International collective of humanitarian organizations led by volunteers and guided by its Congressional Charter and the Fundamental Principles of the International Red Cross Movement, to provide relief to victims of disaster and help people prevent, prepare for, and respond to emergencies.
Stimulation at an intensity below that where a differentiated response can be elicited.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
Prepaid health and hospital insurance plan.
Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.
Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.
Any immunization following a primary immunization and involving exposure to the same or a closely related antigen.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Those forces and content of the mind which are not ordinarily available to conscious awareness or to immediate recall.
A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (GRANULOMATOUS DISEASE, CHRONIC) often die as a result of recurrent bacterial infections.
Class I-restricted activation of CD8-POSITIVE LYMPHOCYTES resulting from ANTIGEN PRESENTATION of exogenous ANTIGENS (cross-presentation). This is in contrast to normal activation of these lymphocytes (direct-priming) which results from presentation of endogenous antigens.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
The relationships between symbols and their meanings.
A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.
The time from the onset of a stimulus until a response is observed.
Learning in which the subject must respond with one word or syllable when presented with another word or syllable.
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Elements of limited time intervals, contributing to particular results or situations.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
Lists of words to which individuals are asked to respond ascertaining the conceptual meaning held by the individual.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.
Genetic loci associated with a QUANTITATIVE TRAIT.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.
Investigative technique commonly used during ELECTROENCEPHALOGRAPHY in which a series of bright light flashes or visual patterns are used to elicit brain activity.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The interference of one perceptual stimulus with another causing a decrease or lessening in perceptual effectiveness.
Mental process to visually perceive a critical number of facts (the pattern), such as characters, shapes, displays, or designs.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Any method used for determining the location of and relative distances between genes on a chromosome.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Substances that are recognized by the immune system and induce an immune reaction.
The sum or the stock of words used by a language, a group, or an individual. (From Webster, 3d ed)
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
A discipline concerned with relations between messages and the characteristics of individuals who select and interpret them; it deals directly with the processes of encoding (phonetics) and decoding (psychoacoustics) as they relate states of messages to states of communicators.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
The genetic process of crossbreeding between genetically dissimilar parents to produce a hybrid.
Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Protection conferred on a host by inoculation with one strain or component of a microorganism that prevents infection when later challenged with a similar strain. Most commonly the microorganism is a virus.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
An encapsulated lymphatic organ through which venous blood filters.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
The knowledge or perception that someone or something present has been previously encountered.
Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.
Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.
Established cell cultures that have the potential to propagate indefinitely.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
The rate dynamics in chemical or physical systems.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
Proteins prepared by recombinant DNA technology.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A verbal or nonverbal means of communicating ideas or feelings.
Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.
A single-stranded DNA-dependent RNA polymerase that functions to initiate, or prime, DNA synthesis by synthesizing oligoribonucleotide primers. EC 2.7.7.-.
Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
The selecting and organizing of visual stimuli based on the individual's past experience.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The circulation in a portion of the body of one individual of blood supplied from another individual.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
The adaptive superiority of the heterozygous GENOTYPE with respect to one or more characters in comparison with the corresponding HOMOZYGOTE.
The process whereby a representation of past experience is elicited.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures.
Immunoglobulins produced in response to VIRAL ANTIGENS.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Diseases of plants.
Glycoproteins found on the membrane or surface of cells.
The act of "taking account" of an object or state of affairs. It does not imply assessment of, nor attention to the qualities or nature of the object.
Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Vaccines or candidate vaccines containing inactivated HIV or some of its component antigens and designed to prevent or treat AIDS. Some vaccines containing antigens are recombinantly produced.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
A formulation for presenting an antigen to induce specific immunologic responses. It consists of an assembly of antigens in multimeric form. The assembly is attached to a matrix with a built-in adjuvant, saponin. ISCOMs induce strong serum antibody responses, and are used as highly immunogenic forms of subunit vaccines.
Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain.
Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.
The capacity of an organism to defend itself against pathological processes or the agents of those processes. This most often involves innate immunity whereby the organism responds to pathogens in a generic way. The term disease resistance is used most frequently when referring to plants.
The process by which a DNA molecule is duplicated.
Techniques used for determining the values of photometric parameters of light resulting from LUMINESCENCE.
Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.
Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Delivery of medications through the nasal mucosa.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.
The coordination of a sensory or ideational (cognitive) process and a motor activity.
An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC
Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it.
Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
The major group of transplantation antigens in the mouse.
Transport proteins that carry specific substances in the blood or across cell membranes.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Antibodies produced by a single clone of cells.
The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.
A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.)
The principle that items experienced together enter into a connection, so that one tends to reinstate the other.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The ability to respond to segments of the perceptual experience rather than to the whole.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
The mating of plants or non-human animals which are closely related genetically.
A characteristic showing quantitative inheritance such as SKIN PIGMENTATION in humans. (From A Dictionary of Genetics, 4th ed)
Mice bearing mutant genes which are phenotypically expressed in the animals.
Conceptual functions or thinking in all its forms.
Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of PLANTS.
The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body.
Enzymes that catalyze the template-directed incorporation of ribonucleotides into an RNA chain. EC 2.7.7.-.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.
A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A cognitive process involving the formation of ideas generalized from the knowledge of qualities, aspects, and relations of objects.
Vaccines consisting of one or more antigens that stimulate a strong immune response. They are purified from microorganisms or produced by recombinant DNA techniques, or they can be chemically synthesized peptides.
Includes both producing and responding to words, either written or spoken.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The production of offspring by selective mating or HYBRIDIZATION, GENETIC in animals or plants.
Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation.
An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Learning to respond verbally to a verbal stimulus cue.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Proteins found in any species of bacterium.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The science of language, including phonetics, phonology, morphology, syntax, semantics, pragmatics, and historical linguistics. (Random House Unabridged Dictionary, 2d ed)
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

Control of immune responses by savenger liver endothelial cells. (1/459)

The liver appears to be an organ favoring the induction of immune tolerance rather than immunity. Among the hepatic cell populations possibly involved in regulation of immune responses, liver sinusoidal endothelial cells (LSEC) are well suited to fulfill this role. LSEC are resident cells lining the hepatic sinusoidal wall and therefore are in intimate contact with leukocytes passing through the liver. They are equipped with numerous scavenger receptors rendering antigen-uptake in these cells extremely efficient. Antigen processing and MHC-restricted presentation of exogenous antigens for CD4 as well as CD8 T cells occurs equally with high efficiency. Importantly, CD4 and CD8 T cells that engaged in cognate interaction with LSEC have a tolerant phenotype. Thus LSEC contribute an important immune function to the liver: control of the immune response against circulating soluble antigens.  (+info)

Immunopathogenic mechanisms in psoriasis. (2/459)

Psoriasis is a common autoimmune skin disease characterized by T cell-mediated hyperproliferation of keratinocytes. The disease has a strong but complex genetic background with a concordance of approximately 60% in monozygotic twins, and recent linkage and high resolution association studies indicate that HLA-Cw*0602 is itself a major susceptibility allele for psoriasis. Patients carrying this allele have been shown to have different clinical features and earlier age of disease onset, and patients homozygous for this allele have about 2.5 times higher disease risk than heterozygotes. Published data indicate that CD8+ T cells may play a major effector role in psoriasis. Epidermal infiltration of predominantly oligoclonal CD8+ T cells, and probably also of CD4+ T cells in the dermis, is a striking feature of chronic psoriasis lesions, indicating that these cells are responding to specific antigens. We argue that CD4+ T cells are essential for initiating and maintaining the pathogenic process of psoriasis but that cross-primed CD8+ T cells are the main effector cells responding to antigens in the HLA-Cw*0602 binding pocket of keratinocytes. It is further proposed that CD8+ T cells are involved in the control of the Th1 polarization, which is observed in psoriasis lesions, through a complex interplay between CD4+, CD8+ T cells and cross-presenting dendritic cells. It is also suggested that spontaneous remissions or fluctuations in disease activity may be determined by a balance within the lesions between effector and suppressor CD4+ and CD8+ T cells.  (+info)

Cellular protein is the source of cross-priming antigen in vivo. (3/459)

Cross-priming is essential for generating cytotoxic T lymphocytes to viral, tumor, and tissue antigens that are expressed exclusively in parenchymal cells. In this process, the antigen-bearing parenchymal cells must somehow transfer their antigens to bone marrow-derived professional antigen-presenting cells. Although intact proteins, small peptides, or peptide-heat shock protein complexes can all be acquired and presented by antigen-presenting cells, the physiologically relevant form of antigen that is actually transferred from parenchymal cells and cross-presented in vivo is unknown and controversial. To address this issue we have investigated the ability of fibroblasts stably expressing chicken ovalbumin constructs targeted to different subcellular compartments to cross-prime cytotoxic T lymphocytes. Although these transfectants generated similar amounts of the immunogenic ovalbumin peptide, their cross-priming activity differed markedly. Instead, the cells cross-priming ability correlated with their steady-state levels of ovalbumin protein and/or the physical form/location of the protein. Moreover, in subcellular fractionation experiments, the cross-priming activity colocalized with antigenic protein. In addition, depletion of intact protein antigen from these cell fractions eliminated their cross-priming activity. In contrast, the major heat shock protein candidates for cross-presentation were separable from the cell's main sources of cross-priming antigen. Therefore, cellular proteins, rather than peptides or heat shock protein/peptide complexes, are the major source of antigen that is transferred from antigen-bearing cells and cross-presented in vivo.  (+info)

Antigen bias in T cell cross-priming. (4/459)

Activated CD8+ T cells detect virally infected cells and tumor cells by recognition of major histocompatibility complex class I-bound peptides derived from degraded, endogenously produced proteins. In contrast, CD8+ T cell activation often occurs through interaction with specialized antigen-presenting cells displaying peptides acquired from an exogenous cellular source, a process termed cross-priming. Here, we observed a marked inefficiency in exogenous presentation of epitopes derived from signal sequences in mouse models. These data indicate that certain virus- and tumor-associated antigens may not be detected by CD8+ T cells because of impaired cross-priming. Such differences in the ability to cross-present antigens should form important considerations in vaccine design.  (+info)

CD8+ T cell cross-priming via transfer of proteasome substrates. (5/459)

"Cross-priming" describes the activation of naive CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses.  (+info)

Despite differences between dendritic cells and Langerhans cells in the mechanism of papillomavirus-like particle antigen uptake, both cells cross-prime T cells. (6/459)

As human papillomavirus-like particles (HPV-VLP) represent a promising vaccine delivery vehicle, delineation of the interaction of VLP with professional APC should improve vaccine development. Differences in the capacity of VLP to signal dendritic cells (DC) and Langerhans cells (LC) have been demonstrated, and evidence has been presented for both clathrin-coated pits and proteoglycans (PG) in the uptake pathway of VLP into epithelial cells. Therefore, we compared HPV-VLP uptake mechanisms in human monocyte-derived DC and LC, and their ability to cross-present HPV VLP-associated antigen in the MHC class I pathway. DC and LC each took up virus-like particles (VLP). DC uptake of and signalling by VLP was inhibited by amiloride or cytochalasin D (CCD), but not by filipin treatment, and was blocked by several sulfated and non-sulfated polysaccharides and anti-CD16. In contrast, LC uptake was inhibited only by filipin, and VLP in LC were associated with caveolin, langerin, and CD1a. These data suggest fundamentally different routes of VLP uptake by DC and LC. Despite these differences, VLP taken up by DC and LC were each able to prime naive CD8(+) T cells and induce cytolytic effector T cells in vitro.  (+info)

HIV-1 Nef equips dendritic cells to reduce survival and function of CD8+ T cells: a mechanism of immune evasion. (7/459)

The accessory HIV-1 Nef protein is a crucial determinant for viral replication and pathogenesis. During HIV infection, loss of immune control in the setting of a strong and broad HIV-specific T-lymphocyte response, leads to a lethal outcome through AIDS. Moreover, dysfunction of dendritic cells (DCs) may contribute to the immune suppression associated with AIDS progression. We recently demonstrated that exogenous Nef selectively activates immature DCs manipulating their phenotypical, morphological, and functional developmental program. Here, we tracked whether Nef, targeting DCs, could be involved in the dysregulation of CD8+ T cell responses. We found that Nef inhibits the capacity of DCs to prime alloreactive CD8+ T cell responses down-regulating their proliferation and functional competence. This coincides with the induction of CD8+ T cell apoptosis. Nef oversees apoptotic killing of CD8+ T cells up-regulating TNF-alpha and FasL production by DCs and interfering with the death receptor pathway in CD8+ T cells and thus activating caspase 8. Our findings suggest that Nef may contribute to the immune evasion associated with HIV-1 infection, subverting DC biology. This may help explain the pleiotropic function that Nef plays during infection and makes this protein an attractive target for preventive and therapeutic intervention.  (+info)

Mature human Langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monocyte-derived dendritic cells. (8/459)

The emerging heterogeneity of dendritic cells (DCs) mirrors their increasingly recognized division of labor at myriad control points in innate and acquired cellular immunity. We separately generated blood monocyte-derived DCs (moDCs), as well as Langerhans cells (LCs) and dermal-interstitial DCs (DDC-IDCs) from CD34(+) hematopoietic progenitor cells. Differential expression of CD11b, CD52, CD91, and the CD1 isoforms proved useful in distinguishing these three DC types. All mature DCs uniformly expressed comparable levels of HLA-DR, CD83, CD80, and CD86, and were potent stimulators of allogeneic T cells after exposure either to recombinant human CD40L trimer or a combination of inflammatory cytokines with PGE(2). moDCs, however, required 0.5-1 log greater numbers than LCs or DDC-IDCs to stimulate comparable T cell proliferation. Only moDCs secreted the bioactive heterodimer IL-12p70, and moDCs phagocytosed significantly more dying tumor cells than did either LCs or DDC-IDCs. LCs nevertheless proved superior to moDCs and DDC-IDCs in stimulating CTL against a recall viral Ag by presenting passively loaded peptide or against tumor Ag by cross-priming autologous CD8(+) T cells. LCs also secreted significantly more IL-15 than did either moDCs or DDC-IDCs, which is especially important to the generation of CTL. These findings merit further comparisons in clinical trials designed to determine the physiologic relevance of these distinctions in activity between LCs and other DCs.  (+info)

Recent studies have demonstrated that TLR3 forms dimeric complexes with 45-bp segments of dsRNA, and that single TLR3 dimers formed with a 48-bp dsRNA ON are capable of activating transfected cells expressing high amounts of TLR3 (27). A goal of this study was to determine how TLR3/dsRNA complexes, formed with dsRNA ONs of varying lengths, function in primary cells, and to translate these findings into the development of well-defined, TLR3-dependent adjuvants. In this study, we examined the activation of DC by dsRNA ONs because this response is key for inducing acquired antiviral immunity. We have previously shown that the interaction of TLR3-ECD protein with dsRNA is highly dependent on dsRNA length and TLR3-ECD concentration (27), which implies that the ability of a specifically sized dsRNA ON to bind TLR3 and activate a cell is governed, in part, by the membrane density of TLR3 in the endosomes. Thus, the large differences in TLR3 expression levels that we observed between DC subsets are ...
Conjugating Ag to the modified SMEZ-2 superantigen construct M1 enables specific targeting to MHC class II+ APC in vivo without the toxic polyclonal T cell response associated with direct TCR engagement. Our results show that conjugated Ag is efficiently processed and presented to CD4+, and cross-presented to CD8+ T cells. Of particular significance, this form of Ag delivery provides access to pathway of cross-presentation operating in all DC populations assessed, including the three major DC subtypes in murine spleen. This finding contrasts with many other studies in which splenic CD4−CD8+ DC have been shown to be superior at cross-presentation than both of the CD8− DC subtypes (8, 9, 29). The knowledge that Ag can be efficiently targeted to promote cross-presentation in a variety of DC subtypes should be particularly useful in the design of vaccines against intracellular pathogens and tumors in which CD8+ T cell responses are desirable.. It has previously been reported that Ag incorporated ...
Cross-presentation is an important mechanism to elicit both immune defenses and tolerance. Although only a few DC subsets possess the machinery required for cross-presentation, little is known about differences in cross-presenting capabilities of DCs belonging to the same subpopulation but localized in different lymphoid organs. In this study, we demonstrate that steady-state thymic CD8(+) DCs can efficiently cross-prime naïve CD8(+) T cells in the absence of costimulation. Surprisingly, cross-priming by splenic CD8(+) DCs was dependent on licensing factors such as GM-CSF. In the absence of GM-CSF, antigen-MHC-class-I complexes were detected on thymic but not on splenic CD8(+) DCs, indicating that the cross-presentation capacity of the thymic subpopulation was higher. The observed cross-priming differences between thymic and splenic CD8(+) DCs did not correlate with differential antigen capture or costimulatory molecules found on the surface of DCs. Moreover, we did not detect overall ...
Cross-priming is a critical component of T cell responses to cancers and viruses, and involves transfer of antigen from antigen donor cells to the antigen presenting cells. In spite of the centrality of antigen in this process, the influence of the quantity of antigen expressed by the antigen donor cell on the efficiency of cross-priming remains unexamined. Here, I describe the creation of a novel system where the model antigen ovalbumin is expressed in P815 (d haplotype) cells under the control of an inducible promoter, producing a large amount of antigen synthesis upon induction. However, even in the un-induced condition, a very low level of ovalbumin can be detected using sensitive methods to amplify the weak signal. I have used titrated quantities of uninduced and induced cells, expressing vastly different quantities of ovalbumin, and have monitored cross-priming of the endogenous anti-OVA CD8+ T cell response quantitatively in C57BL/6 mice (b haplotype), using in vivo cytolytic T lymphocyte assays.
ABSTRACT: Cytotoxic T lymphocytes (CTL) responses are required to fight many diseases such as viral infections and tumors. At the same time, they can cause disease when induced inappropriately. Which factors regulate CTL and decide whether they should remain silent or react is open to debate. The phenomenon called cross-priming has received attention in this respect. That is, CTL expansion occurs if antigen is recognized on the surface of professional antigen presenting cells (APCs). This is in contrast to direct presentation where antigen is seen on the surface of the target cells (e.g. infected cells or tumor cells). Here we introduce a mathematical model, which takes the phenomenon of cross-priming into account. We propose a new mechanism of regulation which is implicit in the dynamics of the CTL: According to the model, the ability of a CTL response to become established depends on the ratio of cross-presentation to direct presentation of the antigen. If this ratio is relatively high, CTL ...
DCs are a critical component of immune responses in cancer primarily due to their ability to cross-present tumor-associated antigens. Cross-presentation by DCs in cancer is impaired, which may represent one of the obstacles for the success of cancer immunotherapies. Here, we report that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) blocked cross-presentation by DCs without affecting direct presentation of antigens by these cells. This effect did not require direct cell-cell contact and was associated with transfer of lipids. Neutrophils (PMN) and PMN-MDSC transferred lipid to DCs equally well; however, PMN did not affect DC cross-presentation. PMN-MDSC generate oxidatively truncated lipids previously shown to be involved in impaired cross-presentation by DCs. Accumulation of oxidized lipids in PMN-MDSC was dependent on myeloperoxidase (MPO). MPO-deficient PMN-MDSC did not affect cross-presentation by DCs. Cross-presentation of tumor-associated antigens in vivo by DCs was improved ...
Antigen uptake by dendritic cells and intracellular routing of antigens to specific compartments is regulated by C-type lectin receptors that recognize glycan structures. The OVA-LeX-induced enhancement of T cell cross-priming is MGL1-dependent as shown by reduced CD8+ effector T cell frequencies in MGL1-deficient mice. Moreover MGL1-mediated cross-presentation of OVA-LeX neither required TAP-transporters nor Cathepsin-S and […]. Read More ». ...
DCs are fundamental players in antitumor immunity through a process known as antigen cross-presentation, in which they process tumor-derived antigens into the MHC class I pathway for presentation to T cells that have the ability to kill cancer cells. This DC function is also required for the success of cancer vaccines and immunotherapy, but it is well established that tumor-associated DCs are defective in their ability to perform antigen cross-presentation. DCs from cancer patients and tumor-bearing animal models also accumulate higher amounts of lipids compared with DCs from healthy individuals, a process that has been implicated in defective cross-presentation by DCs. The mechanism underlying this association was unknown.. In collaboration with the group of Valerian Kagan, Ph.D., D.Sc., at the University of Pittsburgh, Gabrilovich and colleagues analyzed in great detail the events that take place in the DCs from tumor-bearing mice models and found that impaired cross-presentation, which ...
First described in 1973 by Ralf Steinman, dendritic cells have since attracted considerable attention. Their properties of antigen capture, presentation and T cell activation, place them both as a key bridge between the innate and adaptive immunity, as well as a switch between tolerance and immunity. Although, the human and mouse DC network share many similarities, one subset was discovered in mouse that had not yet found its equivalent in human: the CD8+ DC characterised by their ability produce IL-12, but most particularly to uptake dead cells and cross-present these exogenous antigens on MHC class I molecules. This function has been shown to be essential in the immune defense against many viruses, intracellular bacteria and tumors as well as for the maintenance of self tolerance. Four studies in J. Exp. Med provide insight into a potential human homologue to the mouse cross-presentation specialist CD8+ DC. A nice minireview from two DC experts: Villadangos and Shortman. ...
Researchers in Gommermans lab are aiming to shed light on the pathological processes associated with multiple sclerosis disease progression. To do this they need to look at many markers within intact tissues to understand what the immune cells are doing and how they correlate with tissue damage in the brain. Using IMC allows them to take a comprehensive approach to viewing the tissue ecosystem, with a goal of understanding the relevance of the different immune cell subsets and their location and how this relates to mechanisms in multiple sclerosis disease process. Gommerman is Professor and Graduate Coordinator at the University of Toronto in the Department of Immunology, where she spearheaded a new Applied MSc. In addition to examining the role of B lymphocytes in multiple sclerosis patients, her group focuses on how members of the TNF superfamily of molecules regulate immunity and autoimmunity. Gommerman also is the lead PI on a study to examine the effect of global migration on ...
The Journal of Immunology Targeting the Effector Site with IFN- -Inducing TLR Ligands Reactivates Tumor-Resident CD8 T Cell Responses to Eradicate Established Solid Tumors 1 Andrew J. Currie, 2,3 * Robbert
IRVINE, Calif. - August 14, 2019 - AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, announced today updated clinical data from its ongoing glioblastoma Phase 2 clinical trial, investigating AIVITAs platform immunotherapy targeting tumor-initiating cells. Blood plasma biomarker analyses have identified a robust immune response and a decrease of tumor biomarkers in 65% of treated patients, in a sample that represents 29% of the total Phase 2 clinical trial size.. Blood was collected from subjects at multiple time points, one week after each dose administration, and assayed for 450 different immune and tumor biomarkers. Treatment elicited a robust immune response, with biomarkers suggesting progressive activation of dendritic cell cross-presentation and progressive activation of a type II hypersensitivity antibody-mediated cytotoxic response. Most notably, 65% of the treated glioblastoma patients also showed a robust decrease of 27 different biomarkers ...
Antigen (Ag) crosspresentation by dendritic cells (DCs) involves the presentation of internalized Ags on MHC class I molecules to initiate CD8+ T
Induction of macrophage necrosis is a strategy used by virulent Mycobacterium tuberculosis (Mtb) to avoid innate host defense. In contrast, attenuated Mtb causes apoptosis, which limits bacterial replication and promotes T cell cross-priming by antigen-presenting cells. Here we show that Mtb infecti …
The induction of cytotoxic CD8+ T cell responses requires the presentation of antigenic peptides by MHC class I molecules (MHC I). MHC I usually present peptides derived from endogenous proteins. However, some subtypes of dendritic cells (DCs) have developed the ability to efficiently present peptides derived from exogenous antigens on MHC I via a process called cross-presentation. Cross-presentation is intimately linked to the induction of anti-viral, -bacterial and -tumor cytotoxic T cell (CTL) responses, as well as a wide variety of CTL-mediated diseases and transplant rejections. The molecular and cellular mechanisms underlying cross-presentation have been studied intensively since its original description, yet understanding of this process is incomplete and on the forefront of immunological research. Numerous pathways and models, some of them conflicting, have been described so far. Here, we review the various pathways reported as involved in cross-presentation, highlighting the complexity of this
Purpose: We previously reported that autophagy in tumor cells plays a critical role in cross-presentation of tumor antigens and that autophagosomes are efficient antigen carriers for cross-priming of tumor-reactive CD8+ T cells. Here, we sought to characterize further the autophagosome-enriched vaccine named DRibble (DRiPs-containing blebs), which is derived from tumor cells after inhibition of protein degradation, and to provide insights into the mechanisms responsible for their efficacy as a novel cancer immunotherapy.. Experimental Design: DRibbles were characterized by Western blot and light or transmission electron microscopy. The efficiency of cross-presentation mediated by DRibbles was first compared with that of whole-tumor cells and pure proteins. The mechanisms of antigen cross-presentation by DRibbles were analyzed, and the antitumor efficacy of the DRibble vaccine was tested in 3LL Lewis lung tumors and B16F10 melanoma.. Results: The DRibbles sequester both long-lived and short-lived ...
The development of effective cancer vaccines remains an urgent, but as yet unmet, clinical need. cell responses associated with therapeutic benefit. Anti-tumor protection was dependent on cross-presenting Batf3+DC, pDC and CD8+T cells. CD103+DC from the skin/tumor dLN of the immunized mice appeared responsible for activation of Ag-specific na?ve CD8+T cells, but were dependent on pDC for optimal effectiveness. Similarly, human XBP1 improved the capacity of human blood- and skin-derived DC to activate human T cells. These data support an important intrinsic role for XBP1 in DC for effective cross-priming and orchestration of Batf3+DCCpDC interactions, thereby enabling Gap 27 effective vaccine induction of protective anti-tumor immunity. Keywords: XBP1, DC, Cancer Vaccines, Cross-priming, CD8+T cells Introduction Immunotherapies utilizing vaccines, antibodies, and T Gap 27 cells have the potential to (re)activate and optimize the bodys immune system to fight off cancer (1). Although vaccines are ...
The development of effective cancer vaccines remains an urgent, but as yet unmet, clinical need. cell responses associated with therapeutic benefit. Anti-tumor protection was dependent on cross-presenting Batf3+DC, pDC and CD8+T cells. CD103+DC from the skin/tumor dLN of the immunized mice appeared responsible for activation of Ag-specific na?ve CD8+T cells, but were dependent on pDC for optimal effectiveness. Similarly, human XBP1 improved the capacity of human blood- and skin-derived DC to activate human T cells. These data support an important intrinsic role for XBP1 in DC for effective cross-priming and orchestration of Batf3+DCCpDC interactions, thereby enabling Gap 27 effective vaccine induction of protective anti-tumor immunity. Keywords: XBP1, DC, Cancer Vaccines, Cross-priming, CD8+T cells Introduction Immunotherapies utilizing vaccines, antibodies, and T Gap 27 cells have the potential to (re)activate and optimize the bodys immune system to fight off cancer (1). Although vaccines are ...
Background: Treatments that generate T cell-mediated immunity to a patients unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galalpha1-3Galbeta1-4GlcNAc (alpha-Gal) in situ leading to opsonization with pre-existing natural anti-alpha-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity. Methods: Various immunological effects of coating tumor cells with alpha-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI
TY - JOUR. T1 - Differential capacity of human interleukin-4 and interferon-alpha monocyte-derived dendritic cells for cross-presentation of free versus cell-associated antigen. AU - Ruben, J.M.. AU - Bontkes, H.J.. AU - Westers, T.M.. AU - Hooijberg, E.. AU - Ossenkoppele, G.J.. AU - de Gruijl, T.D.. AU - van de Loosdrecht, A.A.. PY - 2015. Y1 - 2015. U2 - 10.1007/s00262-015-1741-1. DO - 10.1007/s00262-015-1741-1. M3 - Article. C2 - 26216454. VL - 64. SP - 1419. EP - 1427. JO - Cancer Immunology and Immunotherapy. JF - Cancer Immunology and Immunotherapy. SN - 0340-7004. IS - 11. ER - ...
S. cerevisiae, a nonpathogenic yeast, has recently gained interest as a vaccine vehicle for the treatment of cancer and infectious diseases. The construct is safe, as the yeast is heat killed before administration. It can be easily engineered to express antigens in large quantities and can be cultured rapidly. In addition, S. cerevisiae can induce a robust host immune response, delivering antigen to both MHC class I and II pathways by cross-priming (1, 4-6, 26). All of these qualities make S. cerevisiae an attractive vehicle for cancer immunotherapy. In this study, we sought to determine for the first time whether vaccination with a yeast construct expressing a TAA could break tolerance and induce antigen-specific T-cell and antitumor responses. The data presented here show that vaccination with yeast-CEA not only elicits CEA-specific CD4+ and CD8+ T-cell responses but also decreases tumor volume and increases overall survival in tumor-bearing mice. For comparison, CEA-Tg mice were also ...
The Dutch Cancer Society (KWF) has awarded 25.5 million euros to 50 new research projects in 16 different institutes.. 8 grants are awarded to Radboudumc researchers, 2 for our department:. Research project: Induction of neo-antigen specific T cells by specialised cross-presenting dendritic cells in epithelial ovarian cancer ...
Singh SK, Streng-Ouwehand I, Litjens M, Burgdorf S, Kurts C, Kalay H. Saeland E, Unger WWJ, and VAN KOOYK Y. Design of neo-glycoconjugates that target the Mannose Receptor and enhance TLR independent cross-presentation and Th1 polarization. Eur. J. Immunol, 41(4):916-25, 2011 ...
TY - JOUR. T1 - A subset of toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells. AU - Datta, Sandip K.. AU - Redecke, Vanessa. AU - Prilliman, Kiley R.. AU - Takabayashi, Kenji. AU - Corr, Maripat. AU - Tallant, Thomas. AU - DiDonato, Joseph. AU - Dziarski, Roman. AU - Akira, Shizuo. AU - Schoenberger, Stephen P.. AU - Raz, Eyal. PY - 2003/4/15. Y1 - 2003/4/15. N2 - Dendritic cells (DCs) are capable of cross-presenting exogenous Ag to CD8+ CTLs. Detection of microbial products by Toll-like receptors (TLRs) leads to activation of DCs and subsequent orchestration of an adaptive immune response. We hypothesized that microbial TLR ligands could activate DCs to cross-present Ag to CTLs. Using DCs and CTLs in an in vitro cross- presentation system, we show that a subset of microbial TLR ligands, namely ligands of TLR3 (poly(inosinic-cytidylic) acid) and TLR9 (immunostimulatory CpG DNA), induces cross-presentation. In contrast to presentation of Ag to CD4+ T ...
Absence of Cross-Presenting Cells in the Salivary Gland and Viral Immune Evasion Confine Cytomegalovirus Immune Control to Effector CD4 T ...
In this work, we have shown that overexpression of Bcl-2 protects peripheral CD8 T cells from deletion in response to cross-presented self antigen. The OT-I.Eμ-Bcl-2 and OT-I.vav.Bcl-2 cells appeared similar to wild-type OT-I cells in their ability to be activated and proliferate in response to cross-presented self-antigen. If sufficiently high numbers of OT-I.Eμ-Bcl-2 T cells were transferred, they induced autoimmune diabetes (Table I). As a pro-survival molecule Bcl-2 protects lymphocytes in vitro and in vivo against apoptosis induced by growth factor deprivation, DNA damage or treatment with corticosteroids or calcium ionophores (16). For activated T cells in vivo, bcl-2 transgene expression prolongs T cell survival following injection of mice with the superantigen staphylococcus enterotoxin B (SEB; reference 16), the transfer of HY-TCR CD8 T cells into male recipients (18), the immunization of mice expressing a transgenic LCMV-TCR in CD8 T cells with LCMV peptide (19) and the immunization ...
To determine if mesothelin is recognized by CD8+ T cells, we screened antigen-pulsed T2 cells in a quantitative ELISPOT-based assay using pre- and postvaccination CD8+ T cell-enriched PBLs from the 14 patients treated previously with the allogeneic, GM-CSF-secreting pancreatic tumor vaccine. Previously, we reported the association of in vivo postvaccination DTH responses to autologous tumor in three out of eight patients receiving the highest two doses of vaccine. PBLs obtained before vaccination and 28 d after the first vaccination were initially analyzed. T2-A3 cells pulsed with the two A3 binding epitopes were incubated overnight with CD8+ T cell-enriched lymphocytes isolated from the peripheral blood of patients 11 (an A3 non-DTH responder) and 13 (an A3 DTH responder), and analyzed using an IFN-γ ELISPOT assay. The ELISPOT assay was chosen because it requires relatively few lymphocytes, is among the most sensitive in vitro assays for quantitating antigen-specific T cells, and correlates ...
Topical antigen (Ag) application mimics natural Ag exposure across the skin. Soluble Ag introduced through this route requires cross-presentation by dendritic cells (DCs) to generate CD8 T cell responses, including skin-homing ...
Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. We functionalized tailored nanoemulsions encapsulating tumor antigens to target Clec9A (Clec9A-TNE). Clec9A-TNE encapsulating OVA antigen targeted and activated cross-presenting DCs without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. OVA-Clec9A-TNE-induced DC activation required CD4 and CD8 epitopes, CD40, and IFN-α. Clec9A-TNE encapsulating HPV E6/E7 significantly suppressed HPV-associated tumor growth, while ...
Immunostimulatory cytidyl guanosyl (CpG) motifs are of great interest as cancer vaccine adjuvants. They act as potent inducers of Th1 responses, including the activation of cytotoxic CD8(+) T lymphocytes (CTL). Whereas animal models have provided clear evidence that CpG enhances antitumor immunity, clinical trials in humans have thus far been less successful. Applying cryosurgery as an instant in situ tumor destruction technique, we now show that timing of CpG administration crucially affects colocalization of antigen and CpG within EEA-1(+) and LAMP-1(+) compartments within dendritic cells in vivo. Moreover, antigen/CpG colocalization is directly correlated with antigen cross-presentation, the presence of CTL, and protective antitumor immunity. Thus, failure or success of CpG as a vaccine adjuvant may depend on colocalization of antigen/CpG inside DCs and hence on the timing of CpG administration. These data might aid in the design of future immunotherapeutic strategies for cancer patients ...
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The vertebrate immune system uses multiple, sometimes redundant, mechanisms to contain pathogenic microorganisms that are always evolving to evade host defenses. Thus, the cowpox virus (CPXV) uses genes encoding CPXV12 and CPXV203 to prevent direct MHC class I presentation of viral peptides by infected cells. However, CD8 T cells are effectively primed against CPXV by cross-presentation of viral Ags in young mice. Old mice accumulate defects in both CD8 T cell activation and cross-presentation. Using a double-deletion mutant (∆12∆203) of CPXV, we show that direct priming of CD8 T cells in old mice yields superior recall responses, establishing a key contribution of this mechanism to host antipoxvirus responses and enhancing our fundamental understanding of how viral manipulation of direct presentation impacts pathogenesis ...
The presence of TILs has been shown to be a favorable prognostic indicator in a number of cancers, and gene expression profiling demonstrated that patients with high baseline tumor expression of genes related to both innate and adaptive immune response were more likely to favorably respond to immunotherapy (7, 23, 24). The presence of TILs in tumors has been shown to be associated with type I IFN transcriptional profile, and additional studies demonstrated the critical role for type I IFN in CD8a+ DC-mediated antigen cross-presentation and priming of tumor-specific CD8+ T cells (8, 9). These findings provide a strong rationale to explore tumor therapeutic strategies that activate the type I IFN pathway. Indeed, combination therapy using intratumoral CpG oligonucleotides with antibodies targeting immune checkpoints has been shown to be an effective therapeutic strategy resulting in depletion of Tregs at the injected tumor site and in regression of distant tumors (25).. Here, to trigger ...
Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 18 transcription factors that are expressed in DCs, we have identified PU.1, IRF8, and BATF3 transcription factors as being sufficient to reprogram both mouse and human fibroblasts to induced DCs (iDCs). iDCs acquire a conventional DC type 1-like transcriptional program, with features of interferon-induced maturation. iDCs secrete inflammatory cytokines and have the ability to engulf, process, and present antigens to T cells. Furthermore, we demonstrate that murine iDCs generated here were able to cross-present antigens to CD8+ T cells. Our reprogramming system should facilitate better understanding of ...
Superparamagnetic iron oxide nanoparticles (SPIO) have been synthesized and explored for use as carriers of various nanoadjuvants via loading into dendritic cells (DCs). In our study, homogeneous and superparamagnetic nanoparticles are susceptible to internalization by DCs and SPIO-pulsed DCs showed excellent biocompatibility and capacity for ovalbumin (OVA) cross-presentation. Herein, we found that SPIO-loaded DCs can promote the maturation and migration of DCs in vitro. SPIO coated with 3-aminopropyltrimethoxysilane (APTS) and meso-2,3-dimercaptosuccinic acid (DMSA), which present positive and negative charges, respectively, were prepared. We aimed to investigate whether the surface charge of SPIO can affect the antigen cross-presentation of the DCs. Additionally, the formation of interleukin-1β (IL-1β) was examined after treatment with oppositely charged SPIO to identify the nanoadjuvants mechanism. In conclusion, our results suggest that SPIO are biocompatible and can induce the migration of DCs
Enhanced apoptosis of BCG-infected macrophages has been shown to induce stronger dendritic cell-mediated cross-priming of T cells, leading to higher protection against tuberculosis (TB). Uncovering host effectors underlying BCG-induced apoptosis may then prove useful to improve BCG efficacy through …
Protein antigen (Ag)-based immunotherapies have the advantage to induce T cells with a potentially broad repertoire of specificities. However, soluble protein Ag is generally poorly cross-presented in
In mouse, a subset of dendritic cells (DCs) known as CD8alpha+ DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8alpha+ DCs in
Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. We tested whether the gut microbiota modulates antitumor immune response following RT distal to the gut. Vancomycin, an antibiotic that acts mainly on gram-positive bacteria and is restricted to the gut, potentiated the RT-induced antitumor immune response and tumor growth inhibition. This synergy was dependent on TAA cross presentation to cytolytic CD8+ T cells and on IFN-γ. Notably, butyrate, a metabolite produced by the vancomycin-depleted gut bacteria, abrogated the vancomycin effect. In conclusion, depletion of vancomycin-sensitive bacteria enhances the antitumor activity of RT, which has important clinical ramifications.. ...
BACKGROUND: Recent studies have shown that the thromboxaneA 2 -dependent pathway is dependent upon the adenosine diphosphate (ADP)-P2Y 12 pathway and that strong P2Y 12 receptor blockade alone causes inhibition of platelet aggregation that is minimally enhanced by aspirin. Data from the PLATO trial suggested that among ticagrelor-treated patients, high compared with low dose (,100mg\day) aspirin is associated with increased risk for ischemic events. OBJECTIVES: In the current prospective, randomized, placebo-controlled, double-blind, cross-over study, we sought to evaluate the impact of aspirin withdrawal on platelet reactivity in acute coronary syndrome (ACS) patients treated with a potent P2Y 12 blocker ...
Cancer, Bladder, Bladder Cancer, Mannose, Patients, Tumor, Patient, Risk, Risk Factors, Antigen, Antigen-presenting Cells, Antigens, Cancer Vaccines, Cancers, Cells, Chorionic Gonadotropin, Cross-presentation, Early Intervention, Gm-csf, Gonadotropin
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Free Essay: The immune system performs specific defense against agents, the antigens that are foreign or harmful to the body. Exogenous antigens are often in...
Peripheral blood lymphocytes from 9 monoclonal gammopathies of undetermined significance (MGUS) and 27 multiple myelomas (MM) were studied with a panel of monoclonal antibodies (MoAb) that recognize B and T lymphocytes and plasma cells. No difference in the percentage of B lymphocytes, identified by B1 and B4 MoAb, was observed in MGUS and MM patients versus normal controls. However, high percentages of circulating lymphocytes expressing plasma cell-associated antigens were detected in MM (HAN-PC1+ = 29.4 +/- 20.4%; TEC-T10+ = 27.8 +/- 19.2%) whereas they were in the normal range in MGUS (HAN-PC1+ = 8.8 +/- 5.8% p = 0.006; TEC-T10+ = 5.7 +/- 4.7% p less than 0.001). Almost identical results were obtained using PCA-1 MoAb in 17 of these patients. TEC-T10+ and PCA-1+ lymphocytes were sorted and re-analyzed with phycoerythrin conjugated MoAb in 3 healthy subjects, 2 MGUS, and 4 MM patients. In normal subjects and in MGUS the majority of PCA-1+ cells belonged to the B lineage (Leu 2-, Leu3-, Leu ...
Our team studies antigen presentation by DC. It has demonstrated cross-presentation ability of human plasmacytoid DC (pDC) and conventional DC1 bearing the chemokine receptor XCR1. We showed that DC perform cross-presentation of HIV antigens to specific CD8+ T lymphocytes specific for HIV very efficiently not only from apoptotic infected cells, but also from live cells. We are seeking to exploit this antigen presentation from live cells to kill cells which are HIV reservoirs or, with Armelle Prévost-Blondel, metastatic melanoma cells. (Immune activation and suppression during HIV infecton). We study the roles of different DC and monocyte/macrophage populations in T cell response polarization et in type I or III IFN production during HIV infection. We were the first to show during this infection the depletion of circulating DC et the accumulation of pro-inflammatory slan+ monocytes. Our aim is to reduce the reservoirs and the immune hyper activation and immune suppression which are linked to ...
The new Echo1USA Polymer XCR is in stock and ready for any sort of CQB gaming!. XCR Pistol in Black. XCR Pistol in Tan. 350 fps out of the box with an 8mm bearing gearbox for 20~ bps with a lipo and it is lipo ready!. ...
The ability of dendritic cells (DCs) to take up whole tumor cells and process their antigens for presentation to T cells (cross-priming) is an important mechanism for induction of tumor specific immunity. In vitro generated DCs were loaded with killed allogeneic breast cancer cells and offered to autologous naïve CD8+ T cells in 2-week and/or 3-week cultures. CD8+ T cell differentiation was measured by their capacity to secrete effector cytokines (interferon-γ) and kill breast cancer cells. Specificity was measured using peptides derived from defined breast cancer antigens. We found that DCs loaded with killed breast cancer cells can prime naïve CD8+ T cells to differentiate into effector cytotoxic T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A*0201- breast cancer cells can kill HLA-A*0201+ breast cancer cells. Among the tumor specific CTLs, we found that CTLs specific for HLA-A2 restricted peptides derived from three well known shared breast tumor antigens,
Supplementary Materials Supplemental Textiles (PDF) JEM_20180660_sm. mediates the cross-priming of CD8+ T cells (Hildner et al., 2008). In mice, lymphoid resident Batf3-dependent DCs are characterized by manifestation of CD8, whereas Batf3-dependent tissueCresident and migratory lymphoid DCs are instead CD103+CD11b? (Edelson et al., 2010). Homologous DCs in human being tissue are characterized by manifestation of CD141 (Bachem PSI et al., 2010; Jongbloed et al., 2010; Haniffa et al., 2012). Studies in proto-oncogene (Hirota et al., 1998; Joensuu and DeMatteo, 2012). Imatinib mesylate is definitely a small molecule inhibitor of KIT and enhances median overall survival in metastatic disease from 9 mo to 5 yr (Demetri et al., 2002; Blanke et al., 2008). The antitumor effect of imatinib is definitely partially mediated by CD8+ T cells through inhibition of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), which is produced by tumor cells as a product of constitutive Kit signaling ...
POSTDOCTORAL POSITIONS AVAILABLE My laboratory is investigating various aspects of how the immune system carries out surveillance to detect viral infections, cancers and cell death. Among the areas of research are: (1) The alarm signals and the receptors that alert the immune system to potential danger; (2) The mechanisms by which sentinel cells (dendritic cells) acquire and display antigens to CD8 T cells (cross presentation), a process that is essential for immune surveillance of tissues; and, (3) The antigen presentation pathway by which virally infected or cancer cells display their antigens to effector CD8 T cells (MHC class I antigen presentation), a process that is essential for the immune system to detect and eliminate these pathological cells. The laboratory is in a new state of the art research building and part of a very strong and interactive immunology community at UMass Medical School. UMass Medical School is located in Worcester Massachusetts, just outside of Boston. Interested ...
June 1, 2018 - Socium Therapeutics, Inc. (Socium) announced that it had finalized the acquisition of Aeterna Zentaris live recombinant oral allogenic immunotherapy platform (Platform), including AEZS-120, the most advanced product candidate for prostate cancer which is ready to enter a Phase I clinical trial. As part of the acquisition, Socium owns all intellectual property, regulatory dossiers, pre-clinical data and cellular material related to the Platform.. Tim Salmon, Co-founder, President and CEO of Socium, commented, The Platform, which we refer to as the CReST Platform (Cross-presenting Recombinant Salmonella typhi Ty21a), represents a major step forward in immuno-oncology. The CReST Platform provides for oral delivery; leverages the long, safe human use of S. typhi Ty21a to treat typhoid fever; activates the largest concentration of immune cells in the gut; and induces tumor-antigen-specific killer T-cell activation in vivo. Candidates from the CReST Platform will be tested in ...
Scientific evidence worldwide proves Mulberry Leaf Extract is one of the most powerful natural herbal supplements; blood sugar, cholesterol, weight managment
Cross-Modal Priming Task. The Cross-Modal Priming Task (CMPT), developed by David Swinney, is an online measure used to detect ... Results showed that priming was not activated at any of the probe positions-signifying a poverty of resources available to ... Here, the idea is that multiple meanings are activated at the moment an ambiguity is encountered in a sentence, which primes ... However, if one meaning or another is activated, then the response time should be quicker for the priming of that meaning. ...
Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the ... peaceful coexistence of cross-priming and direct priming?. Eur J Immunol. 2003, 33 (10): 2645-54. PMID 14515248. doi:10.1002/ ... Antigen bias in T cell cross-priming. Science. 2004, 304 (5675): 1314-7. PMID 15166378. doi:10.1126/science.1096268.. ... Bevan, Michael J. Cross-priming. Nature Immunology (Nature Publishing Group). 2006, 7 (4): 363-365. PMID 16550200. doi:10.1038/ ...
The Prime Meridian crosses the hill. Botley Hill is a Marilyn (a hill with topographic prominence of at least 150m), and the ... By coincidence Botley Hill lies due south of the Greenwich Observatory, as the Prime Meridian of the world passes over the top ...
He was double-crossed by Superboy-Prime. Evil Eye - A large one-eyed green monster with tentacles from the Monsterlands. ... They find a small prison containing Superboy-Prime in the Monsterlands as Superboy-Prime states that he can hear what Mister ... Killed by Superboy-Prime. Wicked Witch of the West - An evil green-skinned witch in an eyepatch from the Wozenderlands. "The ... He then proceeds to summon the Monster Society of Evil leaving Dummy behind who is tricked by Superboy-Prime into freeing him. ...
Faranda, Franco (2010-03-05). "Le prime croci" [The first crosses] (html). NoteArtistiche (in Italian). Retrieved 2014-08-07. ... Sandberg-Vavalà, Evelyn (1985). La croce dipinta italiana e l'iconografia della Passione [The painted Italian cross and the ... and even further down and precisely on the end of the cross read a fragment of the text A. D. MCLXXXVII. M.... Opus. Alberto. ...
The Prime Meridian crosses Calp. There are some remains that testify the presence of inhabitants in the region of Calp in ...
Pennington-Cross, Anthony. Subprime & Prime Mortgages: Loss Distributions. OFHEO Working Paper Number 03-1, Office of Federal ... Ambrose, Brent W., and Anthony Pennington-Cross. "Local Economic Risk Factors and the Primary and Secondary Mortgage Markets." ...
The Prime Meridian crosses El Verger. The municipal boundaries confront those of Beniarbeig, Benimeli, Murla, Dénia, Ondara and ...
First-cross Ewes & Prime Lambs; Eggs - Free-range eggs; Poultry Meat - Broilers raised and sold onsite, Oranges - Washington ... The school also holds annual sporting carnivals, including the Swimming, Cross-Country and Athletics Carnivals, where students ...
The Institute's prime objectives include: strengthening cross-border collaboration globally; upholding professional excellence ...
Prime Ministers of Finland customarily receive the Grand Cross. (Certain leftist politicians refused the cross or didn't wear ... Grand Cross with collar, jewels and swords was awarded only once, to Carl Gustaf Emil Mannerheim 4 June 1944. Grand Cross with ... The classes of the Order of the White Rose of Finland are: Grand Cross of the White Rose of Finland with Collar Grand Cross of ... Grand Cross with swords has been awarded to three Finnish Lieutenant Generals: Hjalmar Siilasvuo, Edvard Hanell and Aksel Airo ...
The Prime Meridian crosses the northeast corner of Telscombe parish. The town has a school, Telscombe Cliffs Primary. The ...
A line has been crossed' - Prime Minister sidelines controversial MPs". Sky News. Australia. 29 April 2012. Retrieved 26 June ... Prime Minister Julia Gillard commented that "It's clear that there have been real problems at the HSU. That's distressing I ... There is a line which has been crossed here." She said the decision was solely hers but that Thomson agreed with her. Later he ... During Question Time on 16 August 2011, Prime Minister Gillard was asked if her confidence in Thomson was based on a thorough ...
The school's prime rival is cross-town Burlington High School. Rice Memorial's mascot is the Green Knight. State Championships ...
Honorary Knight Grand Cross Riaz Pasha KCMG Prime Minister of Egypt. Charles Bruce CMG Lt.-Governor and Government Secretary of ... Khalifa Syed Mahomed Hassan, Prime Minister of Patiala. Brigade Surgeon Isidore Bernadotte Lyon, Bombay Medical Establishment. ... Knight Grand Cross, etc.) and then divisions (Military, Civil, etc.) as appropriate. Joseph Edgar Boehm, Royal Academy. George ...
The parish covers an area of 2,333.222 hectares (5,765.52 acres). The Prime Meridian crosses the coast to the east of Roos. The ...
"Primary sterile necrotic cells fail to cross-prime CD8(+) T cells". Oncoimmunology. 1 (7): 1017-1026. doi:10.4161/onci.21098. ...
C. Kurts, B. W. S. Robinson, P. A. Knolle: Cross-priming in Health and Disease. In: Nat Rev Immunol. 10(6), 2010, S. 403-414. V ... C. Kurts, B. W. S. Robinson, P. A. Knolle: Cross-priming in Health and Disease. In: Nat Rev Immunol. 10(6), 2010, S. 403-414. C ... Alternative cross-priming through CCL17-CCR4-mediated CTL attraction towards NKT cell-licensed dendritic cells. In: Nat Immunol ... Christian Kurts in known for publications in the fields of cross-presentation, and immune tolerance as well as his work on the ...
At Wrestlelution 6 on October 20, Justice lost the Prime Television Title to Matt Cross. On the May 10, 2010 edition of Raw at ... At Pressure Rising, Justice turned heel on Prime Wrestling Commissioner, Justin LaBar, Matt Cross, and Gregory Iron as he ... On the April 21, 2013 edition of Prime Wrestling, Justice defeated Facade for the Prime Television Championship due to an ... 473 of the top 500 wrestlers in the PWI 500 in 2018 Pro Wrestling Ohio / Prime Wrestling Prime Television Championship (1 time ...
"Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming". Nature Medicine. 7 (3): 297-303 ...
The town has also produced three Prime Ministers and a number of Victoria Cross winners. Life Members G. Blatch I. Newby D. R. ...
Effects of Cross-Religious Primes on Prosocial Behavior" (PDF). The International Journal for the Psychology of Religion. 26 (4 ... Cross-culturally, representational models of gods' minds take an array of diverse forms, such as anthropomorphic or zoomorphic ... For instance, the cross-cultural prevalence of omniscient, moralistic gods (i.e., Big Gods) is positively correlated with ... Another recent cross-cultural study compiled experimental economic game data from multiple large- and small-scale societies ...
The Prime Meridian crosses the coast to the north-west of Withernsea. According to the 2011 UK census, Withernsea parish had a ...
... 's television stations are identical to Bendigo's: ABC, Prime, WIN, Southern Cross Ten and SBS. Author James Aldridge ... The local inhabitants gave the expedition a rousing farewell as they crossed into New South Wales. Folklore alleges Burke and ... Morrell, Timothy (October-December 2013). "LORRAINE CONNELLY-NORTHEY: CROSS-CULTURAL CONSTRUCTS". Art Collector (66). Swan Hill ...
Prime Minister Gordon Coates who had criss-crossed the electorate with three other ministers was humiliated; though Coates ... Parker was endorsed by former Prime Minister Sir Joseph Ward who campaigned in the electorate for him. Reform The Reform Party ...
This prime mover was praised for its reliability and good cross country ability. It was criticized for having low power, a ...
... best exemplified by the arboreal crosses in the temple shrines of the Cross Group in Palenque. The king was the prime ... For earlier periods, such crosses and shrines can, perhaps, be thought of as being connected to the central 'cross', or world ... The focus of these rituals were often crosses, or rather, 'cross shrines', and prayers were directed at rain and earth deities ... crosses, dressed as women, and especially a 'Talking Cross', played the main roles. In the Alta Verapaz, the role of saints and ...
Cross lobbied Prime Minister Laurier for Rutherford to be appointed to the Senate. He was unsuccessful, but Rutherford was made ... Cross had by now joined the Sifton cabinet, which placated most members of the Cross-Rutherford faction. In the 1913 election, ... Oliver was implacably opposed to Cross and viewed him as a rival for dominance of the Liberal Party in Alberta, and his ... Calgary's case was made most enthusiastically by Minister of Public Works Cushing, Edmonton's by Attorney-General Cross. Banff ...
The Prime Meridian crosses the Desert de les Palmes roughly in the middle. The Columbretes Islands can be seen on clear days in ... It is located near the Mediterranean coastline, crossed by the highway between Barcelona and Valencia. This mountain range has ...
Exploring the role of cognitive control in syntactic processing: Evidence from cross-language priming in bilingual children. ... Evidence from cross-language priming in bilingual children". Linguistic Approaches to Bilingualism. 8 (5): 606-636. doi:10.1075 ... ANDERSSEN, MERETE; LUNDQUIST, BJÖRN; WESTERGAARD, MARIT (2018-07-10). "Cross-linguistic similarities and differences in ...
Red Cross Youth. *Singapore Scout Association. *Girl Guides Singapore. *St. John Ambulance Brigade ...
27th Prime Minister of Cambodia. .mw-parser-output .nobold{font-weight:normal}. (Prime Minister of Kampuchea). ... at which many of Pol Pot's troops crossed into Thailand itself.[358] The Vietnamese advanced on Tasanh, which the Khmer Rouge ... Prime Minister of Democratic Kampuchea. 1976-1979 Succeeded by. Khieu Samphan Preceded by. None Director of the Higher ... As part of the new Presidium, Pol Pot became the country's Prime Minister.[259] It was at this point that he took on the public ...
"Chi Crosses the Sea". Transcription: "Chi, umi o wataru" (Japanese: チー、海をわたる。). August 10, 2009 (2009-08-10). ... An English-dubbed version of the first season streamed on Amazon Prime Video on April 21, 2018.[8] ...
The Red Cross estimates that the death toll left after Typhoon Durian passed through the Phillipines may hit 1,000. ... making him leader of the opposition and presumptive candidate for prime minister in the next general election." -- Mwalcoff 01: ... I don't know, that bridge can be crossed if it is ever gotten to. Thethinredline 23:07, 14 December 2006 (UTC) *Well, it looks ... Why haven't we mentioned the (alleged?) shooting between Hamas and Fatah, as Palestinian PM Ismail Haniya tried to cross the ...
Roberts claimed that the Duke was among men, including "a former prime minister" and Alan Dershowitz, who had sex with her ... 21 February 2011: Knight Grand Cross of the Royal Victorian Order (GCVO)[113] *2 June 2003 - 21 February 2011: Knight Commander ... gorged with a coronet Or composed of crosses patée and fleurs de lis a chain affixed thereto passing between the forelegs and ...
Prime symbol '. The prime symbol is often used to modify notation for graph invariants so that it applies to the line graph ... A split is called a strong split when it is not crossed by any other split. A split is called nontrivial when both of its sides ... A graph is called prime when it has no nontrivial splits.. square. 1. The square of a graph G is the graph power G2; in the ... 3. Modularity of a graph clustering, the difference of the number of cross-cluster edges from its expected value.. monotone. A ...
Prime Meenister. Haidar Abu Bakr al-Attas. Muhammad Said al-Attar. Abdul Aziz Abdul Ghani. Faraj Said Bin Ghanem. Abd al-Karim ... Prime Meenister. Abdul Aziz Abdul Ghani. Abd al-Karim al-Iryani. Abdul Aziz Abdul Ghani. ...
As a result o the 2013 Bulgarie protests against monopoly an heich electricity prices, the conservative govrenment o Prime ... Plevneliev acame Meenister o Regional Development an Public Wirks unner Prime Meenister Borisov on 27 Julie 2009. ... the Bulgarie ambassador in Paris as Prime Meenister an Meenister o Foreign Affairs. ...
... having once crossed paths they are joined in quantum entanglement; and the third book, The Homing Pigeons, places characters in ...
The Opening of the Fifth Seal (1608-1614, oil, 225 × 193 cm., New York, Metropolitan Museum) has been suggested to be the prime ... Christ on the Cross Adored by Two Donors. *Santo Domingo el Antiguo Altarpiece ...
Australian Prime Minister Scott Morrison calls her release a "miracle". (CNN). 24 November 2020 - COVID-19 pandemic. COVID-19 ... 1942 - Australian pilot Ron Middleton earns a posthumous Victoria Cross for valour in bringing his crew and crippled bomber ...
An indoor-chair may only reliably be able to cross completely flat surfaces, limiting them to household use. An indoor-outdoor ... Wheelchair cushions are the prime method of delivering this protection and are nearly universally used. Wheelchair cushions are ... A very few specialist designs offer a true cross-country capability. Powerchairs have access to the full range of wheelchair ... Access starts outside of the building, with the provision of reduced height kerb-cuts where wheelchair users may need to cross ...
Brooks, Tim; Marsh, Earle (2007). The Complete Directory to Prime Time Network and Cable TV Shows 1946-Present (Ninth Edition) ... Daktari was based upon the 1965 film Clarence, the Cross-Eyed Lion, which also stars Thompson as Dr. Tracy and Miller as his ... This was referred to in an inside joke from the preview trailer for the movie Clarence, the Cross-Eyed Lion, that Leo (which ... Tracy's pets, a cross-eyed lion named Clarence and a chimpanzee named Judy, were also popular characters. ...
"Australia's Prime Ministers. National Archives of Australia. Retrieved 29 June 2010.. *. "Prime Ministers of Australia, John ... During the debate over what became the Family Law Act 1975, he crossed the floor to oppose a Coalition amendment which he ... Hughes, Colin (1976). Mr Prime Minister: Australian Prime Ministers 1901-1972. Oxford University Press. ISBN 0-19-550471-2. .. ... He was the only Senator in Australia's history to be Prime Minister and the only Prime Minister to have ever served in the ...
Consider the prime definition of apple in the Merriam-Webster Collegiate Dictionary: "the fleshy usu. rounded and red or yellow ... because there is no way of cross-checking them till they turn blue); and they may contradict the existing structure to no good ... "prime minister" of Spain is the "president of the government" not simply "the president". What do you reckon is better in this ...
Cross-sectional imaging (CT or MRI) *Plain films are generally sufficient in making a joint dislocation diagnosis. However, ... The shoulder is a prime example of this. Any shoulder dislocation should be followed up with thorough physiotherapy.[16] ... cross-sectional imaging can subsequently be used to better define and evaluate abnormalities that may be missed or not clearly ...
... to his divine ascension and finds this ascent of life to divine life is the human journey and his prime purpose of life. [11] ... He recommends that the only way to reconcile the materialistic mind with the other truth would be to cross over the layers of ...
Grand Crosses of the Order of Saint James of the Sword. *Grand Crosses Special Class of the Order of Merit of the Federal ... Prime Ministers. See list. *Pridi Banomyong. Thawan Thamrongnawasawat. Khuang Aphaiwong. Plaek Phibunsongkhram. Pote Sarasin. ... If the prime minister failed to curb [the drug trade], over the years the number of deaths would easily surpass this toll."[68] ... After he became Prime Minister, Abhisit opened an investigation led by former attorney-general Kampee Kaewcharoen, claiming ...
Prime Minister from 2012 to 2017 The presidential elections that should have been organized in 2005 were postponed until ... Laurent Gbagbo as president ran against former Prime Minister Alassane Ouattara.[69] On 2 December, the Electoral Commission ... and fighting over the prime cocoa-growing areas resumed. France sent in troops to maintain the cease-fire boundaries,[45] and ... became prime minister. These events were seen by some observers as substantially strengthening Gbagbo's position.[50] ...
The main access for students from the north is the Cross Country Route. Around 33% of native South West students stay in the ... Office of the Deputy Prime Minister, 2004. "Competitive European Cities: Where do the Core Cities stand? Urban Research Summary ... In particular, Cornwall's inclusion in the region is disputed by Cornish nationalists.[14] The cross-party Cornish ... X-Fab UK (semiconductor fabrication plant, former Plessey Semiconductors) is next to the A386 Bickleigh Cross roundabout; ...
The Prime Minister, Theresa May, returned to Downing Street from campaigning for the upcoming snap general election.[102] May, ... Charing Cross and Cannon Street were also closed.[36] The Home Secretary approved the deployment of a military counter ... "TEXT-UK Prime Minister May's statement following London attack". Reuters. 4 June 2017.. ...
Many scholars believe that the ancestors of the modern Belarusians settled in the region of what is now Belarus between the sixth and eighth centuries. Three early Slavic tribes (the Dregovich, Krivichi, and Radimich) settled there.[25] The Belarusian people trace their distinct culture to the Grand Duchy of Lithuania, earlier Kievan Rus and the Principality of Polatsk. Most Belarusians are descendants of the East Slav tribes Dregovichs, Krivichs and Radimichs, as well as of a Yotvingians and other Baltic tribes, who lived in the west and north-west of today's Belarus.[26] Belarusians began to emerge as a people during the 13th through 14th centuries in the Grand Duchy of Lithuania; mostly on the lands of the upper basins of Neman River, Dnieper River and the Western Dvina River.[27] In the 13th-18th centuries Belarusians were known as Ruthenians and spoke Ruthenian language, while being part of the Grand Duchy of Lithuania, which conquered the lands of White Ruthenia, Black Ruthenia and ...
On April 18, a British soldier was killed in an attack on a medical facility, and a Red Cross depot was bombed with numerous ... June 4 - Eight Lehi Letter bombs addressed to high British government officials, including Prime Minister Clement Attlee, were ... Prime Minister Clement Attlee announced that 100,000 Jews would not be permitted into Palestine long as the "illegal armies" of ... who had identified and arrested Lehi leader and future Israeli Prime Minister Yitzhak Shamir, was assassinated near his Haifa ...
"3.3 A cryo-EM structure of a nonenveloped virus reveals a priming mechanism for cell entry". Cell. 141 (3): 472-82. doi:10.1016 ... to map one image onto another is calculated by cross-correlation. However, a micrograph often contains particles in multiple ...
... was probably first inhabited by those who crossed on the land bridge from the European mainland. Human footprints ...
As the prime minister has made clear, these allegations were wholly untrue and were part of a concerted plot by police officers ... In May 1989, a charity version of the Gerry and the Pacemakers song "Ferry Cross the Mersey" was released in aid of those ... Prime Minister Margaret Thatcher and Home Secretary Douglas Hurd visited Hillsborough the day after the disaster and met ... Prime Minister David Cameron also responded to the April 2016 verdict by saying that it represented a "long overdue" but " ...
Prime Meenister o Poland. 20t Prime Meenister o the Seicont Republic o Poland. ... Recipients o the Militar Order o the Cross o the Eagle, Cless I ... Grand Crosses o the Order o Leopold (Belgium). *Grand Crosses o ... Prime Meenister o Poland. 15th Prime Meenister o the Seicont Republic o Poland. ... Prime Meenister. Kazimierz Bartel, Himsel, Kazimierz Świtalski, Walery Sławek, Aleksander Prystor, Janusz Jędrzejewicz, Leon ...
In response, Pakistan also started similar kinds of cross-border interference. By 1975, Pakistani Prime Minister Zulfiqar Ali ... Royal Prime Minister[edit]. Further information: Prime Minister of Afghanistan. Daoud was appointed Prime Minister in September ... Prime Minister of Afghanistan. 1953-1963 Succeeded by. Mohammad Yusuf Preceded by. Mohammed Zahir Shah. (King) Heads of State ... Mohammed Daoud Khan or Daud Khan (July 18, 1909 - April 28, 1978) was the 5th Prime Minister of Afghanistan from 1953 to 1963 ...
Forsythe, David P. (2005). The Humanitarians: The International Committee of the Red Cross Cambridge University Press. ISBN 0- ... The former Prime Ministers of Singapore, Lee Kuan Yew, and of Malaysia, Mahathir bin Mohamad both claimed in the 1990s that ... The foundation of the International Committee of the Red Cross, the 1864 Lieber Code and the first of the Geneva Conventions in ... Canadian law professor John Humprey and French lawyer Rene Cassin were responsible for much of the cross-national research and ...
The city has been described as the "most unique"[6] in the United States,[7][8][9][10][11] owing in large part to its cross- ... with New Orleans as a prime beneficiary.[32] ... University of Holy Cross, a Catholic liberal arts college ... Vertical cross-section, showing maximum levee height of 23 feet (7.0 m) ... In the early 1740s traders from the British colonies of the Atlantic coast crossed into the Appalachian Mountains. The Native ...
Periodic Reporting for period 1 - PROCROP (Professional cross-priming for ovary and prostate cancer). Reporting period: 2015-09 ... Dectin-1/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses Author(s): Maria M. M. Kaisar, ... such immune mechanism is termed crosspriming). This unique opportunity for superior DCs for immunotherapy comes from the fact ...
... a process referred to as cross-presentation (2). T cell activation through cross-presentation (cross-priming), can be readily ... Prior experiments have sought to determine the contribution of direct priming and cross-priming in the induction of tumor- and ... T cells because of impaired cross-priming. Such differences in the ability to cross-present antigens should form important ... Antigen Bias in T Cell Cross-Priming. By Monika C. Wolkers, Nathalie Brouwenstijn, Arnold H. Bakker, Mireille Toebes, Ton N. M ...
... a phenomenon termed cross-priming. Although in vitro studies have suggested that both TAP-dependent and TAP-independent ... but cross-priming could not be demonstrated. These results support the TAP-dependent mechanism of cross-priming. ... In vivo cross-priming of MHC class I-restricted antigens requires the TAP transporter Immunity. 1996 Apr;4(4):349-55. doi: ... a phenomenon termed cross-priming. Although in vitro studies have suggested that both TAP-dependent and TAP-independent ...
... cross-sectional association. Download Prime PubMed App to iPhone, iPad, or Android ... AgedAged, 80 and overBiomarkersCognitive DysfunctionCross-Sectional StudiesFemaleHumansMaleVitamin DVitamin D Deficiency ... Vitamin D insufficiency and mild cognitive impairment: cross-sectional association.. Eur J Neurol. 2012 Jul; 19(7):1023-9.EJ ... "Vitamin D Insufficiency and Mild Cognitive Impairment: Cross-sectional Association." European Journal of Neurology, vol. 19, no ...
... through a process known as cross-priming. To initiate cross-priming, APCs must both capture extracellular antigen and receive ... through a process known as cross-priming. To initiate cross-priming, APCs must both capture extracellular antigen and receive ... Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon Nat Immunol. 2003 Oct;4(10):1009-15. doi: 10.1038/ ... These data identify expression of IFN-alpha/beta as a mechanism for the induction of cross-priming during virus infections. ...
MF59-primed, P , 0.001; plain-primed, P = 0.0011; all antigens on all visits except A/Cambodia/2007 on day 202). MF59-primed ... high titers of cross-reactive antibody remained detectable among MF59-primed subjects. We conclude that distant priming with ... MF59-Primed Subjects Generate Cross-Reactive Antibody.. Fig. 3 and Table 2 show MN antibody against wild-type H5N1 viruses and ... "plain-primed") or MF59-adjuvanted ("MF59-primed") H5N3 vaccine. Of the 12 plain-primed recipients, 7 subjects received 2 doses ...
Hypochlorous acid enhances immunogenicity and uptake of allogeneic ovarian tumor cells by dendritic cells to cross-prime tumor- ... Hypochlorous Acid: A Natural Adjuvant That Facilitates Antigen Processing, Cross-Priming, and the Induction of Adaptive ... Hypochlorous Acid: A Natural Adjuvant That Facilitates Antigen Processing, Cross-Priming, and the Induction of Adaptive ... Hypochlorous Acid: A Natural Adjuvant That Facilitates Antigen Processing, Cross-Priming, and the Induction of Adaptive ...
Neutrophil involvement in cross-priming CD8+ T cell responses to bacterial antigens. J. Immunol. 173: 1994-2002. ... To analyze the role of DCs in CD8+ T cell cross-priming, we vaccinated irradiated mice reconstituted with bone marrow from ... Whether other DC populations, such as Langerhans cells, can also cross-prime CTLs is controversial (33, 34). In this study, we ... The OVA/ISCOM vaccine induced highly efficient cross-priming of OVA-specific CTLs with an average CTL frequency of 8.5% of ...
This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation. ... This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation. ... This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation. ... Immunogenic cross-presentation, also referred to as cross-priming, requires the presence of pathogen-derived molecules (PAMPs) ...
Download Prime PubMed App to iPhone or iPad. ... study among adolescents in Sri Lank were found in PRIME PubMed ... AdolescentAge FactorsAnemia, Iron-DeficiencyBody HeightBody WeightChildChild Nutrition DisordersCross-Sectional StudiesFemale ... Prevalence and severity of micronutrient deficiency: a cross-sectional study among adolescents in Sri Lanka. Asia Pac J Clin ... Prevalence and Severity of Micronutrient Deficiency: a Cross-sectional Study Among Adolescents in Sri Lanka. Asia Pac J Clin ...
1976) Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in ... CTL Priming by OVA-loaded Spleen Cells Occurs by Cross-priming.. OVA-specific CTL can be generated by injecting B6 mice ... In this report, we show that induction of CTL by priming with OVA-loaded spleen cells occurs by cross-priming on host bone ... In addition to the already reported CTL cross-priming phenomenon, we have recently shown that cross-presentation is effective ...
Cytotoxic T cells can be primed through the direct pathway, or the cross-priming pathway. The latter involves exogenously ... In these studies we have used this same HEK-NP model to study the effects of LCMV-NP cross priming on the LCMV immunodominance ... We also highlight a regulatory role for cross priming in immunodominance by showing that a single dose of HEK-NP can completely ... An evaluation of the efficiency of lymphocytic choriomeningitis virus - nucleoprotein cross priming in vivo. ...
... Type. Master thesis ... where half of the targets in each category was English primed by Norwegian and the other half were Norwegian primed by English ... These experiments were analyzed together in order to account for priming effect for each word pair in both language direction ( ... The accumulated results from all experiments suggest that, at least when the prime is visible for 100ms, the meaning bearing ...
... Type ... German and Spanish native speakers living in Norway were tested in a cross-linguistic primed lexical decision task. The test ... German L1 speakers will experience a stronger priming effect from Norwegian prime words than Spanish L1 speakers, as German is ... psycholinguisticspriminglexical decision tasksecond language learningbeginner learnersGermanSpanishNorwegian ...
Conceptual processing in Chinese-English bilinguals: an fMRI study of cross-language conceptual priming. In recent years, ... we should observe a behavioral cross language priming effect. Furthermore, if the neural representations of the conceptual ... we would not observe a cross language priming effect on a neuronal nor behavioral level. ... The underlying mechanisms of repetition priming effects have been well characterized by the theory of transfer appropriate ...
Cross-priming with samples of five other Triturus species showed extremely poor levels of cross-species utility. Still, these ... Cross-priming with samples of five other Triturus species showed extremely poor levels of cross-species utility. Still, these ... Di- and tetranucleotide microsatellite markers for the Alpine newt (Triturus alpestris): characterization and cross-priming in ... characterization and cross-priming in five congeners. Molecular Ecology Resources, 3(2):186-188. ...
DCs can efficiently cross-prime naïve CD8(+) T cells in the absence of costimulation. Surprisingly, cross-priming by splenic ... DCs can efficiently cross-prime naïve CD8(+) T cells in the absence of costimulation. Surprisingly, cross-priming by splenic ... indicating that the cross-presentation capacity of the thymic subpopulation was higher. The observed cross-priming differences ... indicating that the cross-presentation capacity of the thymic subpopulation was higher. The observed cross-priming differences ...
To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway. Our results ... The nanoparticle-based vaccine actively targeted human CLEC9A-expressing BDCA3+ DCs - the equivalent of murine cross-priming ... for cross priming with the aim to generate efficient CTL antitumor responses. ... To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway. Our results ...
... but cross-priming could not be demonstrated. These results support the TAP-dependent mechanism of cross-priming. ... but cross-priming could not be demonstrated. These results support the TAP-dependent mechanism of cross-priming.", ... but cross-priming could not be demonstrated. These results support the TAP-dependent mechanism of cross-priming. ... but cross-priming could not be demonstrated. These results support the TAP-dependent mechanism of cross-priming. ...
Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross- ... Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross- ... exhibits efficient cross-priming in both human and mouse models in vitro (6, 17). Although cross-priming has been confirmed as ... T cells by the cross-priming mechanism (5, 8, 11-16, 44-46). However, other studies suggest that the mechanism of cross-priming ...
Cross-Priming of CD8 by Lymphoid Dendritic Cells and Uptake of Apoptotic Antigen-Coupled Cells by Sandy Griffith et al. ... Cd8+ but Not Cd8− Dendritic Cells Cross-Prime Cytotoxic T Cells in Vivo. *Joke M.M. den Haan, Sophie M. Lehar, Michael J. Bevan ... Cross-Priming of CD8 by Lymphoid Dendritic Cells and Uptake of Apoptotic Antigen-Coupled Cells. *. Sandy Griffith, Steve ... Cross-presentation, dendritic cells, tolerance and immunity.. *W R Heath, F R Carbone ...
Cross-presentation and Cross-priming of Tumor Antigens. Cancer cells frequently stimulate Signal 1 alone, and inefficiently ... which activate naïve T cells in a process called cross-priming. This process can also cause T cell unresponsiveness or cross- ... This is achieved by a process called APCs such as DCs can efficiently prime T cells, where they display MHC antigen complexes ( ...
The highest pooled specificity was from cross-priming amplification (CPA) (six studies; pooled specificity 97%, 95-99%). The ... Cross-priming amplification for rapid detection of Mycobacterium tuberculosis in sputum specimens. Journal of Clinical ... Cross-Priming Amplification, EasyNAT®TB (CPA). Seven studies (6551 participants) reported the results of CPA (Ustar ... A multicenter study of cross-priming amplification for tuberculosis diagnosis at peripheral level in China. Tuberculosis. 94, ...
Structural priming persists cross-linguistically. One specific form of structural priming is syntactic priming. Picture ... Structural priming is a form of positive priming, in that it induces a tendency to repeat or more easily process a current ... This is trivially true for any type-type prime. However, other structural priming patterns exist that complicate this ... This persistence in sentential form is structural priming. At least four theories exist to explain structural priming: ...
Cross-priming is also called immunogenic cross-presentation. This mechanism is vital for priming of CTLs against viruses and ... ISBN 978-0-8153-4123-9.CS1 maint: location (link) Kurts, Christian; Robinson, Bruce; Knolle, Percy (2010-06-01). "Cross-priming ... Priming of naïve T cells requires dendritic cell antigen presentation. Priming of naive CD8 T cells generates cytotoxic T cells ... Afterwards the researchers compare subsequent infections in primed and non-primed individuals to see if they mount a stronger ...
3D). This finding suggests that Diprovocim activates antigen cross-presentation by DCs and cross-priming of CD8 T cells in vivo ... Measurement of Cross-Priming of CD8 T Cells.. C57BL/6J male mice were injected i.m. with 100 μg OVA mixed with vehicle or with ... To further investigate whether cross-priming stimulated by Diprovocim results in the development of killing ability by CD8+ T ... 2014) Molecular mechanisms of TLR2-mediated antigen cross-presentation in dendritic cells. J Immunol 192:4233-4241. ...
Depending on their state of maturation, dendritic cells (DCs) can cross-prime or cross-tolerize T cells. Mature DCs provide T- ...
... cross-priming) is an important mechanism for induction of tumor specific immunity. In vitro generated DCs were loaded with ... We found that DCs loaded with killed breast cancer cells can prime naïve CD8+ T cells to differentiate into effector cytotoxic ... T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A*0201- breast cancer cells can kill HLA-A* ... Cross-priming of breast cancer specific CTLs. HLA-A*0201+ CTLs were generated as described in Figure 1, except that DCs were ...
Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the ... Primary FT necrotic cells abort cross-priming of CD8+ T cells. (A) B78OVA-FTheat cells were mixed with B78-FT cells at a 1:8 ... Peptidases released by necrotic cells control CD8+ T cell cross-priming Jaba Gamrekelashvili,1,2 Tamar Kapanadze,1,2 Miaojun ... Hyperthermia enhances CTL cross-priming. J Immunol. 2006;176(4):2134-2141.. View this article via: PubMed Google Scholar ...
  • Activation of cross-priming by IFN-alpha/beta was independent of CD4+ T cell help or interaction of CD40 and CD40 ligand, and involved direct stimulation of dendritic cells. (
  • Challenges for vaccine design are targeting Ag to dendritic cells (DCs) in vivo, facilitating cross-presentation, and conditioning the microenvironment for Th1 type immune responses. (
  • Attention has focused on exploiting dendritic cells (DCs) as professional APCs capable of presenting exogenous Ag not only on MHC class II, but also on MHC class I, a process termed cross-presentation. (
  • Cross-presentation, dendritic cells, tolerance and immunity. (
  • Priming of naïve T cells requires dendritic cell antigen presentation. (
  • Cross-priming refers to the stimulation of antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) by dendritic cell presenting an antigen acquired from the outside of the cell. (
  • Depending on their state of maturation, dendritic cells (DCs) can cross-prime or cross-tolerize T cells. (
  • RT drastically enhances the cross-priming capacity of tumor-infiltrating dendritic cells (TIDC) from wild-type mice but not type I IFN receptor-deficient mice. (
  • MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals. (
  • In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. (
  • Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo," Nature Medicine , vol. 5, no. 4, pp. 405-411, 1999. (
  • Mini-review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross-priming and direct priming? (
  • Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. (
  • More importantly, gDE7 activated mouse CD11c + CD8α + and human BDCA3 + dendritic cells (DC), specialized in antigen cross-presentation to CD8 + T cells, under in vitro conditions. (
  • These data indicate that certain virus- and tumor-associated antigens may not be detected by CD8 + T cells because of impaired cross-priming. (
  • Such differences in the ability to cross-present antigens should form important considerations in vaccine design. (
  • In an alternative pathway, professional antigen-presenting cells (APCs) internalize material derived from virally infected or transformed cells and then present the exogenously derived antigens to naïve CD8 + T cells, a process referred to as cross-presentation ( 2 ). (
  • T cell activation through cross-presentation (cross-priming), can be readily demonstrated for a number of antigens ( 3 - 5 ) but has not been observed for all antigens, including those that are efficiently presented through the endogenous pathway ( 6 , 7 ). (
  • Recent in vitro evidence suggests two alternative mechanisms by which bone marrow-derived APCs may process exogenous antigens for presentation to CTL in vivo, a phenomenon termed cross-priming. (
  • CD8+ T cell responses can be generated against antigens that are not expressed directly within antigen-presenting cells (APCs), through a process known as cross-priming. (
  • Proactive priming before the next pandemic could induce immune memory responses to novel influenza antigens. (
  • This is known to be effective for class I-restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. (
  • Levitsky, Hyam I. / In vivo cross-priming of MHC class I-restricted antigens requires the TAP transporter . (
  • The first mechanism is inducement of long-lasting defences, like circulating immune molecules, by the priming antigens in the host body, which remain until the secondary encounter. (
  • Antigens targeted to DCs via the C‐type lectin Langerin/CD207 are cross‐presented to CD8 + T cells in vivo . (
  • Class I-restricted activation of CD8-POSITIVE LYMPHOCYTES resulting from ANTIGEN PRESENTATION of exogenous ANTIGENS (cross-presentation). (
  • This is in contrast to normal activation of these lymphocytes (direct-priming) which results from presentation of endogenous antigens. (
  • Although it was thought that local tissue-resident DCs phagocytose microbial antigens and migrate to the draining lymph node to prime naive T cells ( 2 ), this paradigm has been challenged by several recent studies in which lymph node-resident DCs were shown to be the only APCs to present antigens to T cells ( 3 ). (
  • However, because no antigen presentation was demonstrated from the migrant DC population and the lymph node-resident CD8α + DCs were exclusively associated with CTL priming capacity, the study implied that the migrant DCs acted as simple ferries for peripheral antigens ( 5 ). (
  • Until recently, the intracellular mechanisms involved in cross-presentation of soluble antigens have been unclear. (
  • Altogether, our findings propose a model for cross-presentation of SLP which tends to enlarge the repertoire of potential candidates for retro-translocation of exogenous antigens to the cytosol. (
  • Many compartments are involved in cross-presentation of soluble antigens [9] that critically depend on the nature of the antigen. (
  • Furthermore, lysosomes have been recently reported to participate in cross-presentation of some antigens [12] . (
  • Although in vitro studies have suggested that both TAP-dependent and TAP-independent pathways exist, we have now demonstrated an absolute requirement for a functional TAP for cross-priming to occur in vivo. (
  • In such chimeras, in vivo priming of naive CTL was observed when antigen was targeted to the ER in a TAP-independent fashion, but cross-priming could not be demonstrated. (
  • Adoptive transfer of transgenic OT-I T cells revealed highly efficient cross-presentation of the OVA/ISCOM vaccine in vivo, whereas cross-presentation of soluble OVA was poor even at a 100-fold higher concentration. (
  • However, controversy still exists as to whether indirect presentation (the cross-priming mechanism) can contribute to effective in vivo priming of tumor-specific CD8 + T cells that are capable of eradicating cancer in patients. (
  • I have used titrated quantities of uninduced and induced cells, expressing vastly different quantities of ovalbumin, and have monitored cross-priming of the endogenous anti-OVA CD8 + T cell response quantitatively in C57BL/6 mice ( b haplotype), using in vivo cytolytic T lymphocyte assays. (
  • We show that in vivo DC are required to cross-prime CTL precursors. (
  • In vitro , increased HER2 uptake by DC increased cross-presentation of E75, the immunodominant epitope derived from the HER2 protein, an observation confirmed in two in vivo mouse models. (
  • Thus, both migrant and resident DCs play an important role in priming CD8 and CD4 T cell responses, and their relative importance depends on the mode of infection in vivo. (
  • in vivo the receptor inhibits T lymphocytes cross-priming and dampens adaptative memory immune response. (
  • We show that infection with lymphocytic choriomeningitis virus induces cross-priming by a mechanism dependent on type I interferon (IFN-alpha/beta). (
  • This process can also cause T cell unresponsiveness or cross-tolerance (Chapters 7 and 11 in Immunology IV). (
  • These data identify expression of IFN-alpha/beta as a mechanism for the induction of cross-priming during virus infections. (
  • Subjects primed with MF59-adjuvanted vaccine responded significantly better than those primed with plain vaccine, most notably in early induction and duration of cross-reacting antibody responses. (
  • Therefore, induction of immune memory and cross-clade neutralizing antibodies are essential components of a pre-pandemic vaccine strategy. (
  • Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4 + helper T cells. (
  • Furthermore, we see that the induction of LCMV-NP cross priming boosts anti-viral immunity to subsequent LCMV infections. (
  • There are two hypothetical scenarios of immune induction, on which immune priming mechanism could be based. (
  • In LCMV-infected RelB(-/-) mice, induction of cross-priming to an independently injected soluble protein, which depends on the IFN-alpha/beta made during the viral infection, was also impaired. (
  • Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. (
  • The project applies recent compelling knowledge on the identity of the main antigen-presenting DC subsets for vaccine elicitation of cytotoxic T lymphocytes endowed with the ability to seek and destroy tumour cells (such immune mechanism is termed crosspriming). (
  • In contrast, CD8 + T cell activation often occurs through interaction with specialized antigen-presenting cells displaying peptides acquired from an exogenous cellular source, a process termed cross-priming. (
  • The prevaccination frequency of circulating memory B cells reactive to A/Vietnam/1194/2004 was low in both primed and unprimed individuals. (
  • However, at day 21 after boosting, MF59-adjuvanted primed subjects displayed a higher frequency of H5N1-specific memory B cells than plain-primed or unprimed subjects. (
  • We conclude that distant priming with clade 0-like H5N3 induces a pool of cross-reactive memory B cells that can be boosted rapidly years afterward by a mismatched MF59-adjuvanted vaccine to generate high titers of cross-reactive neutralizing antibodies rapidly. (
  • This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8 + T cell formation. (
  • Cytotoxic T cells can be primed through the direct pathway, or the cross-priming pathway. (
  • It has been previously reported that Lymphocytic Choriomeningitis nucleoprotein expressed in HEK cells (HEK-NP) could be cross presented to CD8+ T cells. (
  • In this study, we demonstrate that steady-state thymic CD8(+) DCs can efficiently cross-prime naïve CD8(+) T cells in the absence of costimulation. (
  • The observation that thymic CD8(+) DCs are more efficient than splenic CD8(+) DCs in T-cell cross-priming in the absence of licensing factors indicates that the requirements for efficient antigen presentation differ between these cells. (
  • A clinical trial of vaccination with granulocyte macrophage-colony stimulating factor-transduced pancreatic cancer lines was designed to test whether cross-presentation by locally recruited APCs can activate pancreatic tumor-specific CD8 + T cells. (
  • This is achieved by a process called APCs such as DCs can efficiently prime T cells, where they display MHC antigen complexes (Signal 1) together with co-stimulatory molecules (Signal 2), which activate naïve T cells in a process called cross-priming. (
  • Subsequently, the primed cells will differentiate either into effector cells or into memory cells that can mount stronger and faster response to second and upcoming immune challenges. (
  • Priming of naive CD8 T cells generates cytotoxic T cells capable of directly killing pathogen-infected cells. (
  • CD4 cells develop into a diverse array of effector cell types depending on the nature of the signals they receive during priming. (
  • We have shown that the therapeutic effect of ablative RT depends largely on CD8 + T cells and that RT increases T-cell priming ( 3 ). (
  • Cross-priming is a critical component of T cell responses to cancers and viruses, and involves transfer of antigen from antigen donor cells to the antigen presenting cells. (
  • The experiments show, paradoxically, that minute quantities of antigen expressed by a large number of cells are far more efficient at cross-priming than exponentially larger quantities of antigen expressed by fewer cells. (
  • rather, my data suggests it is linked to highly efficient transfer of antigen to cross-priming antigen presenting cells. (
  • Thus, I conclude that antigen transfer in cross priming is in some ways a quantized process, wherein the number of encounters between donor and acceptor cells, or the number of opportunities for antigen transfer, is as important to cross-priming as the quantity of antigen expressed in the antigen donor cell and available for sampling by professional antigen presenting cells. (
  • Furthermore, the DC-derived MFG-E8 negatively regulates the cross-priming and effector functions of antigen-specific T cells upon recognition of necrotic cells. (
  • This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. (
  • This increased E75 cross-presentation, mediated by trastuzumab treatment, enabled more efficient expansion of E75-specific cytotoxic T cells (E75-CTL). (
  • Priming of autologous T cells by DCs loaded with MV-infected MPM cells led to a significant proliferation of tumor-specific CD8 T cells. (
  • Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross‐presentation to CD8 + T cells. (
  • Langerin/OVA combined with imiquimod could not prime CD8 + T cells and resulted in poor cytotoxicity in subsequent responses. (
  • The aim of this project is to address the most important of these questions:1)To characterize, in depth CD8 memory cells ge nerated against soluble proteins by cross-priming compared to those generated after viral or bacterial infection against the same antigen2) To study the effect of antigen localisation on the development of memory CD8 T cells. (
  • Cross-priming experiments showed that antigen-presenting cells pulsed with either mesothelioma or leukemia tumor lysates can process and present each of the CD4 + peptides identified. (
  • The technique temporarily inhibits production of a prime protective mechanism used by tumors -- a molecular pump called P-glycoprotein that flushes drugs out of cells. (
  • The researchers achieved similar results by priming cells with three other cross-linking drugs. (
  • For autoimmune conditions like type 1 diabetes to progress, self-reactive CD8 + T cells would need to interact with peptide-antigen cross-presented on the surface of antigen-presenting cells in a major histocompatibility complex (MHC) class I-restricted fashion. (
  • In this study, we show cross-presentation of islet-derived autoantigens by B cells. (
  • Thus, B cells govern the transition from clinically silent insulitis to frank diabetes by cross-presenting autoantigen to self-reactive CD8 + T cells. (
  • These results support the TAP-dependent mechanism of cross-priming. (
  • Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. (
  • Cross-presentation is an important mechanism to elicit both immune defenses and tolerance. (
  • Error-based learning Another explanation is that syntactic priming is a form of implicit learning supported by a prediction error-based learning mechanism. (
  • This mechanism is vital for priming of CTLs against viruses and tumours. (
  • It seems that the results of immune priming research are showing that the mechanism differs and is dependent on the kind of insect species and microbe used for given experiment. (
  • Second mechanism describes a drop after the initial priming response, but stronger defence upon secondary challenge. (
  • Recent studies have shown that local ablative radiation of established tumors can lead to increased T-cell priming and T-cell-dependent tumor regression, but the underlying mechanism remains unclear. (
  • We propose a new mechanism of regulation which is implicit in the dynamics of the CTL: According to the model, the ability of a CTL response to become established depends on the ratio of cross-presentation to direct presentation of the antigen. (
  • Specifically, we claim that the mechanism that allows speakers to correctly select the target language in cross-language priming may be the same that is needed in cognitive tasks to alternate between different sets of rules. (
  • Proper localized RT given at appropriate doses and scheduling may tip the balance in favor of antitumor immunity both through endogenous priming mechanisms and in combination with immunotherapy ( 2, 3 , 9 ). (
  • Experiment 1 was a one-directional lexical decision task, where all primes were English words and their respective targets were Norwegian or non-words (L2-L1). (
  • In a previous experiment, Stremme, Troland, and Johansson (2014) found that beginner learners of Norwegian also experience an effect of meaning related words in a primed lexical decision task. (
  • German and Spanish native speakers living in Norway were tested in a cross-linguistic primed lexical decision task. (
  • 2014) at også nybegynnere i norsk opplevde en effekt av betydningsrelaterte ord i en primet leksikalsk avgjørelsesoppgave (lexical decision task). (
  • Preliminary findings indicated that cross-reactive hemagglutination-inhibition (HI) responses were induced following the booster vaccination ( 14 ). (
  • The related effect of cross-tolerance can also effectively eliminate responses to selected self components. (
  • This work provides strong support for the physiological role that cross priming plays in normal cell-mediated immune responses. (
  • MFG-E8 deficiency enhances an ability of necrotic cell-primed DC to stimulate antitumor immune responses against established tumors. (
  • In summary, these results show that the RelB/NF-kappaB pathway is required for optimal IFN-alpha production after LCMV infection and suggest a crucial role for RelB in IFN-alpha-stimulated cross-priming of CD8(+) T cell responses. (
  • Altogether, Langerin + dDCs prime long‐lasting cytotoxic responses, while cross‐presentation by LCs negatively influences CD8 + T‐cell priming. (
  • Immunization with one alphavirus cross-primes cellular and humoral immune responses to a second alphavirus. (
  • The exclusive ability of the CD8α + DCs to prime CTL responses was shown whether the HSV-1 was injected by a needle into the footpad (f.p.) ( 10 ), via the intravenous route ( 8 ), or by dermal abrasion ( 11 ). (
  • These responses are generated by cross-priming and are independent of CD40. (
  • Priming of antigen-specific naive lymphocytes occurs when antigen is presented to them in immunogenic form (capable of inducing an immune response). (
  • Cross-priming of breast cancer specific CTLs. (
  • If migrant DCs act merely as simple ferries, how are CD8α + DCs licensed to prime CTLs? (
  • Our results provide strong evidence that cross priming is an efficient route with which to induce cell-mediated immunity. (
  • However, the question remains as to which immunologic components link activation of innate immunity by RT with increased cross-priming and production of an antitumor T-cell response. (
  • Cross-presentation in viral immunity and self-tolerance. (
  • This study also shows that, contrary to what is currently believed, the cellular component of the T. molitor immune system does not necessarly play a major role in providing immune protection through individual immune priming or TGIP.In a second chapter, we have stimulated the immune system of adult females with two Gram-positive bacteria to study maternal transfer of immunity to the eggs. (
  • Structural priming is a form of positive priming, in that it induces a tendency to repeat or more easily process a current sentence that is similar in structure to a previously presented prime. (
  • The underlying mechanisms of repetition priming effects have been well characterized by the theory of transfer appropriate processing (Morris, Bransford, & Franks, 1977). (
  • The innate response during immune priming differs based on the experimental setup, but generally it involves enhancement of humoral innate immune mechanisms and increased levels of hemocytes. (
  • While the mechanisms through which immune priming is achieved remain unknown, individuals that survived to a given parasite are better protected against subsequent exposures. (
  • This allowed us to highlight the main characteristics and mechanisms curently identified, and the ecology and the evolution of the phenomenon.Costs and benefits associated to immune priming and TGIP suggest that Gram-positive bacteria might have been a major selective pressure at the origin of these phenomena in T. molitor. (
  • However, the mechanisms by which autoantigen is cross-presented remain to be identified. (
  • I have further defined a parameter of this efficiency as the "dispersal" of low-level antigen into a larger number of delivery vehicles, which itself enhances antigen availability for cross priming by an order of magnitude in a minimalist in vitro system. (
  • One specific form of structural priming is syntactic priming. (
  • Syntactic repetition In the Bock study, the sentences presented match their primes in syntactic structure. (
  • Further, CD8α + DCs were shown to express higher levels of proteins required for the cross-presentation pathway compared with the CD8α − population ( 13 ). (
  • Here, we characterize the cross-presentation pathway of SLP Melan-A 16-40 containing the HLA-A2-restricted epitope 26-35 (A27L) in human DCs. (
  • Using confocal microscopy and specific inhibitors, we show that SLP 16-40 is rapidly taken up by DC and follows a classical TAP- and proteasome-dependent cross-presentation pathway. (
  • These experiments were analyzed together in order to account for priming effect for each word pair in both language direction (English-Norwegian and Norwegian-English). (
  • The accumulated results from all experiments suggest that, at least when the prime is visible for 100ms, the meaning bearing units for the prime words are activated aiding the process of word recognition in any of the language directions across these series of experiments. (
  • The experiments focusing on immune priming are based on exposing the insect to dead or sublethal dose of bacteria or microbes to elicit the initial innate immune response. (
  • Two cross-modal priming experiments tested in Dutch whether such contextual alternatives are automatically available to listeners. (
  • Trans-generational immune priming (TGIP) describes the transfer of parental immunological experience to its progeny, which may help the survival of the offspring when challenged with the same pathogen. (
  • This immune priming can cross generations (trans-generational immune priming - TGIP), preparing offspring for prevailing parasite environment. (
  • Thus, immune priming and TGIP should be more efficient and less costly with respect to pathogens exposing the host to the greatest probability of re-infection. (
  • During my thesis, I found that the expression of individual immune priming and TGIP in the mealworm beetle, Tenebrio molitor, is dependent of a range of pathogens that might have been a major selective pressure on the immune system of this insect species. (
  • Proactive pre-pandemic priming could induce long-lasting immune memory and allow a single booster vaccine to induce protection when needed. (
  • These epitopes can be organized into a hierarchy, based on their ability to induce T cell priming. (
  • HOCl modification also enhances cross-presentation of the tumor Ag tyrosinase-related protein 2 via class I MHC. (
  • To initiate cross-priming, APCs must both capture extracellular antigen and receive specific activation signals. (
  • Cross-priming is also called immunogenic cross-presentation. (
  • can malaria DNA vaccines on their own be as immunogenic and protective as prime-boost approaches to immunization? (
  • Priming is the first contact that antigen-specific T helper cell precursors have with an antigen. (
  • Many organisms can improve their immune response as a function of their immunological experience, a phenomenon called immune priming. (
  • Dengue vaccine development is complicated by the possibility of vaccine-enhanced severe dengue disease due to antibody-dependent enhancement by pre-existing cross-reactivity, as well as homotypic antibodies. (
  • Furthermore, we have also observed a physiological priming effect (i.e., decreased blood flow) in an fMRI experiment using the same paradigm (Thompson-Schill, D'esposito, & Kan, 1999). (
  • Furthermore, if the neural representations of the conceptual system were overlapping, we should also observe a physiological priming effect in a population of neurons that are recruited for conceptual processing. (
  • Notably, provision of exogenous IFN-alpha did not restore the ability of RelB(-/-) mice to cross-prime. (
  • These include the co-administration of cytokines, prime-boost strategies, optimising codon usage or the use of CpG motifs. (
  • Afterwards the researchers compare subsequent infections in primed and non-primed individuals to see if they mount a stronger or modified response. (
  • We examined conceptual processing in Chinese-English early bilinguals using a repetition priming procedure during functional magnetic resonance imaging (fMRI). (
  • Repetition priming refers to an individual's enhanced performance on a task as a result of repeated exposure to the same stimulus. (
  • In these studies we have used this same HEK-NP model to study the effects of LCMV-NP cross priming on the LCMV immunodominance hierarchy following viral challenge. (
  • We have investigated the nature of APC activation signals associated with virus infection that stimulate cross-priming. (
  • The phenomenon called cross-priming has received attention in this respect. (
  • Several paradigms exist to elicit structural priming. (
  • In other words, the magnitude of the priming effect can be interpreted as an index of shared processes between the two encounters-the greater the overlap, the bigger the priming effect. (
  • This means that in addition to class I-restricted cross-presentation, other factors are required for CTL cross-priming. (
  • Synthesis of gem-Difluoroalkenes by Merging Ni-Catalyzed C-F and C-C Bond Activation in Cross-Electrophile Coupling. (
  • By merging C-F and C-C bond activation in the cross-electrophile coupling, we developed an efficient cyanide-free synthesis of diverse functional-group-rich cyano-substituted gem-difluoroalkenes using cyclobutanone oxime esters and trifluoromethyl alkenes as precursors. (
  • Cross-priming versus cross-tolerance: are two signals enough? (
  • Thematic congruency A structure known as the unaccusative, which is unmarked morphologically in English, is capable of priming passive transitive sentences. (
  • Contrastive associates - but not non- contrastive associates - were facilitated only when primes were produced in sentences with contrastive intonation, indicating that contrastive intonation makes unmentioned contextual alternatives immediately available. (
  • The counterbalanced baseline accounted for the lexical reaction times, such that when the mean lexical reaction time was accounted for, the priming effects are clearer. (
  • The vocabulary test scores did not correlate with the priming effects, indicating a difference between implicit and explicit language knowledge, but for the German L1 speakers, a positive correlation between the reaction times and the vocabulary test scores was observed. (
  • Effects of priming individualism and collectivism. (
  • Differential Neurobehavioral Effects of Cross-Modal Selective Priming on Phonetic and Emotional Prosodic Information in Late Second Language Learners. (
  • Both individual and trans-generational immune priming might be adaptive and may have evolved from repeated challenges by the same pathogens during the host lifetime or across generation. (
  • The observed cross-priming differences between thymic and splenic CD8(+) DCs did not correlate with differential antigen capture or costimulatory molecules found on the surface of DCs. (
  • Immunization with one alphavirus cross-primes cellular and humoral imm" by J A. Wolcott, C J. Wust et al. (
  • Although only a few DC subsets possess the machinery required for cross-presentation, little is known about differences in cross-presenting capabilities of DCs belonging to the same subpopulation but localized in different lymphoid organs. (
  • Using priming techniques, recent experimental research indicates that cross-cultural differences can be re. (
  • By isolating splenic DCs that have captured an equal number of antigen-coated beads after systemic administration of labeled beads into mice, cross-presentation was shown to be much more efficient in CD8α + DCs compared with CD8α − DCs ( 12 ). (