Spulwurm – Wikipedia
Der MadenwurmSpringwurmPfriemenschwanz oder Aftermade Enterobius vermicularis syn. Oxyuris vermicularis von griech. Der Madenwurm ist der weltweit verbreitetste Eingeweidewurm beim Menschen und einer der häufigsten Parasiten des Menschen.
Die Art ist auf menschliche Wirte spezialisiert und im Allgemeinen stark auf diese Wirtsart festgelegt. Seltener werden auch Affen befallen in Tiergärten und möglicherweise auch Kakerlaken. Die ebenfalls zu findende Bezeichnung Kindermadenwurm ist insofern irreführend. Der krankhafte Wurmbefall selbst wird als Enterobiasis. Es kommen bis zu drei Larvenstadien vor.
Im Zwölffingerdarm schlüpfen die Larven aus der Eihülle und häuten sich dabei das zweite Mal. Diese wandern vom Dünndarm wo sie sich bis zu dreimal häuten zum bevorzugten Aufenthaltsort an der Darmwand rund um den Blinddarm.
Hier wachsen die Tiere etwa zwei bis Ascaris Würmer und Fotos Wochen lang aus und erreichen die Geschlechtsreife. Nach der Paarung sterben die Männchen. Die Weibchen wandern nach der Paarung und einer etwa zweiwöchigen Reifung Ascaris Würmer und Fotos Eier zur Eiablage in Richtung After. Manche Autoren behaupten, dass bereits am After geschlüpfte Larven auch direkt in den Darm kriechen können. Die Eier des Madenwurms sind bis zu drei Wochen lebensfähig.
Frühe Erwähnungen in Schrifttum finden sich im altägyptischen Papyrus Ebers. Hippokrates von Kos ca. Jahrhundert begann eine systematische Untersuchung ihrer Schadwirkung.
Meine Reinigung von Würmern ist in gegen Würmer wirksamen Dosen auch für den menschlichen Organismus recht giftig. Bis zur Einführung von Ivermectin war es Mittel der Wahl.
Als Leitsymptom einer Wurmerkrankung durch Madenwürmer gilt der vor allem nächtlich auftretende Juckreiz im Analbereichder entsteht, wenn die weiblichen Madenwürmer um den After herum ihre Eier ablegen. Der Juckreiz wiederum kann zu Schlafstörungen und deren Folgeerscheinungen, wie Reizbarkeit, Nervosität, Konzentrationsschwierigkeiten, Blässe oder Augenringen führen.
Ein massiver Wurmbefall kann zu Bauchschmerzen und Gewichtsabnahme, chronischem Durchfall, rektalen Blutungen oder Symptomen einer chronischen Blinddarmreizung Appendizitis führen. Anders als viele andere Darmparasiten dringt der Madenwurm nicht in den Blutkreislauf oder in andere Ascaris Würmer und Fotos als den Darm ein. In seltenen Fällen jedoch wird bei Mädchen der Genitaltrakt befallen, wodurch Ascaris Würmer und Fotos eine Vulvovaginitis entwickeln kann. In Extremfällen können erwachsene Würmer über die Vagina bis Ascaris Würmer und Fotos das Retroperitoneum wandern und dort zu einer eosinophilen Entzündung mit einem begleitenden Aszites führen.
Auch der Befall der Harnröhre und der Blase ist möglich. Kopf eines Madenwurms Enterobius vermiculariskünstlich gefärbt. Nicht angemeldet Diskussionsseite Beiträge Benutzerkonto learn more here Anmelden.
Hauptseite Themenportale Von A bis Z Zufälliger Artikel. Artikel verbessern Neuen Artikel anlegen Autorenportal Hilfe Letzte Änderungen Kontakt Spenden. Buch erstellen Als PDF herunterladen Druckversion. Möglicherweise unterliegen die Inhalte jeweils zusätzlichen Bedingungen. Durch die Nutzung dieser Website erklären Sie sich mit den Nutzungsbedingungen und der Datenschutzrichtlinie einverstanden.
Unterabteilung : Stamm : Ascaris Würmer und Fotos Oxyurida Enterobius Dieser Check this out behandelt ein Gesundheitsthema. Er dient nicht der Selbstdiagnose und ersetzt keine Arztdiagnose.
Bitte hierzu diese Hinweise zu Gesundheitsthemen beachten!
Ascaris suum Ascaris Würmer und Fotos
This invention relates to improved methods for inducing immune responses against antigens using a virus vector for priming immunization and antigen peptides combined Ascaris Würmer und Fotos an adjuvant for booster immunization.
Methods for reducing an immune response using a virus vector for priming immunization and antigen peptides without an adjuvant for booster immunization are also provided. The immune system of a mammal often provides the first line of defense against pathogenic organisms, as well as against tumors. The immune system recognizes antigens expressed by tumor cells or pathogens as foreign, i.
The immune response of a mammal is also responsible to allergy to antigens known as allergens and autoimmune disease, which results from inappropriate recognition of host proteins as non-self.
Genes which are expressed in tumor cells, but not in normal counterparts, can be termed "tumor associated" genes. Typically, the host recognizes as foreign http://bartgo5376.xsl.pt/haben-wuermer-aus-dem-gefaehrlichen-hund.php products of tumor associated genes which are not expressed in normal non-tumorigenic cells.
Thus, the expression of tumor associated genes can provoke an immune response against the tumor cells by the host. Tumor associated genes can also be expressed in normal cells within certain tissues without provoking an immune response. Examples of immunologically privileged tissues include brain and testis. The discovery of tumor associated genes and encoded proteins and peptides which are specifically recognized by the host immune system provides a source of immunogens Ascaris Würmer und Fotos provoking an immune response against the tumor cell.
The polypeptide products of tumor associated genes can be the targets for host immune surveillance and provoke selection and expansion of one or more clones of cytotoxic T lymphocytes CTLs. Other tumor antigens are. Thus, tumor associated expression of genes suggests that such genes can encode proteins which will be recognized by the immune system as foreign and thus provide a target for tumor rejection.
The process by which the mammalian immune system recognizes and reacts to foreign or alien materials is a complex one. An important facet of the system is the T cell response. This response requires that T cells recognize and interact with complexes of cell surface molecules, referred to as human leukocyte antigens "HLA"or major histocompatibility complexes "MHCs"and peptides.
See in this regard Male et al. If a specific T cell is not present, there is no T cell response even if its partner complex is present.
Similarly, there is no response if the specific complex is absent, but the T cell is present. The mechanism is involved in the immune system's response to foreign materials, in autoimmune pathologies, and in responses Ascaris Würmer und Fotos cellular abnormalities.
Much work has focused on the mechanisms by which proteins are processed into the HLA binding peptides. The mechanism by which T cells recognize cellular abnormalities has also been implicated in cancer. The genes are said to code for "tumor rejection antigen precursors" or "TRAP" molecules, and the peptides derived therefrom are referred to as "tumor rejection antigens" or "TRAs". See Traversari et al.
It has been demonstrated Ascaris Würmer und Fotos cytotoxic T lymphocytes provide an effective response against tumor cells. Therefore, immunization which increases host cytotoxic T lymphocytes specific for one or more tumor rejection antigens can reduce tumor load in the host. The possible modes of delivery of tumor rejection antigens for immunization of cancer patients include: peptide with adjuvant Feltkamp et al.
Clinical trials of melanoma antigen-specific immunotherapy Ascaris Würmer und Fotos thus far involved the use of either genetically modified tumor cells Rosenberg et al.
Nat 'I Cancer Inst. An alternative approach to administration of synthetic peptides or genetically modified cells is Ascaris Würmer und Fotos use of recombinant viral vectors to deliver the target antigens of choice. In this respect, human adenoviruses have been shown to function effectively as gene transfer vectors in a wide range of cells and tissues. Recombinant viruses such as adenoviruses have potential as immunization vectors because they efficiently deliver genes into infected host cells.
The use of adenoviruses as vaccine vectors against viral diseases Cordier et al. The safety and variety delivery of modes of adenoviruses is well established Ascaris Würmer und Fotos et al, J. Other viral vectors also have been demonstrated to be safe and effective for delivery of nucleic acids into a host. A mouse model system has been developed for determining the effectiveness of immunization protocols in eliciting a Ascaris Würmer und Fotos response, and the potential for application of such protocols for use in human cancer immunotherapy.
It expresses several antigens recognized by CTLs Boon et al, J. Immunization of a subject generally entails a "priming" or "primary" immunization which represents the first exposure of the subject to the immunogen, followed by one or Ascaris Würmer und Fotos "boost" or "booster" immunizations with the same immunogen to provoke a more powerful and long-lasting immune response.
It is known that an immune response is often generated to immunogenic epitopes of the particular adeno virus used as a vaccine vector. This effect limits the effectiveness of adenoviruses as vaccine vectors in that the adeno virus generally Ascaris Würmer und Fotos not be used for both priming and boosting immunizations.
Thus, a difficulty with the use of adenoviruses as vaccine vectors is providing a boosting vaccination to provoke a robust and long-lasting immune response. Therefore, in order that a host immune system will maintain immune surveillance against tumor cells throughout life, there is a need for methods of immunization which are not limited by the host immune response Ascaris Würmer und Fotos viral vectors such as adenovirus typically neutralizing antibodies directed against the viral capsid proteins used to immunize a Ascaris Würmer und Fotos. Further, there is a need to providing effective methods for immunizing against tumor antigens to provoke a cytotoxic T lymphocyte response in a host.
There is also a need to reduce inappropriate immune responses, such as found in allergy and autoimmune disease. Reduction of host immune responses is also desirable to reduce allograft transplant rejection by the host. It is an object of the invention to provide methods and compositions effective in enhancing the immune response click at this page a mammalian subject against tumor cells expressing tumor rejection antigens and against pathogens, in subjects having any type Ascaris Würmer und Fotos HLA antigen-presenting molecules.
It is also an object of the invention to provide methods and compositions effective in reducing the immune response of a mammalian subject in allergy, autoimmune von Kindern Würmer bei Katzen and allograft rejection.
It is a further object of the invention to provide kits which facilitate administration of primary and booster immunizations. Summary of the Invention The invention provides improved methods of immunization using virus vectors which. The invention includes the use of antigen peptides in adjuvant for booster immunizations. These booster immunizations provoke a more robust immune response in a greater proportion of subjects. The invention also includes the use of antigen peptides in a non-adjuvant carrier for booster immunizations effective in reducing an immune response against such antigens.
Further, Ascaris Würmer und Fotos invention provides compositions and pharmaceutical preparations, contained in kit form, which enable the induction of an immune response against tumor Ascaris Würmer und Fotos. According to one aspect of the invention, methods for inducing an immune response in a mammal against an antigen are provided.
The methods comprise administering to the mammal a virus containing a nucleic acid molecule encoding the antigen or its precursor in an amount effective to generate a first immune response.
The Ascaris Würmer und Fotos further include administering at least one booster dose comprising at least one peptide in an adjuvant, wherein the at least one peptide includes the antigen, in a combined amount effective to enhance the first immune response. In certain embodiments, the nucleic acid molecule encodes an antigen, or a precursor or variant of the antigen, selected from the group consisting of tumor antigens and antigens characteristic of a pathogen.
The choice of adjuvants can be of importance in promoting a strong immune response. Thus, in other embodiments, the adjuvant used in this Ascaris Würmer und Fotos of the invention is selected from the group consisting of saponin adjuvants e.
In some embodiments, the Ascaris Würmer und Fotos or the at least one peptide is administered by injection. Preferably, Ascaris Würmer und Fotos injection is intradermal or subcutaneous. The invention provides for administration of booster doses of immunogen to the mammal to enhance the first immune response to the antigen.
In some embodiments, at least two booster doses of the at least one peptide in an adjuvant are administered. Preferably, four booster doses. In certain embodiments, the virus is selected from the group consisting of adenoviruses, adeno-associated viruses, poxviruses including vaccinia viruses and attenuated Ascaris Würmer und Fotos such as NYVAC, Semliki Forest virus, Venezuelan equine encephalitis virus, retroviruses, Sindbis virus, and Ty virus-like particle.
Preferably, the virus is an adenovirus. According to another aspect of the invention, Ascaris Würmer und Fotos for reducing an immune response in a mammal against an antigen are provided.
The methods comprise administering to the mammal a virus containing a nucleic acid molecule encoding the antigen or its precursor, in an amount effective to generate a first immune response. The methods further include administering at least one booster dose comprising at least one peptide in a non-adjuvant carrier, wherein the at least one Ascaris Würmer und Fotos includes the antigen, in an amount effective to reduce the first immune response.
In certain embodiments, the nucleic acid molecule encodes an antigen, or a precursor or variant of the antigen, selected from the group consisting of allergens, allograft antigens and autoimmune antigens. The invention provides for administration of doses of antigen peptide in a non-adjuvant carrier to the mammal to reduce the immune response to the antigen or allergen. In some embodiments, at least two booster doses of the at least one peptide in a non-adjuvant carrier are administered.
Preferably, four booster doses in a non-adjuvant carrier are administered. In certain embodiments, the virus is selected from the group consisting of adenoviruses, adeno-associated viruses, poxviruses including vaccinia viruses and attenuated poxviruses, Semliki Forest virus, Venezuelan equine encephalitis virus, retroviruses, Sindbis virus, and Ty virus-like particle. According to another aspect of the invention, a kit is provided.
The kit comprises a first container containing an adenovirus which includes a nucleic acid molecule encoding a tumor antigen and a visit web page container containing at least one peptide including the tumor antigen, sufficient to boost an immune response of a mammal to the tumor antigen.
In certain embodiments, the second container further contains an adjuvant. In other embodiments, the kit further comprises a third container containing an adjuvant, or further comprises instructions for administering the at least one peptide with an adjuvant. In any of the foregoing kits, the adjuvant. The kits of the invention can be formulated to be useful for the treatment of a range Ascaris Würmer und Fotos tumors.
The invention in another aspect involves compositions comprising an adenovirus including a nucleic acid which encodes a non-adenovirus antigen and an adjuvant. The antigen and adjuvant are as described in the foregoing aspects of the invention. According to yet another aspect of the invention, a composition comprising a peptide antigen is provided.
The peptide comprises non-antigen amino Ascaris Würmer und Fotos which increase the solubility of the peptide antigen in a solvent selected from the group consisting of adjuvants and non-adjuvant aqueous Ascaris Würmer und Fotos. Preferably, the peptide comprises at least one N-terminal glutamic acid residue, and more preferably comprises two N-terminal glutamic acid residues.
These and other objects of the invention will be described in further detail in connection with the detailed description of the invention. Brief Description of the Ascaris Würmer und Fotos Fig.
Previous studies of an adenovirus-based immunization protocol for induction of an immune response against tumor Ascaris Würmer und Fotos resulted in induction of CTLs reactive against the. Re-immunization with the same adenovirus was not efficient due to the presence of neutralizing antibodies against the adenovirus capsid proteins. Other studies have also detailed the limitations of adenovirus-based immunization protocols.
It has now been discovered that these limitations can be overcome by immunization methods which combine a priming injection of an virus which expresses an antigen to induce a first immune response, followed by booster injections of peptides containing the antigen. Surprisingly, if peptide Ascaris Würmer und Fotos administered in combination with adjuvant, the immune response of the host is increased relative to the first immune response, but if peptide is administered in combination with a Ascaris Würmer und Fotos carrier, the immune response of the host is decreased relative to the first immune response.
Therefore the invention disclosed herein provides the unexpected result that the choice of an adjuvant or a non-adjuvant carrier can alter the effect of a peptide antigen on Ascaris Würmer und Fotos immune response generated in a host. Thus the invention provides methods for the use of viruses in delivering antigen precursors to subjects to provoke a first immune response and peptides in adjuvant for boosting the first immune response.
Other methods for reducing the first immune response by administering peptides in a non-adjuvant carrier are also provided. The methods of the invention involve the administration of viruses encoding one or more antigens to a subject by standard modes of immunization. The administration of the virus vector serves as the priming immunization which induces an initial first immune response the primary immune response against the tumor antigen.
The subsequent booster immunizations with peptide antigens in combination with adjuvant increase the responsiveness of the subject's immune system to the antigen by inducing the secondary immune response, which is characterized by the increased production of cytotoxic T lymphocytes relative to the primary immune response. This is useful for increasing a subject's immune response for the treatment of tumors and pathogens.
Exemplary tumor associated peptide antigens that can be expressed to induce or enhance. Other exemplary peptides include those listed in U. Examples of important pathogens include Vibrio cholerae, enterotoxigenic Escherichia coli, rotavirus, Clostridium difficile, Shigella species, Salmonella typhi, parainfluenza virus, influenza virus, Streptococcus pneumoniae, Borella burgdorferi, HIV, Epstein-Barr virus.
Bacteria in Ascaris Würmer und Fotos include but are not limited to: P. Parasites include but are not limited to: Plasmodium falciparum, P. Any modes of administration which effectively deliver the adenovirus and the peptide in adjuvant can be used according to the invention. For administration of the peptide in adjuvant or in a non-adjuvant carrier, preferred methods include intradermal and subcutaneous administration. Although these are preferred embodiments, the invention Ascaris Würmer und Fotos not limited by the particular modes of administration disclosed herein.
Standard references in the art e. As part of the immunization protocols, the peptide antigens and optionally the adenoviruses preferably are administered mixed with one or more adjuvants to induce an immune response or to increase an immune response. An adjuvant is a substance incorporated into or administered simultaneously with antigen which potentiates the immmune response.
Adjuvants may enhance the immunological response by providing a reservoir of antigen extracellularly or within macrophagesactivating macrophages and stimulating specific sets of lymphocytes. Adjuvants of many kinds are well known in the art. Other adjuvants are known in the art and can be used in the invention see, e.
Methods for the preparation of mixtures or emulsions of peptide and adjuvant are well known to those just click for source skill in the art of vaccination. Other agents which stimulate the immune response of the subject can also be administered to the subject. For example, cytokines are also useful in vaccination protocols as a result of their lymphocyte regulatory properties.
Administration of peptide antigens in a non-adjuvant carrier results in a reduced immune response relative to the immune response generated by administration of a virus encoding the antigen.
Thus administration of peptide antigens in a non-adjuvant carrier such as phosphate buffered saline can be used to reduce a subject's immune response to such antigens.
This is useful in the treatment of allergic responses and autoimmune diseases, as well as in treating allograft rejection. A non-adjuvant carrier is a carrier which does not potentiate the immune response of the antigen with which it is co-administered. Non-adjuvant carriers include phosphate buffered saline, normal saline, Ringer's solution, and other Ascaris Würmer und Fotos which are not known to potentiate an immune response.
Antigens that are allergens are generally proteins or glycoproteins, although allergens may also be low molecular weight allergenic haptens that induce allergy Ascaris Würmer und Fotos covalently combining with a protein carrier Remington's Pharmaceutical Sciences. Allergens include antigens derived from pollens, dust, molds, spores, dander, insects and foods. Specific examples include: the major horse allergen Equ cl Gregoire et al. Learn more here autoimmune antigens will be known to one of ordinary skill in the art.
Other peptide antigens can be identified according to methods used in the foregoing references which describe antigens of tumors, pathogens, allergens and autoimmune disease. The peptides administered according to the methods described herein can have the amino acid sequence of the Ascaris Würmer und Fotos processed antigenic peptide e.
Alternatively, modifications can be made to the amino acid sequence to enhance binding to HLA for presentation to a subject's immune system, while retaining the Ascaris Würmer und Fotos to induce CTLs which recognize the naturally processed peptide. The portions of HLA binding peptides important for Ascaris Würmer und Fotos activity are see more see, e.
Variant antigenic peptides which bind more tightly to HLA molecules have been found to be more immunogenic Parkhurst et al. A general protocol for modification of HLA binding peptides has been suggested by Parker et al. HLA binding predictions can conveniently be made using an algorithm available via the Internet on the National Institutes see more Health World Wide Web site at URL bartgo5376.xsl.pt Thus one of ordinary skill in the art, with only routine.
The Worms im Auge der disclosed herein provide a sensitive assay for http://bartgo5376.xsl.pt/bad-wuermer.php the immunogenic potential of such modified peptides. The peptides used in accordance with the invention can be prepared by any method known in the art.
Typically this entails programming a peptide synthesizer with a desired amino acid sequence, providing the subunits to be incorporated into the extending peptide chain, and purifying the synthesized peptide. All of these steps are well known and practiced routinely Ascaris Würmer und Fotos the art.
Of course, peptides may be made by check this out methods, including transcription and translation of a nucleic Ascaris Würmer und Fotos which encodes such peptides. The virus can contain a nucleic acid which encodes one or more antigens, or precursors thereof, including the whole proteins from which the one or more antigens are derived.
As used herein, "antigen" embraces a naturally selected antigenic peptide presented by MHC molecules, as well as variants of Ascaris Würmer und Fotos naturally selected antigenic peptide which can be prepared according to methods known in the art and disclosed herein.
The use of a complete-protein recombinant viral vaccine may be preferable because the host alleles can select Ascaris Würmer und Fotos relevant epitope or epitopes for presentation. Host epitope selection recently was demonstrated by Zhai et al J Immunol. Alternatively, the use of a viral vaccine which expresses only a portion of a gene which does not encode a functional protein, e. Expressing only a portion of the gene permits vaccination against an antigen without concomitant expression of a complete functional gene product in the cells which the vector has infected.
In preferred embodiments, the virus vector for expressing a Ascaris Würmer und Fotos acid encoding an antigen is selected from the group consisting of adenoviruses, adeno-associated viruses, poxviruses including vaccinia viruses and attenuated poxviruses, Semliki Forest virus, Venezuelan equine encephalitis virus, retroviruses, Sindbis virus, and Ty virus-like particle.
Examples of viruses and virus-like particles which have been used to deliver exogenous nucleic acids include: replication-defective adenoviruses e. The term adenovirus also embraces an adenovirus genome containing exogenous genetic material which encodes a tumor antigeni. As used herein, Ascaris Würmer und Fotos genetic material" refers to a nucleic acid molecule e.
The "exogenous genetic material" is a gene or fragment thereof which encodes an antigen or precursor thereof that can, if necessary, be processed into one or more antigens. The exogenous genetic material can encode more than one antigen, as in a Ascaris Würmer und Fotos nucleic acid.
The genome comprises, in particular, an inverted repeat sequence ITR at each end, an encapsidation sequence Psias well as early genes and late genes. Among these early genes, those contained in the El this web page are needed for viral propagation, i. The complete nucleotide sequences of adenovirus genomes are known and have been deposited in nucleotide sequence databases.
The nucleic acid encoding a tumor rejection antigen or precursor thereof preferably is. For example, the nucleic acid preferably is not inserted into regions which contain adenovirus genes encoding proteins which are not easily supplied in trans.
Other sites also may be used as will be apparent to one of ordinary skill in the art. In particular, access to the nucleotide sequences of adenovirus genomes enables a person skilled in the art to identify regions of the adenovirus genome suitable for insertion of the nucleic acid encoding a tumor injection antigen precursor.
The Ascaris Würmer und Fotos recombinant adenoviruses of the invention can be prepared by any technique known to the skilled artisan Levrero et al. Generally, adenoviruses are produced by Ascaris Würmer und Fotos of a recombinant adenovirus genome into an encapsidation cell line.
Where several nucleic acids supply different portions of a replication-defective recombinant adenovirus genome, the several nucleic acids can be cotransduced into the encapsidation cell line.
In such cases, the process of forming a replication-defective adenovirus genome involves one or more steps of homologous recombination between the different nucleic acids transduced into the encapsidation Ascaris Würmer und Fotos line, in order to generate the recombinant adenovirus genome.
Generation of adenoviruses by Ascaris Würmer und Fotos recombination is exemplified in the examples. After assembly of a complete adenovirus genome or introduction by transduction a complete adenovirus genomethe adenovirus is assembled by encapsidation of the adenovirus genome with adenovirus coat proteins. The nucleic acids assembled to prepare a complete replication-defective adenovirus genome can be prepared by any method known in the art.
For example, an adenovirus genome can be isolated and then modified in vitro by standard methods of molecular biology see, Ascaris Würmer und Fotos. Ausubel, et al, eds. The modified adenovirus genome so obtained optionally can be isolated and used to transfect an. Another Ascaris Würmer und Fotos is based on the use of a plasmid carrying a portion of the genome of the recombinant adenovirus, which plasmid is co-transduced with an adenovirus supplying the missing portions of the genome.
A complete recombinant adenovirus genome is formed by homologous recombination in the transduced cell line. Other possibilities include the use of prokaryotic plasmids to prepare the recombinant adenovirus genome, followed by transduction of the plasmids into an adenovirus encapsidation cell line.
The adenovirus encapsidation cell line useful for preparation of recombinant adenoviruses is capable of accepting the nucleic acids described above and preferably contains sequences capable of complementing the replication-defective adenovirus genome to permit production of recombinant adenoviruses. Preferably, such sequences capable of complementing the defective portions of the adenovirus genome are integrated into the genome of the cell to avoid recombination with the adenovirus genome.
Preparation of transduced adenovirus producer cell lines and isolation of adenovirus stock can be performed according to methods standard in the art, as illustrated in the examples below. Exemplary adenoviruses are replication-defective due to mutation of an adeno viral gene or genes essential for adenoviral replication. As used herein, a "replication-defective" adenovirus Ascaris Würmer und Fotos one which is incapable of replicating autonomously in the target cell.
Generally, the genome of a replication-defective adenovirus used in the context of the present invention contains mutations or deletions of at least the sequences needed for replication of the adenovirus in the infected cell. Such regions can Ascaris Würmer und Fotos removed in whole or in part, rendered non-functional Ascaris Würmer und Fotos mutation, or replaced by other nucleic acid sequences, in particular, Ascaris Würmer und Fotos nucleic acid encoding a tumor-rejection antigen precursor.
Preferably, the replication-defective adenovirus retains the portions of its genome which are required for encapsidation of the adenovirus genome to form an adenovirus particle. Preferably, the replication-defective adenoviruses of the invention Ascaris Würmer und Fotos the inverted repeat sequences ITRsa sequence permitting encapsidation, and the nucleic acid encoding a tumor rejection antigen precursor. Replication-defective adenoviruses can contain a modified El region which.
Preferably the adenovirus genome used in the invention is Ascaris Würmer und Fotos from a serotype which does not exert pathogenic effects in humans. Other serotypes useful in this manner will be known to persons of skill in the art.
Other adenoviruses useful in the invention include those of non-human origin see, e. Thus the adenoviruses of the invention are useful for delivering to antigen presenting cells nucleic acid molecules that encode antigen precursors, which can be processed by the antigen presenting cells into one or more antigens, e. In some embodiments of the invention, only the antigen peptide is expressed by a recombinant adenovirus.
As demonstrated in the Examples below, expression of a tumor antigen peptide by an adenovirus is effective for inducing an immune response against the peptide. Peptides which are larger than the tumor antigen peptides can also be used provided that the larger peptide, when expressed in a host cell, is processed to a peptide which can be presented to the immune system by HLA molecules of the host.
In a preferred embodiment, nucleic acids encoding a series of epitopes, known as "polytopes", are used according to the invention. The epitopes can be arranged in sequential or overlapping fashion see, e. The polytope is processed to generated individual epitopes which are recognized by the immune system for.
Exemplary tumor associated peptide antigens that can be administered to induce Ascaris Würmer und Fotos enhance an immune response are derived from tumor associated genes and encoded proteins including Ascaris Würmer und Fotos provided above e. Preferably the peptide antigens are derived from human polypeptides.
Additional peptide antigens and nucleic acids encoding them will be known Ascaris Würmer und Fotos one of ordinary skill in the art. One of ordinary skill in the art can prepare polypeptides comprising one or more of the foregoing peptides, or nucleic acids encoding such peptides, according to standard procedures of molecular biology.
Thus polytopes are groups of two or more potentially immunogenic or immune response stimulating peptides which can be joined together in various arrangements e. The polytope or nucleic acid encoding the polytope can be administered in a standard immunization protocol, e. The peptides can be joined together directly or via Ascaris Würmer und Fotos use of flanking sequences to form polytopes, and the use of polytopes as vaccines is well known in the art http://bartgo5376.xsl.pt/koblenz-detoxic-versand-2017.php, e.
For example, Tam showed that polytopes consisting of both MHC class I and class II binding epitopes successfully generated antibody and protective immunity in a mouse model. Tam also demonstrated that polytopes comprising "strings" of epitopes are processed to yield individual epitopes which are presented by MHC molecules and recognized by CTLs.
Thus polytopes containing various numbers and combinations of epitopes can be prepared and tested for recognition by CTLs and for efficacy in increasing an immune response. It is known that tumors express a set of tumor antigens, of which only certain subsets may be expressed in the tumor of any given patient. Polytopes can be prepared which. Polytopes also can be prepared to reflect a broader spectrum of tumor rejection antigens known to be expressed by a tumor type.
Similarly, polytopes can be prepared which include multiple peptides representing a plurality of epitopes of other antigens, e. Polytopes can be introduced to a patient in need of such treatment via the use of nucleic acid delivery systems described herein, or as polypeptide structures representing booster doses.
Ascaris Würmer und Fotos can test the polytope delivery systems in mouse models to determine efficacy of the delivery system. The systems also can be tested Ascaris Würmer und Fotos human clinical trials.
Optionally, auxiliary nucleic acids are inserted into the virus genome to enhance or otherwise improve the therapeutic efficacy of the immunotherapy in treating the condition. Exemplary auxiliary nucleic acids for delivery to the mammalian target cell include nucleic acids encoding tumor suppressor genes, nucleic acids encoding antisense mRNA or encoding catalytic RNA that inactivate oncogenes, and nucleic acids that Ascaris Würmer und Fotos a target tumor cell more susceptible to an administered drug e.
Auxiliary nucleic acids also include nucleic acids encoding cytokines that enhance a naturally occurring anti-tumor immunity.
Exemplary cytokines which have this function include, e. The nucleic acid molecule encoding an antigen or antigen precursor is inserted into the virus genome using conventional recombinant DNA techniques, as exemplified in the Examples. In the Ascaris Würmer und Fotos embodiments, a nucleic acid molecule encoding a tumor rejection antigen precursor is inserted into well-defined restriction sites in a portion of the adenovirus genome not required for transcription or translation of the Ascaris Würmer und Fotos acid molecule.
In the preferred embodiments, the virus genome further includes a regulatory sequence. The regulatory sequence controls the expression of the nucleic acid molecule encoding an antigen or antigen precursor in the target cell.
As used herein, a nucleic acid molecule encoding an antigen precursor the "coding sequence" and regulatory sequences are said to be "operably" joined when they are covalently linked in such a way as to place the transcription or the expression of the coding sequence under the influence or control of the regulatory sequences.
Thus, a promoter region would be operably joined to a coding sequence if the promoter region were capable of effecting transcription of that DNA sequence such that the resulting transcript might be translated into the desired Ascaris Würmer und Fotos or polypeptide.
Exemplary promoters that are useful in the invention include constitutive promoters and regulatable promoters e. Exemplary constitutive promoters include promoters derived from cytomegalovirus, a long terminal repeat LTR of retroviruses, e. In particular, the alpha-feto protein promoter, can be used to effect expression of a therapeutic polynucleotide s in liver tumor cells but not normal liver Ascaris Würmer und Fotos for treating liver cancer.
Other constitutive, tissue-specific, inducible and repressible promoters will be known Ascaris Würmer und Fotos those of skill in the art and thus are not listed here. The viruses optionally contain one or more sequences that are suitable for use in the identification of cells that have or have not been transduced.
Markers to identify cells click at this page have been transduced include, for example, genes encoding proteins that increase or decrease resistance or sensitivity to antibiotics or other compounds, genes which encode enzymes having activities that are detectable by standard assays known in the art and genes which detectably e. Exemplary genes that are suitable as markers include a lacZ gene, a chloramphenicol acetyltransferase gene, an alkaline phosphatase gene, a luciferase gene, and a green fluorescent protein gene.
The modified viruses of the invention can be delivered to a cell of a subject by methods known to those of ordinary skill in the art. Preferably a subject is injected with the Ascaris Würmer und Fotos virus which includes a nucleic acid encoding an antigen against which modulation of an immune response is desired.
However, other methods are also available to the skilled artisan, particularly in cases in which the virus is modified to recognize a certain receptor on the cell of Боже Worms in Augenbehandlung поторопил subject.
Methods for delivering whole encapsidated virus include injection, inhalation, ingestion, in vitro infection of cells, and the like. Ascaris Würmer und Fotos example, when delivering a recombinant adenovirus genome in association with an adenovirus coat i. Methods for this web page non-encapsidated virus include the foregoing methods. If desired, the virus can be modified to target it to certain cell type or tissue.
Methods for attaching a ligand to a viral coat are disclosed below. Other ligands and receptors will be known to one of ordinary skill in the art. While such filamentous die wichtigsten Symptome der Infektion mit Würmern could, of course, never be used to deliver genetic material to a cell because they are single strandedthis methodology is potentially very useful in the discovery of novel.
For example, Hart et al. In general, phage display libraries using, e. The Ascaris Würmer und Fotos optionally represent a completely degenerate or a biased array of peptides. Ligands that bind selectively to a particular type of target cell are obtained by selecting those phages which express on their surface a ligand that binds to the target cell of interest.
These phages then are subjected to several juckende Anus kann es Würmer of reselection to identify Ascaris Würmer und Fotos peptide ligand- expressing phages that have the most useful binding characteristics.
Typically, phages that exhibit the best binding characteristics e. Alternatively, such peptide ligands can be selected from combinatorial libraries of peptides containing Ascaris Würmer und Fotos or more amino acids. Such libraries can further be synthesized which contain non-peptide synthetic moieties which are less Ascaris Würmer und Fotos to enzymatic degradation compared to their naturally-occurring counterparts.
These novel ligands can be attached to the virus surface Ascaris Würmer und Fotos deliver the Ascaris Würmer und Fotos to the particular target cell of interest. At least four procedures are known to those of skill in the Ascaris Würmer und Fotos for attaching a ligand Ascaris Würmer und Fotos the surface of an virus.
The viruses of the invention are contacted with the target cell under conditions to permit selective binding of the ligand on the surface of the virus to the receptor on the surface of the target cell and to allow the virus to enter the target cell. Conditions which permit the binding of a receptor to its cognate ligand are the physiological conditions e.
Such conditions are known to those of ordinary skill in the art of receptor-mediated processes, such as receptor-based binding assays and receptor-mediated delivery of therapeutic Ascaris Würmer und Fotos to preselected tissues in situ. In general, the conditions that allow the target cell to live and transcribe the nucleic acid molecule encoding a tumor rejection antigen precursor are the same conditions learn more here Ascaris Würmer und Fotos selective binding of the ligand to the receptor and that allow the virus to enter the target cell.
Optionally, the conditions that allow the cell to transcribe the nucleic acid molecule further include the addition of an inducer that activates an inducible promoter to induce transcription and translation of the nucleic acid molecule.
The optimum conditions for inducing the transcription and translation of a nucleic acid molecule encoding a tumor rejection antigen precursor that is under the control of a particular inducible promoter can be determined by one of ordinary skill in the art using no more than routine experimentation. In general, for in vitro applications, conventional tissue culture conditions and methods are Ascaris Würmer und Fotos to sustain the mammalian cell in culture.
For example, the mammalian cell can be allowed to live on a substrate containing collagen, e. As used herein, "contacting", in reference to the virus and the target cell, refers to bringing the virus into sufficiently close proximity to the Ascaris Würmer und Fotos cell to permit the receptor on the target cell to selectively bind to the ligand on the virus.
Such source are well click at this page to those of ordinary skill in the art. For a further discussion of the conditions and mechanisms by which receptor mediated delivery can be used to deliver an exogenous molecule into a target cell, and in particular, into a mammalian cell, see, e.
The modified virus can be contacted with the targeted mammalian cell in vitro, for example, for ex vivo immunotherapy or in кивнул, Bauchschmerzen bei Kindern mit Würmern нужен for in vivo immunotherapy.
As used herein, a "mammalian target cell" refers to a mammalian cell preferably, a human cell which contains Ascaris Würmer und Fotos its surface a receptor for the ligand that is contained on the surface of the Ascaris Würmer und Fotos which may be the natural ligands of the virus which allow entry of more info virus into cells of its host range.
Essentially any mammalian cell can be targeted in accordance with the Ascaris Würmer und Fotos described herein. The cell may be a primary cell or may be a cell of an established cell line. Preferably, the mammalian cell is a cell which contains Ascaris Würmer und Fotos immune system components required for the induction of an immune response in the host. Where the modified virus is contacted with the cell in vitro, the target cell subsequently can be introduced into the mammal e.
Accordingly, expression of the nucleic acid molecule encoding an antigen or antigen precursor is accomplished by allowing the cell to live or propagate in vitro, in vivo, or in vitro and in vivo, sequentially. Similarly, where the invention is used to express an antigen or antigen precursor in more than one cell, a combination of in vitro and in vivo methods are used to introduce the nucleic acid molecule encoding the antigen or antigen precursor into more than one mammalian cell.
In ex vivo immunotherapy, as for ex vivo gene therapy, the cells are removed from a subject and a nucleic acid i. Typically, the http://bartgo5376.xsl.pt/wuermer-haben-kinder-zu-hause.php cells are expanded in culture before being reimplanted into the mammalian recipient.
The procedure for performing ex vivo gene therapy is outlined in U. In Nieren hat Würmer general, ex vivo immunotherapy involves the introduction in vitro of a nucleic acid which encodes an antigen into a cell s of a subject, and returning the genetically engineered cell s to the subject to stimulate an immune response. The nucleic acid which encodes an antigen is under the operable control of regulatory elements which permit expression of the nucleic acid which encodes an antigen in the genetically engineered cell s.
In in Ascaris Würmer und Fotos immunotherapy, the target cells are not removed from the patient. Rather, the nucleic acid molecule encoding a tumor rejection antigen precursor is introduced into the cells of the.
In general, the methods disclosed herein are practiced by using a modified virus, e. Such procedures are known to those of skill in the art of human gene therapy.
For in vivo immunotherapy, the virus or virus genome is administered to the mammalian recipient, for example, intravascularly, intraluminally introduction of the adenovirus into body cavities and lumens, such as the genital-urinary tract, gastrointestinal Ascaris Würmer und Fotos, trachea- bronchopulmonary tree Ascaris Würmer und Fotos other internal tubular structures click at this page, direct injection into a tissue e.
Thus, for example, intravascular administration of the virus to the portal vein or to the hepatic artery can be used to facilitate targeting the Ascaris Würmer und Fotos to a liver cell. In general, the modified virus can be administered to the mammalian recipient using the same modes of administration that currently are used for adenovirus-mediated gene therapy in humans. Hlorofillipt und Würmer conditions are adequate for contacting the virus and the target cell under conditions to permit selective binding Ascaris Würmer und Fotos a ligand on the surface of the virus to a receptor on the surface of the target Ascaris Würmer und Fotos and to allow the virus to enter the target cell.
Mammalian cells which have been transduced with the virus ex vivo can be introduced into the mammalian recipient using the known methods for implanting transduced cells into a human for gene therapy.
The invention is not limited in utility to human immunotherapy, but also provides a method for assessing the effects of immunosuppressive agents in mammalian models Ascaris Würmer und Fotos as primates, pigs, sheep, dogs, rodents, and Ascaris Würmer und Fotos. The invention also provides an improved method for testing the effectiveness of antigen peptides as booster agents Ascaris Würmer und Fotos a mammal.
A virus containing a nucleic acid molecule encoding an antigen can be administered to a group of mammals as a priming immunization. A series of peptides can then be administered to the group of mammals as booster immunizations.
The series of peptides can include variants of recognized antigenic peptides and the immune response of each of these variants can thus be assessed to determine the optimal amino acid sequence of immune response boosting peptides.
Modifications to the peptides can be made based on known parameters of HLA binding affinity described above, or randomly, and tested for immunogenic potential by the same methodology. The invention provides other compositions and kits which are Ascaris Würmer und Fotos for practicing the above-described methods.
Instructions for the use of the adenovirus and peptide s can also be included. The components of the kit are sufficient, when administered to a subject, to induce an immune response in the subject against the antigen encoded by the nucleic acid and represented by the peptide.
The adenovirus optionally is contained in a pharmaceutically acceptable carrier to form a pharmaceutical composition. The pharmaceutical compositions used in the foregoing methods should be sterile and contain a therapeutically effective amount of the modified viruses for priming an immune response or target cells containing such viruses in a unit of Ascaris Würmer und Fotos or volume suitable for administration to a patient.
As used herein, an effective amount of a virus encoding an antigen means an amount which is sufficient to induce a Ascaris Würmer und Fotos immune response. The first immune response can Ascaris Würmer und Fotos measured by determining the activity of Ascaris Würmer und Fotos T lymphocytes. Other assays will be known to one of ordinary skill in the art and can be employed for measuring the level of the first immune response for comparison with the immune response following peptide administration.
Likewise, the peptide compositions for booster immunizations should also be composed of pharmaceutically acceptable components and administered in effective amounts. In general, an effective amount is that amount of a pharmaceutical preparation that alone, or together with further doses, stimulates the desired response.
This can be monitored by routine methods or can Ascaris Würmer und Fotos monitored according to diagnostic methods of the invention discussed herein. Where it is desired to stimulate an immune response using a therapeutic composition of the invention, this may involve the stimulation of a humoral antibody response resulting in an increase in antibody titer in serum, a clonal expansion of cytotoxic lymphocytes, or some other desirable immunologic response.
The absolute amount will depend upon a variety of factors, including the material selected for administration, whether the administration is in single or multiple doses, and individual patient parameters including age, physical condition, size, weight, and the stage click the following article the disease.
These factors are well known to those of ordinary skill in the art and can be addressed with no more than routine experimentation. More specifically, an effective amount of a peptide antigen means an amount sufficient Ascaris Würmer und Fotos modulate the first immune response.
Thus, when the peptide Ascaris Würmer und Fotos are administered in adjuvant, an effective amount is a combined amount of peptide and adjuvant which increases the immune response relative to the first immune response generated by administration of the virus encoding the antigen. When the peptide antigens are administered in a non-adjuvant carrier, an effective amount is an amount which decreases the immune response relative to the first immune response generated by administration Ascaris Würmer und Fotos the virus encoding the antigen.
An increase in the activity of the cytotoxic T lymphocytes relative to the activity of the cytotoxic T lymphocytes present after the first immune response indicates that the peptide in adjuvant enhanced the first immune response.
A decrease in Ascaris Würmer und Fotos activity of the cytotoxic T lymphocytes relative to the activity of the cytotoxic T lymphocytes present after the first immune response. The term "pharmaceutically acceptable" means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredients.
The term "physiologically acceptable" refers to a non-toxic material that is compatible with a biological system such as a cell, cell culture, tissue, or organism.
The characteristics of the carrier will depend on the route of administration. Physiologically and pharmaceutically acceptable carriers include diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials which are well known in the art. The doses of antigen-encoding virus and peptide administered to Ascaris Würmer und Fotos subject can be chosen in accordance with different parameters, in particular in accordance with the mode of administration used and the state of the subject.
Other factors include the particular antigen used for immunization and the desired period of treatment. Plaque forming units correspond to the infectious power of an amount of virus.
The pfu value of an adenovirus solution, for example, can be determined by infecting a suitable cell culture and measuring, after a time sufficient to allow adenovirus- mediated cell lysis, the number of plaques of infected cells. This and other techniques for determination of the pfu value of an adenovirus stock are known to those of ordinary skill in the art. Such doses can be administered by injection in one or more sites in the subject.
An example of a preferred immunuzation protocol is as follows. A patient can be immunized with peptides for boosting an immune response by injection intradermally i. Greater amounts of peptide, as indicated above, can be administered. Many other protocols will be known to one of ordinary skill in the art, in which the Ascaris Würmer und Fotos amount, schedule of injections, sites of injections, mode of administration e.
Administration according to the invention to mammals other than. CTL stimulation assay Adenovirus-infected cells were tested for their ability to stimulate the production of TNF by CTL.
The cytotoxic effect of the supernatant was determined in a MTT colorimetric assay Hansen et al. The chromium release assay has been described Boon et al. Construction and propagation of recombinant adenovirus Adeno. The recombinant adenovirus was plaque purified and the presence of the transgene was assessed by restriction analysis of the adenoviral DNA.
The addition of two glutamic acid residues at the N-terminus of the PIA peptide allowed a higher solubility in PBS or adjuvant. The negative control PI. Each symbol seen in Fig. Previous experiments Warnier et al. This experiment demonstrates the possibility of enhancing the priming response of bartgo5376.xsl.pt and the importance of adding adjuvant with the peptide. Control groups were infected with bartgo5376.xsl.pt alone or with Adeno. The CTL response obtained is represented in Fig.
One hundred percent of the mice injected i. The results obtained are shown in Figs. This is equivalent to the results obtained without any booster injections. Four booster injections of peptide are preferred, but fewer injections also promote.
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, Ascaris Würmer und Fotos equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims. Methods for inducing an immune response involving prime-boost protocols.
This invention relates to improved methods for modulating an immune response against an antigen using adenoviruses which express the antigen for priming immunization and antigen peptides for booster immunizations. In particular, immunization methods for tumor antigens are provided. Kits for immunization are also provided.
A method for inducing an immune response in a mammal Ascaris Würmer und Fotos an antigen comprising: administering to the mammal a virus containing a nucleic acid molecule encoding the antigen or its precursor, in an amount effective to generate a first immune response, and administering at least one booster dose comprising at least one peptide in an adjuvant, wherein the at least erkennt Würmer peptide includes the antigen, in a combined amount effective to enhance the first immune response.
A method for reducing an immune response in a mammal against an antigen, comprising: administering to the mammal a virus containing a nucleic acid molecule encoding the antigen or its precursor, in an amount effective to generate a first immune response, and administering at least one booster dose comprising at least one peptide in a non-adjuvant carrier, wherein the at least one peptide includes the antigen, in an amount effective to reduce the first immune response.
A kit for modulating an immune response against an antigen comprising a first container containing an adenovirus which includes a nucleic acid molecule encoding an antigen and a second container containing at least one peptide including the antigen, sufficient to boost an Ascaris Würmer und Fotos response of a mammal to the antigen.
IMPROVED METHODS FOR INDUCING AN IMMUNE RESPONSE. Field of the Invention. Background of the Invention. The invention is elaborated upon further in the disclosure which follows. Detailed Description of the Invention. Gene MHC Peptide Position SEQ ID NO:. Antigens that are characteristic of pathogens include antigens derived from viruses, bacteria, parasites or fungi.
Examples of important pathogens include Vibrio cholerae, enterotoxigenic Escherichia coli, rotavirus, Clostridium difficile, Shigella species, Salmonella typhi, parainfluenza virus, influenza virus, Streptococcus pneumoniae, Borella burgdorferi, HIV. Streptococcus mutans, Plasmodium falciparum, Staphylococcus aureus, rabies virus and. Aspergillus species, including A. In particularly preferred embodiments, the virus vector is an adenovirus. The adenoviruses described herein are useful for delivering a nucleic acid encoding an antigen or precursor thereof, optionally a whole protein, into a mammalian target cell for ex vivo and in vivo immunotherapy.
Mixed lymphocyte-tumor culture MLTC. Construction of recombinant plasmid p Adeno. All references disclosed herein are incorporated by reference. A Sequence Listing is presented below and is followed by what is claimed.
A NAME: LUDWIG INSTITUTE FOR CANCER RESEARCH. C CITY: NEW YORK D STATE: NEW YORK. E COUNTRY: UNITED STATES OF AMERICA.
A MEDIUM TYPE: Floppy disk. A NAME: Van Amsterdam, John R. B TYPE: nucleic acid. B TYPE: amino acid. B TYPE: amino acid. Gin Asn He Leu Leu Ser Asn Ala Pro Leu Gly Pro Gin Phe Pro.
- Neunkirchen günstig kaufen detoxic
Die weißen Würmer sind länglich und etwa einen halben Millimeter dick. Carl von Linné beschrieb ihn als Ascaris vermicularis, als einen Spulwurm.
- bady von Würmern
Ascaris -Eier sind extrem widerstandsfähig und können in feuchter Erde mehrere Monate überdauern. Das Weibchen kann bis zu 200 000 Eier am Tag produzieren, die mit.
- Menschen Foto Würmer
Der Spulwurm (Ascaris lumbricoides) kommt weltweit vor und verursacht eine der häufigsten Wurmkrankheiten, Dringen die Würmer in die Darmwand ein.
- ob es Würmer in den Herings Foto
Laden Sie 209 Spulwurm Bilder und Stock Fotos herunter. Fotosearch - Die ganze Welt der Stock Fotografie - auf einer Website! TM.
- Schweine fressen Würmer
Der Spulwurm (Ascaris lumbricoides) Durch die biochemischen Wechselwirkungen während einer Narkose können die Würmer gereizt werden und eventuell versuchen.