Preliminary results on the effects of CD40/CD40L interactions and SAC-induction on IFN-gamma expression in human schistosomiasis

In this communication the authors analyzed the pattern of expression of IFN-gamma as a surrogate type 1 response in different clinical forms of schistosomiasis in response to stimulation involving T-cell dependent and T-cell independent pathways, to investigate which pathways were functional in human schistosomiasis, and to further characterize the nature of Th1 response impairment in this parasitic disease.

Immunodéficience commune variable: ce qu'il faut savoir [Common variable immune deficiency: what you need to know].

Common variable immune deficiency is the most frequent primary immune deficiency, characterized mainly by a disorder of B lymphocytes differentiation and a deficit in immunoglobulins. The clinical manifestations include recurrent infections, non-infectious lung and digestive involvements, autoimmune diseases, and an increased susceptibility to cancers. Recent breakthroughs have been made in the understanding of some genetic mechanisms of the disease. Replacement therapy with intravenous immunoglobulins remains the treatment of choice, which allows significant improvement in the survival and quality of life. However progress should be made in the understanding of the pathophysiology and in the early detection of this disease, since a delay in the diagnosis may have harmful consequences in terms of morbidity and mortality.

Genetic and environmental components of phenotypic variation in immune response and body size of a colonial bird, Delichon urbica (the house martin).

Directional selection for parasite resistance is often intense in highly social host species. Using a partial cross-fostering experiment we studied environmental and genetic variation in immune response and morphology in a highly colonial bird species, the house martin (Delichon urbica). We manipulated intensity of infestation of house martin nests by the haematophagous parasitic house martin bug Oeciacus hirundinis either by spraying nests with a weak pesticide or by inoculating them with 50 bugs. Parasitism significantly affected tarsus length, T cell response, immunoglobulin and leucocyte concentrations. We found evidence of strong environmental effects on nestling body mass, body condition, wing length and tarsus length, and evidence of significant additive genetic variance for wing length and haematocrit. We found significant environmental variance, but no significant additive genetic variance in immune response parameters such as T cell response to the antigenic phytohemagglutinin, immunoglobulins, and relative and absolute numbers of leucocytes. Environmental variances were generally greater than additive genetic variances, and the low heritabilities of phenotypic traits were mainly a consequence of large environmental variances and small additive genetic variances. Hence, highly social bird species such as the house martin, which are subject to intense selection by parasites, have a limited scope for immediate microevolutionary response to selection because of low heritabilities, but also a limited scope for long-term response to selection because evolvability as indicated by small additive genetic coefficients of variation is weak.

Additives and Protein-DNA Combinations Modulate the Humoral Immune Response Elicited by a Hepatitis C Virus Core-encoding Plasmid in Mice

Humoral and cellular immune responses are currently induced against hepatitis C virus (HCV) core following vaccination with core-encoding plasmids. However, the anti-core antibody response is frequently weak or transient. In this paper, we evaluated the effect of different additives and DNA-protein combinations on the anti-core antibody response. BALB/c mice were intramuscularly injected with an expression plasmid (pIDKCo), encoding a C-terminal truncated variant of the HCV core protein, alone or combined with CaCl2, PEG 6000, Freund's adjuvant, sonicated calf thymus DNA and a recombinant core protein (Co.120). Mixture of pIDKCo with PEG 6000 and Freund's adjuvant accelerated the development of the anti-core Ab response. Combination with PEG 6000 also induced a bias to IgG2a subclass predominance among anti-core antibodies. The kinetics, IgG2a/IgG1 ratio and epitope specificity of the anti-core antibody response elicited by Co.120 alone or combined with pIDKCo was different regarding that induced by the pIDKCo alone. Our data indicate that the antibody response induced following DNA immunization can be modified by formulation strategies.

Visualizing anti-tumor immune responses in vivo.

Real-time imaging of stromal and immune cells in tumors is an emerging field that will greatly help us to understand the role of these non-malignant tumor components in tumor progression and therapy.

Neuroendocrine Tumors (NETs): A population-based study of incidence and survival in Girona province, 1994-2004

Els tumors neuroendocrins (TNEs) són un grup de neoplàsies poc freqüents i heterogènies i amb un ampli espectre d’agressivitat. Hi ha molt poca informació epidemiològica a nivell mundial, l’objectiu d’aquest estudi ha estat el de reportar-ne les dades a la província de Girona. Hem inclòs tots els codis de la ICD-O3 que codifiquen un TNE, període 1994-2002. Hem identificat 698 tumors. Es reporten les dades tant de la casuística com les taxes d’incidència i supervivència de cada TNE per separat. Els resultats són consistents amb les publicacions europees. El fet d’haver reportat la incidència i la supervivència dels TNEs a Girona contribueix a un millor coneixement d’aquestes neoplàsies.

Schistosoma mansoni heat shock protein 70 elicits an early humoral immune response in S. mansoni infected baboons

A study was undertaken to search for DNA recombinant Schistosoma mansoni proteins responsible for eliciting an antibody response from the host at a very early phase after infection. A S. mansoni adult worm cDNA expression library was screened using pooled sera from baboons with four weeks of infection. Based on their specific reactivity with the S. mansoni infected sera and no reactivity when tested against the pre-infection sera from the same baboons, four clones were selected for further studies. Sequence analysis revealed that they were homologous to the S. mansoni heat shock protein 70 (hsp70). The insert sizes of the four selected clones varied from 1150 to 2006 bp. The preliminary characterization for antibody reactivity against a panel of baboon sera showed that the longest clone was the most reactive, eight out of eight acute and three out of four chronic sera reacting positively to this clone. The shortest clone was the least reactive. Our results suggest that the S. mansoni hsp70 elicits an early and strong antibody response in baboons and that antibodies to this protein can be detected in chronically infected animals. Therefore S. mansoni hsp70 may be a valid target for immunodiagnosis. However further studies are needed to identify the portion of the hsp70 that best fits the requirements for a valuable diagnostic antigen.

Humoral immune responses induced by Kudoa sp. (Myxosporea: Multivalvulida) antigens in BALB/c mice

The majority of Kudoa species infect the somatic muscle of fish establishing cysts. As there is no effective method to detect infected fish without destroying them these parasited fish reach the consumer. This work was developed to determine whether this parasite contains antigenic compounds capable of provoking an immune response in laboratory animals, in order to consider the possible immunopathological effects in man by the ingestion of Kudoa infected fish. BALB/c mice were injected by the subcutaneous route with the following extracts suspended in aluminium hydroxide: group 1 (black Kudoa sp. pseudocyst extract), group 2 (white Kudoa sp. pseudocyst extract), and group 3 (non-infected hake meat extract). Specific antibody levels were measured by ELISA against homologous and heterologous antigens. The highest responses were obtained from the black Kudoa sp. pseudocyst extract (group 1).The low optic density levels detected in group 3 proved that the results obtained in groups 1 and 2 were a consequence of the parasitic extract injection. The IgG1 was the predominant subclass. IgE detected in groups 1 and 2 showed the possible allergenic nature of some of the components of the parasitic extract. High IgA levels and medium IgG2a and IgG3 levels were obtained in groups 1 and 2. Low IgG2b responses were shown. No cross-reactions between Kudoa sp. pseudocyst extracts and the non-infected hake meat extract were observed.

Effects of corticosterone on innate and humoral immune functions and oxidative stress in barn owl nestlings.

The costs of coping with stressful situations are traded-off against other functions such as immune responses. This trade-off may explain why corticosterone secretion reduces immune reactions. Corticosterone differentially affects various immunity components. However, which component is suppressed varies between studies. It remains unclear whether the trade-off in energy, nutrition, autoimmunity or oxidative stress accounts for differential immunosuppression. In this study, we investigated whether corticosterone differentially affects the constitutive innate and humoral acquired immunity. We used barn owl nestlings, implanting 50% with a corticosterone-releasing pellet and the other 50% with a placebo pellet. To measure the effect on humoral immunity we vaccinated 50% of the corticosterone-nestlings and 50% of the placebo-nestlings with the antigens 'Tetravac' and the other 50% were injected with PBS. To assess the costs of elevated corticosterone, we measured body mass and resistance to oxidative stress. Administration of corticosterone increased corticosterone levels whereas vaccination induced the production of antibodies. Corticosterone reduced the production of antibodies, but it did not significantly affect the constitutive innate immunity. Corticosterone reduced body growth and resistance to oxidative stress. Under stressful conditions barn owl nestlings seem to keep the constitutive innate immunity, whereas elevated corticosterone levels negatively affected inducible immune responses. We found evidence that mounting a humoral immune reaction is not costly in terms of growth, but reduces the resistance to oxidative stress independently of corticosterone administration. We suggest that humoral immunity is suppressed because the risk of immunopathologies may be disproportionately high when mounting an antibody response under stressful situations.

Disease-driven T cell activation predicts immune responses to vaccination against melanoma.

Tumor vaccines may induce activation and expansion of specific CD8 T cells which can subsequently destroy tumor cells in cancer patients. This phenomenon can be observed in approximately 5-20% of vaccinated melanoma patients. We searched for factors associated with T cell responsiveness to peptide vaccines. Peptide antigen-specific T cells were quantified and characterized ex vivo before and after vaccination. T cell responses occurred primarily in patients with T cells that were already pre-activated before vaccination. Thus, peptide vaccines can efficiently boost CD8 T cells that are pre-activated by endogenous tumor antigen. Our results identify a new state of T cell responsiveness and help to explain and predict tumor vaccine efficacy.

Highly diverse TCRα chain repertoire of pre-immune CD8(+) T cells reveals new insights in gene recombination.

Although the T-cell receptor αδ (TCRαδ) locus harbours large libraries of variable (TRAV) and junctional (TRAJ) gene segments, according to previous studies the TCRα chain repertoire is of limited diversity due to restrictions imposed by sequential coordinate TRAV-TRAJ recombinations. By sequencing tens of millions of TCRα chain transcripts from naive mouse CD8(+) T cells, we observed a hugely diverse repertoire, comprising nearly all possible TRAV-TRAJ combinations. Our findings are not compatible with sequential coordinate gene recombination, but rather with a model in which contraction and DNA looping in the TCRαδ locus provide equal access to TRAV and TRAJ gene segments, similarly to that demonstrated for IgH gene recombination. Generation of the observed highly diverse TCRα chain repertoire necessitates deletion of failed attempts by thymic-positive selection and is essential for the formation of highly diverse TCRαβ repertoires, capable of providing good protective immunity.

Cellular immune responses and disease control in acute AIDS-associated Kaposi's sarcoma.

Kaposi's sarcoma-associated herpesvirus (KSHV) specific T cell responses and KSHV viremia were analyzed in seven HIV-infected patients with active Kaposi's sarcoma lesions who initiated highly active antiretroviral therapy, and were compared between patients with improved Kaposi's sarcoma and those with progressive Kaposi's sarcoma requiring further systemic chemotherapy. Patients with controlled Kaposi's sarcoma disease demonstrated undetectable Kaposi's sarcoma viremia together with KSHV-specific CD8 T cells secreting interferon-gamma and tumor necrosis factor-alpha, whereas progressors showed increasing viremia with weak or no T-cell responses. These data point toward a potential role of KSHV-specific immunity in the control of AIDS-associated Kaposi's sarcoma.

Whole blood assay to access T cell-immune responses to Mycobacterium tuberculosis antigens in healthy Brazilian individuals

The production of interferon gamma (IFNgamma) guarantees effective T cell-mediated immunity against Mycobacterium tuberculosis infection. In the present study, we simply compare the in vitro immune responses to Mycobacterium antigens in terms of IFNg production in a total of 10 healthy Brazilian volunteers. Whole blood and mononuclear cells were cultivated in parallel with PPD, Ag85B, and M. bovis hsp65, and five-days supernatants were harvested for cytokine detection by ELISA. The inter-assay result was that the overall profile of agreement in response to antigens was highly correlated (r² = 0.9266; p = 0.0102). Potential analysis is in current progress to dictate the usefulness of this method to access the immune responses also in tuberculosis patients and its contacts.

Immune monitoring design within the developmental pipeline for an immunotherapeutic or preventive vaccine

Immunotherapy is defined as the treatment of disease by inducing, enhancing, or suppressing an immune response, whereas preventive vaccination is intended to prevent the development of diseases in healthy subjects. Most successful prophylactic vaccines rely on the induction of high titers of neutralizing antibodies. It is generally thought that therapeutic vaccination requires induction of robust T-cell mediated immunity. The diverse array of potential or already in use immunotherapeutic and preventive agents all share the commonality of stimulating the immune system. Hence, measuring those vaccination-induced immune responses gives the earliest indication of vaccine take and its immune modulating effects.