Peptide vaccines for cancer therapy.

For around four decades, vaccines of different kinds have been developed to treat different types of cancer. However, promising results encountered in the early phase contrasted with the results recorded in clinical studies. Recent discoveries in the vaccine field, adjuvants and delivery systems, and antigen presentation have lead to new patented approaches. The current review is focused on general description of peptide vaccines involving cancer antigen presentation, specific immune response, cell death dependent pathways, and target therapy for modified or mutated oncogenes. A rapid evolving research in the area may evolve in fruitful outcomes in the near future.

Asociación del polimorfismo del gen ICOS (c.1564 t/c) con hepatitis autoinmune tipo 1 en población mestiza venezolana / Association of icos (c.1564 T/C) gene poymorphims with autoimmune hepatitis type 1 in Venezuelan mestizo population)

Introducción: Un evento inmunopatológico característico en la hepatitis autoinmune (HAI) es la activación prolongada de la respuesta Th1. Diferentes promotores genéticos pueden predisponer a esta activación provocando ruptura de la inmunotolerancia. Uno de estos promotores es ICOS perteneciente a la familia de CD28, moléculas involucradas en funciones que regulan las respuestas Th1 y Th2 previniendo la activación prolongada de la respuesta Th1. Objetivo: Determinar el polimorfismo del gen ICOS (c.1564 T/C) en pacientes mestizos venezolanos con HAI tipo 1 y su posible asociación con la expresión clínica. Materiales y Métodos: Se investigaron 70 pacientes con HAI tipo 1 y 121 individuos sanos, ambos grupos venezolanos de tercera generación. La determinación del polimorfismo se realizó mediante reacción en cadena de la polimerasa (PCR) seguida por polimorfismos en la longitud de los fragmentos de restricción (RFLP). Resultados: El alelo silvestre T fue el más frecuente tanto en pacientes como en controles siendo mayor en el segundo grupo (60,7% vs 70,4%; p=0,05; pc=ns OR 1,45 p<0,05). El alelo mutado C se observó más en los pacientes con respecto al grupo control (39,3% vs 29,6%; p=0,05; pc=ns OR 1,45 (p<0,05). En las frecuencias genotípicas, se demostraron los genotipos heterocigotos (T/C) y homocigotos para el alelo mutado (C/C) más prevalentes en el grupo de pacientes que en controles y el genotipo silvestre T/T más frecuente en controles que en pacientes siendo estas diferencias significativas al 10% (χ2=5,31;2GL;p=0,07); OR 2,08 (p<0,05). Los pacientes con el genotipo heterocigoto demostraron niveles más elevados de globulinas, de IgG y mayor presencia de anticuerpos anti-mitocondriales que los observados en el genotipo T/T con diferencia estadística significativa al 10%. Además, se observa menor presencia de anticuerpos antinucleares en el genotipo T/C vs. T/T (p<0,10; pc=ns). Conclusiones: En el estudio del polimorfismo del gen ICOS (c.1564 T/C) los genotipos heterocigoto T/C y homocigoto mutado C/C son más frecuentes en pacientes mestizos venezolanos con HAI tipo 1 que en controles con riesgo significativo. Este polimorfismo se asocia a ciertas variables inmunodiagnósticas.

Introduction: A characteristic immunopathological event in autoinmune hepatitis (AIH) type 1 is the prolonged activation of Th1 response. Different promoters might predispose to this activation inducing immunotolerance breaking. ICOS is one of these promoters which belong to CD28 family, molecules involved in Th1 and Th2 regulating functions to prevent Th1 longer activation. Objective: To determine gen ICOS (c.1564 T/C) polymorphism in Venezuelan mestizo patients with AIH type 1 and its possible association with clinical expression. Materials and Methods: Seventy patients with AIH type 1 and 121 healthy individuals, both third generation Venezuelan groups, were investigated. Polymorphism determination was performed by polymerase chain reaction (PCR) following by restriction fragments longitudinal polymorphisms (RFLP). Results: The most frequent allele was wild T either in patients and controls, being higher in the second group (60,7% vs. 70,4%; p=0,05; pc=ns OR 1,45 p<0,05). The mutant C allele was observed more in patients than controls (39,3% vs. 29,6%; p=0,05; pc=ns OR 1,45 (p<0,05). In the genotypes frequencies, heterozygote genotypes (T/C) and homozygote mutant allele (C/C) were prevalent in the patient’s group while in the control´s group the wild genotype T/T was the most frequent being these differences significantly to 10% (χ2=5,31;2GL;p=0,07); OR 2,08 (p<0,05). Compared to the T/T genotype group, patients with heterozygote genotype shown higher levels of globulins, IgG and presence of anti-mithocondrial antibodies with a significant difference to 10%. Moreover, presence of antinuclear antibodies was less frequent in the T/C genotype vs. T/T (p<0,10; pc=ns). Conclusion: Heterozygote genotype T/C and homozygote mutant genotype C/C of gen ICOS (c.1564 T/C) with a significantly risk are more frequent in Venezuelan mestizo patients with AIH type 1 than in controls with a significantly risk. This polymorphism is associated with certain immunodiagnostic variables.

Increased number of non-invariant NKT cells and low number of circulating CD1-expressing leukocytes in patients infected with hepatitis C virus.

Natural killer T (NKT) cells represent an heterogeneous T cell population involved in host immunity against several microorganisms. They also have important immunoregulatory functions. Studies on circulating levels of NKT cells during HCV infection have been focused on the invariant NKT (iNKT) subset which recognizes the non-classical Ag-presenting molecule CD1d, with little information about the non-invariant NKT (non-iNKT) cell subset. In the present study, we assessed the number of both NKT cells subsets and the surface expression of CD1a, b, c and d isoforms in peripheral blood of 31 HCV-infected patients and 31 ages matched healthy individuals. A significant increase of circulating non-iNKT cells was observed in HCV-infected patients as compared to controls (74 ± 57 cells/µL vs 42 ± 16 cells/µL respectively, p<0.0042) with no differences in the iNKT subset. In addition, the percentage of CD1a, CD1c and CD1d-expressing leukocytes was significantly low in patients as compared to controls. These findings suggest that both components, non-iNKT cells and CD1 molecules expression are involved in the control of natural immunity against HCV.

Efecto de la proteína E2 del virus de hepatitis C sobre la activación de células NK / Effect of E2 protein of hepatitis C virus on the activation of NK cells

En estudios previos, se ha descrito un disminución de la activación y actividad citotóxica de las células NK en los pacientes infectados con hepatitis C; sin embargo, se desconoce el mecanismo por el cual éste fenómeno ocurre. En el presente reporte se estudió el efecto de la proteína E2 de la envoltura del virus o de la estimulación de su receptor con el anticuerpo anti-CD81 sobre la fosforilación de tirosinas, serinas, las enzimas: proteína quinasa C y fosfoinositol 3 quinasa, el factor de transcrición Nfkb y el intercambiador de nueclotidos VAV de células NK de controles normales estimulados con anti-CD16. Ambos, la proteína E2 y anti-CD81, combinado o por separado inducen una disminución de la fosforilación de tirosinas y serinas, así como una marcada disminución de la fosforilación de PKC, NFkB, PI3K y en menor grado VAV. Se concluye que la proteína E2 sola y en conjunto con anti-CD81 inducen señales inhibitorias responsables de la disminución en la activación de las células NK de pacientes infectados por el VHC y que éste fenómeno puede ser responsable de la cronicidad que se reporta en dicha enfermedad

The decrease in NK cell activation and cytotoxic activity in patients infected with hepatitis C virus has been described; however, the mechanism by whcih this phenomenon occurs is not known. In the present report, the effect of the E2 protein of the virus envelope or the stimulation of its receptor CD81 with the antibody anti-CD81 on the phosphorylation of tyrosines, serine, the enzymes protein kinase C, phosphoinositol kinase 3 (PI3K), the transcription factor NfkB and the nucleotide exchange protein VAV was assessed in NK cells from normal controls stimulated with anti-CD16. Both the protein E2 and anti-CD81 by themselves or combined, generated a decrease in tyrosine, serine, and a marked decrease in the phosphorylation of PKC, NfkB, PI3k and in less extent in VAV. It is concluded that the E2 protein alone and combined with anti-CD81 induce inhibitory signals responseible for the decrease in the activation of NK cells of infected HCV patients and it could be responsible for the chronicity observed in this disease

Allele and haplotype frequencies at human leukocyte antigen class I and II genes in Venezuela's population.

Population studies represent an integral part and link in understanding the complex chain of host-pathogen interactions, disease pathogenesis, and MHC gene polymorphisms. Genes of Mongoloid, Caucasoid, and Negroid populations have created a distinctive HLA genetic profile in the Venezuelan population. Our objective was to determine the predominant HLA class I and II alleles and haplotype frequencies in the hybrid population of Venezuela. The study population consisted of 486 healthy unrelated native Venezuelans and 180 families. We examined the frequency of HLA A-B-C, HLA-DQ and HLA-DR genes by polymerase chain reaction and subsequent hybridization with sequence-specific oligonucleotide probes. Phenotypic, allelic and haplotype frequencies were estimated by direct counting and using the maximum-likelihood method. The predominant HLA class I alleles were A*02, A*24, A*68, B*35, B*44, B*51, B*07, B*15 and Cw*07. Regarding HLA class II, the most frequent alleles were DQB1*03 and DRB1*04, DRB1*15, DRB1*13, DRB1*07. The prevailing haplotype was HLA-A*02B*35 DQB1*03 DRB1*04. Some of these alleles and haplotype frequencies were predominantly present in Amerindians (A*02, A*24, B*35, Cw*07, DRB1*04, A*24 B*35). Previous reports have shown high incidence of A*02, B*44, B*51, DRB1*15, DRB1*13, DRB1*07 alleles in several European populations and A*68, B*07, B*15 alleles in African Americans, which could have contributed to the ethnic admixture of the Venezuelan population. We conclude that our results provide strong evidence that Venezuela's population represents an admixture of the primitive Mongoloid Aborigines, Caucasoid Europeans and Western African Negroid migrants.

Asociación del polimorfismo del gen PTPN22 (C1858T) con hepatitis autoinmune tipo 1 en la población mestiza venezolana / Association of polymorphism of PTPN22 gene (C1858T) with type 1 autoimmune hepatitis in the Venezuelan mestizo population

Introducción: La Hepatitis Autoinmune (HAI) tipo 1 es una enfermedad hepática progresiva en la cual se demuestra susceptibilidad genética asociada a determinantes compartidos de moléculas HLA clase II. Sin embargo, 30 a 50% de estos pacientes, no asocian alelos HLA de susceptibilidad por lo que otros promotores genéticos que pudiesen predisponer a la ruptura de inmunotolerancia están siendo investigados. La Proteína Linfoide Tirosina Fosfatasa (LYP) codificada por el gen PTPN22, ejerce una potente inhibición en el linfocito T activado. El polimorfismo de este gen en la posición 1858 (sustitución de citosina (C) por una timina (T)) se describe asociada a múltiples patologías autoinmunes pero aún no se ha reportado en HAI tipo 1. Objetivo: Determinar la posible asociación del polimorfismo del gen PTPN22 en mestizos venezolanos con HAI tipo 1. Material y Métodos: Nuestra población consistió de 62 pacientes con HAI tipo 1 y 107 individuos sanos, ambos grupos venezolanos de tercera generación. La determinación del polimorfismo se realizó mediante la amplificación de la región en estudio (posición 1850 del codón 620) con la técnica de PCR estandarizada seguida por digestión de enzimas de restricción (Xcm I). Resultados: El genotipo más frecuente fue el genotipo homocigoto silvestre (C/C) tanto en pacientes (90.3%) como en controles (98.1%,) sin diferencia significativa. El polimorfismo C1858T (genotipo C/T) del gen PTP22 se identificó con mas frecuencia en los pacientes con diferencia estadísti-camente signifi cativa al relacionarlo con el grupo control (p= 0.029, OR=5,6). El genotipo homocigoto TT no se observó en ninguno de los individuos estudiados. Conclusión: El polimorfismo del gen PTPN22 a nivel C1858T descrito en otras enfermedades de origen au-toinmune también se detecta en HAI tipo 1, probable-mente confiriendo susceptibilidad a esta enfermedad en la población mestiza venezolana.

Background: Autoimmune hepatitis (AIH) type 1 is a progressive inflammatory disorder of the liver with genetic association to human leukocyte antigens. How-ever, the genetic background of AIH type 1 is considered to be polygenic. Lymphoid tyrosine phosphatase, encoded by the PTPN22 gene, exerts an important down regulatory effect on T cell activation in immune response. The single nucleotide polymorphism C1858T within the PTPN22 gene has been associated with in-creased susceptibility to a number of autoimmune dis-orders. Objective: The aim of this study was to assess the association of the single nucleotide polymorphism C1858T of the PTPN22 gene in Venezuelan Mestizos patients with AIH type 1. Materials and Methods: 62 Venezuelan Mestizos patients with AIH type 1 and 107 healthy volunteers were investigated. Cases and controls were genotyped for C1858T polymorphism by restriction fragment length polymorphism analysis of PCR products. Results: The wild-type C/C homozygous genotype was the most common variant in both patients (90.3 %) and controls (98.1 %). The heterozygous genotype C/T was significantly found in AIH patients compared to controls (OR = 5.6, P = 0.029). The T/T homozygous mutant genotype was not observed in either population. Conclusions: These results suggest that the PTPN22 1858C/T genotype could confer differential susceptibility to AIH type 1 in Venezuelan Mestizos patients. In addition, these findings provide strong evidence that lymphoid tyrosine phosphatase could be a critical player in multiple autoimmune disorders.

CD16 cross-linking induces increased expression of CD56 and production of IL-12 in peripheral NK cells.

Human NK cells are classified into two populations according to the intensity of CD56 surface expression, as well as possession of CD16, FcRIII. CD56(dim)CD16(bright) make up 90% circulating NK cells, whereas CD56(bright)CD16(-/dim) comprises the remaining 10%. Here we report that peripheral NK cells upon CD16 cross-linking up-regulates the expression of activating markers and receptors such as CD25, CD69, NKp44, NKp30, CD40L and the intensity of CD56 expression. Additionally, co-culturing immature DCs with CD16 activated NK cells was found to significantly increase the expression of maturation markers on DCs. These results suggest that CD16 cross-linking on resting peripheral blood NK cells triggers the activation of these cells and induces the appearance of CD56(bright) NK cells. The latter were found capable of producing pro-inflammatory cytokines, IFN-gamma and TNF-alpha and notably IL-12.

Cómo escribir un proyecto de investigación clínica / How to write a clinical research project

Pese a la importancia que tiene la investigación clínica como fundamento científico del quehacer clínico, nos encontramos con muy pocas publicaciones dirigidas a promover y orientar a los médicos que quieren dedicar parte de su actividad profesional al diseño y ejecución de proyectos de investigación. La tarea de preparar un proyecto generalmente requiere de varios meses de organización, escritura y revisión. La investigación requiere de una planificación cuidadosa y exhaustiva que nunca puede dejarse a la improvisación; planificación que imponen los organismos que financian los proyectos para su evaluación, pero también se debe hacer cuando la investigación es autofinanciada.

Modulation of T cell activation by stomatin-like protein 2.

T cell activation through the Ag receptor (TCR) requires sustained signaling from signalosomes within lipid raft microdomains in the plasma membrane. In a proteomic analysis of lipid rafts from human T cells, we identified stomatin-like protein (SLP)-2 as a candidate molecule involved in T cell activation through the Ag receptor. In this study, we show that SLP-2 expression in human primary lymphocytes is up-regulated following in vivo and ex vivo activation. In activated T cells, SLP-2 interacts with components of TCR signalosomes and with polymerized actin. More importantly, up-regulation of SLP-2 expression in human T cell lines and primary peripheral blood T cells increases effector responses, whereas down-regulation of SLP-2 expression correlates with loss of sustained TCR signaling and decreased T cell activation. Our data suggest that SLP-2 is an important player in T cell activation by ensuring sustained TCR signaling, which is required for full effector T cell differentiation, and point to SLP-2 as a potential target for immunomodulation.

Immunophenotype characteristics of peripheral blood mononuclear leukocytes of chronic idiopathic urticaria patients.

The pathogenesis of chronic idiopathic urticaria (CIU) is not completely understood although autoimmunity has been proposed. The aim of the study was to assess the expression of different leukocyte antigens, by flow cytometry, assaying total blood of 29 patients with CIU and of 20 sex and age matched controls. Moreover, we assessed soluble CD154 a marker of immune cell activation, predominantly memory T cells. When patients were divided depending an their response to the autologous serum skin test (ASST), three different groups were encountered: group 1 (n=11): with negative ASST-, group 2 (n=11): positive ASST (ASST+) with normal lymphocyte counts and group 3 (n=7): ASST+ with low lymphocyte counts (< 1500 cells/mm3). A significant increase in CD19+ percentage and not in the absolute count (P < 0.05) was observed in group 1 as compared to controls and to the other groups. In contrast, CD30+, CD45RO+ and CD4+/CD45RO+ percentages and biologically active soluble CD154 levels were significantly higher (P < 0.05) in group 3 as compared to group 1 or to controls. In ASST positive groups, CD45RO+ and CD4+/CD45RO+ positiveness correlates with wheal diameter. In conclusion, memory cells may play a role in these different types of patients and in understanding CIU pathogenesis.

Immunophenotype characteristics of peripheral blood mononuclear leukocytes of chronic idiopathic urticaria patients

La patogénesis de la urticaria crónica idiopática (CIU) no se conoce completamente; sin embargo, la autoinmunidad juega un papel importante en un subgrupo de pacientes. El objetivo de este estudio fue la determinación de antígenos leucocitarios en sangre total, utilizando citometría de flujo, de 29 pacientes con CIU y 20 controles de similar edad y sexo. Adicionalmente, se determinó el CD154 soluble como marcador de activación de células inmunes, predominantemente linfocitos T de memoria. Se describieron 3 grupos de pacientes de acuerdo al resultado de la prueba de suero antólogo (ASST): grupo 1: negativo (n = 11), grupo 2: prueba positiva y contaje linfocitario normal (n = 11) y grupo 3 prueba positiva y contaje linfocitario bajo (< 1500 células/mm3) (n = 7). En el grupo 1, se observó un aumento significativo (P < 0,05) en el porcentaje de células CD19+ aunque no en su número absoluto cuando se comparó con los controles y los pacientes con ASST +. En contrapartida, el porcentaje de células positivas para CD30, CD45RO y CD4/CD45RO y los niveles de CD154 soluble biológicamente activo fueron significativamente mayores (P < 0,05) en el grupo 3, en comparación con los controles y el grupo 1. Además, en los grupos con ASST positiva, los porcentajes de células CD45RO+ y CD4/CD45RO+ se correlacionan con el tamaño del habón a la ASST. En conclusión, las células de memoria pudieran jugar un papel importante en la patogénesis de la CIU.

Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptake.

The evaluation of new antimalarial agents using older methods of monitoring sensitivity to antimalarial drugs are laborious and poorly suited to discriminate stage-specific activity. We used flow cytometry to study the effect of established antimalarial compounds, cysteine protease inhibitors, and a quinolone against asexual stages of Plasmodium falciparum. Cultured P. falciparum parasites were treated for 48 h with different drug concentrations and the parasitemia was determined by flow cytometry methods after DNA staining with propidium iodide. P. falciparum erythrocytic life cycle stages were readily distinguished by flow cytometry. Activities of established and new antimalarial compounds measured by flow cytometry were equivalent to results obtained with microscopy and metabolite uptake assays. The antimalarial activity of all compounds was higher against P. falciparum trophozoite stages. Advantages of flow cytometry analysis over traditional assays included higher throughput for data collection, insight into the stage-specificity of antimalarial activity avoiding use of radioactive isotopes.

Total and biologically active serum-soluble CD154 in patients with chronic idiopathic urticaria.

The pathogenesis of chronic idiopathic urticaria (CIU) is not understood completely; however, autoimmunity has been implicated. Because membrane and soluble forms of CD154 have been reported to be increased, in several autoimmune diseases, we have quantified the soluble CD154 (sCD154) molecule by a sandwich enzyme-linked immunosorbent assay in serum samples of 32 patients with CIU (aged 32 +/- 12 years) and compared them with 32 age- and sex-matched nonallergic controls. A marked increase was observed in patients with CIU as compared with controls (4.8 +/- 2.6 ng/mL versus 2.9 +/- 0.9 ng/mL; p < 0.0005). No significant differences were found between groups of patients with positive or negative autologous serum skin test. A biological assay to determine sCD154 showed that patients with positive autologous serum skin test have the highest levels (4.9 +/- 1.2 ng/mL) of biologically active sCD154 as compared with their negative counterparts (2.2 +/- 1.3 ng/mL; p < .001) and controls (0.6 +/- 0.3 ng/mL; p < 0.001). Active sCD154 can be derived from mast cell activation or other leukocytes. It is concluded that active sCD154 may be involved in the immune activation observed in patients with CIU.

Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptake

The evaluation of new antimalarial agents using older methods of monitoring sensitivity to antimalarial drugs are laborious and poorly suited to discriminate stage-specific activity. We used flow cytometry to study the effect of established antimalarial compounds, cysteine protease inhibitors, and a quinolone against asexual stages of Plasmodium falciparum. Cultured P. falciparum parasites were treated for 48 h with different drug concentrations and the parasitemia was determined by flow cytometry methods after DNA staining with propidium iodide. P. falciparum erythrocytic life cycle stages were readily distinguished by flow cytometry. Activities of established and new antimalarial compounds measured by flow cytometry were equivalent to results obtained with microscopy and metabolite uptake assays. The antimalarial activity of all compounds was higher against P. falciparum trophozoite stages. Advantages of flow cytometry analysis over traditional assays included higher throughput for data collection, insight into the stage-specificity of antimalarial activity avoiding use of radioactive isotopes.

IL-2 and IL-12 alter NK cell responsiveness to IFN-gamma-inducible protein 10 by down-regulating CXCR3 expression.

Cytokine treatment of NK cells results in alterations in multiple cellular responses that include cytotoxicity, cytokine production, proliferation, and chemotaxis. To understand the molecular mechanisms underlying these responses, microarray analysis was performed and the resulting gene expression patterns were compared between unstimulated, IL-2, IL-2 plus IL-12, and IL-2 plus IL-18-stimulated NK92 cells. RNase protection assays and RT-PCR confirmed microarray predictions for changes in mRNA expression for nine genes involved in cell cycle progression, signal transduction, transcriptional activation, and chemotaxis. Multiprobe RNase protection assay also detected changes in the expression of CCR2 mRNA, a gene that was not imprinted on the microarray. We subsequently expanded our search for other chemokine receptor genes absent from the microarray and found an IL-2- and IL-12-dependent decrease in CXCR3 receptor mRNA expression in NK92 cells. A detailed analysis of CXCR3 expression in primary NK cells revealed that an IL-2 and an IL-12 together significantly decreased the CXCR3 receptor mRNA and receptor surface expression by 6 and 24 h of treatment, respectively. This decrease in receptor expression was associated with a significant reduction in chemotaxis in the presence of IFN-gamma-inducible protein-10. The decline in CXCR3 mRNA was due to transcriptional and posttranscriptional mechanisms as the addition of actinomycin D to IL-2- and IL-12-treated NK92 slightly altered the half-life of the CXCR3 mRNA. Collectively, these data suggest that IL-2 and IL-12 directly affect NK cell migratory ability by rapid and direct down-regulation of chemokine receptor mRNA expression.

Disminución de la respuesta proliferativa de los linfocitos frente a antígenos ambientales, como indicador precoz / Precocious indicator of the lympocytary injuries induce by the immunodeficiency virus human

A fin de evaluar las células CD4+/CD29+ y sus respuestas frente a diferentes antígenos en estadíos de la infección por el Virus de Imunodeficiencia Humana (VIH), estudiamos 26 pacientes seropositivos asintomáticos (SP) y 15 pacientes con Síndrome de Inmunodeficiencia Adquirida (SIDA) simultaneamente con 20 individuos controles sanos (CS) y 10 hombres homo y bisexuales seronegativos (SN) y 15 pacientes con Síndrome de Inmunodeficiencia Adquirida (SIDA) simultáneamente con 20 individuos controles sanos (CS) y 10 hombres homo y bisexuales seronegativos (SN). Los fenotipos CD3, CD4, CD29 y CD45RA fueron analizados por citometría de flujo de dos colores. Encontramos depleción significativa de los linfocitos T CD4+ y de las subpoblaciones de células memoria (CD4+/CD29+) y virgen (CD45/CD45RA+) en los pacientes SP y SIDA, en comparación con los grupos CS y SN. Las respuestas proliferativas con dosis óptimas de Candida Albicans, Estreptokinasa y Toxoide Tetánico fueron exploradas en células mononucleares de sangre periférica (CMSP) y en poblaciones enriquecidas de células CD4+ y CD4/CD29+. En pacientes SP, la respuesta ante C. Albicans de CMSP estaba significativamente disminuída con respecto a la de CS (15.308 vs 35.951 cpm). La reducción de la proliferación frente a estreptokinasa fue evidente solamente con preparaciones enriquecidas de linfocitos Cd4+/cd29+ (3.084 vs 10.367 cpm). Una vez analizados los resultados, evidenciamos entre los pacientes SP, 7 individuos respondedores a por lo menos un antígeno y 7 no respondedores. En este último grupo, la ausencia de proliferación era independiente del número absoluto de células memoria y virgen. La respuesta frente a Toxoide Tetánico, aunque disminuida en SP, no era significativamente diferente de la CS. Nuestros resultados sugieren que la respuesta defectuosa frente a antígenos ambientales comunes, no relacionada con el número absoluto de linfocitos CD4+/CD29+, es probablemente un indicador temprano de lesión linfocitaria inducida por el VIH

Aspectos inmunopatogenos de la infeccion por el virus de la inmunodeficiencia humana en Venezuela / Immunopathogenic aspects of infection by the human immunodeficiency virus in Venezuela

A prospective study was begun on the immunopathogenic characteristics of infection with human immunodeficiency virus (HIV) in order to elucidate the natural history of the disease induced by the virus in Venezuela. The results of a study of 240 individuals with variety of clinical manifestations are presented. The most important findings were depletion of the CD3+, CD4+ subpopulation in most individuals studied, including asymptomatic carriers; significant reduction of the large granular lymphocyte (CD3-, CD16+) pool in AIDS cases; decrease in cytotoxic activity in relation to the viral infection, along with an increase induced by recombinant interleukin 2; and reduction of the CD4 subpopulation in patients with free serum antigen. It is of utmost importance that ongoing research projects to clarity the immunopathogenic mechanisms of HIV be continued so that the characteristics peculiar to HIV infection may be determined, since they can affect clinical manifestation and the desease's development in the Venezuelan population

Immunopathology of human schistosmiasis mansoni: II. NK activity and stimulation by specific antigen

Dezesseis doentes infectados e näo tratados com S.mansoni (5 com infecçäo recente e 11 com doenças crônica), foram submetidos à avaliaçäo de atividade de células exterminadoras naturais (NK) "in vitro" frente a células alvo de linhagem K562. Os níveis de atividade das células NK em 9 de 11 doentes (82%) com a infecçäo crônica foram significativamente menores (média = 15 ñ 6%) quando comparados aos pacientes com infecçäo recente (média = 4 ñ 9%, p <0,001) e aos indivíduos do grupo controle (média = 38 ñ 13%, p < 0,001). Porém, tanto nos doentes como nos controles, a atividade de células NK foi estimulada pelo antígeno solúvel do parasito adulto (SAWA), indicando que as células NK, mesmo na fase crônica da infecçäo, têm capacidade de responder ao antígeno dos parasitos. Estes resultados sugerem a possível participaçäo das células NK no mecanismo efetor de defesa contra o S.mansoni