Inmunologia (Barcelona, Spain : 1987)最新文献

The Non-obese diabetic (NOD) mice exhibit a susceptibility to spontaneous development of autoimmune diabetes and is the most widely used experimental model for the study of the disease. The NOD strain was established by inbreeding in 1980. This model has a MHC-matched diabetes resistant homologous, NOR/Lt mice, an insulitis-resistant and diabetes-free strain produced from an isolated genetic contamination within a NOD/Lt line. To evaluate the role of transgenes, transgenic mice can be generated in CD-1 mice for technical advantages and then backcrossed to inbred strains. To obtain transgenic mice in NOD or NOR background starting from CD-1, at least 20 backcrosses are required, spending more than two years in the process.

Nucleotide repeats (microsatellites) mapped to specific locations on each chromosome are used to evaluate genomic polymorphism. From 23 microsatellites we selected eleven that were variant in PCR amplimer size between CD-1 colony and NOD or NOR strains. We used these microsatellites to identify individuals that were used for backcrossing, thus accelerating the acquisition of a new genetic background. Results yield a defined analysis of the genome in question and profiles were compared to detect genetic variation among individuals. After the selection of mice for backcrossing at the third generation, the 11 specific markers were acquired at the 5th generation and maintained to the 10th generation. Diabetes incidence and insulitis score correlated with the acquisition of genetic background, demonstrating that using this strategy, 5–6 crosses are enough to obtain the genotype of interest, shortening the process in more than one year and a half.

Little is known about the relevance of the polymorphisms in the function of HLA-DP. Acute lymphoblastic leukemia (ALL) is the most frequent cancer in children and adolescents in Zulia population. Chronic myeloid leukemia (CML) is similar in adolescents, young adults and mild adults. The epidemiologic studies suggest the presence of several factors related to the susceptibility. Forty-eight patients with ALL and 48 with CML, were compared with 48 controls from The Blood Bank of Zulia State, Venezuela, all of them unrelated racially mestizos. To evaluate the positive and negative associations between HLA allele and leukemias, the HLA-DPA1 locus and HLA-DPA1*01,*02,*03 and *04 alleles were studied using PCR Olerup SSPTM (Genovision). HLA-DPA1*01:05 (RR = 3.65; P ≤ .05) and DPA1*01:06 (RR = 13.88; P ≤ .05) alleles showed a positive association with ALL. Furthermore, HLA-DPA1*01:03:01-01:03:02 (RR = 0.46; P ≤ .05), DPA1*01:07 (RR = 10; P ≤ .05) and DPA1*02:01:01-02:01:06 (RR = 0.29; P ≤ .05) were negatively associated with ALL. Moreover, HLA-DPA1*01:05 (RR = 0.08; P ≤ .05), DPA1*01:08 (RR = 0.06; P ≤ .05) and DPA1*01:09 (RR = 0.14; P ≤ .05) showed a negative association with CML. Curiously, the genotype HLA-DPA1*01:03:01-01:03:02/02:01:01-02:02:06 showed a frequency of 40.4% in controls, 8.5% in ALL patients and 64.6% in CML patients. These marked differences in the frequency of distribution of HLA-DPA1* alleles and genotypes in CML and ALL patients, probably reveals a important pathogenic differences for the two types of leukemia.

Stiff person syndrome is a rare CNS disorder characterized by progressive muscular rigidity (trunk muscles), with superimposed spasms. High titres of antibodies to glutamic acid decarboxylase (GAD-Ab) are present in more than 70 % of patients. Adult-onset cerebellar ataxia (CA) is the second most frequent disease associated with high titers of GAD-Ab, and characterized by an almost isolated cerebellar syndrome. Both syndromes are frequently associated with autoimmune type 1 diabetes (T1D). The immunogenetic basis of SPS is supported by the DQB1*0201 allele, a susceptibility allele for T1D. Several T1D autoantigens are related to proteins of the nervous system. The concordance of both neurological diseases with T1D and the presence of anti-GAD antibodies suggest a common aetiology.

Plasmacytoid dendritic cells (pDC) are also known as natural type-I-interferon-producing cell (IPC) owing its name to an outstanding capacity to secrete large amounts of type I interferons (IFN) upon viral infections, thus constituting important mediators in antiviral immunity. This review aims to summarize some of the human pDC attributes, such as their origin, migration, as well as recent findings on interaction of pDC with other cells within the immune system. In addition, we will review the differences and similarities between pDC and their leukemic counterparts (LpDC), with a special focus on the validity of using cell lines derived from leukemic pDC as a model to study normal pDC.

The MSP-1 merozoite surface protein is related to the invasion phenomenon of malaria to red cells, while the EBA-140 antigen protein interacts with the sialoglycoproteins on the surface of erythrocytes. The identification of peptides from both proteins that bind to HLA class II has a particular importance for the development of vaccines.

In the present work, a predictive binding to HLA class II theory, based on S/k proportion of entropy was applied, for the prediction of proteins MSP-1 and EBA-140 binding phenomenon to the totality of 20 amino acid sequences of both molecules. The probability, combinatory and entropy values were calculated for 948 and 732 nonamer overlapping sequences of MSP-1 and EBA-140, respectively. Three theoretical proteins of 500 aminoacids of lenght each were computationally built in order to apply the developed binding theory to all their nonamer overlapping peptides.

It was predicted that for the two studied merozoite proteins, 298 sequences are related to the binding macrostate and 1409 to the not-binding macrostate. The developed theoretical prediction can facilitate the selection of peptides during the process of vaccine development. For the three theoretical proteins built, it was found that 111, 84 and 72 are predicted as included into the binding macrostate, while sequences 381, 408, and 420 are predicted as related to the not-binding macrostate.

The predictions are an evidence of a physical and mathematical order in antigen presentation, which can be useful to the development of vaccines.