosis of X-linked agammaglobulinemia on regular substitution of immunoglobulins were included into study. The patients showed episodes of infections but the clinical course was mild with good response to antibiotics. All patients developed, with time, the chronic sinusitis with proliferation of mucous membrane, two patients showed bronchiectases.

Haploinsufficiency at the human IFNGR2 locus contributes to mycobacterial disease.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the known genetic etiologies of which impair the production of, or the response to interferon-gamma (IFN-γ). We report here a patient (P1) with MSMD whose cells display mildly impaired responses to IFN-γ, at levels, however, similar to those from MSMD patients with autosomal recessive (AR) partial IFN-γR2 or STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed only one candidate variation for both MSMD-causing and IFN-γ-related genes.

Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues.

A shot in the arm for cancer treatment: two MUC1 tetanus toxoid vaccines were synthesized and induced a strong immune response in mice. The antibodies elicited by the vaccines show a high selectivity for the tumor cells in mammary carcinoma tissues and also distinguish between tumor tissues at different stages.

[Mechanisms of immunoglobulins activity].

Intravenous immunoglobulin (IVIG) products are derived from plasma pools of thousands of healthy donors. These immunoglobulin concentrates contain large number of antibodies as well trace levels various other immunologically active molecules. Therapeutic Ig formulations contain intact IgG molecules, with variable amounts of monomeric and dimeric form existing in a dynamic equilibrium.

Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients.

We have studied the effect of intravenous immunoglobulins (IVIG) on monocyte subpopulations and cytokine production in patients with CVID. The absolute number of CD14(+)CD16(++) monocytes decreased on average 2.5-fold 4h after IVIG and after 20h returned to the baseline.

Dengue antibodies in Polish travellers returning from the tropics. Evaluation of serological tests.

Dengue is a viral disease caused by an RNA virus of the genus Flavivirus, family Flaviviridae, occurring as four serotypes (DEN-1, -2, -3, -4). It is transmitted to humans by the Aedes mosquitoes, mainly A. aegypti.

The B-cell compartment in the peripheral blood of children with different types of primary humoral immunodeficiency.

The aim of this study was to evaluate the B-cell compartment in the peripheral blood of children with different types of hypogammaglobulinemia: common variable immunodeficiency (CVID), transient hypogammaglobulinemia of infancy (THI), and selective IgA deficiency (SIgAD). We analyzed by flow cytometry the changes in the B-cell subsets with age and showed that children with an early-onset CVID develop similar pattern of B-cell subsets as adult patients with CVID with age, as the levels of memory B cells (CD19/CD27) and class-switched memory B cells (CD19/CD27/IgD/IgM), in contrast to age-matched control group, did not increase with age. Children with SIgAD displayed similar changes as patients with CVID only within the class-switched memory B-cell subpopulation.

Sulfated and non-sulfated glycopeptide recognition domains of P-selectin glycoprotein ligand 1 and their binding to P- and E-selectin.

Total synthesis through block glycosylation and selective chemical O-sulfation of tyrosine residues yielded the glycopeptide recognition domain A (X=SO(3) (-)) of the P-selectin glycoprotein ligand 1, in which the terminal sialic acid of the complex hexasaccharide side chain was replaced by (S)-cyclohexyl lactic acid. In binding assays the O-sulfated structure A showed high affinity towards P-selectin, the non-sulfated towards E-selectin.

Rapid full engraftment and successful immune reconstitution after allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in Omenn syndrome.

OS is a variant of SCID characterized by generalized erythroderma, alopecia, eosinophilia, and elevated IgE levels. It is fatal unless treated with allogeneic HSCT, which is the only curative approach. However, treatment related complications and graft rejection are major obstacles to the success of treatment.

A false expression of CD8 antigens on CD4+ T cells in a routine flow cytometry analysis.

The two-colour flow cytometry method applied in a routine enumeration of peripheral blood T lymphocyte subsets reveals that in some patients the entire population of CD4+ lymphocytes seems to express CD8 determinants as well. However, expression of the CD8 antigens on the cell surface is much lower in comparison with typical CD8+ cells. Moreover, in one-colour staining with an anti-CD8 antibody, cells with weak CD8 expression are not observed and only one typical population of CD8+ lymphocytes is seen.

Sepsis caused by Veillonella parvula infection in a 17-year-old patient with X-linked agammaglobulinemia (Bruton's disease).

A case of a male, 17-year-old, X-linked agammaglobulinemia patient with bacteremia caused by Veillonella parvula, without a defined primary site of infection, is presented. The report demonstrates that V. parvula should not be regarded as a nonpathogenic microorganism, at least not in patients with certain forms of immunodeficiency disease.

The expression of CD40 on monocytes of children with primary humoral immunodeficiencies.

The interactions between CD40 and CD40L (CD154) are critical for effective humoral immune response. CD40 signaling facilitates T lymphocyte dependent B cell proliferation and immunoglobulin isotype switch. The objective of our study was to investigate the CD40 and CD40L expression on peripheral blood mononuclear cells (PBMC) of children with symptomatic transient hypogammaglobulinemia (THI), common variable immunodeficiency (CVID) and selective IgA deficiency (SIgAD).