IMMUNOCHEMICAL

Author: PEDRAZA LENTINO CARLOS EDUARDO.
Year: 2002.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: ESCUELA DE DOCTORADO Y DE FORMACIÓN CONTINUADA.

Summary: The CNS is affected by inflammatory processes in response to bacterial infections, trauma and processes related to the pathogenesis of neurodegenerative diseases such as Parkinson's, Alzheimer's disease (AD), multiple sclerosis (MS) or dementia associated with the human immunodeficiency virus ( HIV). The glial reactivity and increased expression of proinflammatory cytokines are common features of the inflammatory process associated with neurodegenerative diseases. The cytokines are proteins of low molecular weight (between 8 and 26 KDa) are synthesized in nearly all cell types. These have been classified into proinflammatory (IL-1beta, TNF-alpha, INF-gamma, IK-6) and anti-inflammatory (IL-4, IL-10, IL-12). The proinflammatory cytokines, in turn, induce CNS cells in the expression of NOS - 2 causing a production high and sustained NO.El NO is synthesized by nitric oxide sintasas (NOS) that three isoforms have been described: NOS - 1, NOS - 2 and NOS-3. The NOS - 2 is induced transcripcionalmente in response to mediators of inflammation generate high amounts of NO (nanomoles) for long periods of time may have cytotoxic effects. The most important physiological interaction of NO is its binding to FE2 + group hemo of guanilil cyclase soluble inducing the formation of cyclic GMP (cGMP) from GTP. The cGMP has been implicated in many of the physiological actions of NO, both in peripheral tissues such as vascular. In the CNS processes modulates synaptic plasticity and memory formation, and visual sensory processing, brain development, secretion and neuroendocrine regulation of cerebral blood flow. Little is known about the regulation of the formation of cGMP-dependent NO CNS cells during neuroinflamación. In this paper we provide evidence showing that agents as inflammatory cytokines IL-1beta and TNF-alpha, LPS and peptides Abeta regulate the metabolism of cGMP cell astrogliales rat in culture, as well as in the brains of rats adult, indicating that during the neuroinflamación signaling via NP-cGMP is altered.

Author: SÁNCHEZ SÁNCHEZ NOELIA.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS.
Place of preparation: Y TOXICOLOGIA (CSIC-UCM).

Summary: SUMMARY: apoptosis, or programmed cell death, is a physiological process involved in the normal development and maintenance of homesotasis of tissues. This process is regulated through a complex mechanism that are involved numerous molecular mediators. Some cell surface receptors are capable of inhibiting apoptosis by releasing signals repressive molecules proapoptóticas or encourage molecules anti-apoptóticas. PI3K and Akt two enzymes are strongly related to the inhibition of apoptotic signals, as they are capable of fosforilar and inhibit a variety of pro-apoptóticos regulators as caspase 9 or Bad. The dendritic cells are potent antigen presenting played a key role in initiating the immune response. You are cells suffer a process of maturation where it increases their ability to display antigenic and its sensitivity to quimioquinas CCl19 and CCL21, responsible for their migration to the lymph nodes. The ability of dendritic cells, once mature, respoder these two quimioquinas, it is given by the increase in its cell surface receptor quimioquinas CCR7 during the ripening process. The signals sent CCR7, once activated, are beginning to be characterized. CCR7, like other recipients heptahelicoidales transmits signals through members of the family of G protein G proteins are heterotrimeros comprising one alpha subunit, a beta subunit and a gamma subunit. Commonly, the receivers quimioquinas transmit signals regulating chemotactic through family members Gi. It has recently been described that CCR7 besides regulating chemotactic regulates other processes such as citoarquitectura of dendritic cells and their abilities endocíticas. Suggesting that the receiver is able to regulate a variety of signaling pathways in the dendritic cells mature. This paper shows that CCR7 is able to induce intracellular signals that inhibit the development of apoptosis in dendritic cells mature deprivadas serum, for 6 hours. Among the signals induced by CCR7 are the activation of PI3K, Akt and the transcription factor NF-kappa B. The resultadosde this work suggest that the transmission of signals anti-apoptóticas may be an important mechanism by which CCR7 contribute to the improvement of the adaptive immune response.

Author: FUENTES VILLAREJO PATRICIA.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE CIENCIAS QUÍMICAS.
Place of preparation: FUNDACIÓN JIMÉNEZ DÍAZ.

Summary: The family of herpesvirus, responsible for serious diseases in patients immunologically immature or immunocompromised, comprises: herpes simplex-1 and -2, varicela-zoster virus, cytomegalovirus, Epstein-Barr virus and herpes viruses - 6, -7, and -8. During the evolutionary process viruses have developed mechanisms that allow them to evade the recognition and therefore its elimination by the immune system. Thus, viruses are able to manipulate the expression of class I antigens, modulate the expression of molecules coestimuladoras, accession activation of cytokine receptors and quimoquinas and their ligands. So far, there is little information on the mechanisms used by the herpesvirus -6 and -7 y- 8 (HHV-6, -7, and -8) to interfere with the development of an effective immune response. In our laboratory we have studied how the HHV-6, interferes with the expression of molecules involved in the activation of the immune system (CD25, CD69 and HLA class I and II). We have demonstrated that HHV-6 decreases in surface expression of class I and CD69. In the first case, the protein encoded by the gene U21 of HHV-6, and in particular, the reasons for departure to lysosomes in the cytoplasmic region, are responsible for directing class I antigens lysosomes for degradation . This causes a decrease in their expression on the cell surface. In the second case, the inhibition of the expression of CD69 is due to a mechanism transcriptional level. The transcription factor YY-1 appears to be implicated in the repression of transcription of the gene for CD69 in cells infected with HHV-6. These results demonstrate that HHV-6 causes a profound inhibition of the immune system and the likely decline in the synthesis of IL-2 and its receptor might be "devastating" on lymphocyte proliferation.

Author: PINEDA DE LA LOSA FERNANDO.
Year: 2005.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: LABORATORIO DE DIAGNÓSTICO Y APLICACIONES TERAPÉUTICAS Y DPTO. DE QUÍMICA FÍSICA II, FACULTAD DE FARMACIA. UCM.

Summary: The work has been done in this report is immediately applicable in the prevention and therapy of allergic diseases. The use of recombinant allergens such as diagnosis, prevention and treatment of asthma, is currently one of the most advanced ways to control the disease. We have designed kits quantification commercial allergen Alt at 1 Alternaria alternata. The election system expression of cDNA is important to determine the structural properties of the natural protein, it is essential to note that their molecular properties in terms of structural and functional characterization, physical chemical properties such as molecular weight, solubility and loads are equivalent. The expression of recombinant DNA provides a production system protein extraction difficult. The estandarizaciones allergen individual permit at a future greater uniformity between the lots and between different specialties business. Therefore, the work done by D. Fernando Pineda of the Slab is interesting not only because its application in the field of public health, which include the pharmaceutical industry, but also has socio-economic impact, a factor that currently must be payable to any research project.