Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.
Endogenous superantigens responsible for inducing strong proliferative responses in T-cells in mixed lymphocyte reactions (see LYMPHOCYTE CULTURE TEST, MIXED). They are encoded by mouse mammary tumor viruses that have integrated into the germ line as DNA proviruses (MINOR LYMPHOCYTE STIMULATORY LOCI).
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Deletion of sequences of nucleic acids from the genetic material of an individual.
Actual loss of portion of a chromosome.
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.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
An orphan nuclear receptor that is closely related to members of the thyroid-steroid receptor gene family. It was originally identified in NERVE CELLS and may play a role in mediation of NERVE GROWTH FACTOR-induced CELL DIFFERENTIATION. However, several other functions have been attributed to this protein including the positive and negative regulation of APOPTOSIS.
Functional inactivation of T- or B-lymphocytes rendering them incapable of eliciting an immune response to antigen. This occurs through different mechanisms in the two kinds of lymphocytes and can contribute to SELF TOLERANCE.
HEMATOPOIETIC PROGENITOR CELLS that have migrated to the THYMUS where they differentiate into T-LYMPHOCYTES. Thymocytes are classified into maturational stages based on the expression of CELL SURFACE ANTIGENS.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin.
The major group of transplantation antigens in the mouse.
Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions.
Inbred AKR mice are a strain of laboratory mice that are homozygous at all gene loci and have a high incidence of developing certain diseases, such as leukemia and autoimmune disorders, making them useful for research purposes in biomedicine.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
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.
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.
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.
Inbred BALB/c mice are a strain of laboratory mice that have been selectively bred to be genetically identical to each other, making them useful for scientific research and experiments due to their consistent genetic background and predictable responses to various stimuli or treatments.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
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.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
An encapsulated lymphatic organ through which venous blood filters.
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.
Inbred CBA mice are a strain of laboratory mice that have been selectively bred to be genetically identical and uniform, which makes them useful for scientific research, particularly in the areas of immunology and cancer.
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.
Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.
An individual that contains cell populations derived from different zygotes.
Inbred C3H mice are a strain of laboratory mice that have been selectively bred to maintain a high degree of genetic uniformity and share specific genetic characteristics, including susceptibility to certain diseases, which makes them valuable for biomedical research purposes.
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.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
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.
Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.
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.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Refers to animals in the period of time just after birth.
The type species of BETARETROVIRUS commonly latent in mice. It causes mammary adenocarcinoma in a genetically susceptible strain of mice when the appropriate hormonal influences operate.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
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)
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.
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.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Substances that are recognized by the immune system and induce an immune reaction.
Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.
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 survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
Antibodies produced by a single clone of cells.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
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.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Progenitor cells from which all blood cells derive.
Any method used for determining the location of and relative distances between genes on a chromosome.
Biochemical identification of mutational changes in a nucleotide sequence.
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.
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 parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Established cell cultures that have the potential to propagate indefinitely.
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.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
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.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
An individual in which both alleles at a given locus are identical.
Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Proteins found in any species of bacterium.
'Abnormalities, Multiple' is a broad term referring to the presence of two or more structural or functional anomalies in an individual, which may be genetic or environmental in origin, and can affect various systems and organs of the body.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Cytotoxic T lymphocytes to an unmutated tumor rejection antigen P1A: normal development but restrained effector function in vivo. (1/361)

Unmutated tumor antigens are chosen as primary candidates for tumor vaccine because of their expression on multiple lineages of tumors. A critical issue is whether unmutated tumor antigens are expressed in normal cells, and if so, whether such expression imposes special restrictions on cytotoxic T lymphocyte (CTL) responses. In this study, we use a transgenic approach to study the development and effector function of T cells specific for P1A, a prototypical unmutated tumor antigen. We report here that although P1A is expressed at low levels in normal tissues, including lymphoid tissues, the P1A-specific transgenic T cells develop normally and remain highly responsive to the P1A antigen. The fact that transgenic expression of P1A antigen in the thymus induces T cell clonal deletion demonstrates that normal hematopoietic cells can process and present the P1A antigen and that P1A-specific T cells are susceptible to clonal deletion. By inference, P1A-specific T cells must have escaped clonal deletion due to low expression of P1A in the thymus. Interestingly, despite the fact that an overwhelming majority of T cells in the T cell receptor for antigen (TCR)-transgenic mice are specific for P1A, these mice are no more resistant to a P1A-expressing plasmocytoma than nontransgenic littermates. Moreover, when the same TCR-transgenic mice were challenged simultaneously with B7-1(+) and B7-1(-) tumors, only B7-1(+) tumors were rejected. Therefore, even though P1A can be a tumor rejection antigen, the effector function of P1A-specific CTL is restrained in vivo. These results have important implications for the strategy of tumor immunotherapy.  (+info)

Chimerism and xenotransplantation. New concepts. (2/361)

In both transplant and infectious circumstances, the immune response is governed by migration and localization of the antigen. If the antigenic epitopes of transgenic xenografts are sufficiently altered to avoid evoking the destructive force of innate immunity, the mechanisms of engraftment should be the same as those that permit the chimerism-dependent immunologic confrontation and resolution that is the basis of allograft acceptance. In addition to "humanizing" the epitopes, one of the unanswered questions is whether the species restriction of complement described in 1994 by Valdivia and colleagues also necessitates the introduction of human complement regulatory genes in animal donors. Because the liver is the principal or sole source of most complement components, the complement quickly is transformed to that of the donor after hepatic transplantation. Thus, the need for complementary regulatory transgenes may vary according to the kind of xenograft used. Much evidence shows that physiologically important peptides produced by xenografts (e.g., insulin, clotting factors, and enzymes) are incorporated into the metabolic machinery of the recipient body. To the extent that this is not true, xenotransplantation could result in the production of diseases that are analogous to inborn errors of metabolism. In the climate of pessimism that followed the failures of baboon to human liver xenotransplantation in 1992-1993, it seemed inconceivable that the use of even more discordant donors, such as the pig, could ever be seriously entertained; however, this preceded insight into the xenogeneic and allogeneic barriers that has brought transplantation infectious immunity to common ground. With this new insight and the increasing ease of producing transgenic donors, the goal of clinical xenotransplantation may not be so distant.  (+info)

Cutting edge: negative selection of immature thymocytes by a few peptide-MHC complexes: differential sensitivity of immature and mature T cells. (3/361)

We quantitated the number of peptide-class II MHC complexes required to affect the deletion or activation of 3A9 TCR transgenic thymocytes. Deletion of immature double positive thymocytes was very sensitive, taking place with approximately three peptide-MHC complexes per APC. However, the activation of mature CD4+ thymocytes required 100-fold more complexes per APC. Therefore, a "biochemical margin of safety" exists at the level of the APC. To be activated, autoreactive T cells in peripheral lymphoid tissues require a relatively high level of peptide-MHC complexes.  (+info)

Chronic modulation of the TCR repertoire in the lymphoid periphery. (4/361)

Using TCR V beta 5 transgenic mice as a model system, we demonstrate that the induction of peripheral tolerance can mold the TCR repertoire throughout adult life. In these mice, three distinct populations of peripheral T cells are affected by chronic selective events in the lymphoid periphery. First, CD4+V beta 5+ T cells are deleted in the lymphoid periphery by superantigens encoded by mouse mammary tumor viruses-8 and -9 in an MHC class II-dependent manner. Second, mature CD8+V beta 5+ T cells transit through a CD8lowV beta 5low deletional intermediate during tolerance induction by a process that depends upon neither mouse mammary tumor virus-encoded superantigens nor MHC class II expression. Third, a population of CD4-CD8-V beta 5+ T cells arises in the lymphoid periphery in an age-dependent manner. We analyzed the TCR V alpha repertoire of each of these cellular compartments in both V beta 5 transgenic and nontransgenic C57BL/6 mice as a function of age. This analysis revealed age-related changes in the expression of V alpha families among different cellular compartments, highlighting the dynamic state of the peripheral immune repertoire. Our work indicates that the chronic processes maintaining peripheral T cell tolerance can dramatically shape the available TCR repertoire.  (+info)

Survival of naive CD4 T cells: roles of restricting versus selecting MHC class II and cytokine milieu. (5/361)

The diversity of naive CD4 T cells plays an important role in the adaptive immune response by ensuring the capability of responding to novel pathogens. In the past, it has been generally accepted that naive CD4 T cells are intrinsically long-lived; however, there have been studies suggesting some CD4 T cells are short-lived. In this report, we identify two populations of naive CD4 T cells: a long-lived population as well as a short-lived population. In addition, we identify two factors that contribute to the establishment of long-lived naive CD4 T cells. We confirm earlier findings that MHC class II interaction with the TCR on CD4 T cells is important for survival. Furthermore, we find that MHC class II alleles with the correct restriction element for Ag presentation mediate the peripheral survival of naive CD4 T cells more efficiently than other positively selecting alleles, regardless of the selecting MHC in the thymus. The second component contributing to the survival of naive CD4 T cells is contact with the cytokines IL-4 and IL-7. We find that the physiological levels of IL-4 and IL-7 serve to enhance the MHC class II-mediated survival of naive CD4 T cells in vivo.  (+info)

Two mechanisms for the non-MHC-linked resistance to spontaneous autoimmunity. (6/361)

Genetic susceptibility and resistance to most autoimmune disorders are associated with highly polymorphic genes of the MHC and with non-MHC-linked polygenic modifiers. It is known that non-MHC-linked polymorphisms can override or enhance the susceptibility to an autoimmune disease provided by pathogenic MHC genes, but the mechanisms remain elusive. In this study, we have followed the fate of two highly diabetogenic beta cell-specific T cell receptors (Kd and I-Ag7 restricted, respectively) in NOR/Lt mice, which are resistant to autoimmune diabetes despite expressing two copies of the diabetogenic MHC haplotype H-2g7. We show that at least two mechanisms of non-MHC-linked control of pathogenic T cells operate in these mice. One segregates as a recessive trait and is associated with a reduction in the peripheral frequency of diabetogenic CD8+ (but not CD4+) T cells. The other segregates as a dominant trait and is mediated by IL-4- and TGF-beta1-independent immune suppressive functions provided by lymphocytes that target diabetogenic CD4+ and CD8+ T cells, without causing their deletion, anergy, immune deviation, or ignorance. These results provide explanations as to how non-MHC-linked polymorphisms can override the susceptibility to an autoimmune disease provided by pathogenic MHC haplotypes, and demonstrate that protective non-MHC-linked genes may selectively target specific lymphoid cell types in cellularly complex autoimmune responses.  (+info)

Autoantigen-independent deletion of diabetogenic CD4+ thymocytes by protective MHC class II molecules. (7/361)

Some MHC class II genes provide dominant resistance to certain autoimmune diseases via mechanisms that remain unclear. We have shown that thymocytes bearing a highly diabetogenic, I-Ag7-restricted beta-cell-reactive TCR (4.1-TCR) undergo negative selection in diabetes-resistant H-2g7/x mice by engaging several different antidiabetogenic MHC class II molecules on thymic (but not peripheral) hemopoietic cells, independently of endogenous superantigens. Here we have investigated 1) whether this TCR can also engage protective MHC class II molecules (I-Ab) on cortical thymic epithelial cells in the absence of diabetogenic (I-Ag7) molecules, and 2) whether deletion of 4.1-CD4+ thymocytes in I-Ab-expressing mice might result from the ability of I-Ab molecules to present the target beta-cell autoantigen of the 4.1-TCR. We show that, unlike I-Ag7 molecules, I-Ab molecules can restrict neither the positive selection of 4.1-CD4+ thymocytes in the thymic cortex nor the presentation of their target autoantigen in the periphery. Deletion of 4.1-CD4+ thymocytes by I-Ab molecules in the thymic medulla, however, is a peptide-specific process, since it can be triggered by hemopoietic cells expressing heterogeneous peptide/I-Ab complexes, but not by hemopoietic cells expressing single peptide/I-Ab complexes. Thus, unlike MHC-autoreactive or alloreactive TCRs, which can engage deleting MHC molecules in the thymic cortex, thymic medulla, and peripheral APCs, the 4.1-TCR can only engage deleting MHC molecules (I-Ab) in the thymic medulla. We therefore conclude that this form of MHC-induced protection from diabetes is based on the presentation of an anatomically restricted, nonautoantigenic peptide to highly diabetogenic thymocytes.  (+info)

Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter. (8/361)

Immature B cells that encounter self-antigen are eliminated from the immune repertoire by negative selection. Negative selection has been proposed to take place by two distinct mechanisms: deletion by apoptosis or alteration of the antigen receptor specificity by receptor editing. While convincing evidence exists for each, the two models are inherently contradictory. In this paper, we propose a resolution to this contradiction by demonstrating that the site of first antigen encounter dictates which mechanism of negative selection is utilized. We demonstrate that the bone marrow microenvironment provides signals that block antigen-induced deletion and promote RAG reinduction. In the periphery, the absence of these signals allows the immature B cell to default to apoptosis as a result of BCR engagement.  (+info)

Clonal deletion is a process in the immune system where T cells or B cells that have receptors which are highly reactive to self-antigens are eliminated during development in the thymus or bone marrow, respectively. This helps prevent the development of autoimmune diseases, where the immune system attacks the body's own tissues and organs.

During the development of T cells in the thymus, immature T cells undergo a selection process to ensure that they do not react strongly to self-antigens. Those that do are eliminated through a process called negative selection or clonal deletion. Similarly, developing B cells in the bone marrow that produce antibodies with high affinity for self-antigens are also deleted.

Clonal deletion is an essential mechanism for maintaining self-tolerance and preventing the development of autoimmune diseases. However, if this process fails or is impaired, it can lead to the development of autoimmunity.

Minor lymphocyte stimulatory antigens (MLSA) are a group of low-profile, nonpolymorphic antigens that can induce a weak proliferative response in T-lymphocytes. They are present on the surface of various cells, including leukocytes and lymphocytes. MLSA are not as well-studied or characterized as major histocompatibility complex (MHC) antigens, but they can still play a role in immune responses, particularly in allograft rejection and autoimmune diseases.

MLSA are also known as minor histocompatibility antigens, and they can stimulate a T-cell response when presented in the context of MHC molecules. The response to MLSA is generally weaker than the response to MHC antigens, but it can still contribute to graft rejection and other immune-mediated disorders.

It's worth noting that the term "minor" in this context refers to the relative strength of the immune response, rather than the importance or significance of these antigens. MLSA can still have important implications for transplantation, immunotherapy, and other areas of medicine.

Gene deletion is a type of mutation where a segment of DNA, containing one or more genes, is permanently lost or removed from a chromosome. This can occur due to various genetic mechanisms such as homologous recombination, non-homologous end joining, or other types of genomic rearrangements.

The deletion of a gene can have varying effects on the organism, depending on the function of the deleted gene and its importance for normal physiological processes. If the deleted gene is essential for survival, the deletion may result in embryonic lethality or developmental abnormalities. However, if the gene is non-essential or has redundant functions, the deletion may not have any noticeable effects on the organism's phenotype.

Gene deletions can also be used as a tool in genetic research to study the function of specific genes and their role in various biological processes. For example, researchers may use gene deletion techniques to create genetically modified animal models to investigate the impact of gene deletion on disease progression or development.

The thymus gland is an essential organ of the immune system, located in the upper chest, behind the sternum and surrounding the heart. It's primarily active until puberty and begins to shrink in size and activity thereafter. The main function of the thymus gland is the production and maturation of T-lymphocytes (T-cells), which are crucial for cell-mediated immunity, helping to protect the body from infection and cancer.

The thymus gland provides a protected environment where immune cells called pre-T cells develop into mature T cells. During this process, they learn to recognize and respond appropriately to foreign substances while remaining tolerant to self-tissues, which is crucial for preventing autoimmune diseases.

Additionally, the thymus gland produces hormones like thymosin that regulate immune cell activities and contribute to the overall immune response.

A sequence deletion in a genetic context refers to the removal or absence of one or more nucleotides (the building blocks of DNA or RNA) from a specific region in a DNA or RNA molecule. This type of mutation can lead to the loss of genetic information, potentially resulting in changes in the function or expression of a gene. If the deletion involves a critical portion of the gene, it can cause diseases, depending on the role of that gene in the body. The size of the deleted sequence can vary, ranging from a single nucleotide to a large segment of DNA.

A chromosome deletion is a type of genetic abnormality that occurs when a portion of a chromosome is missing or deleted. Chromosomes are thread-like structures located in the nucleus of cells that contain our genetic material, which is organized into genes.

Chromosome deletions can occur spontaneously during the formation of reproductive cells (eggs or sperm) or can be inherited from a parent. They can affect any chromosome and can vary in size, from a small segment to a large portion of the chromosome.

The severity of the symptoms associated with a chromosome deletion depends on the size and location of the deleted segment. In some cases, the deletion may be so small that it does not cause any noticeable symptoms. However, larger deletions can lead to developmental delays, intellectual disabilities, physical abnormalities, and various medical conditions.

Chromosome deletions are typically detected through a genetic test called karyotyping, which involves analyzing the number and structure of an individual's chromosomes. Other more precise tests, such as fluorescence in situ hybridization (FISH) or chromosomal microarray analysis (CMA), may also be used to confirm the diagnosis and identify the specific location and size of the deletion.

Immune tolerance, also known as immunological tolerance or specific immune tolerance, is a state of unresponsiveness or non-reactivity of the immune system towards a particular substance (antigen) that has the potential to elicit an immune response. This occurs when the immune system learns to distinguish "self" from "non-self" and does not attack the body's own cells, tissues, and organs.

In the context of transplantation, immune tolerance refers to the absence of a destructive immune response towards the transplanted organ or tissue, allowing for long-term graft survival without the need for immunosuppressive therapy. Immune tolerance can be achieved through various strategies, including hematopoietic stem cell transplantation, costimulation blockade, and regulatory T cell induction.

In summary, immune tolerance is a critical mechanism that prevents the immune system from attacking the body's own structures while maintaining the ability to respond appropriately to foreign pathogens and antigens.

1. Receptors: In the context of physiology and medicine, receptors are specialized proteins found on the surface of cells or inside cells that detect and respond to specific molecules, known as ligands. These interactions can trigger a range of responses within the cell, such as starting a signaling pathway or changing the cell's behavior. There are various types of receptors, including ion channels, G protein-coupled receptors, and enzyme-linked receptors.

2. Antigen: An antigen is any substance (usually a protein) that can be recognized by the immune system, specifically by antibodies or T-cells, as foreign and potentially harmful. Antigens can be derived from various sources, such as bacteria, viruses, fungi, parasites, or even non-living substances like pollen, chemicals, or toxins. An antigen typically contains epitopes, which are the specific regions that antibodies or T-cell receptors recognize and bind to.

3. T-Cell: Also known as T lymphocytes, T-cells are a type of white blood cell that plays a crucial role in cell-mediated immunity, a part of the adaptive immune system. They are produced in the bone marrow and mature in the thymus gland. There are several types of T-cells, including CD4+ helper T-cells, CD8+ cytotoxic T-cells, and regulatory T-cells (Tregs). T-cells recognize antigens presented to them by antigen-presenting cells (APCs) via their surface receptors called the T-cell receptor (TCR). Once activated, T-cells can proliferate and differentiate into various effector cells that help eliminate infected or damaged cells.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

T-lymphocytes, also known as T-cells, are a type of white blood cell that plays a key role in the adaptive immune system's response to infection. They are produced in the bone marrow and mature in the thymus gland. There are several different types of T-cells, including CD4+ helper T-cells, CD8+ cytotoxic T-cells, and regulatory T-cells (Tregs).

CD4+ helper T-cells assist in activating other immune cells, such as B-lymphocytes and macrophages. They also produce cytokines, which are signaling molecules that help coordinate the immune response. CD8+ cytotoxic T-cells directly kill infected cells by releasing toxic substances. Regulatory T-cells help maintain immune tolerance and prevent autoimmune diseases by suppressing the activity of other immune cells.

T-lymphocytes are important in the immune response to viral infections, cancer, and other diseases. Dysfunction or depletion of T-cells can lead to immunodeficiency and increased susceptibility to infections. On the other hand, an overactive T-cell response can contribute to autoimmune diseases and chronic inflammation.

A clone is a group of cells that are genetically identical to each other because they are derived from a common ancestor cell through processes such as mitosis or asexual reproduction. Therefore, the term "clone cells" refers to a population of cells that are genetic copies of a single parent cell.

In the context of laboratory research, cells can be cloned by isolating a single cell and allowing it to divide in culture, creating a population of genetically identical cells. This is useful for studying the behavior and characteristics of individual cell types, as well as for generating large quantities of cells for use in experiments.

It's important to note that while clone cells are genetically identical, they may still exhibit differences in their phenotype (physical traits) due to epigenetic factors or environmental influences.

Self tolerance, also known as immunological tolerance or biological tolerance, is a critical concept in the field of immunology. It refers to the ability of the immune system to distinguish between "self" and "non-self" antigens and to refrain from mounting an immune response against its own cells, tissues, and organs.

In other words, self tolerance is the state of immune non-responsiveness to self antigens, which are molecules or structures that are normally present in an individual's own body. This ensures that the immune system does not attack the body's own cells and cause autoimmune diseases.

Self tolerance is established during the development and maturation of the immune system, particularly in the thymus gland for T cells and the bone marrow for B cells. During this process, immature immune cells that recognize self antigens are either eliminated or rendered tolerant to them, so that they do not mount an immune response against the body's own tissues.

Maintaining self tolerance is essential for the proper functioning of the immune system and for preventing the development of autoimmune diseases, in which the immune system mistakenly attacks the body's own cells and tissues.

1. Receptors: In the context of physiology and medicine, receptors are specialized proteins found on the surface of cells or inside cells that detect and respond to specific molecules, known as ligands. Receptors play a crucial role in signal transduction, enabling cells to communicate with each other and respond to changes in their environment.
2. Antigen: An antigen is any substance (usually a protein) that can be recognized by the immune system and stimulate an immune response. Antigens can be foreign substances such as bacteria, viruses, or pollen, or they can be components of our own cells, such as tumor antigens in cancer cells. Antigens are typically bound and presented to the immune system by specialized cells called antigen-presenting cells (APCs).
3. T-Cell: T-cells, also known as T lymphocytes, are a type of white blood cell that plays a central role in cell-mediated immunity. T-cells are produced in the bone marrow and mature in the thymus gland. There are two main types of T-cells: CD4+ helper T-cells and CD8+ cytotoxic T-cells. Helper T-cells assist other immune cells, such as B-cells and macrophages, in mounting an immune response, while cytotoxic T-cells directly kill infected or cancerous cells.
4. Alpha-Beta: Alpha-beta is a type of T-cell receptor (TCR) that is found on the surface of most mature T-cells. The alpha-beta TCR is composed of two polypeptide chains, an alpha chain and a beta chain, that are held together by disulfide bonds. The alpha-beta TCR recognizes and binds to specific antigens presented in the context of major histocompatibility complex (MHC) molecules on the surface of APCs. This interaction is critical for initiating an immune response against infected or cancerous cells.

Nuclear Receptor Subfamily 4, Group A, Member 1 (NR4A1) is a protein that in humans is encoded by the NR4A1 gene. NR4A1 is a member of the nuclear receptor superfamily, which are transcription factors that regulate gene expression in response to hormonal and other signals.

NR4A1 is also known as Nur77, TR3, or NGFI-B and it plays important roles in various biological processes such as cell proliferation, differentiation, apoptosis, and inflammation. It can be activated by a variety of stimuli including stress, hormones, and growth factors. Once activated, NR4A1 translocates to the nucleus where it binds to specific DNA sequences and regulates the expression of target genes.

Mutations in the NR4A1 gene have been associated with several diseases, including cancer, inflammatory bowel disease, and rheumatoid arthritis. Therefore, NR4A1 is a potential therapeutic target for these conditions.

Clonal anergy is a term used in immunology to describe a state of immune tolerance or unresponsiveness in certain T cells, a type of white blood cell that plays a central role in the body's immune response. This condition arises when T cells are exposed to persistent antigens, such as those derived from viruses or tumors, and fail to become fully activated.

In normal circumstances, when a T cell encounters an antigen presented by an antigen-presenting cell (APC), it becomes activated and undergoes clonal expansion, producing many copies of itself that are specific for that particular antigen. These activated T cells then migrate to the site of infection or tissue damage and help coordinate the immune response to eliminate the threat.

However, in some cases, persistent exposure to an antigen can lead to a state of exhaustion or anergy in the T cells, where they are no longer able to respond effectively to that antigen. This is thought to occur due to chronic stimulation and activation of the T cells, which can lead to the upregulation of inhibitory receptors and the downregulation of activating receptors on their surface.

Clonal anergy is a mechanism by which the immune system attempts to prevent excessive or inappropriate immune responses that could cause tissue damage or autoimmunity. However, it can also be a barrier to effective immunotherapy for diseases such as cancer, where T cells need to be activated and able to recognize and eliminate tumor cells.

In summary, clonal anergy is a state of immune tolerance in certain T cells that have been persistently exposed to antigens, leading to their failure to become fully activated and respond effectively to those antigens.

Thymocytes are a type of white blood cell that develops in the thymus gland. They are immature T-cells, which are a type of lymphocyte that plays a central role in cell-mediated immunity. Thymocytes undergo a process of maturation and selection in the thymus, where they learn to recognize and respond to foreign substances while remaining tolerant to self-tissues. This helps to ensure that the immune system can effectively fight off infections and diseases without attacking the body's own cells and tissues.

Thymocytes are characterized by the expression of both CD4 and CD8 co-receptors on their surface, which help them to interact with other cells of the immune system. During the maturation process, thymocytes that fail to properly rearrange their T-cell receptor genes or that react strongly to self-antigens are eliminated, while those that can recognize and respond to foreign antigens while remaining tolerant to self are allowed to mature and enter the circulation as functional T-cells.

Abnormalities in thymocyte development and function have been implicated in a variety of immune disorders, including autoimmune diseases and certain types of cancer.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

CD8 antigens are a type of protein found on the surface of certain immune cells called cytotoxic T lymphocytes or cytotoxic T cells. These cells play a critical role in the adaptive immune response, which is the specific and targeted response of the immune system to foreign substances (antigens) that invade the body.

CD8 antigens help cytotoxic T cells recognize and respond to infected or abnormal cells, such as those that have been infected by a virus or have become cancerous. When a cytotoxic T cell encounters a cell displaying a specific antigen bound to a CD8 molecule, it becomes activated and releases toxic substances that can kill the target cell.

CD8 antigens are also known as cluster of differentiation 8 antigens or CD8 receptors. They belong to a larger family of proteins called major histocompatibility complex class I (MHC class I) molecules, which present antigens to T cells and play a crucial role in the immune system's ability to distinguish between self and non-self.

Autoantigens are substances that are typically found in an individual's own body, but can stimulate an immune response because they are recognized as foreign by the body's own immune system. In autoimmune diseases, the immune system mistakenly attacks and damages healthy tissues and organs because it recognizes some of their components as autoantigens. These autoantigens can be proteins, DNA, or other molecules that are normally present in the body but have become altered or exposed due to various factors such as infection, genetics, or environmental triggers. The immune system then produces antibodies and activates immune cells to attack these autoantigens, leading to tissue damage and inflammation.

Skin transplantation, also known as skin grafting, is a surgical procedure that involves the removal of healthy skin from one part of the body (donor site) and its transfer to another site (recipient site) that has been damaged or lost due to various reasons such as burns, injuries, infections, or diseases. The transplanted skin can help in healing wounds, restoring functionality, and improving the cosmetic appearance of the affected area. There are different types of skin grafts, including split-thickness grafts, full-thickness grafts, and composite grafts, which vary in the depth and size of the skin removed and transplanted. The success of skin transplantation depends on various factors, including the size and location of the wound, the patient's overall health, and the availability of suitable donor sites.

H-2 antigens are a group of cell surface proteins found in mice that play a critical role in the immune system. They are similar to the human leukocyte antigen (HLA) complex in humans and are involved in the presentation of peptide antigens to T cells, which is a crucial step in the adaptive immune response.

The H-2 antigens are encoded by a cluster of genes located on chromosome 17 in mice. They are highly polymorphic, meaning that there are many different variations of these proteins circulating in the population. This genetic diversity allows for a wide range of potential peptide antigens to be presented to T cells, thereby enhancing the ability of the immune system to recognize and respond to a variety of pathogens.

The H-2 antigens are divided into two classes based on their function and structure. Class I H-2 antigens are found on almost all nucleated cells and consist of a heavy chain, a light chain, and a peptide fragment. They present endogenous peptides, such as those derived from viruses that infect the cell, to CD8+ T cells.

Class II H-2 antigens, on the other hand, are found primarily on professional antigen-presenting cells, such as dendritic cells and macrophages. They consist of an alpha chain and a beta chain and present exogenous peptides, such as those derived from bacteria that have been engulfed by the cell, to CD4+ T cells.

Overall, H-2 antigens are essential components of the mouse immune system, allowing for the recognition and elimination of pathogens and infected cells.

Superantigens are a unique group of antigens that can cause widespread activation of the immune system. They are capable of stimulating large numbers of T-cells (a type of white blood cell) leading to massive cytokine release, which can result in a variety of symptoms such as fever, rash, and potentially life-threatening conditions like toxic shock syndrome. Superantigens are often produced by certain bacteria and viruses. They differ from traditional antigens because they do not need to be processed and presented by antigen-presenting cells to activate T-cells; instead, they directly bind to the major histocompatibility complex class II molecules and the T-cell receptor's variable region, leading to polyclonal T-cell activation.

'Inbred AKR mice' is a strain of laboratory mice used in biomedical research. The 'AKR' designation stands for "Akita Radioactive," referring to the location where this strain was first developed in Akita, Japan. These mice are inbred, meaning that they have been produced by many generations of brother-sister matings, resulting in a genetically homogeneous population with minimal genetic variation.

Inbred AKR mice are known for their susceptibility to certain types of leukemia and lymphoma, making them valuable models for studying these diseases and testing potential therapies. They also develop age-related cataracts and have a higher incidence of diabetes than some other strains.

It is important to note that while inbred AKR mice are widely used in research, their genetic uniformity may limit the applicability of findings to more genetically diverse human populations.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Autoimmunity is a medical condition in which the body's immune system mistakenly attacks and destroys healthy tissues within the body. In normal function, the immune system recognizes and fights off foreign substances such as bacteria, viruses, and toxins. However, when autoimmunity occurs, the immune system identifies self-molecules or tissues as foreign and produces an immune response against them.

This misguided response can lead to chronic inflammation, tissue damage, and impaired organ function. Autoimmune diseases can affect various parts of the body, including the joints, skin, glands, muscles, and blood vessels. Some common examples of autoimmune diseases are rheumatoid arthritis, lupus, multiple sclerosis, type 1 diabetes, Hashimoto's thyroiditis, and Graves' disease.

The exact cause of autoimmunity is not fully understood, but it is believed to involve a combination of genetic, environmental, and lifestyle factors that trigger an abnormal immune response in susceptible individuals. Treatment for autoimmune diseases typically involves managing symptoms, reducing inflammation, and suppressing the immune system's overactive response using medications such as corticosteroids, immunosuppressants, and biologics.

CD4 antigens, also known as CD4 proteins or CD4 molecules, are a type of cell surface receptor found on certain immune cells, including T-helper cells and monocytes. They play a critical role in the immune response by binding to class II major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells and helping to activate T-cells. CD4 antigens are also the primary target of the human immunodeficiency virus (HIV), which causes AIDS, leading to the destruction of CD4-positive T-cells and a weakened immune system.

Inbred strains of mice are defined as lines of mice that have been brother-sister mated for at least 20 consecutive generations. This results in a high degree of homozygosity, where the mice of an inbred strain are genetically identical to one another, with the exception of spontaneous mutations.

Inbred strains of mice are widely used in biomedical research due to their genetic uniformity and stability, which makes them useful for studying the genetic basis of various traits, diseases, and biological processes. They also provide a consistent and reproducible experimental system, as compared to outbred or genetically heterogeneous populations.

Some commonly used inbred strains of mice include C57BL/6J, BALB/cByJ, DBA/2J, and 129SvEv. Each strain has its own unique genetic background and phenotypic characteristics, which can influence the results of experiments. Therefore, it is important to choose the appropriate inbred strain for a given research question.

A radiation chimera is not a widely used or recognized medical term. However, in the field of genetics and radiation biology, a "chimera" refers to an individual that contains cells with different genetic backgrounds. A radiation chimera, therefore, could refer to an organism that has become a chimera as a result of exposure to radiation, which can cause mutations and changes in the genetic makeup of cells.

Ionizing radiation, such as that used in cancer treatments or nuclear accidents, can cause DNA damage and mutations in cells. If an organism is exposed to radiation and some of its cells undergo mutations while others do not, this could result in a chimera with genetically distinct populations of cells.

However, it's important to note that the term "radiation chimera" is not commonly used in medical literature or clinical settings. If you encounter this term in a different context, I would recommend seeking clarification from the source to ensure a proper understanding.

The H-Y antigen is a complex of historically significant, male-specific proteins that are encoded by genes on the Y chromosome. These antigens were first discovered through studies of tissue rejection in animal models and were later found to be important in the field of transplantation immunology.

In a medical definition, the H-Y antigen refers to a group of antigens that are expressed on the cell surface of nucleated cells in males, including those found in tissues such as skin, muscle, and blood cells. They are recognized by the immune system as foreign when transplanted into females, leading to a rejection response.

The H-Y antigen has been the subject of extensive research due to its role in sex determination and differentiation, as well as its potential implications for autoimmune diseases and cancer biology. However, it's worth noting that the clinical relevance of the H-Y antigen is limited, and its study is primarily of academic interest.

Lymphocyte activation is the process by which B-cells and T-cells (types of lymphocytes) become activated to perform effector functions in an immune response. This process involves the recognition of specific antigens presented on the surface of antigen-presenting cells, such as dendritic cells or macrophages.

The activation of B-cells leads to their differentiation into plasma cells that produce antibodies, while the activation of T-cells results in the production of cytotoxic T-cells (CD8+ T-cells) that can directly kill infected cells or helper T-cells (CD4+ T-cells) that assist other immune cells.

Lymphocyte activation involves a series of intracellular signaling events, including the binding of co-stimulatory molecules and the release of cytokines, which ultimately result in the expression of genes involved in cell proliferation, differentiation, and effector functions. The activation process is tightly regulated to prevent excessive or inappropriate immune responses that can lead to autoimmunity or chronic inflammation.

BALB/c is an inbred strain of laboratory mouse that is widely used in biomedical research. The strain was developed at the Institute of Cancer Research in London by Henry Baldwin and his colleagues in the 1920s, and it has since become one of the most commonly used inbred strains in the world.

BALB/c mice are characterized by their black coat color, which is determined by a recessive allele at the tyrosinase locus. They are also known for their docile and friendly temperament, making them easy to handle and work with in the laboratory.

One of the key features of BALB/c mice that makes them useful for research is their susceptibility to certain types of tumors and immune responses. For example, they are highly susceptible to developing mammary tumors, which can be induced by chemical carcinogens or viral infection. They also have a strong Th2-biased immune response, which makes them useful models for studying allergic diseases and asthma.

BALB/c mice are also commonly used in studies of genetics, neuroscience, behavior, and infectious diseases. Because they are an inbred strain, they have a uniform genetic background, which makes it easier to control for genetic factors in experiments. Additionally, because they have been bred in the laboratory for many generations, they are highly standardized and reproducible, making them ideal subjects for scientific research.

T-lymphocyte subsets refer to distinct populations of T-cells, which are a type of white blood cell that plays a central role in cell-mediated immunity. The two main types of T-lymphocytes are CD4+ and CD8+ cells, which are defined by the presence or absence of specific proteins called cluster differentiation (CD) molecules on their surface.

CD4+ T-cells, also known as helper T-cells, play a crucial role in activating other immune cells, such as B-lymphocytes and macrophages, to mount an immune response against pathogens. They also produce cytokines that help regulate the immune response.

CD8+ T-cells, also known as cytotoxic T-cells, directly kill infected cells or tumor cells by releasing toxic substances such as perforins and granzymes.

The balance between these two subsets of T-cells is critical for maintaining immune homeostasis and mounting effective immune responses against pathogens while avoiding excessive inflammation and autoimmunity. Therefore, the measurement of T-lymphocyte subsets is essential in diagnosing and monitoring various immunological disorders, including HIV infection, cancer, and autoimmune diseases.

B-lymphocytes, also known as B-cells, are a type of white blood cell that plays a key role in the immune system's response to infection. They are responsible for producing antibodies, which are proteins that help to neutralize or destroy pathogens such as bacteria and viruses.

When a B-lymphocyte encounters a pathogen, it becomes activated and begins to divide and differentiate into plasma cells, which produce and secrete large amounts of antibodies specific to the antigens on the surface of the pathogen. These antibodies bind to the pathogen, marking it for destruction by other immune cells such as neutrophils and macrophages.

B-lymphocytes also have a role in presenting antigens to T-lymphocytes, another type of white blood cell involved in the immune response. This helps to stimulate the activation and proliferation of T-lymphocytes, which can then go on to destroy infected cells or help to coordinate the overall immune response.

Overall, B-lymphocytes are an essential part of the adaptive immune system, providing long-lasting immunity to previously encountered pathogens and helping to protect against future infections.

Lymphocyte depletion is a medical term that refers to the reduction in the number of lymphocytes (a type of white blood cell) in the body. Lymphocytes play a crucial role in the immune system, as they help to fight off infections and diseases.

Lymphocyte depletion can occur due to various reasons, including certain medical treatments such as chemotherapy or radiation therapy, immune disorders, viral infections, or bone marrow transplantation. This reduction in lymphocytes can make a person more susceptible to infections and diseases, as their immune system is weakened.

There are different types of lymphocytes, including T cells, B cells, and natural killer (NK) cells, and lymphocyte depletion can affect one or all of these types. In some cases, lymphocyte depletion may be temporary and resolve on its own or with treatment. However, in other cases, it may be more prolonged and require medical intervention to manage the associated risks and complications.

The Major Histocompatibility Complex (MHC) is a group of cell surface proteins in vertebrates that play a central role in the adaptive immune system. They are responsible for presenting peptide antigens to T-cells, which helps the immune system distinguish between self and non-self. The MHC is divided into two classes:

1. MHC Class I: These proteins present endogenous (intracellular) peptides to CD8+ T-cells (cytotoxic T-cells). The MHC class I molecule consists of a heavy chain and a light chain, together with an antigenic peptide.

2. MHC Class II: These proteins present exogenous (extracellular) peptides to CD4+ T-cells (helper T-cells). The MHC class II molecule is composed of two heavy chains and two light chains, together with an antigenic peptide.

MHC genes are highly polymorphic, meaning there are many different alleles within a population. This diversity allows for better recognition and presentation of various pathogens, leading to a more robust immune response. The term "histocompatibility" refers to the compatibility between donor and recipient MHC molecules in tissue transplantation. Incompatible MHC molecules can lead to rejection of the transplanted tissue due to an activated immune response against the foreign MHC antigens.

The spleen is an organ in the upper left side of the abdomen, next to the stomach and behind the ribs. It plays multiple supporting roles in the body:

1. It fights infection by acting as a filter for the blood. Old red blood cells are recycled in the spleen, and platelets and white blood cells are stored there.
2. The spleen also helps to control the amount of blood in the body by removing excess red blood cells and storing platelets.
3. It has an important role in immune function, producing antibodies and removing microorganisms and damaged red blood cells from the bloodstream.

The spleen can be removed without causing any significant problems, as other organs take over its functions. This is known as a splenectomy and may be necessary if the spleen is damaged or diseased.

CD4-positive T-lymphocytes, also known as CD4+ T cells or helper T cells, are a type of white blood cell that plays a crucial role in the immune response. They express the CD4 receptor on their surface and help coordinate the immune system's response to infectious agents such as viruses and bacteria.

CD4+ T cells recognize and bind to specific antigens presented by antigen-presenting cells, such as dendritic cells or macrophages. Once activated, they can differentiate into various subsets of effector cells, including Th1, Th2, Th17, and Treg cells, each with distinct functions in the immune response.

CD4+ T cells are particularly important in the immune response to HIV (human immunodeficiency virus), which targets and destroys these cells, leading to a weakened immune system and increased susceptibility to opportunistic infections. The number of CD4+ T cells is often used as a marker of disease progression in HIV infection, with lower counts indicating more advanced disease.

"CBA" is an abbreviation for a specific strain of inbred mice that were developed at the Cancer Research Institute in London. The "Inbred CBA" mice are genetically identical individuals within the same strain, due to many generations of brother-sister matings. This results in a homozygous population, making them valuable tools for research because they reduce variability and increase reproducibility in experimental outcomes.

The CBA strain is known for its susceptibility to certain diseases, such as autoimmune disorders and cancer, which makes it a popular choice for researchers studying those conditions. Additionally, the CBA strain has been widely used in studies related to transplantation immunology, infectious diseases, and genetic research.

It's important to note that while "Inbred CBA" mice are a well-established and useful tool in biomedical research, they represent only one of many inbred strains available for scientific investigation. Each strain has its own unique characteristics and advantages, depending on the specific research question being asked.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

Beta-chain gene rearrangement in the T-cell antigen receptor (TCR) refers to the genetic process that occurs during the development of T cells, a type of white blood cell crucial for adaptive immunity. The TCR is a heterodimeric protein complex expressed on the surface of T cells, responsible for recognizing and binding to specific peptide antigens presented in the context of major histocompatibility complex (MHC) molecules.

The beta-chain of the TCR is encoded by a set of gene segments called V (variable), D (diversity), J (joining), and C (constant) segments, located on chromosome 7 in humans. During T-cell development in the thymus, the following rearrangement events occur:

1. A random selection and recombination of a V, D, and J segment take place, forming a variable region exon that encodes the antigen-binding site of the beta-chain. This process introduces nucleotide insertions or deletions at the junctions between these segments, further increasing diversity.
2. The rearranged VDJ segment then combines with a C segment through RNA splicing to form a continuous mRNA sequence that encodes the complete beta-chain protein.
3. The resulting beta-chain pairs with an alpha-chain (encoded by similar gene segments on chromosome 14) to create a functional TCR heterodimer, which is then expressed on the T-cell surface.

This gene rearrangement process allows for the generation of a vast array of unique TCRs capable of recognizing various peptide antigens, ensuring broad coverage against potential pathogens and tumor cells.

A chimera, in the context of medicine and biology, is a single organism that is composed of cells with different genetics. This can occur naturally in some situations, such as when fraternal twins do not fully separate in utero and end up sharing some organs or tissues. The term "chimera" can also refer to an organism that contains cells from two different species, which can happen in certain types of genetic research or medical treatments. For example, a patient's cells might be genetically modified in a lab and then introduced into their body to treat a disease; if some of these modified cells mix with the patient's original cells, the result could be a chimera.

It's worth noting that the term "chimera" comes from Greek mythology, where it referred to a fire-breathing monster that was part lion, part goat, and part snake. In modern scientific usage, the term has a specific technical meaning related to genetics and organisms, but it may still evoke images of fantastical creatures for some people.

'C3H' is the name of an inbred strain of laboratory mice that was developed at the Jackson Laboratory in Bar Harbor, Maine. The mice are characterized by their uniform genetic background and have been widely used in biomedical research for many decades.

The C3H strain is particularly notable for its susceptibility to certain types of cancer, including mammary tumors and lymphomas. It also has a high incidence of age-related macular degeneration and other eye diseases. The strain is often used in studies of immunology, genetics, and carcinogenesis.

Like all inbred strains, the C3H mice are the result of many generations of brother-sister matings, which leads to a high degree of genetic uniformity within the strain. This makes them useful for studying the effects of specific genes or environmental factors on disease susceptibility and other traits. However, it also means that they may not always be representative of the genetic diversity found in outbred populations, including humans.

Flow cytometry is a medical and research technique used to measure physical and chemical characteristics of cells or particles, one cell at a time, as they flow in a fluid stream through a beam of light. The properties measured include:

* Cell size (light scatter)
* Cell internal complexity (granularity, also light scatter)
* Presence or absence of specific proteins or other molecules on the cell surface or inside the cell (using fluorescent antibodies or other fluorescent probes)

The technique is widely used in cell counting, cell sorting, protein engineering, biomarker discovery and monitoring disease progression, particularly in hematology, immunology, and cancer research.

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

1. Receptors: In the context of physiology and medicine, receptors are specialized proteins found on the surface of cells or inside cells that detect and respond to specific molecules, known as ligands. These interactions can trigger a variety of responses within the cell, such as starting a signaling cascade or changing the cell's metabolism. Receptors play crucial roles in various biological processes, including communication between cells, regulation of immune responses, and perception of senses.

2. Antigen: An antigen is any substance (usually a protein) that can be recognized by the adaptive immune system, specifically by B-cells and T-cells. Antigens can be derived from various sources, such as microorganisms (like bacteria, viruses, or fungi), pollen, dust mites, or even components of our own cells (for instance, in autoimmune diseases). An antigen's ability to stimulate an immune response is determined by its molecular structure and whether it can be recognized by the receptors on immune cells.

3. B-Cell: B-cells are a type of white blood cell that plays a critical role in the adaptive immune system, particularly in humoral immunity. They originate from hematopoietic stem cells in the bone marrow and are responsible for producing antibodies, which are proteins that recognize and bind to specific antigens. Each B-cell has receptors on its surface called B-cell receptors (BCRs) that can recognize a unique antigen. When a B-cell encounters its specific antigen, it becomes activated, undergoes proliferation, and differentiates into plasma cells that secrete large amounts of antibodies to neutralize or eliminate the antigen.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

The CD4-CD8 ratio is a measurement of the relative numbers of two types of immune cells, CD4+ T cells (also known as helper T cells) and CD8+ T cells (also known as cytotoxic T cells), in the blood. The CD4-CD8 ratio is commonly used as a marker of immune function and health.

CD4+ T cells play an important role in the immune response by helping to coordinate the activity of other immune cells, producing chemical signals that activate them, and producing antibodies. CD8+ T cells are responsible for directly killing infected cells and tumor cells.

A normal CD4-CD8 ratio is typically between 1.0 and 3.0. A lower ratio may indicate an impaired immune system, such as in cases of HIV infection or other immunodeficiency disorders. A higher ratio may be seen in some viral infections, autoimmune diseases, or cancer. It's important to note that the CD4-CD8 ratio should be interpreted in conjunction with other laboratory and clinical findings for a more accurate assessment of immune function.

CD8-positive T-lymphocytes, also known as CD8+ T cells or cytotoxic T cells, are a type of white blood cell that plays a crucial role in the adaptive immune system. They are named after the CD8 molecule found on their surface, which is a protein involved in cell signaling and recognition.

CD8+ T cells are primarily responsible for identifying and destroying virus-infected cells or cancerous cells. When activated, they release cytotoxic granules that contain enzymes capable of inducing apoptosis (programmed cell death) in the target cells. They also produce cytokines such as interferon-gamma, which can help coordinate the immune response and activate other immune cells.

CD8+ T cells are generated in the thymus gland and are a type of T cell, which is a lymphocyte that matures in the thymus and plays a central role in cell-mediated immunity. They recognize and respond to specific antigens presented on the surface of infected or cancerous cells in conjunction with major histocompatibility complex (MHC) class I molecules.

Overall, CD8+ T cells are an essential component of the immune system's defense against viral infections and cancer.

Histocompatibility antigens Class II are a group of cell surface proteins that play a crucial role in the immune system's response to foreign substances. They are expressed on the surface of various cells, including immune cells such as B lymphocytes, macrophages, dendritic cells, and activated T lymphocytes.

Class II histocompatibility antigens are encoded by the major histocompatibility complex (MHC) class II genes, which are located on chromosome 6 in humans. These antigens are composed of two non-covalently associated polypeptide chains, an alpha (α) and a beta (β) chain, which form a heterodimer. There are three main types of Class II histocompatibility antigens, known as HLA-DP, HLA-DQ, and HLA-DR.

Class II histocompatibility antigens present peptide antigens to CD4+ T helper cells, which then activate other immune cells, such as B cells and macrophages, to mount an immune response against the presented antigen. Because of their role in initiating an immune response, Class II histocompatibility antigens are important in transplantation medicine, where mismatches between donor and recipient can lead to rejection of the transplanted organ or tissue.

Ovalbumin is the major protein found in egg white, making up about 54-60% of its total protein content. It is a glycoprotein with a molecular weight of around 45 kDa and has both hydrophilic and hydrophobic regions. Ovalbumin is a single polypeptide chain consisting of 385 amino acids, including four disulfide bridges that contribute to its structure.

Ovalbumin is often used in research as a model antigen for studying immune responses and allergies. In its native form, ovalbumin is not allergenic; however, when it is denatured or degraded into smaller peptides through cooking or digestion, it can become an allergen for some individuals.

In addition to being a food allergen, ovalbumin has been used in various medical and research applications, such as vaccine development, immunological studies, and protein structure-function analysis.

"Newborn animals" refers to the very young offspring of animals that have recently been born. In medical terminology, newborns are often referred to as "neonates," and they are classified as such from birth until about 28 days of age. During this time period, newborn animals are particularly vulnerable and require close monitoring and care to ensure their survival and healthy development.

The specific needs of newborn animals can vary widely depending on the species, but generally, they require warmth, nutrition, hydration, and protection from harm. In many cases, newborns are unable to regulate their own body temperature or feed themselves, so they rely heavily on their mothers for care and support.

In medical settings, newborn animals may be examined and treated by veterinarians to ensure that they are healthy and receiving the care they need. This can include providing medical interventions such as feeding tubes, antibiotics, or other treatments as needed to address any health issues that arise. Overall, the care and support of newborn animals is an important aspect of animal medicine and conservation efforts.

Medical Definition:

Mammary tumor virus, mouse (MMTV) is a type of retrovirus that specifically infects mice and is associated with the development of mammary tumors or breast cancer in these animals. The virus is primarily transmitted through mother's milk, leading to a high incidence of mammary tumors in female offspring.

MMTV contains an oncogene, which can integrate into the host's genome and induce uncontrolled cell growth and division, ultimately resulting in the formation of tumors. While MMTV is not known to infect humans, it has been a valuable model for studying retroviral pathogenesis and cancer biology.

Autoimmune diseases are a group of disorders in which the immune system, which normally protects the body from foreign invaders like bacteria and viruses, mistakenly attacks the body's own cells and tissues. This results in inflammation and damage to various organs and tissues in the body.

In autoimmune diseases, the body produces autoantibodies that target its own proteins or cell receptors, leading to their destruction or malfunction. The exact cause of autoimmune diseases is not fully understood, but it is believed that a combination of genetic and environmental factors contribute to their development.

There are over 80 different types of autoimmune diseases, including rheumatoid arthritis, lupus, multiple sclerosis, type 1 diabetes, Hashimoto's thyroiditis, Graves' disease, psoriasis, and inflammatory bowel disease. Symptoms can vary widely depending on the specific autoimmune disease and the organs or tissues affected. Treatment typically involves managing symptoms and suppressing the immune system to prevent further damage.

Interleukin-2 (IL-2) is a type of cytokine, which are signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis. Specifically, IL-2 is a growth factor for T cells, a type of white blood cell that plays a central role in the immune response. It is primarily produced by CD4+ T cells (also known as T helper cells) and stimulates the proliferation and differentiation of activated T cells, including effector T cells and regulatory T cells. IL-2 also has roles in the activation and function of other immune cells, such as B cells, natural killer cells, and dendritic cells. Dysregulation of IL-2 production or signaling can contribute to various pathological conditions, including autoimmune diseases, chronic infections, and cancer.

Antigen presentation is the process by which certain cells in the immune system, known as antigen presenting cells (APCs), display foreign or abnormal proteins (antigens) on their surface to other immune cells, such as T-cells. This process allows the immune system to recognize and mount a response against harmful pathogens, infected or damaged cells.

There are two main types of antigen presentation: major histocompatibility complex (MHC) class I and MHC class II presentation.

1. MHC class I presentation: APCs, such as dendritic cells, macrophages, and B-cells, process and load antigens onto MHC class I molecules, which are expressed on the surface of almost all nucleated cells in the body. The MHC class I-antigen complex is then recognized by CD8+ T-cells (cytotoxic T-cells), leading to the destruction of infected or damaged cells.
2. MHC class II presentation: APCs, particularly dendritic cells and B-cells, process and load antigens onto MHC class II molecules, which are mainly expressed on the surface of professional APCs. The MHC class II-antigen complex is then recognized by CD4+ T-cells (helper T-cells), leading to the activation of other immune cells, such as B-cells and macrophages, to eliminate the pathogen or damaged cells.

In summary, antigen presentation is a crucial step in the adaptive immune response, allowing for the recognition and elimination of foreign or abnormal substances that could potentially harm the body.

CD28 is a co-stimulatory molecule that plays an important role in the activation and regulation of T cells, which are key players in the immune response. It is a type of protein found on the surface of T cells and interacts with other proteins called B7-1 (also known as CD80) and B7-2 (also known as CD86) that are expressed on the surface of antigen-presenting cells (APCs).

When a T cell encounters an APC that is presenting an antigen, the T cell receptor (TCR) on the surface of the T cell recognizes and binds to the antigen. However, this interaction alone is not enough to fully activate the T cell. The engagement of CD28 with B7-1 or B7-2 provides a critical co-stimulatory signal that promotes T cell activation, proliferation, and survival.

CD28 is also an important target for immune checkpoint inhibitors, which are drugs used to treat cancer by blocking the inhibitory signals that prevent T cells from attacking tumor cells. By blocking CD28, these drugs can enhance the anti-tumor response of T cells and improve cancer outcomes.

Regulatory T-lymphocytes (Tregs), also known as suppressor T cells, are a subpopulation of T-cells that play a critical role in maintaining immune tolerance and preventing autoimmune diseases. They function to suppress the activation and proliferation of other immune cells, thereby regulating the immune response and preventing it from attacking the body's own tissues.

Tregs constitutively express the surface markers CD4 and CD25, as well as the transcription factor Foxp3, which is essential for their development and function. They can be further divided into subsets based on their expression of other markers, such as CD127 and CD45RA.

Tregs are critical for maintaining self-tolerance by suppressing the activation of self-reactive T cells that have escaped negative selection in the thymus. They also play a role in regulating immune responses to foreign antigens, such as those encountered during infection or cancer, and can contribute to the immunosuppressive microenvironment found in tumors.

Dysregulation of Tregs has been implicated in various autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis, as well as in cancer and infectious diseases. Therefore, understanding the mechanisms that regulate Treg function is an important area of research with potential therapeutic implications.

Enterotoxins are types of toxic substances that are produced by certain microorganisms, such as bacteria. These toxins are specifically designed to target and affect the cells in the intestines, leading to symptoms such as diarrhea, vomiting, and abdominal cramps. One well-known example of an enterotoxin is the toxin produced by Staphylococcus aureus bacteria, which can cause food poisoning. Another example is the cholera toxin produced by Vibrio cholerae, which can cause severe diarrhea and dehydration. Enterotoxins work by interfering with the normal functioning of intestinal cells, leading to fluid accumulation in the intestines and subsequent symptoms.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

An antigen is a substance (usually a protein) that is recognized as foreign by the immune system and stimulates an immune response, leading to the production of antibodies or activation of T-cells. Antigens can be derived from various sources, including bacteria, viruses, fungi, parasites, and tumor cells. They can also come from non-living substances such as pollen, dust mites, or chemicals.

Antigens contain epitopes, which are specific regions on the antigen molecule that are recognized by the immune system. The immune system's response to an antigen depends on several factors, including the type of antigen, its size, and its location in the body.

In general, antigens can be classified into two main categories:

1. T-dependent antigens: These require the help of T-cells to stimulate an immune response. They are typically larger, more complex molecules that contain multiple epitopes capable of binding to both MHC class II molecules on antigen-presenting cells and T-cell receptors on CD4+ T-cells.
2. T-independent antigens: These do not require the help of T-cells to stimulate an immune response. They are usually smaller, simpler molecules that contain repetitive epitopes capable of cross-linking B-cell receptors and activating them directly.

Understanding antigens and their properties is crucial for developing vaccines, diagnostic tests, and immunotherapies.

Steroid receptors are a type of nuclear receptor protein that are activated by the binding of steroid hormones or related molecules. These receptors play crucial roles in various physiological processes, including development, homeostasis, and metabolism. Steroid receptors function as transcription factors, regulating gene expression when activated by their respective ligands.

There are several subtypes of steroid receptors, classified based on the specific steroid hormones they bind to:

1. Glucocorticoid receptor (GR): Binds to glucocorticoids, which regulate metabolism, immune response, and stress response.
2. Mineralocorticoid receptor (MR): Binds to mineralocorticoids, which regulate electrolyte and fluid balance.
3. Androgen receptor (AR): Binds to androgens, which are male sex hormones that play a role in the development and maintenance of male sexual characteristics.
4. Estrogen receptor (ER): Binds to estrogens, which are female sex hormones that play a role in the development and maintenance of female sexual characteristics.
5. Progesterone receptor (PR): Binds to progesterone, which is a female sex hormone involved in the menstrual cycle and pregnancy.
6. Vitamin D receptor (VDR): Binds to vitamin D, which plays a role in calcium homeostasis and bone metabolism.

Upon ligand binding, steroid receptors undergo conformational changes that allow them to dimerize, interact with co-regulatory proteins, and bind to specific DNA sequences called hormone response elements (HREs) in the promoter regions of target genes. This interaction leads to the recruitment of transcriptional machinery, ultimately resulting in the modulation of gene expression. Dysregulation of steroid receptor signaling has been implicated in various diseases, including cancer, metabolic disorders, and inflammatory conditions.

Peptides are short chains of amino acid residues linked by covalent bonds, known as peptide bonds. They are formed when two or more amino acids are joined together through a condensation reaction, which results in the elimination of a water molecule and the formation of an amide bond between the carboxyl group of one amino acid and the amino group of another.

Peptides can vary in length from two to about fifty amino acids, and they are often classified based on their size. For example, dipeptides contain two amino acids, tripeptides contain three, and so on. Oligopeptides typically contain up to ten amino acids, while polypeptides can contain dozens or even hundreds of amino acids.

Peptides play many important roles in the body, including serving as hormones, neurotransmitters, enzymes, and antibiotics. They are also used in medical research and therapeutic applications, such as drug delivery and tissue engineering.

Graft survival, in medical terms, refers to the success of a transplanted tissue or organ in continuing to function and integrate with the recipient's body over time. It is the opposite of graft rejection, which occurs when the recipient's immune system recognizes the transplanted tissue as foreign and attacks it, leading to its failure.

Graft survival depends on various factors, including the compatibility between the donor and recipient, the type and location of the graft, the use of immunosuppressive drugs to prevent rejection, and the overall health of the recipient. A successful graft survival implies that the transplanted tissue or organ has been accepted by the recipient's body and is functioning properly, providing the necessary physiological support for the recipient's survival and improved quality of life.

Monoclonal antibodies are a type of antibody that are identical because they are produced by a single clone of cells. They are laboratory-produced molecules that act like human antibodies in the immune system. They can be designed to attach to specific proteins found on the surface of cancer cells, making them useful for targeting and treating cancer. Monoclonal antibodies can also be used as a therapy for other diseases, such as autoimmune disorders and inflammatory conditions.

Monoclonal antibodies are produced by fusing a single type of immune cell, called a B cell, with a tumor cell to create a hybrid cell, or hybridoma. This hybrid cell is then able to replicate indefinitely, producing a large number of identical copies of the original antibody. These antibodies can be further modified and engineered to enhance their ability to bind to specific targets, increase their stability, and improve their effectiveness as therapeutic agents.

Monoclonal antibodies have several mechanisms of action in cancer therapy. They can directly kill cancer cells by binding to them and triggering an immune response. They can also block the signals that promote cancer growth and survival. Additionally, monoclonal antibodies can be used to deliver drugs or radiation directly to cancer cells, increasing the effectiveness of these treatments while minimizing their side effects on healthy tissues.

Monoclonal antibodies have become an important tool in modern medicine, with several approved for use in cancer therapy and other diseases. They are continuing to be studied and developed as a promising approach to treating a wide range of medical conditions.

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Lymph nodes are small, bean-shaped organs that are part of the immune system. They are found throughout the body, especially in the neck, armpits, groin, and abdomen. Lymph nodes filter lymph fluid, which carries waste and unwanted substances such as bacteria, viruses, and cancer cells. They contain white blood cells called lymphocytes that help fight infections and diseases by attacking and destroying the harmful substances found in the lymph fluid. When an infection or disease is present, lymph nodes may swell due to the increased number of immune cells and fluid accumulation as they work to fight off the invaders.

Interleukin-2 (IL-2) receptors are a type of cell surface receptor that bind to and interact with the cytokine interleukin-2. IL-2 is a protein that plays an important role in the immune system, particularly in the activation and proliferation of T cells, a type of white blood cell that helps protect the body from infection and disease.

IL-2 receptors are composed of three subunits: alpha (CD25), beta (CD122), and gamma (CD132). These subunits can combine to form different types of IL-2 receptors, each with different functions. The high-affinity IL-2 receptor is made up of all three subunits and is found on the surface of activated T cells. This type of receptor has a strong binding affinity for IL-2 and plays a crucial role in T cell activation and proliferation.

The intermediate-affinity IL-2 receptor, which consists of the beta and gamma subunits, is found on the surface of resting T cells and natural killer (NK) cells. This type of receptor has a lower binding affinity for IL-2 and plays a role in activating and proliferating these cells.

IL-2 receptors are important targets for immunotherapy, as they play a key role in the regulation of the immune response. Drugs that target IL-2 receptors, such as aldesleukin (Proleukin), have been used to treat certain types of cancer and autoimmune diseases.

Bone marrow transplantation (BMT) is a medical procedure in which damaged or destroyed bone marrow is replaced with healthy bone marrow from a donor. Bone marrow is the spongy tissue inside bones that produces blood cells. The main types of BMT are autologous, allogeneic, and umbilical cord blood transplantation.

In autologous BMT, the patient's own bone marrow is used for the transplant. This type of BMT is often used in patients with lymphoma or multiple myeloma who have undergone high-dose chemotherapy or radiation therapy to destroy their cancerous bone marrow.

In allogeneic BMT, bone marrow from a genetically matched donor is used for the transplant. This type of BMT is often used in patients with leukemia, lymphoma, or other blood disorders who have failed other treatments.

Umbilical cord blood transplantation involves using stem cells from umbilical cord blood as a source of healthy bone marrow. This type of BMT is often used in children and adults who do not have a matched donor for allogeneic BMT.

The process of BMT typically involves several steps, including harvesting the bone marrow or stem cells from the donor, conditioning the patient's body to receive the new bone marrow or stem cells, transplanting the new bone marrow or stem cells into the patient's body, and monitoring the patient for signs of engraftment and complications.

BMT is a complex and potentially risky procedure that requires careful planning, preparation, and follow-up care. However, it can be a life-saving treatment for many patients with blood disorders or cancer.

Cytotoxic T-lymphocytes, also known as CD8+ T cells, are a type of white blood cell that plays a central role in the cell-mediated immune system. They are responsible for identifying and destroying virus-infected cells and cancer cells. When a cytotoxic T-lymphocyte recognizes a specific antigen presented on the surface of an infected or malignant cell, it becomes activated and releases toxic substances such as perforins and granzymes, which can create pores in the target cell's membrane and induce apoptosis (programmed cell death). This process helps to eliminate the infected or malignant cells and prevent the spread of infection or cancer.

A phenotype is the physical or biochemical expression of an organism's genes, or the observable traits and characteristics resulting from the interaction of its genetic constitution (genotype) with environmental factors. These characteristics can include appearance, development, behavior, and resistance to disease, among others. Phenotypes can vary widely, even among individuals with identical genotypes, due to differences in environmental influences, gene expression, and genetic interactions.

Hematopoietic stem cells (HSCs) are immature, self-renewing cells that give rise to all the mature blood and immune cells in the body. They are capable of both producing more hematopoietic stem cells (self-renewal) and differentiating into early progenitor cells that eventually develop into red blood cells, white blood cells, and platelets. HSCs are found in the bone marrow, umbilical cord blood, and peripheral blood. They have the ability to repair damaged tissues and offer significant therapeutic potential for treating various diseases, including hematological disorders, genetic diseases, and cancer.

Chromosome mapping, also known as physical mapping, is the process of determining the location and order of specific genes or genetic markers on a chromosome. This is typically done by using various laboratory techniques to identify landmarks along the chromosome, such as restriction enzyme cutting sites or patterns of DNA sequence repeats. The resulting map provides important information about the organization and structure of the genome, and can be used for a variety of purposes, including identifying the location of genes associated with genetic diseases, studying evolutionary relationships between organisms, and developing genetic markers for use in breeding or forensic applications.

DNA Mutational Analysis is a laboratory test used to identify genetic variations or changes (mutations) in the DNA sequence of a gene. This type of analysis can be used to diagnose genetic disorders, predict the risk of developing certain diseases, determine the most effective treatment for cancer, or assess the likelihood of passing on an inherited condition to offspring.

The test involves extracting DNA from a patient's sample (such as blood, saliva, or tissue), amplifying specific regions of interest using polymerase chain reaction (PCR), and then sequencing those regions to determine the precise order of nucleotide bases in the DNA molecule. The resulting sequence is then compared to reference sequences to identify any variations or mutations that may be present.

DNA Mutational Analysis can detect a wide range of genetic changes, including single-nucleotide polymorphisms (SNPs), insertions, deletions, duplications, and rearrangements. The test is often used in conjunction with other diagnostic tests and clinical evaluations to provide a comprehensive assessment of a patient's genetic profile.

It is important to note that not all mutations are pathogenic or associated with disease, and the interpretation of DNA Mutational Analysis results requires careful consideration of the patient's medical history, family history, and other relevant factors.

A plasmid is a small, circular, double-stranded DNA molecule that is separate from the chromosomal DNA of a bacterium or other organism. Plasmids are typically not essential for the survival of the organism, but they can confer beneficial traits such as antibiotic resistance or the ability to degrade certain types of pollutants.

Plasmids are capable of replicating independently of the chromosomal DNA and can be transferred between bacteria through a process called conjugation. They often contain genes that provide resistance to antibiotics, heavy metals, and other environmental stressors. Plasmids have also been engineered for use in molecular biology as cloning vectors, allowing scientists to replicate and manipulate specific DNA sequences.

Plasmids are important tools in genetic engineering and biotechnology because they can be easily manipulated and transferred between organisms. They have been used to produce vaccines, diagnostic tests, and genetically modified organisms (GMOs) for various applications, including agriculture, medicine, and industry.

Polymerase Chain Reaction (PCR) is a laboratory technique used to amplify specific regions of DNA. It enables the production of thousands to millions of copies of a particular DNA sequence in a rapid and efficient manner, making it an essential tool in various fields such as molecular biology, medical diagnostics, forensic science, and research.

The PCR process involves repeated cycles of heating and cooling to separate the DNA strands, allow primers (short sequences of single-stranded DNA) to attach to the target regions, and extend these primers using an enzyme called Taq polymerase, resulting in the exponential amplification of the desired DNA segment.

In a medical context, PCR is often used for detecting and quantifying specific pathogens (viruses, bacteria, fungi, or parasites) in clinical samples, identifying genetic mutations or polymorphisms associated with diseases, monitoring disease progression, and evaluating treatment effectiveness.

Exons are the coding regions of DNA that remain in the mature, processed mRNA after the removal of non-coding intronic sequences during RNA splicing. These exons contain the information necessary to encode proteins, as they specify the sequence of amino acids within a polypeptide chain. The arrangement and order of exons can vary between different genes and even between different versions of the same gene (alternative splicing), allowing for the generation of multiple protein isoforms from a single gene. This complexity in exon structure and usage significantly contributes to the diversity and functionality of the proteome.

Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:

1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.

Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.

Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.

Human chromosome pair 22 consists of two rod-shaped structures present in the nucleus of each cell in the human body. Each chromosome is made up of DNA tightly coiled around histone proteins, forming a complex structure called a chromatin.

Chromosome pair 22 is one of the 22 autosomal pairs of human chromosomes, meaning they are not sex chromosomes (X or Y). Chromosome 22 is the second smallest human chromosome, with each arm of the chromosome designated as p and q. The short arm is labeled "p," and the long arm is labeled "q."

Chromosome 22 contains several genes that are associated with various genetic disorders, including DiGeorge syndrome, velocardiofacial syndrome, and cat-eye syndrome, which result from deletions or duplications of specific regions on the chromosome. Additionally, chromosome 22 is the location of the NRXN1 gene, which has been associated with an increased risk for autism spectrum disorder (ASD) and schizophrenia when deleted or disrupted.

Understanding the genetic makeup of human chromosome pair 22 can provide valuable insights into human genetics, evolution, and disease susceptibility, as well as inform medical diagnoses, treatments, and research.

Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.

During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.

Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

'Escherichia coli' (E. coli) is a type of gram-negative, facultatively anaerobic, rod-shaped bacterium that commonly inhabits the intestinal tract of humans and warm-blooded animals. It is a member of the family Enterobacteriaceae and one of the most well-studied prokaryotic model organisms in molecular biology.

While most E. coli strains are harmless and even beneficial to their hosts, some serotypes can cause various forms of gastrointestinal and extraintestinal illnesses in humans and animals. These pathogenic strains possess virulence factors that enable them to colonize and damage host tissues, leading to diseases such as diarrhea, urinary tract infections, pneumonia, and sepsis.

E. coli is a versatile organism with remarkable genetic diversity, which allows it to adapt to various environmental niches. It can be found in water, soil, food, and various man-made environments, making it an essential indicator of fecal contamination and a common cause of foodborne illnesses. The study of E. coli has contributed significantly to our understanding of fundamental biological processes, including DNA replication, gene regulation, and protein synthesis.

Mutagenesis is the process by which the genetic material (DNA or RNA) of an organism is changed in a way that can alter its phenotype, or observable traits. These changes, known as mutations, can be caused by various factors such as chemicals, radiation, or viruses. Some mutations may have no effect on the organism, while others can cause harm, including diseases and cancer. Mutagenesis is a crucial area of study in genetics and molecular biology, with implications for understanding evolution, genetic disorders, and the development of new medical treatments.

DNA primers are short single-stranded DNA molecules that serve as a starting point for DNA synthesis. They are typically used in laboratory techniques such as the polymerase chain reaction (PCR) and DNA sequencing. The primer binds to a complementary sequence on the DNA template through base pairing, providing a free 3'-hydroxyl group for the DNA polymerase enzyme to add nucleotides and synthesize a new strand of DNA. This allows for specific and targeted amplification or analysis of a particular region of interest within a larger DNA molecule.

In situ hybridization, fluorescence (FISH) is a type of molecular cytogenetic technique used to detect and localize the presence or absence of specific DNA sequences on chromosomes through the use of fluorescent probes. This technique allows for the direct visualization of genetic material at a cellular level, making it possible to identify chromosomal abnormalities such as deletions, duplications, translocations, and other rearrangements.

The process involves denaturing the DNA in the sample to separate the double-stranded molecules into single strands, then adding fluorescently labeled probes that are complementary to the target DNA sequence. The probe hybridizes to the complementary sequence in the sample, and the location of the probe is detected by fluorescence microscopy.

FISH has a wide range of applications in both clinical and research settings, including prenatal diagnosis, cancer diagnosis and monitoring, and the study of gene expression and regulation. It is a powerful tool for identifying genetic abnormalities and understanding their role in human disease.

Restriction mapping is a technique used in molecular biology to identify the location and arrangement of specific restriction endonuclease recognition sites within a DNA molecule. Restriction endonucleases are enzymes that cut double-stranded DNA at specific sequences, producing fragments of various lengths. By digesting the DNA with different combinations of these enzymes and analyzing the resulting fragment sizes through techniques such as agarose gel electrophoresis, researchers can generate a restriction map - a visual representation of the locations and distances between recognition sites on the DNA molecule. This information is crucial for various applications, including cloning, genome analysis, and genetic engineering.

"Saccharomyces cerevisiae" is not typically considered a medical term, but it is a scientific name used in the field of microbiology. It refers to a species of yeast that is commonly used in various industrial processes, such as baking and brewing. It's also widely used in scientific research due to its genetic tractability and eukaryotic cellular organization.

However, it does have some relevance to medical fields like medicine and nutrition. For example, certain strains of S. cerevisiae are used as probiotics, which can provide health benefits when consumed. They may help support gut health, enhance the immune system, and even assist in the digestion of certain nutrients.

In summary, "Saccharomyces cerevisiae" is a species of yeast with various industrial and potential medical applications.

A homozygote is an individual who has inherited the same allele (version of a gene) from both parents and therefore possesses two identical copies of that allele at a specific genetic locus. This can result in either having two dominant alleles (homozygous dominant) or two recessive alleles (homozygous recessive). In contrast, a heterozygote has inherited different alleles from each parent for a particular gene.

The term "homozygote" is used in genetics to describe the genetic makeup of an individual at a specific locus on their chromosomes. Homozygosity can play a significant role in determining an individual's phenotype (observable traits), as having two identical alleles can strengthen the expression of certain characteristics compared to having just one dominant and one recessive allele.

22q11 Deletion Syndrome, also known as DiGeorge Syndrome or Velocardiofacial Syndrome, is a genetic disorder caused by the deletion of a small piece of chromosome 22 at a specific location (q11.2). This deletion results in the poor development of several body systems, including the following:

* The third and fourth pharyngeal pouches, which give rise to various structures in the neck, such as the parathyroid glands and thymus. As a result, affected individuals often have hypocalcemia (low levels of calcium in the blood) due to decreased parathyroid hormone production, and may have immune deficiencies due to abnormal or missing thymus tissue.
* The fourth pharyngeal arch, which forms parts of the aortic arch, the cranial base, and the neck. This can lead to congenital heart defects, such as tetralogy of Fallot or interrupted aortic arch.
* The branchial arches, which contribute to the formation of the face and neck. This can result in distinctive facial features, such as a prominent nasal bridge, hooded eyelids, a small jaw, and low-set ears.

The severity of 22q11 Deletion Syndrome can vary widely, even among members of the same family. Common symptoms include heart defects, palate abnormalities, immune deficiencies, developmental delays, learning disabilities, behavioral problems, and hearing loss. Some individuals with this syndrome may also have psychiatric disorders, such as schizophrenia or anxiety disorders.

Treatment for 22q11 Deletion Syndrome typically involves a multidisciplinary approach, addressing each of the affected body systems. For example, heart defects may require surgical repair, while immune deficiencies may be managed with medications or thymus transplantation. Calcium supplements and vitamin D may be prescribed to treat hypocalcemia. Speech therapy, occupational therapy, and special education services can help address developmental delays and learning disabilities.

Genetic recombination is the process by which genetic material is exchanged between two similar or identical molecules of DNA during meiosis, resulting in new combinations of genes on each chromosome. This exchange occurs during crossover, where segments of DNA are swapped between non-sister homologous chromatids, creating genetic diversity among the offspring. It is a crucial mechanism for generating genetic variability and facilitating evolutionary change within populations. Additionally, recombination also plays an essential role in DNA repair processes through mechanisms such as homologous recombinational repair (HRR) and non-homologous end joining (NHEJ).

Bacterial proteins are a type of protein that are produced by bacteria as part of their structural or functional components. These proteins can be involved in various cellular processes, such as metabolism, DNA replication, transcription, and translation. They can also play a role in bacterial pathogenesis, helping the bacteria to evade the host's immune system, acquire nutrients, and multiply within the host.

Bacterial proteins can be classified into different categories based on their function, such as:

1. Enzymes: Proteins that catalyze chemical reactions in the bacterial cell.
2. Structural proteins: Proteins that provide structural support and maintain the shape of the bacterial cell.
3. Signaling proteins: Proteins that help bacteria to communicate with each other and coordinate their behavior.
4. Transport proteins: Proteins that facilitate the movement of molecules across the bacterial cell membrane.
5. Toxins: Proteins that are produced by pathogenic bacteria to damage host cells and promote infection.
6. Surface proteins: Proteins that are located on the surface of the bacterial cell and interact with the environment or host cells.

Understanding the structure and function of bacterial proteins is important for developing new antibiotics, vaccines, and other therapeutic strategies to combat bacterial infections.

'Abnormalities, Multiple' is a broad term that refers to the presence of two or more structural or functional anomalies in an individual. These abnormalities can be present at birth (congenital) or can develop later in life (acquired). They can affect various organs and systems of the body and can vary greatly in severity and impact on a person's health and well-being.

Multiple abnormalities can occur due to genetic factors, environmental influences, or a combination of both. Chromosomal abnormalities, gene mutations, exposure to teratogens (substances that cause birth defects), and maternal infections during pregnancy are some of the common causes of multiple congenital abnormalities.

Examples of multiple congenital abnormalities include Down syndrome, Turner syndrome, and VATER/VACTERL association. Acquired multiple abnormalities can result from conditions such as trauma, infection, degenerative diseases, or cancer.

The medical evaluation and management of individuals with multiple abnormalities depend on the specific abnormalities present and their impact on the individual's health and functioning. A multidisciplinary team of healthcare professionals is often involved in the care of these individuals to address their complex needs.

An allele is a variant form of a gene that is located at a specific position on a specific chromosome. Alleles are alternative forms of the same gene that arise by mutation and are found at the same locus or position on homologous chromosomes.

Each person typically inherits two copies of each gene, one from each parent. If the two alleles are identical, a person is said to be homozygous for that trait. If the alleles are different, the person is heterozygous.

For example, the ABO blood group system has three alleles, A, B, and O, which determine a person's blood type. If a person inherits two A alleles, they will have type A blood; if they inherit one A and one B allele, they will have type AB blood; if they inherit two B alleles, they will have type B blood; and if they inherit two O alleles, they will have type O blood.

Alleles can also influence traits such as eye color, hair color, height, and other physical characteristics. Some alleles are dominant, meaning that only one copy of the allele is needed to express the trait, while others are recessive, meaning that two copies of the allele are needed to express the trait.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

A genetic complementation test is a laboratory procedure used in molecular genetics to determine whether two mutated genes can complement each other's function, indicating that they are located at different loci and represent separate alleles. This test involves introducing a normal or wild-type copy of one gene into a cell containing a mutant version of the same gene, and then observing whether the presence of the normal gene restores the normal function of the mutated gene. If the introduction of the normal gene results in the restoration of the normal phenotype, it suggests that the two genes are located at different loci and can complement each other's function. However, if the introduction of the normal gene does not restore the normal phenotype, it suggests that the two genes are located at the same locus and represent different alleles of the same gene. This test is commonly used to map genes and identify genetic interactions in a variety of organisms, including bacteria, yeast, and animals.

Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.

Southern blotting is a type of membrane-based blotting technique that is used in molecular biology to detect and locate specific DNA sequences within a DNA sample. This technique is named after its inventor, Edward M. Southern.

In Southern blotting, the DNA sample is first digested with one or more restriction enzymes, which cut the DNA at specific recognition sites. The resulting DNA fragments are then separated based on their size by gel electrophoresis. After separation, the DNA fragments are denatured to convert them into single-stranded DNA and transferred onto a nitrocellulose or nylon membrane.

Once the DNA has been transferred to the membrane, it is hybridized with a labeled probe that is complementary to the sequence of interest. The probe can be labeled with radioactive isotopes, fluorescent dyes, or chemiluminescent compounds. After hybridization, the membrane is washed to remove any unbound probe and then exposed to X-ray film (in the case of radioactive probes) or scanned (in the case of non-radioactive probes) to detect the location of the labeled probe on the membrane.

The position of the labeled probe on the membrane corresponds to the location of the specific DNA sequence within the original DNA sample. Southern blotting is a powerful tool for identifying and characterizing specific DNA sequences, such as those associated with genetic diseases or gene regulation.

Thus, clonal deletion can help protect individuals against autoimmunity. Clonal deletion is thought to be the most common type ... Incomplete clonal deletion results in apoptosis of most autoreactive B and T lymphocytes. Complete clonal deletion can lead to ... T lymphocytes can instead undergo clonal arrest, clonal anergy, and clonal editing. If autoreactive cells escape clonal ... In immunology, clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self ...
A clonal chromosome deletion 2p21 was found in endomyometriosis by Verhest et al. while Pai evidenced a strict relationship ... Verhest A, Simonart T, Noel JC (1996). A unique clonal chromosome 2 deletion in endomyometriosis. Cancer Genet Cytogenet 1996; ...
"Intrathymic and extrathymic clonal deletion of T cells." Current opinion in immunology 7.2 (1995): 196-205. Crotty, Shane, et ... The memory B cell has already undergone clonal expansion, differentiation and affinity maturation, so it is able to divide ...
They were also shown to be more efficient in T regulatory cells selection than clonal deletion. The last abundant subset of ... Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, von Andrian UH (October 2006). "Clonal deletion of thymocytes by ... Experiments from this study reveal that clonal deletion of autoreactive CD4+ T cells, apart from CD8+ T cells, requires ... Two processes of central tolerance take place in thymic medulla, namely clonal deletion (recessive tolerance) and T Regulatory ...
"Resolving the Enigma of the Clonal Expansion of mtDNA Deletions". Genes (Basel). 9 (3): 126. doi:10.3390/genes9030126. PMC ...
"Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway". Journal of Immunology. 181 (1): 320-8. ...
Both clonal anergy and clonal deletion have been shown to operate in vetoed T cells. The veto cell need only carry the self-MHC ... Avoiding self-reactivity in the T cell compartment is maintained by: clonal deletion in the thymus and suppressive cells that ... "Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7". Blood. ... evidence for a deletion-based mechanism mediated by TNF-alpha". Blood. 105 (6): 2585-93. doi:10.1182/blood-2002-11-3463. PMID ...
Most T cells are, in time, eliminated in the thymus by a process of clonal deletion. However, some of them escape this process ...
Just as in T cells, clonal deletion and clonal anergy can physically eliminate autoreactive B cell clones. Receptor editing is ... This negative selection is known as clonal deletion, one of the mechanisms for B cell tolerance. Approximately 99 percent of ... The mechanism of clonal anergy is important to maintain tolerance to many autologous antigens. Active suppression is the other ... This same positive and negative selection mechanism, but in peripheral tissues, is known as clonal anergy. ...
If they bind a self peptide, then they are signaled to apoptose (process of clonal deletion). The thymic epithelial cells ... clonal deletion) Receptor editing: the self-reactive B cell changes specificity by rearranging genes and develops a new BCR ... The results were explained by Burnet's clonal selection hypothesis. Burnet and Medawar won the Nobel Prize in 1960 for their ...
Both activated T cells and B cells express Fas and undergo clonal deletion by the AICD mechanism. Activated T cells that ...
This can induce T cell clonal deletion, T cell anergy or the proliferation of regulatory T cells (Tregs). Collectively, these ...
In either case, the B cell is allowed to proliferate or is killed off through a process called clonal deletion. Normally, the ...
... the others being clonal deletion and immunoregulation). This phenomenon was first described in B lymphocytes by Gustav Nossal ... "clonal selection"). This specific clonal army then combats the pathogen until the body is free of the infection. Following ... The clonal expansion of those cells can lead to autoimmune diseases, wherein the body attacks itself. In order to prevent this ... This process - called "clonal expansion" - allows the body to quickly mobilise an army of clones, as and when required. Such ...
Nature 333, 742-746 (1988); Swat, W., Ignatowicz, L., von Boehmer, H. and Kisielow, P.: Clonal deletion of immature CD4+8+ ... Nature 351, 150 (1991). Central tolerance by deletion of immature T cells in TCR transgenic mice. Teho H. S., Kisielow, P., ... Science 251, 1225 (1991). Peripheral tolerance by deletion of and reversible anergy in matureT cells. Borgulya, P., Kishi, H., ...
... evidence against clonal deletion as the mechanism of tolerance induction". Scandinavian Journal of Immunology. 8 (1): 29-37. ...
It was published that mTECs mediate clonal deletion (recessive tolerance), via presentation of TRAs, which leads to the ... namely clonal deletion or T regulatory cells selection, respectively. N.B.: All the below cited references utilized mouse as a ... that specific TRAs skew autoreactive T cells into TRegs with much higher efficiency than they do in the case of clonal deletion ... Rossi SW, Jenkinson WE, Anderson G, Jenkinson EJ (June 2006). "Clonal analysis reveals a common progenitor for thymic cortical ...
Tolerogenic DCs are essential in maintenance of central and peripheral tolerance through induction of T cell clonal deletion, T ... These tolerogenic properties are executed by deletion of T cells, induction of Tregs and anergized T cells, then by expression ...
... also called clonal anemone Vegetative cloning, a form of asexual reproduction in plants Clonal reproduction Clonal deletion, a ... Look up clonal in Wiktionary, the free dictionary. Clonal may refer to: Clonal interference, a phenomenon that occurs when two ... a model for how the immune system responds to infection Clonal anergy, a lack of reaction by the body's defense mechanisms to ... Cloning This disambiguation page lists articles associated with the title Clonal. If an internal link led you here, you may ...
... clonal deletion, receptor editing, anergy, or ignorance (B cell ignores signal and continues development). This negative ...
... who were the first to propose the deletion of self-reactive lymphocytes to establish tolerance, now termed clonal deletion. ... The deletion threshold is much more stringent for T cells than for B cells since T cells alone can cause direct tissue damage. ...
... most mother's fetal-specific CD8+ T cells undergo clonal deletion and express low levels of chemokine receptors and ligands - ...
... clonal anergy, deletion, and ignorance. While autoimmunity is thought to result from the breakdown of central and peripheral ... This mutant form of the anti-CD3 acts by only delivering a partial signal to the T-cell, leading to inactivation, deletion, and ... although a few T-cells will escape thymic deletion. However, these potentially self-reactive cells in the periphery are held in ...
... demonstrating that neither thymus nor clonal deletion is necessary to induce tolerance. In 1989 was successfully induced ...
... clonal anergy MeSH G04.610.484.120 - clonal deletion MeSH G04.610.484.800 - self tolerance MeSH G04.610.484.910 - tachyphylaxis ...
Clonal deletion theory, proposed by Burnet, according to which self-reactive lymphoid cells are destroyed during the ... Pike B, Boyd A, Nossal G (1982). "Clonal anergy: the universally anergic B lymphocyte". Proceedings of the National Academy of ... Consequently, auto-reactive B cells, that escape deletion, cannot find the antigen or the specific helper T cell. Suppressor ... In addition, two other theories are under intense investigation: Clonal ignorance theory, according to which autoreactive T ...
Clonal anergy Clonal deletion Clonal selection Clone (cell biology) CMKLR1 Colony stimulating factor 1 receptor Colony- ...
Autoimmunity Alloimmunity Cross-reactivity Tolerance Central tolerance Peripheral tolerance Clonal anergy Clonal deletion ... Mimotope Tumor antigen Antigen-antibody interaction Immunogenetics Affinity maturation Somatic hypermutation Clonal selection V ...
... ignorance of antigen and direct inactivation of effector T cells by either clonal deletion, conversion to regulatory T cells ( ... Deletion of self-reactive T cells in the thymus is only 60-70% efficient, and naive T cell repertoire contains a significant ... There are also extrinsic mechanisms of deletion mediated by the cytotoxic activity of Fas/FasL or TRAIL/TRAILR interaction. ...
... acquires a strong selective advantage creating a clinically apparent clonal population harboring the same pattern of deletions ... reported on a case in which chromothripsis, normally a catastrophic event in which chromosomes undergo massive deletion and ...
Thus, clonal deletion can help protect individuals against autoimmunity. Clonal deletion is thought to be the most common type ... Incomplete clonal deletion results in apoptosis of most autoreactive B and T lymphocytes. Complete clonal deletion can lead to ... T lymphocytes can instead undergo clonal arrest, clonal anergy, and clonal editing. If autoreactive cells escape clonal ... In immunology, clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self ...
We propose clonal deletion--immunization followed by deletion--as a \new way to achieve tolerance. Immunization of a donor ... A "New" Road to Tolerance: Clonal Deletion and Drugs Added When Needed (DAWN).. Terasaki PI, Everly ML, Kaneku H, Hoshino J, ... The theory of clonal deletion is supported by experimental evidence as well as earlier experiences with kidney transplants and ... To date 22 patients who underwent clonal deletion have been surviving for 1.5 to 2.5 years with only low-dose prednisone. In ...
Deletion (21)(q21.2q22.12) as a sole clonal cytogenetic abnormality in a lobular capillary hemangioma of the nasal cavity. ... 10, 11] underlying microscopic arteriovenous malformations, production of angiogenic factors, and cytogenetic clonal deletion ...
The "Clonal Deletion theory," suggests that self-reactive lymphoid cells are eliminated during immunological development. ... Proposed by Gustav Nossal, the "Clonal Anergy theory" suggests that reactive T- or B-cells become deactivated during ... Further theories currently being investigated include the "Clonal Ignorance theory," and the "Suppressor population or ... Regulatory T cell theory." The "Clonal Ignorance theory" suggests that self-reactive T cells not present in the thymus move to ...
Venanzi ES, Benoist C, Mathis D: Good riddance: thymocyte clonal deletion prevents autoimmunity. Curr Opin Immunol ... Because deletion or inactivation of potentially autoreactive T-cells in the thymus is believed to play a major role in ...
All 3 clonal lines showed out-of-frame deletion at the 29th exon. Dashed lines represent deletions. (. C. -. F. ) Subsequently ... Cas9/gRNA to establish targeted clonal lines. Three non-HD single-cell clones were also developed after EV treatment. Three ...
Whereas clonal deletion and anergy are mechanisms of peripheral tolerance2,3, active suppression by T-regulatory 1 (Tr1) cells ... Whereas clonal deletion and anergy are mechanisms of peripheral tolerance2,3, active suppression by T-regulatory 1 (Tr1) cells ... Kappler, J. W., Roehm, N. & Marrack, P. T cell tolerance by clonal elimination in the thymus. Cell 49, 273-280 (1987) ... Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature 333, 742-746 (1988) ...
Evidence for clonal deletion in tolerant kidney transplant patients. Sci Transl Med, 7 (272), 272ra10. http://dx.doi.org/ ... Narsale A, Almanza F, Tran T, Lam B, Seo D, Vu A, Long SA, Cooney L, Serti E, Davies JD (2023). Th2 cell clonal expansion at ... Savage TM, Shonts BA, Lau S, Obradovic A, Robins H, Shaked A, Shen Y, Sykes M (2020). Deletion of donor-reactive T cell clones ...
Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells ...
... the peripheral clonal deletion associated with peripheral chimerism, the intrathymic clonal deletion associated with ... Those include the clonal destruction of antigen-stimulated mature T cells, ... produced through the clonal destruction mechanism. For this purpose, the tolerogen, antimitotic drugs, their doses, timing, ... intrathymic chimerism, and the clonal anergy. The generation of suppressor T cells was another important mechanism of tolerance ...
Clonal deletion of tumor-specific T cells by interferon-γ confers therapeutic resistance to combination immune checkpoint ...
The presence of multiple mtDNA deletions supports the role of ENDOG in mtDNA maintenance; moreover, the patients clinical ... Although the patients fibroblasts did not present multiple mtDNA deletions or delay in the replication process, interestingly ... mitochondrial myopathy and multiple mtDNA deletions in muscle. The absence of the ENDOG protein in the patients muscle and ... possibly due to mechanisms favoring the clonal expansion of mtDNA deletions [23], in particular in post-mitotic tissues [24]. A ...
Woodland D, Happ MP, Bill J, Palmer E. Requirement for cotolerogenic gene products in the clonal deletion of I-E reactive T ... RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes. J Exp Med. 1989; 169(6):1903- ... Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986; 83(3):767- ... Woodland DL, Happ MP, Gollob KJ, Palmer E. An endogenous retrovirus mediating deletion of alpha beta T cells. Nature. 1991; 349 ...
... is not confused with the equally important concept of immune tolerance in which immune reactivity is inhibited by clonal ... deletion or silencing of antigen-specific lymphocytes (Xing and Hogquist, 2012). However, the possibility that immune tolerance ... in which immune reactivity is inhibited by clonal deletion or silencing of antigen-specific lymphocytes (5). However, the ...
T cell receptor transgenic mice and confirmed that both direct and indirect antigen presentation lead to clonal deletion of ... Deletion did not persist when chimerism was lost. Importantly, although the percentage of regulatory T cells (Tregs) after ... Deletion did not persist when chimerism was lost. Importantly, although the percentage of regulatory T cells (Tregs) after ... T cell receptor transgenic mice and confirmed that both direct and indirect antigen presentation lead to clonal deletion of ...
... consistent with multiple deletion events (1-36 kb) occurring since clonal expansion of the clade. Most deletions shared a ... Deletions in the fljB locus that occurred subsequent to the initial clonal expansion of the epidemic clade accounted for the ... The clone from Spain is characterized by variable size deletions in the fljB locus, all distinct from deletions observed in the ... of clonal expansion of the epidemic clade. These include a complex pattern of deletions in the fljB locus and surrounding ...
Two indicators of clonal complexity were used, namely, the number of foster clones, described as clones with similar D-N2-J ... Two indicators of clonal complexity were used: the number of foster clones, described as clones with similar D-N2-J ... This study observes that clonal complexity as accessed by IgH HTS is linked to prognostic factors in childhood BCP-ALL, ... This study observed that clonal complexity as accessed by IgH HTS, is linked to prognostic factors in childhood BCP-ALL, ...
Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint ... Abstract 2981: Clonal deletion of tumor-specific T cells by combination checkpoint blockade compromises antitumor efficacy in ...
Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells. ... Figure 5 Gli1 deletion prevents IL-6 and pSTAT3 expression in SPEM. A) RT-qPCR analysis of IL-6 mRNA. Error bars represent the ... I) PCR genotyping confirming homozygous deletion of Oct4 in 3 MEF lines. (J) Immunofluorescence imaging of Oct4 F/F and Oct4 ... Extended Data Figure 7 Efficient deletion of Notch2 in secretory progenitor cells and its effect on cell type distribution a, ...
Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1. Mazor, Tali; Chesnelong, ... Loss of p16 expression is a sensitive marker of CDKN2A homozygous deletion in malignant meningiomas. Tang, Vivian; Lu, Rufei; ...
Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus ...
Abortion, Clonal. Abortions, Clonal. Clonal Abortion. Clonal Abortions. Clonal Deletions. Deletion, Clonal. Deletions, Clonal. ... Clonal Deletions Deletion, Clonal Deletions, Clonal Clonal Abortion - Related but not broader or narrower Concept UI. M0026705 ... Clonal Deletion - Preferred Concept UI. M0026706. Scope note. Removal, via CELL DEATH, of immature lymphocytes that interact ... aborto clonal supresión clonal Scope note:. Eliminación, por MUERTE CELULAR, de linfocitos inmaduros que interactúan con ...
RESULTS: We have identified at the diagnosis clonal IGH rearrangement (VH3-JH5) and IKZF1 deletion (Δ4-7), which we have used ... MATERIAL: We showed that multiplex PCR and MLPA are necessary and complementary to detect IKZF1 deletions.. ... leukemia and was subsequently diagnosed to have lysosomal acid lipase deficiency/Wolman disease with a novel 5 bp deletion "c. ...
... antigens by clonal deletion, whereas thymic epithelial cells induce tolerance by clonal energy and possibly deletion of high ...
... tolerance mechanisms are likely to render high avidity T cells unresponsive or cause T cell elimination by clonal deletion. We ... tolerance mechanisms are likely to render high avidity T cells unresponsive or cause T cell elimination by clonal deletion. We ... tolerance mechanisms are likely to render high avidity T cells unresponsive or cause T cell elimination by clonal deletion. We ... tolerance mechanisms are likely to render high avidity T cells unresponsive or cause T cell elimination by clonal deletion. We ...
Explain T cell clonal deletion and how it functions in autoimmune diseases. Describe clonal deletion of B cells and its purpose ...
Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature. ... Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature. ... Clonal deletion of autoreactive B lymphocytes in bone marrow chimeras. Proc. Natl. Acad. Sci. USA. ... Clonal deletion of autoreactive B lymphocytes in bone marrow chimeras. Proc. Natl. Acad. Sci. USA. ...
The escape of anti-self B cells from tolerance mechanisms like clonal deletion, receptor editing, and anergy results in the ... The results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to ... Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral ...
B lymphocytes are sensitive to clonal deletion? 2.23K viewsGazeta Shëndeti Asked question Art Arti Clonal deletion Delet ... Hoti BE Bimë gjetherënëse Biom Biomet Black people Boshti Bota Bredhi Burimet e vitaminës D Cikli qelizor Clonal deletion Colon ...
Clonal Deletion. *Colitis, Ulcerative. *Colon. *Communicable Diseases. *Connexins. *Cord Blood Stem Cell Transplantation ...
  • T lymphocytes can instead undergo clonal arrest, clonal anergy, and clonal editing. (wikipedia.org)
  • Proposed by Gustav Nossal, the "Clonal Anergy theory" suggests that reactive T- or B-cells become deactivated during development and fail to increase immune responses. (news-medical.net)
  • Those include the clonal destruction of antigen-stimulated mature T cells, the peripheral clonal deletion associated with peripheral chimerism, the intrathymic clonal deletion associated with intrathymic chimerism, and the clonal anergy. (nih.gov)
  • The mechanisms for achieving self/non-self distinction include clonal deletion, clonal anergy, and clonal balance. (johnshopkins.edu)
  • These self-reactive T cells are normally held in check by clonal anergy or clonal balance. (johnshopkins.edu)
  • There is also accumulating evidence that beside clonal deletion and anergy, regulatory T cells−mediated dominant control of self−reactive lymphocytes might contribute to the maintenance of immunologic self−tolerance. (lu.se)
  • It is important to note that not all lymphocytes expressing high affinity for self-antigen undergo clonal deletion. (wikipedia.org)
  • B cells demonstrating high affinity for self antigen can undergo clonal deletion within the bone marrow. (wikipedia.org)
  • T cells that show a high affinity for self MHC/peptide complexes can undergo clonal deletion in the thymus. (wikipedia.org)
  • T cells also have the opportunity to undergo clonal deletion within the thymic medulla if they express high affinity for self MHC/peptide complexes. (wikipedia.org)
  • Because most autoresponsive cells undergo clonal deletion, this allows microorganisms with epitopes similar to host antigen to escape recognition and detection by T and B lymphocytes. (wikipedia.org)
  • B-lymphocytes may also undergo clonal deletion. (bvsalud.org)
  • Most thymocytes that bind with high affinity undergo clonal deletion to limit autoimmunity in the periphery. (atlasofscience.org)
  • Positive selection occurs in the thymic cortex, which suggests it is possible for a cell to undergo positive selection within the cortex and then negative selection in the medulla via clonal deletion. (wikipedia.org)
  • Thus, tolerance induction after IUHCTx depends on both direct and indirect antigen presentation and is secondary to thymic deletion, without de novo Treg induction. (ca.gov)
  • These data demonstrate that T cells become tolerant to autologous and allogeneic HLA antigens expressed in the thymus via two different mechanisms: hematopoietic cells present in the thymus induce tolerance to "self"-antigens by clonal deletion, whereas thymic epithelial cells induce tolerance by clonal energy and possibly deletion of high affinity clones. (rupress.org)
  • If autoreactive cells escape clonal deletion in either the thymus or the bone marrow, there are mechanisms in the periphery involving T regulatory cells to prevent the host from obtaining an autoimmune disease. (wikipedia.org)
  • T cells reactive with self-antigens not represented in the thymus, and probably some low-affinity T cells, escape clonal deletion and populate peripheral lymphoid tissues and blood. (johnshopkins.edu)
  • The "Clonal Ignorance theory" suggests that self-reactive T cells not present in the thymus move to the periphery where they fail to encounter target antigens . (news-medical.net)
  • Clonal deletion results in the elimination of self-reactive T cells during their maturation in the thymus. (johnshopkins.edu)
  • clonal deletion in the thymus is a function not only of antigen concentration, butalso of. (moam.info)
  • Epithelial cells are responsible for clonal deletion within the medulla. (wikipedia.org)
  • However, for both B and T cells in the primary lymphoid organs, clonal deletion is the most common form of negative selection. (wikipedia.org)
  • The "Clonal Deletion theory," suggests that self-reactive lymphoid cells are eliminated during immunological development. (news-medical.net)
  • It is a clonal genetic heterogeneous disease generally thought to arise from the malignant transformation and expansion of a single lymphoid progenitor at various stages of development ( 3 - 5 ). (frontiersin.org)
  • In immunology, clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self before developing into fully immunocompetent lymphocytes. (wikipedia.org)
  • Complete clonal deletion results in apoptosis of all B and T lymphocytes expressing high affinity for self antigen. (wikipedia.org)
  • Incomplete clonal deletion results in apoptosis of most autoreactive B and T lymphocytes. (wikipedia.org)
  • It is important that "disease tolerance" is not confused with the equally important concept of "immune tolerance" in which immune reactivity is inhibited by clonal deletion or silencing of antigen-specific lymphocytes ( 5 ). (frontiersin.org)
  • To assess the technique, we probed clonal isolates of 293-TREx cells that were targeted with three separate sgRNAs against the HuR gene. (biomedcentral.com)
  • Isolates of serogroup A had the same antigenic formula (A:4:P1.9), the same variable regions VR1, VR2 and VR3, and belonged to the same clonal complex (CC5). (who.int)
  • The most frequent clonal complex in these isolates was CC35. (who.int)
  • Clonal expansion of mitochondrial DNA with multiple deletions in autosomal dominant progressive external ophthalmoplegia. (portugene.com)
  • We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. (nih.gov)
  • Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. (nih.gov)
  • Thus, clonal deletion can help protect individuals against autoimmunity. (wikipedia.org)
  • If they demonstrate high affinity for self-antigen, one method of preventing autoimmunity is through clonal deletion. (wikipedia.org)
  • Myelodysplastic syndrome (MDS) in childhood encompasses a diverse group of bone marrow disorders that share a common clonal defect of stem cells and that result in ineffective hematopoiesis with dysplastic changes in the marrow. (medscape.com)
  • Analysis of the genomic deletions in the phase II flagellum locus responsible for the monophasic phenotype suggested that multiple independent clones may be emerging in the United States and Europe ( 9 ). (cdc.gov)
  • Depending on the desired mutation, several experimental options exist in the isolation of clonal lines, such as selection with introduced markers, or screening by PCR amplification of genomic DNA. (biomedcentral.com)
  • However, streamlined approaches to establishing deletion and tagging mutants with minimal genomic perturbation are of interest in applying this methodology. (biomedcentral.com)
  • Genomic sequencing verified small deletions at the targeted locus. (biomedcentral.com)
  • Clonal screening for CRISPR/Cas9-mediated editing events using dot immunoblot is a straightforward and efficient approach that facilitates rapid generation of genomic mutants to study gene function. (biomedcentral.com)
  • All 3 clonal lines showed out-of-frame deletion at the 29th exon. (jci.org)
  • As well as the exon 19 deletion harbored from the tumor during analysis originally, this evaluation recognized the T790M mutation. (msi-sig.org)
  • The tumor managed the original exon 19 deletion, suggesting a monoclonal source and clonal progression. (msi-sig.org)
  • Deletion did not persist when chimerism was lost. (ca.gov)
  • The PAH-induced death signaling pathway resembles the signaling cascade activated during clonal deletion and modeled by B cell receptor cross-linking or by dexamethasone exposure of immature surface Ig + B cells in that apoptosis is mediated by NF-κB down-regulation. (aai.org)
  • These results distinguish the PAH-induced apoptosis pathway from that activated during clonal deletion and indicate that signaling cascades leading to growth arrest and/or apoptosis in pro/pre-B cells differ from those active at later B cell developmental stages. (aai.org)
  • CT10 Chapter 24: A 'New' Road to Tolerance: Clonal Deletion and Drugs Added When Needed (DAWN). (terasaki.org)
  • A "New" Road to Tolerance: Clonal Deletion and Drugs Added When Needed (DAWN). (terasaki.org)
  • We propose clonal deletion--immunization followed by deletion--as a \new\" way to achieve tolerance. (terasaki.org)
  • Special care was taken to overcome the " hard" barriers of allo- or xeno-combinations by reducing the "split tolerance" produced through the clonal destruction mechanism. (nih.gov)
  • In utero hematopoietic cell transplantation (IUHCTx) is a promising method to induce donor-specific tolerance but the mechanisms of antigen presentation that educate host T cells and the relative importance of deletion vs. regulation in this setting are unknown. (ca.gov)
  • Because many T cell-recognized tumor antigens are nonmutated self-proteins, tolerance mechanisms are likely to render high avidity T cells unresponsive or cause T cell elimination by clonal deletion. (birmingham.ac.uk)
  • B7/CD28 in central tolerance: costimulation promotes maturation of regulatory T cell precursors and prevents their clonal deletion. (shengsci.com)
  • A remarkable amount of genotypic variation accumulated during clonal expansion that occurred during the epidemic, including multiple independent acquisitions of a novel prophage carrying the sopE gene and multiple deletion events affecting the phase II flagellin locus. (cdc.gov)
  • Such T cells are often removed via clonal deletion, leaving autoreactive B cells unstimulated and unactivated. (wikipedia.org)
  • Direct and indirect antigen presentation lead to deletion of donor-specific T cells after in utero hematopoietic cell transplantation in mice. (ca.gov)
  • We next performed allogeneic IUHCTx into donor-specific T cell receptor transgenic mice and confirmed that both direct and indirect antigen presentation lead to clonal deletion of effector T cells in chimeras. (ca.gov)
  • In wild-type mice, there was a similar deletion of effector cells without expansion of donor-specific Tregs. (ca.gov)
  • Describe clonal deletion of B cells and its purpose. (nursingdons.com)
  • Here, we demonstrate that developing self-reactive B cells are not always highly sensitive to the deletion mechanisms imposed by membrane-bound self-antigens. (silverchair.com)
  • Because a PAH-induced, clonally nonrestricted deletion of B cells would have important implications for B cell repertoire development, the nature of the PAH-induced intracellular death signal was studied further. (aai.org)
  • As in clonal deletion models, and as predicted by the down-regulation of NF-κB, PAH-induced death of pro/pre-B cells was at least partially dependent on c-Myc down-regulation. (aai.org)
  • PURPOSE: IL-2 promotes activation, clonal expansion, and deletion of T cells. (gwu.edu)
  • Clonal balance depends upon the ratio of stimulatory and inhibitory signals delivered to the T cells. (johnshopkins.edu)
  • For conventional T cells, high affinity TCR-MHC engagement may preferentially generate dominant T cell clonal expansion to combat infection. (atlasofscience.org)
  • The somatic mutation occurs initially in a single cell, which continues to grow and divide, producing a group of cells with the same mutation (a clonal population). (medlineplus.gov)
  • Two indicators of clonal complexity were used, namely, the number of foster clones, described as clones with similar D-N 2 -J rearrangements but other V-rearrangement and N 1 -joining, and the maximum across all foster clones of the number of evolved clones from one foster clone. (frontiersin.org)
  • In total, 32 independent biallelic deletion lines out of 248 screened clones were isolated, and recovery of null mutants ranged from 6 to 36 % for the individual sgRNAs. (biomedcentral.com)
  • Further theories currently being investigated include the "Clonal Ignorance theory," and the "Suppressor population or Regulatory T cell theory. (news-medical.net)
  • Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1 . (bvsalud.org)
  • The most common genetic abnormality in PDGFRA -associated chronic eosinophilic leukemia results from a deletion of genetic material from chromosome 4 , which brings together part of the PDGFRA gene and part of the FIP1L1 gene, creating the FIP1L1-PDGFRA fusion gene. (medlineplus.gov)
  • Histidine-rich protein 2/3 antigen concentrations were reduced with corresponding gene deletions. (cdc.gov)
  • Aquí se describe un método para la eliminación de genes dirigida y sin marcadores en Chlamydia trachomatis mediante mutagénesis de intercambio alélico de casete floxed, FLAEM. (jove.com)
  • Deletions of pfhrp2 and paralogue pfhrp3 (pfhrp2/3) genes threaten Plasmodium falciparum diagnosis by rapid diagnostic test. (cdc.gov)
  • B ) An HD iPSC with a juvenile-onset CAG repeat was transfected with a plasmid vector expressing either Sp Cas9 only (empty vector [EV]) or Sp Cas9/gRNA to establish targeted clonal lines. (jci.org)
  • We developed a procedure for rapid screening of clonal cell lines for the deletion of a protein of interest following CRISPR/Cas9 targeting in the absence of selective pressure based on dot immunoblots. (biomedcentral.com)
  • We know that Jonathan J. Keats, PhD described in 2012 the concept of clonal evolution, where that clone that was the dominant clone might change over time. (ajmc.com)
  • Finally, in contrast to clonal deletion, PAH-induced pro/pre-B cell death was not dependent on p27 Kip1 or p21 WAF1 up-regulation but did coincide with p53 induction. (aai.org)
  • In contrast, small in-frame deletions may not compromise the function of the protein. (biomedcentral.com)
  • The theory of clonal deletion is supported by experimental evidence as well as earlier experiences with kidney transplants and donor-specific transfusions. (terasaki.org)
  • We described the patterns of clonal complexity at diagnosis and investigated its association with patients' characteristics. (frontiersin.org)
  • It also reveals the sequences of clonal rearrangements, therefore, the multiclonal structure, of BCP-ALL. (frontiersin.org)
  • Conditional deletion of CD25 in the corneal epithelium reveals sex dif" by Anmar Abu-Romman, Kaitlin K. Scholand et al. (gwu.edu)
  • and de Paiva, Cintia S., "Conditional deletion of CD25 in the corneal epithelium reveals sex differences in barrier disruption" (2023). (gwu.edu)
  • The main target of regulatory inputs during oncogenic stress is the MDM2 forex oanda trading, R3 CO-CH3 : 6-methylidene-3,20-dioxo- pregn-4-en-17-yl acetate (6-methylenehydroxyprogesterone acetate), H. (top5binarybrokers.com)
  • Monosomy 7 is most often associated with juvenile myelomonocytic leukemia (JMML), and as many as 30% of children with JMML have a deletion of all or part of chromosome 7. (medscape.com)
  • Particular emphasis was placed on the roles of growth arrest and c-Myc, p27 Kip1 , and p21 WAF1 expression, because all of these elements contribute to clonal deletion. (aai.org)
  • Based on these results, it was postulated that B cell deletion required BCR cross-linking and could only be induced by membrane bound self-antigens. (silverchair.com)
  • Validation of knockout candidates by western blot indicated that the normalized protein abundances indicated by the dot blot serve as accurate predictors of deletion. (biomedcentral.com)
  • Deletions that target the open reading frame and result in frame-shifts, particularly early in the mRNA, are very likely to yield a non-functional protein sequence and to target the mRNA for nonsense-mediated decay due to premature stop codons in the new frame (Fig. 1 ). (biomedcentral.com)
  • Complete clonal deletion can lead to opportunities for molecular mimicry, which has adverse effects for the host. (wikipedia.org)
  • Clonal deletion is thought to be the most common type of negative selection. (wikipedia.org)
  • Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. (nih.gov)
  • 1. IgH high-throughput sequencing allows new insights into the clonal architecture of BCP-ALL. (frontiersin.org)
  • With DAWN as a tactic ready for intervention and by using antibodies to monitor the completeness of clonal deletion we assure that patients are subjected to the minimal amount of drugs on a personalized basis. (terasaki.org)
  • To date 22 patients who underwent clonal deletion have been surviving for 1.5 to 2.5 years with only low-dose prednisone. (terasaki.org)
  • We examined 1,002 samples from suspected malaria patients in Djibouti City, Djibouti, to investigate pfhrp2/3 deletions. (cdc.gov)
  • Dashed lines represent deletions. (jci.org)
  • This clonal deletion has been modeled by cross-linking surface Ig (sIg) 3 in immature B cell lines such as WEHI-231 ( 1 , 2 , 3 , 4 ). (aai.org)
  • Clonal deletion provides an incentive for microorganisms to develop epitopes similar to proteins found within the host. (wikipedia.org)
  • The first description of a monophasic Salmonella Typhimurium epidemic in Europe was that of a "Spanish clone," which emerged rapidly during 1997 and was characterized by a deletion in the allantoin-glyoxylate operon and the fljAB operon, phage type U302, and a heptaresistance pattern ACSuGSTSxT (resistant to ampicillin, chloramphenicol, sulfonamide, gentamicin, streptomycin, tetracycline, and co-trimoxazole) ( 10 ). (cdc.gov)