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.
The mechanism, in central lymphoid organs (THYMUS; BONE MARROW), that prevents immature lymphocytes from reacting to SELF-ANTIGENS. This is accomplished by CLONAL ANERGY and CLONAL DELETION.
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.
The mechanism, in peripheral lymphoid organs (LYMPH NODES; SPLEEN; TONSILS; and mucosal-associated lymphoid tissue), that prevents mature lymphocytes from reacting to SELF-ANTIGENS. This is accomplished through a variety of means including CLONAL ANERGY and CLONAL DELETION.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.
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.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
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.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response.
A member of the tumor necrosis factor receptor superfamily. It has specificity for LYMPHOTOXIN ALPHA1, BETA2 HETEROTRIMER and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 14. The receptor plays a role in regulating lymphoid ORGANOGENESIS and the differentiation of certain subsets of NATURAL KILLER T-CELLS. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
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.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Autoimmune diseases affecting multiple endocrine organs. Type I is characterized by childhood onset and chronic mucocutaneous candidiasis (CANDIDIASIS, CHRONIC MUCOCUTANEOUS), while type II exhibits any combination of adrenal insufficiency (ADDISON'S DISEASE), lymphocytic thyroiditis (THYROIDITIS, AUTOIMMUNE;), HYPOPARATHYROIDISM; and gonadal failure. In both types organ-specific ANTIBODIES against a variety of ENDOCRINE GLANDS have been detected. The type II syndrome differs from type I in that it is associated with HLA-A1 and B8 haplotypes, onset is usually in adulthood, and candidiasis is not present.
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 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.
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.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
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.
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.
The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
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.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial 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.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
A costimulatory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 RECEPTOR. It is closely-related to CD274 antigen; however, its expression is restricted to DENDRITIC CELLS and activated MACROPHAGES.
A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.
An encapsulated lymphatic organ through which venous blood filters.
An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.
Substances that are recognized by the immune system and induce an immune reaction.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.
The ability of organisms to sense and adapt to high concentrations of salt in their growth environment.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.
An inhibitory T-lymphocyte receptor that has specificity for CD274 ANTIGEN and PROGRAMMED CELL DEATH 1 LIGAND 2 PROTEIN. Signaling by the receptor limits T cell proliferation and INTERFERON GAMMA synthesis. The receptor also may play an essential role in the regulatory pathway that induces PERIPHERAL TOLERANCE.
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.
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)
Glucose in blood.
The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.
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.
The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an EXERCISE TEST.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Prolonged dry periods in natural climate cycle. They are slow-onset phenomena caused by rainfall deficit combined with other predisposing factors.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
Surgical removal of the thymus gland. (Dorland, 28th ed)
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
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.
Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends.
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.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
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.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.
Elements of limited time intervals, contributing to particular results or situations.
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.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. (Cline et al., Dictionary of Visual Science, 4th ed, p109)
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.
Adaptation to a new environment or to a change in the old.
The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.
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.
A person's view of himself.
Glycoproteins found on the membrane or surface of cells.
Reduction in the number of lymphocytes.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
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.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
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)
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A ubiquitous sodium salt that is commonly used to season food.
Plants that can grow well in soils that have a high SALINITY.
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.
Alteration of the immune system or of an immune response by agents that activate or suppress its function. This can include IMMUNIZATION or administration of immunomodulatory drugs. Immunomodulation can also encompass non-therapeutic alteration of the immune system effected by endogenous or exogenous substances.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
Antibodies produced by a single clone of cells.
An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)
Pathological processes involving any one of the BLOOD VESSELS in the vasculature outside the HEART.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
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.
Liquids transforming into solids by the removal of heat.
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.
Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
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.
PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.
Degree of saltiness, which is largely the OSMOLAR CONCENTRATION of SODIUM CHLORIDE plus any other SALTS present. It is an ecological factor of considerable importance, influencing the types of organisms that live in an ENVIRONMENT.
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.
Inbred strain A mice are genetically identical descendants of a single founder mouse, produced by many generations of brother-sister matings, primarily used in biomedical research for their genetic uniformity and experimental reproducibility.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
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.
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.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
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.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
Sites on an antigen that interact with specific antibodies.
An absence of warmth or heat or a temperature notably below an accustomed norm.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
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.
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
The number of LYMPHOCYTES per unit volume of BLOOD.
Removal of moisture from a substance (chemical, food, tissue, etc.).
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The usually underground portions of a plant that serve as support, store food, and through which water and mineral nutrients enter the plant. (From American Heritage Dictionary, 1982; Concise Dictionary of Biology, 1990)
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.

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.

Central tolerance is a term used in immunology to describe the process by which the immune system learns to tolerate self-antigens, or the proteins and other molecules that are produced by an individual's own cells and tissues. This is an important mechanism for preventing autoimmune diseases, in which the immune system mistakenly attacks the body's own cells and tissues.

Central tolerance is established in the primary lymphoid organs, such as the bone marrow and thymus, during the development of T cells and B cells, which are the white blood cells that play a central role in the adaptive immune response. In the bone marrow, developing B cells that recognize self-antigens are either eliminated or rendered unresponsive (a process called receptor editing). In the thymus, developing T cells that recognize self-antigens are also eliminated or rendered unresponsive through a process called negative selection.

Central tolerance is an important mechanism for preventing autoimmunity, but it is not perfect. Some self-reactive T cells and B cells may escape these processes and enter the peripheral immune system, where they can potentially cause damage if they are activated by self-antigens. To prevent this from happening, the immune system has additional mechanisms of tolerance, called peripheral tolerance, that help to keep these self-reactive cells in check.

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.

Peripheral tolerance, in the context of immunology and medicine, refers to a state of immune system unresponsiveness or non-reactivity to certain antigens (substances that can trigger an immune response) that are encountered outside the central lymphoid organs (thymus and bone marrow). This is a crucial mechanism to prevent the immune system from attacking the body's own cells and tissues, as well as harmless environmental antigens.

Peripheral tolerance is established and maintained through several mechanisms:

1. **Anergy:** T cells (a type of immune cell) that recognize self-antigens can become inactivated or anergic, meaning they cannot respond to those antigens anymore.
2. **Regulatory T cells (Tregs):** These are a special class of T cells that suppress the activation and proliferation of other immune cells. They play a critical role in maintaining peripheral tolerance by preventing autoimmune responses.
3. **Deletion:** Immature T and B cells that recognize self-antigens with high affinity can be eliminated in the periphery, thus preventing them from mounting an immune response against the body's own tissues.
4. **Immune ignorance:** Some self-antigens may not be encountered by the immune system due to their location or limited availability, leading to a state of ignorance and non-reactivity.

Defects in peripheral tolerance can lead to autoimmune diseases, where the immune system attacks the body's own cells and tissues.

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.

Drug tolerance is a medical concept that refers to the decreased response to a drug following its repeated use, requiring higher doses to achieve the same effect. This occurs because the body adapts to the presence of the drug, leading to changes in the function or expression of targets that the drug acts upon, such as receptors or enzymes. Tolerance can develop to various types of drugs, including opioids, benzodiazepines, and alcohol, and it is often associated with physical dependence and addiction. It's important to note that tolerance is different from resistance, which refers to the ability of a pathogen to survive or grow in the presence of a drug, such as antibiotics.

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.

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.

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.

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.

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.

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.

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.

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.

A Glucose Tolerance Test (GTT) is a medical test used to diagnose prediabetes, type 2 diabetes, and gestational diabetes. It measures how well your body is able to process glucose, which is a type of sugar.

During the test, you will be asked to fast (not eat or drink anything except water) for at least eight hours before the test. Then, a healthcare professional will take a blood sample to measure your fasting blood sugar level. After that, you will be given a sugary drink containing a specific amount of glucose. Your blood sugar levels will be measured again after two hours and sometimes also after one hour.

The results of the test will indicate how well your body is able to process the glucose and whether you have normal, impaired, or diabetic glucose tolerance. If your blood sugar levels are higher than normal but not high enough to be diagnosed with diabetes, you may have prediabetes, which means that you are at increased risk of developing type 2 diabetes in the future.

It is important to note that a Glucose Tolerance Test should be performed under the supervision of a healthcare professional, as high blood sugar levels can be dangerous if not properly managed.

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.

Transplantation tolerance, also known as immunological tolerance or transplant tolerance, is a state in which the immune system of a transplant recipient does not mount an immune response against the transplanted organ or tissue. This is an important goal in transplantation medicine to prevent graft rejection and reduce the need for long-term immunosuppressive therapy, which can have significant side effects.

Transplantation tolerance can be achieved through various mechanisms, including the deletion or regulation of donor-reactive T cells, the induction of regulatory T cells (Tregs) that suppress immune responses against the graft, and the modulation of innate immune responses. The development of strategies to induce transplantation tolerance is an active area of research in transplantation medicine.

The Lymphotoxin-beta receptor (LTβR) is a type III transmembrane protein and a member of the tumor necrosis factor receptor superfamily (TNFRSF). It is primarily expressed on the surface of various cell types, including immune cells such as lymphocytes, dendritic cells, and stromal cells in lymphoid organs.

LTβR binds to its ligands, Lymphotoxin-alpha (LTα) and Lymphotoxin-beta (LTβ), which are primarily produced by activated T-cells and B-cells. The binding of LTα/LTβ to LTβR triggers a signaling cascade that leads to the activation of various downstream signaling pathways, including NF-κB and MAPK pathways.

The activation of LTβR plays critical roles in the development and organization of lymphoid tissues, immune responses, and inflammation. Dysregulation of LTβR signaling has been implicated in various autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis.

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.

Dendritic cells (DCs) are a type of immune cell that play a critical role in the body's defense against infection and cancer. They are named for their dendrite-like projections, which they use to interact with and sample their environment. DCs are responsible for processing antigens (foreign substances that trigger an immune response) and presenting them to T cells, a type of white blood cell that plays a central role in the immune system's response to infection and cancer.

DCs can be found throughout the body, including in the skin, mucous membranes, and lymphoid organs. They are able to recognize and respond to a wide variety of antigens, including those from bacteria, viruses, fungi, and parasites. Once they have processed an antigen, DCs migrate to the lymph nodes, where they present the antigen to T cells. This interaction activates the T cells, which then go on to mount a targeted immune response against the invading pathogen or cancerous cells.

DCs are a diverse group of cells that can be divided into several subsets based on their surface markers and function. Some DCs, such as Langerhans cells and dermal DCs, are found in the skin and mucous membranes, where they serve as sentinels for invading pathogens. Other DCs, such as plasmacytoid DCs and conventional DCs, are found in the lymphoid organs, where they play a role in activating T cells and initiating an immune response.

Overall, dendritic cells are essential for the proper functioning of the immune system, and dysregulation of these cells has been implicated in a variety of diseases, including autoimmune disorders and cancer.

Polyendocrinopathies, autoimmune refers to a group of disorders that involve malfunction of multiple endocrine glands, caused by the immune system mistakenly attacking and damaging these glands. The endocrine glands are responsible for producing hormones that regulate various functions in the body.

There are several types of autoimmune polyendocrinopathies, including:

1. Autoimmune Polyendocrine Syndrome Type 1 (APS-1): Also known as Autoimmune Polyglandular Syndrome Type 1 or APECED, this is a rare inherited disorder that typically affects multiple endocrine glands and other organs. It is caused by mutations in the autoimmune regulator (AIRE) gene.
2. Autoimmune Polyendocrine Syndrome Type 2 (APS-2): Also known as Schmidt's syndrome, this disorder typically involves the adrenal glands, thyroid gland, and/or insulin-producing cells in the pancreas. It is more common than APS-1 and often affects middle-aged women.
3. Autoimmune Polyendocrine Syndrome Type 3 (APS-3): This disorder involves the presence of autoimmune Addison's disease, with or without other autoimmune disorders such as thyroid disease, type 1 diabetes, or vitiligo.
4. Autoimmune Polyendocrine Syndrome Type 4 (APS-4): This is a catch-all category for individuals who have multiple autoimmune endocrine disorders that do not fit into the other types of APS.

Symptoms of autoimmune polyendocrinopathies can vary widely depending on which glands are affected and the severity of the damage. Treatment typically involves replacing the hormones that are no longer being produced in sufficient quantities, as well as managing any underlying immune system dysfunction.

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.

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.

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.

Inbred NOD (Nonobese Diabetic) mice are a strain of laboratory mice that are genetically predisposed to develop autoimmune diabetes. This strain was originally developed in Japan and has been widely used as an animal model for studying type 1 diabetes and its complications.

NOD mice typically develop diabetes spontaneously at around 12-14 weeks of age, although the onset and severity of the disease can vary between individual mice. The disease is caused by a breakdown in immune tolerance, leading to an autoimmune attack on the insulin-producing beta cells of the pancreas.

Inbred NOD mice are highly valuable for research purposes because they exhibit many of the same genetic and immunological features as human patients with type 1 diabetes. By studying these mice, researchers can gain insights into the underlying mechanisms of the disease and develop new treatments and therapies.

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.

Antigen-presenting cells (APCs) are a group of specialized cells in the immune system that play a critical role in initiating and regulating immune responses. They have the ability to engulf, process, and present antigens (molecules derived from pathogens or other foreign substances) on their surface in conjunction with major histocompatibility complex (MHC) molecules. This presentation of antigens allows APCs to activate T cells, which are crucial for adaptive immunity.

There are several types of APCs, including:

1. Dendritic cells (DCs): These are the most potent and professional APCs, found in various tissues throughout the body. DCs can capture antigens from their environment, process them, and migrate to lymphoid organs where they present antigens to T cells.
2. Macrophages: These large phagocytic cells are found in many tissues and play a role in both innate and adaptive immunity. They can engulf and digest pathogens, then present processed antigens on their MHC class II molecules to activate CD4+ T helper cells.
3. B cells: These are primarily responsible for humoral immune responses by producing antibodies against antigens. When activated, B cells can also function as APCs and present antigens on their MHC class II molecules to CD4+ T cells.

The interaction between APCs and T cells is critical for the development of an effective immune response against pathogens or other foreign substances. This process helps ensure that the immune system can recognize and eliminate threats while minimizing damage to healthy 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. 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.

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.

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.

Autoantibodies are defined as antibodies that are produced by the immune system and target the body's own cells, tissues, or organs. These antibodies mistakenly identify certain proteins or molecules in the body as foreign invaders and attack them, leading to an autoimmune response. Autoantibodies can be found in various autoimmune diseases such as rheumatoid arthritis, lupus, and thyroiditis. The presence of autoantibodies can also be used as a diagnostic marker for certain conditions.

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.

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.

Adoptive transfer is a medical procedure in which immune cells are transferred from a donor to a recipient with the aim of providing immunity or treating a disease, such as cancer. This technique is often used in the field of immunotherapy and involves isolating specific immune cells (like T-cells) from the donor, expanding their numbers in the laboratory, and then infusing them into the patient. The transferred cells are expected to recognize and attack the target cells, such as malignant or infected cells, leading to a therapeutic effect. This process requires careful matching of donor and recipient to minimize the risk of rejection and graft-versus-host disease.

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.

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.

Epithelial cells are types of cells that cover the outer surfaces of the body, line the inner surfaces of organs and glands, and form the lining of blood vessels and body cavities. They provide a protective barrier against the external environment, regulate the movement of materials between the internal and external environments, and are involved in the sense of touch, temperature, and pain. Epithelial cells can be squamous (flat and thin), cuboidal (square-shaped and of equal height), or columnar (tall and narrow) in shape and are classified based on their location and function.

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.

Forkhead transcription factors (FOX) are a family of proteins that play crucial roles in the regulation of gene expression through the process of binding to specific DNA sequences, thereby controlling various biological processes such as cell growth, differentiation, and apoptosis. These proteins are characterized by a conserved DNA-binding domain, known as the forkhead box or FOX domain, which adopts a winged helix structure that recognizes and binds to the consensus sequence 5'-(G/A)(T/C)AA(C/A)A-3'.

The FOX family is further divided into subfamilies based on the structure of their DNA-binding domains, with each subfamily having distinct functions. For example, FOXP proteins are involved in brain development and function, while FOXO proteins play a key role in regulating cellular responses to stress and metabolism. Dysregulation of forkhead transcription factors has been implicated in various diseases, including cancer, diabetes, and neurodegenerative disorders.

Programmed cell death 1 ligand 2 protein (PD-L2) is a type I transmembrane protein that belongs to the B7 family. It is encoded by the CD274 gene and is primarily expressed on antigen presenting cells, such as dendritic cells and macrophages. PD-L2 can also be found on some non-hematopoietic cells, including epithelial cells and tumor cells.

PD-L2 binds to programmed cell death 1 (PD-1) receptor, which is expressed on activated T cells, B cells, and myeloid cells. The interaction between PD-L2 and PD-1 delivers an inhibitory signal that downregulates the immune response, leading to dampened T cell activation and proliferation, reduced cytokine production, and increased apoptosis of activated T cells.

PD-L2 plays a crucial role in maintaining self-tolerance and preventing autoimmunity by limiting the activity of autoreactive T cells. However, tumor cells can also exploit this pathway to evade immune surveillance and promote their growth and survival. Therefore, blocking the PD-1/PD-L2 interaction has emerged as a promising strategy for cancer immunotherapy.

Glucose intolerance is a condition in which the body has difficulty processing and using glucose, or blood sugar, effectively. This results in higher than normal levels of glucose in the blood after eating, particularly after meals that are high in carbohydrates. Glucose intolerance can be an early sign of developing diabetes, specifically type 2 diabetes, and it may also indicate other metabolic disorders such as prediabetes or insulin resistance.

In a healthy individual, the pancreas produces insulin to help regulate blood sugar levels by facilitating glucose uptake in muscles, fat tissue, and the liver. When someone has glucose intolerance, their body may not produce enough insulin, or their cells may have become less responsive to insulin (insulin resistance), leading to impaired glucose metabolism.

Glucose intolerance can be diagnosed through various tests, including the oral glucose tolerance test (OGTT) and hemoglobin A1c (HbA1c) test. Treatment for glucose intolerance often involves lifestyle modifications such as weight loss, increased physical activity, and a balanced diet with reduced sugar and refined carbohydrate intake. In some cases, medication may be prescribed to help manage blood sugar levels more effectively.

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.

CD274, also known as B7-H1 or PD-L1 (programmed death ligand 1), is a type of protein that functions as an immune checkpoint regulator. It is expressed on the surface of certain cells, including some cancer cells and activated immune cells. CD274 binds to the PD-1 receptor on T cells, which helps to downregulate or turn off their immune response. This can allow cancer cells to evade detection and destruction by the immune system.

CD274 is an important target for immunotherapy in cancer treatment. Drugs called checkpoint inhibitors that block the interaction between CD274 and PD-1 have been developed and approved for use in certain types of cancer, such as melanoma, lung cancer, and kidney cancer. These drugs work by boosting the immune system's ability to recognize and attack cancer cells.

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.

CTLA-4 (Cytotoxic T-Lymphocyte Associated Protein 4) antigen is a type of protein found on the surface of activated T cells, which are a type of white blood cell in the immune system. CTLA-4 plays an important role in regulating the immune response by functioning as a negative regulator of T cell activation.

CTLA-4 binds to CD80 and CD86 molecules on the surface of antigen-presenting cells, which are cells that display foreign antigens to T cells and activate them. By binding to these molecules, CTLA-4 inhibits T cell activation and helps prevent an overactive immune response.

CTLA-4 is a target for cancer immunotherapy because blocking its function can enhance the anti-tumor immune response. Certain drugs called checkpoint inhibitors work by blocking CTLA-4, allowing T cells to remain active and attack tumor cells more effectively.

Peripheral nerves are nerve fibers that transmit signals between the central nervous system (CNS, consisting of the brain and spinal cord) and the rest of the body. These nerves convey motor, sensory, and autonomic information, enabling us to move, feel, and respond to changes in our environment. They form a complex network that extends from the CNS to muscles, glands, skin, and internal organs, allowing for coordinated responses and functions throughout the body. Damage or injury to peripheral nerves can result in various neurological symptoms, such as numbness, weakness, or pain, depending on the type and severity of the damage.

Salt tolerance, in a medical context, refers to the body's ability to maintain normal physiological functions despite high levels of salt (sodium chloride) in the system. While our kidneys usually regulate sodium levels, certain medical conditions such as some forms of kidney disease or heart failure can impair this process, leading to an accumulation of sodium in the body. Some individuals may have a genetic predisposition to better handle higher salt intakes, but generally, a high-salt diet is discouraged due to risks of hypertension and other health issues for most people.

CD (cluster of differentiation) antigens are cell-surface proteins that are expressed on leukocytes (white blood cells) and can be used to identify and distinguish different subsets of these cells. They are important markers in the field of immunology and hematology, and are commonly used to diagnose and monitor various diseases, including cancer, autoimmune disorders, and infectious diseases.

CD antigens are designated by numbers, such as CD4, CD8, CD19, etc., which refer to specific proteins found on the surface of different types of leukocytes. For example, CD4 is a protein found on the surface of helper T cells, while CD8 is found on cytotoxic T cells.

CD antigens can be used as targets for immunotherapy, such as monoclonal antibody therapy, in which antibodies are designed to bind to specific CD antigens and trigger an immune response against cancer cells or infected cells. They can also be used as markers to monitor the effectiveness of treatments and to detect minimal residual disease (MRD) after treatment.

It's important to note that not all CD antigens are exclusive to leukocytes, some can be found on other cell types as well, and their expression can vary depending on the activation state or differentiation stage of the cells.

The Interleukin-2 Receptor alpha Subunit (IL-2Rα), also known as CD25, is a protein that is expressed on the surface of certain immune cells, such as activated T-cells and B-cells. It is a subunit of the interleukin-2 receptor, which plays a crucial role in the activation and regulation of the immune response. The IL-2Rα binds to interleukin-2 (IL-2) with high affinity, forming a complex that initiates intracellular signaling pathways involved in T-cell proliferation, differentiation, and survival. IL-2Rα is also a target for immunosuppressive therapies used to prevent rejection of transplanted organs and to treat autoimmune diseases.

Programmed cell death 1 receptor (PD-1R), also known as CD279, is a type I transmembrane protein that belongs to the immunoglobulin superfamily. It is primarily expressed on the surface of activated T cells, B cells, and myeloid cells. PD-1R plays a crucial role in regulating immune responses by interacting with its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), which are mainly expressed on antigen-presenting cells and various tumor cells.

The interaction between PD-1R and its ligands leads to the inhibition of T cell activation, proliferation, and effector functions, thereby promoting immune tolerance and preventing autoimmunity. In the context of cancer, tumor cells upregulate PD-L1/PD-L2 expression as a mechanism to evade anti-tumor immunity by suppressing T cell activation through PD-1R engagement.

Immunotherapies targeting the PD-1/PD-L1 pathway have shown significant clinical benefits in various cancer types, including melanoma, non-small cell lung cancer, and renal cell carcinoma, among others, by restoring T cell-mediated anti-tumor immunity.

"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.

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.

Blood glucose, also known as blood sugar, is the concentration of glucose in the blood. Glucose is a simple sugar that serves as the main source of energy for the body's cells. It is carried to each cell through the bloodstream and is absorbed into the cells with the help of insulin, a hormone produced by the pancreas.

The normal range for blood glucose levels in humans is typically between 70 and 130 milligrams per deciliter (mg/dL) when fasting, and less than 180 mg/dL after meals. Levels that are consistently higher than this may indicate diabetes or other metabolic disorders.

Blood glucose levels can be measured through a variety of methods, including fingerstick blood tests, continuous glucose monitoring systems, and laboratory tests. Regular monitoring of blood glucose levels is important for people with diabetes to help manage their condition and prevent complications.

Physiological adaptation refers to the changes or modifications that occur in an organism's biological functions or structures as a result of environmental pressures or changes. These adaptations enable the organism to survive and reproduce more successfully in its environment. They can be short-term, such as the constriction of blood vessels in response to cold temperatures, or long-term, such as the evolution of longer limbs in animals that live in open environments.

In the context of human physiology, examples of physiological adaptation include:

1. Acclimatization: The process by which the body adjusts to changes in environmental conditions, such as altitude or temperature. For example, when a person moves to a high-altitude location, their body may produce more red blood cells to compensate for the lower oxygen levels, leading to improved oxygen delivery to tissues.

2. Exercise adaptation: Regular physical activity can lead to various physiological adaptations, such as increased muscle strength and endurance, enhanced cardiovascular function, and improved insulin sensitivity.

3. Hormonal adaptation: The body can adjust hormone levels in response to changes in the environment or internal conditions. For instance, during prolonged fasting, the body releases stress hormones like cortisol and adrenaline to help maintain energy levels and prevent muscle wasting.

4. Sensory adaptation: Our senses can adapt to different stimuli over time. For example, when we enter a dark room after being in bright sunlight, it takes some time for our eyes to adjust to the new light level. This process is known as dark adaptation.

5. Aging-related adaptations: As we age, various physiological changes occur that help us adapt to the changing environment and maintain homeostasis. These include changes in body composition, immune function, and cognitive abilities.

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.

Exercise tolerance is a term used to describe the ability of an individual to perform physical activity or exercise without experiencing symptoms such as shortness of breath, chest pain, or undue fatigue. It is often used as a measure of cardiovascular fitness and can be assessed through various tests, such as a stress test or a six-minute walk test. Exercise intolerance may indicate the presence of underlying medical conditions, such as heart disease, lung disease, or deconditioning.

Antigens are substances (usually proteins) on the surface of cells, viruses, fungi, or bacteria that can be recognized by the immune system and provoke an immune response. In the context of differentiation, antigens refer to specific markers that identify the developmental stage or lineage of a cell.

Differentiation antigens are proteins or carbohydrates expressed on the surface of cells during various stages of differentiation, which can be used to distinguish between cells at different maturation stages or of different cell types. These antigens play an essential role in the immune system's ability to recognize and respond to abnormal or infected cells while sparing healthy cells.

Examples of differentiation antigens include:

1. CD (cluster of differentiation) molecules: A group of membrane proteins used to identify and define various cell types, such as T cells, B cells, natural killer cells, monocytes, and granulocytes.
2. Lineage-specific antigens: Antigens that are specific to certain cell lineages, such as CD3 for T cells or CD19 for B cells.
3. Maturation markers: Antigens that indicate the maturation stage of a cell, like CD34 and CD38 on hematopoietic stem cells.

Understanding differentiation antigens is crucial in immunology, cancer research, transplantation medicine, and vaccine development.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays a crucial role in the modulation of immune responses. It is produced by various cell types, including T cells, macrophages, and dendritic cells. IL-10 inhibits the production of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, IL-8, and IL-12, and downregulates the expression of costimulatory molecules on antigen-presenting cells. This results in the suppression of T cell activation and effector functions, which ultimately helps to limit tissue damage during inflammation and promote tissue repair. Dysregulation of IL-10 has been implicated in various pathological conditions, including chronic infections, autoimmune diseases, and cancer.

CD80 (also known as B7-1) is a cell surface protein that functions as a costimulatory molecule in the immune system. It is primarily expressed on antigen presenting cells such as dendritic cells, macrophages, and B cells. CD80 binds to the CD28 receptor on T cells, providing a critical second signal necessary for T cell activation and proliferation. This interaction plays a crucial role in the initiation of an effective immune response against pathogens and tumors.

CD80 can also interact with another receptor called CTLA-4 (cytotoxic T lymphocyte antigen 4), which is expressed on activated T cells. The binding of CD80 to CTLA-4 delivers a negative signal that helps regulate the immune response and prevent overactivation, contributing to the maintenance of self-tolerance and preventing autoimmunity.

In summary, CD80 is an important antigen involved in the regulation of the adaptive immune response by modulating T cell activation and proliferation through its interactions with CD28 and CTLA-4 receptors.

"Drought" is not a medical term. It is a term used in meteorology and environmental science to refer to a prolonged period of abnormally low rainfall, leading to water shortage and scarcity in the affected areas. Droughts can have various impacts on human health, including dehydration, heat-related illnesses, reduced air quality, increased transmission of waterborne diseases, and mental health issues related to stress and displacement. However, drought itself is not a medical condition.

Homologous transplantation is a type of transplant surgery where organs or tissues are transferred between two genetically non-identical individuals of the same species. The term "homologous" refers to the similarity in structure and function of the donated organ or tissue to the recipient's own organ or tissue.

For example, a heart transplant from one human to another is an example of homologous transplantation because both organs are hearts and perform the same function. Similarly, a liver transplant, kidney transplant, lung transplant, and other types of organ transplants between individuals of the same species are also considered homologous transplantations.

Homologous transplantation is in contrast to heterologous or xenogeneic transplantation, where organs or tissues are transferred from one species to another, such as a pig heart transplanted into a human. Homologous transplantation is more commonly performed than heterologous transplantation due to the increased risk of rejection and other complications associated with xenogeneic transplants.

Thymectomy is a surgical procedure that involves the removal of the thymus gland. The thymus gland is a part of the immune system located in the upper chest, behind the sternum (breastbone), and above the heart. It is responsible for producing white blood cells called T-lymphocytes, which help fight infections.

Thymectomy is often performed as a treatment option for patients with certain medical conditions, such as:

* Myasthenia gravis: an autoimmune disorder that causes muscle weakness and fatigue. In some cases, the thymus gland may contain abnormal cells that contribute to the development of myasthenia gravis. Removing the thymus gland can help improve symptoms in some patients with this condition.
* Thymomas: tumors that develop in the thymus gland. While most thymomas are benign (non-cancerous), some can be malignant (cancerous) and may require surgical removal.
* Myasthenic syndrome: a group of disorders characterized by muscle weakness and fatigue, similar to myasthenia gravis. In some cases, the thymus gland may be abnormal and contribute to the development of these conditions. Removing the thymus gland can help improve symptoms in some patients.

Thymectomy can be performed using various surgical approaches, including open surgery (through a large incision in the chest), video-assisted thoracoscopic surgery (VATS, using small incisions and a camera to guide the procedure), or robotic-assisted surgery (using a robot to perform the procedure through small incisions). The choice of surgical approach depends on several factors, including the size and location of the thymus gland, the patient's overall health, and the surgeon's expertise.

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.

Diabetes Mellitus, Type 1 is a chronic autoimmune disease characterized by the destruction of insulin-producing beta cells in the pancreas, leading to an absolute deficiency of insulin. This results in an inability to regulate blood glucose levels, causing hyperglycemia (high blood sugar). Type 1 diabetes typically presents in childhood or early adulthood, although it can develop at any age. It is usually managed with regular insulin injections or the use of an insulin pump, along with monitoring of blood glucose levels and adjustments to diet and physical activity. Uncontrolled type 1 diabetes can lead to serious complications such as kidney damage, nerve damage, blindness, and cardiovascular disease.

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.

Self care is a health practice that involves individuals taking responsibility for their own health and well-being by actively seeking out and participating in activities and behaviors that promote healthy living, prevent illness and disease, and manage existing medical conditions. Self care includes a wide range of activities such as:

* Following a healthy diet and exercise routine
* Getting adequate sleep and rest
* Managing stress through relaxation techniques or mindfulness practices
* Practicing good hygiene and grooming habits
* Seeking preventive care through regular check-ups and screenings
* Taking prescribed medications as directed by a healthcare provider
* Monitoring symptoms and seeking medical attention when necessary

Self care is an important part of overall health and wellness, and can help individuals maintain their physical, emotional, and mental health. It is also an essential component of chronic disease management, helping people with ongoing medical conditions to manage their symptoms and improve their quality of life.

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.

Cytokines are a broad and diverse category of small signaling proteins that are secreted by various cells, including immune cells, in response to different stimuli. They play crucial roles in regulating the immune response, inflammation, hematopoiesis, and cellular communication.

Cytokines mediate their effects by binding to specific receptors on the surface of target cells, which triggers intracellular signaling pathways that ultimately result in changes in gene expression, cell behavior, and function. Some key functions of cytokines include:

1. Regulating the activation, differentiation, and proliferation of immune cells such as T cells, B cells, natural killer (NK) cells, and macrophages.
2. Coordinating the inflammatory response by recruiting immune cells to sites of infection or tissue damage and modulating their effector functions.
3. Regulating hematopoiesis, the process of blood cell formation in the bone marrow, by controlling the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells.
4. Modulating the development and function of the nervous system, including neuroinflammation, neuroprotection, and neuroregeneration.

Cytokines can be classified into several categories based on their structure, function, or cellular origin. Some common types of cytokines include interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), chemokines, colony-stimulating factors (CSFs), and transforming growth factors (TGFs). Dysregulation of cytokine production and signaling has been implicated in various pathological conditions, such as autoimmune diseases, chronic inflammation, cancer, and neurodegenerative disorders.

A transplantation chimera is a rare medical condition that occurs after an organ or tissue transplant, where the recipient's body accepts and integrates the donor's cells or tissues to such an extent that the two sets of DNA coexist and function together. This phenomenon can lead to the presence of two different genetic profiles in one individual.

In some cases, this may result in the development of donor-derived cells or organs within the recipient's body, which can express the donor's unique genetic traits. Transplantation chimerism is more commonly observed in bone marrow transplants, where the donor's immune cells can repopulate and establish themselves within the recipient's bone marrow and bloodstream.

It is important to note that while transplantation chimerism can be beneficial for the success of the transplant, it may also pose some risks, such as an increased likelihood of developing graft-versus-host disease (GVHD), where the donor's immune cells attack the recipient's tissues.

Immunological models are simplified representations or simulations of the immune system's structure, function, and interactions with pathogens or other entities. These models can be theoretical (conceptual), mathematical, or computational and are used to understand, explain, and predict immunological phenomena. They help researchers study complex immune processes and responses that cannot be easily observed or manipulated in vivo.

Theoretical immunological models provide conceptual frameworks for understanding immune system behavior, often using diagrams or flowcharts to illustrate interactions between immune components. Mathematical models use mathematical equations to describe immune system dynamics, allowing researchers to simulate and analyze the outcomes of various scenarios. Computational models, also known as in silico models, are created using computer software and can incorporate both theoretical and mathematical concepts to create detailed simulations of immunological processes.

Immunological models are essential tools for advancing our understanding of the immune system and developing new therapies and vaccines. They enable researchers to test hypotheses, explore the implications of different assumptions, and identify areas requiring further investigation.

Morphine is a potent opioid analgesic (pain reliever) derived from the opium poppy. It works by binding to opioid receptors in the brain and spinal cord, blocking the transmission of pain signals and reducing the perception of pain. Morphine is used to treat moderate to severe pain, including pain associated with cancer, myocardial infarction, and other conditions. It can also be used as a sedative and cough suppressant.

Morphine has a high potential for abuse and dependence, and its use should be closely monitored by healthcare professionals. Common side effects of morphine include drowsiness, respiratory depression, constipation, nausea, and vomiting. Overdose can result in respiratory failure, coma, and death.

Isoantigens are antigens that are present on the cells or tissues of one individual of a species, but are absent or different in another individual of the same species. They are also known as "alloantigens." Isoantigens are most commonly found on the surface of red blood cells and other tissues, and they can stimulate an immune response when transplanted into a different individual. This is because the recipient's immune system recognizes the isoantigens as foreign and mounts a defense against them. Isoantigens are important in the field of transplantation medicine, as they must be carefully matched between donor and recipient to reduce the risk of rejection.

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.

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.

Physiological stress is a response of the body to a demand or threat that disrupts homeostasis and activates the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis. This results in the release of stress hormones such as adrenaline, cortisol, and noradrenaline, which prepare the body for a "fight or flight" response. Increased heart rate, rapid breathing, heightened sensory perception, and increased alertness are some of the physiological changes that occur during this response. Chronic stress can have negative effects on various bodily functions, including the immune, cardiovascular, and nervous systems.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

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.

Immunosuppression is a state in which the immune system's ability to mount an immune response is reduced, compromised or inhibited. This can be caused by certain medications (such as those used to prevent rejection of transplanted organs), diseases (like HIV/AIDS), or genetic disorders. As a result, the body becomes more susceptible to infections and cancer development. It's important to note that immunosuppression should not be confused with immunity, which refers to the body's ability to resist and fight off infections and diseases.

The anterior chamber is the front portion of the eye, located between the cornea (the clear front "window" of the eye) and the iris (the colored part of the eye). It is filled with a clear fluid called aqueous humor that provides nutrients to the structures inside the eye and helps maintain its shape. The anterior chamber plays an important role in maintaining the overall health and function of the eye.

Graft rejection is an immune response that occurs when transplanted tissue or organ (the graft) is recognized as foreign by the recipient's immune system, leading to the activation of immune cells to attack and destroy the graft. This results in the failure of the transplant and the need for additional medical intervention or another transplant. There are three types of graft rejection: hyperacute, acute, and chronic. Hyperacute rejection occurs immediately or soon after transplantation due to pre-existing antibodies against the graft. Acute rejection typically occurs within weeks to months post-transplant and is characterized by the infiltration of T-cells into the graft. Chronic rejection, which can occur months to years after transplantation, is a slow and progressive process characterized by fibrosis and tissue damage due to ongoing immune responses against the graft.

Peripheral Nervous System (PNS) diseases, also known as Peripheral Neuropathies, refer to conditions that affect the functioning of the peripheral nervous system, which includes all the nerves outside the brain and spinal cord. These nerves transmit signals between the central nervous system (CNS) and the rest of the body, controlling sensations, movements, and automatic functions such as heart rate and digestion.

PNS diseases can be caused by various factors, including genetics, infections, toxins, metabolic disorders, trauma, or autoimmune conditions. The symptoms of PNS diseases depend on the type and extent of nerve damage but often include:

1. Numbness, tingling, or pain in the hands and feet
2. Muscle weakness or cramps
3. Loss of reflexes
4. Decreased sensation to touch, temperature, or vibration
5. Coordination problems and difficulty with balance
6. Sexual dysfunction
7. Digestive issues, such as constipation or diarrhea
8. Dizziness or fainting due to changes in blood pressure

Examples of PNS diseases include Guillain-Barre syndrome, Charcot-Marie-Tooth disease, diabetic neuropathy, and peripheral nerve injuries. Treatment for these conditions varies depending on the underlying cause but may involve medications, physical therapy, lifestyle changes, or surgery.

Acclimatization is the process by which an individual organism adjusts to a change in its environment, enabling it to maintain its normal physiological functions and thus survive and reproduce. In the context of medicine, acclimatization often refers to the body's adaptation to changes in temperature, altitude, or other environmental factors that can affect health.

For example, when a person moves from a low-altitude area to a high-altitude area, their body may undergo several physiological changes to adapt to the reduced availability of oxygen at higher altitudes. These changes may include increased breathing rate and depth, increased heart rate, and altered blood chemistry, among others. This process of acclimatization can take several days or even weeks, depending on the individual and the degree of environmental change.

Similarly, when a person moves from a cold climate to a hot climate, their body may adjust by increasing its sweat production and reducing its heat production, in order to maintain a stable body temperature. This process of acclimatization can help prevent heat-related illnesses such as heat exhaustion and heat stroke.

Overall, acclimatization is an important physiological process that allows organisms to adapt to changing environments and maintain their health and well-being.

The Peripheral Nervous System (PNS) is that part of the nervous system which lies outside of the brain and spinal cord. It includes all the nerves and ganglia ( clusters of neurons) outside of the central nervous system (CNS). The PNS is divided into two components: the somatic nervous system and the autonomic nervous system.

The somatic nervous system is responsible for transmitting sensory information from the skin, muscles, and joints to the CNS, and for controlling voluntary movements of the skeletal muscles.

The autonomic nervous system, on the other hand, controls involuntary actions, such as heart rate, digestion, respiratory rate, salivation, perspiration, pupillary dilation, and sexual arousal. It is further divided into the sympathetic and parasympathetic systems, which generally have opposing effects and maintain homeostasis in the body.

Damage to the peripheral nervous system can result in various medical conditions such as neuropathies, neuritis, plexopathies, and radiculopathies, leading to symptoms like numbness, tingling, pain, weakness, or loss of reflexes in the affected area.

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.

I am not a medical doctor, but I can provide you with some information on this topic. Self-concept is more commonly discussed in psychology than in medicine, but it still has relevance to understanding individual experiences and behaviors in health and illness.

Self-concept refers to an individual's perception, beliefs, and attitudes about themselves, encompassing various dimensions such as:

1. Physical self (how one perceives their physical appearance, abilities, and health)
2. Social self (how one perceives their relationships with others, social roles, and status)
3. Psychological or personal self (how one perceives their personality traits, values, and beliefs)

Self-concept can influence how people view their own health, cope with illness, and engage in health behaviors. For example, a positive self-concept may contribute to better adherence to treatment plans and healthier lifestyle choices, while negative self-concepts might lead to poorer health outcomes due to decreased motivation or self-efficacy.

Understanding an individual's self-concept can help healthcare professionals tailor their communication style, recommendations, and interventions to better meet the patient's needs and preferences.

Membrane glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. They are integral components of biological membranes, spanning the lipid bilayer and playing crucial roles in various cellular processes.

The glycosylation of these proteins occurs in the endoplasmic reticulum (ER) and Golgi apparatus during protein folding and trafficking. The attached glycans can vary in structure, length, and composition, which contributes to the diversity of membrane glycoproteins.

Membrane glycoproteins can be classified into two main types based on their orientation within the lipid bilayer:

1. Type I (N-linked): These glycoproteins have a single transmembrane domain and an extracellular N-terminus, where the oligosaccharides are predominantly attached via asparagine residues (Asn-X-Ser/Thr sequon).
2. Type II (C-linked): These glycoproteins possess two transmembrane domains and an intracellular C-terminus, with the oligosaccharides linked to tryptophan residues via a mannose moiety.

Membrane glycoproteins are involved in various cellular functions, such as:

* Cell adhesion and recognition
* Receptor-mediated signal transduction
* Enzymatic catalysis
* Transport of molecules across membranes
* Cell-cell communication
* Immunological responses

Some examples of membrane glycoproteins include cell surface receptors (e.g., growth factor receptors, cytokine receptors), adhesion molecules (e.g., integrins, cadherins), and transporters (e.g., ion channels, ABC transporters).

Lymphopenia is a term used in medicine to describe an abnormally low count of lymphocytes, which are a type of white blood cell that plays a crucial role in the body's immune system. Lymphocytes help fight off infections and diseases by producing antibodies and attacking infected cells.

A normal lymphocyte count ranges from 1,000 to 4,800 cells per microliter (cells/μL) of blood in adults. A lymphocyte count lower than 1,000 cells/μL is generally considered lymphopenia.

Several factors can cause lymphopenia, including viral infections, certain medications, autoimmune disorders, and cancer. It's important to note that a low lymphocyte count alone may not indicate a specific medical condition, and further testing may be necessary to determine the underlying cause. If left untreated, lymphopenia can increase the risk of infections and other complications.

An epitope is a specific region on an antigen (a substance that triggers an immune response) that is recognized and bound by an antibody or a T-cell receptor. In the case of T-lymphocytes, which are a type of white blood cell that plays a central role in cell-mediated immunity, epitopes are typically presented on the surface of infected cells in association with major histocompatibility complex (MHC) molecules.

T-lymphocytes recognize and respond to epitopes through their T-cell receptors (TCRs), which are membrane-bound proteins that can bind to specific epitopes presented on the surface of infected cells. There are two main types of T-lymphocytes: CD4+ T-cells, also known as helper T-cells, and CD8+ T-cells, also known as cytotoxic T-cells.

CD4+ T-cells recognize epitopes presented in the context of MHC class II molecules, which are typically expressed on the surface of professional antigen-presenting cells such as dendritic cells, macrophages, and B-cells. CD4+ T-cells help to coordinate the immune response by producing cytokines that activate other immune cells.

CD8+ T-cells recognize epitopes presented in the context of MHC class I molecules, which are expressed on the surface of almost all nucleated cells. CD8+ T-cells are able to directly kill infected cells by releasing cytotoxic granules that contain enzymes that can induce apoptosis (programmed cell death) in the target cell.

In summary, epitopes are specific regions on antigens that are recognized and bound by T-lymphocytes through their T-cell receptors. CD4+ T-cells recognize epitopes presented in the context of MHC class II molecules, while CD8+ T-cells recognize epitopes presented in the context of MHC class I molecules.

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.

Animal disease models are specialized animals, typically rodents such as mice or rats, that have been genetically engineered or exposed to certain conditions to develop symptoms and physiological changes similar to those seen in human diseases. These models are used in medical research to study the pathophysiology of diseases, identify potential therapeutic targets, test drug efficacy and safety, and understand disease mechanisms.

The genetic modifications can include knockout or knock-in mutations, transgenic expression of specific genes, or RNA interference techniques. The animals may also be exposed to environmental factors such as chemicals, radiation, or infectious agents to induce the disease state.

Examples of animal disease models include:

1. Mouse models of cancer: Genetically engineered mice that develop various types of tumors, allowing researchers to study cancer initiation, progression, and metastasis.
2. Alzheimer's disease models: Transgenic mice expressing mutant human genes associated with Alzheimer's disease, which exhibit amyloid plaque formation and cognitive decline.
3. Diabetes models: Obese and diabetic mouse strains like the NOD (non-obese diabetic) or db/db mice, used to study the development of type 1 and type 2 diabetes, respectively.
4. Cardiovascular disease models: Atherosclerosis-prone mice, such as ApoE-deficient or LDLR-deficient mice, that develop plaque buildup in their arteries when fed a high-fat diet.
5. Inflammatory bowel disease models: Mice with genetic mutations affecting intestinal barrier function and immune response, such as IL-10 knockout or SAMP1/YitFc mice, which develop colitis.

Animal disease models are essential tools in preclinical research, but it is important to recognize their limitations. Differences between species can affect the translatability of results from animal studies to human patients. Therefore, researchers must carefully consider the choice of model and interpret findings cautiously when applying them to human diseases.

Delayed hypersensitivity, also known as type IV hypersensitivity, is a type of immune response that takes place several hours to days after exposure to an antigen. It is characterized by the activation of T cells (a type of white blood cell) and the release of various chemical mediators, leading to inflammation and tissue damage. This reaction is typically associated with chronic inflammatory diseases, such as contact dermatitis, granulomatous disorders (e.g. tuberculosis), and certain autoimmune diseases.

The reaction process involves the following steps:

1. Sensitization: The first time an individual is exposed to an antigen, T cells are activated and become sensitized to it. This process can take several days.
2. Memory: Some of the activated T cells differentiate into memory T cells, which remain in the body and are ready to respond quickly if the same antigen is encountered again.
3. Effector phase: Upon subsequent exposure to the antigen, the memory T cells become activated and release cytokines, which recruit other immune cells (e.g. macrophages) to the site of inflammation. These cells cause tissue damage through various mechanisms, such as phagocytosis, degranulation, and the release of reactive oxygen species.
4. Chronic inflammation: The ongoing immune response can lead to chronic inflammation, which may result in tissue destruction and fibrosis (scarring).

Examples of conditions associated with delayed hypersensitivity include:

* Contact dermatitis (e.g. poison ivy, nickel allergy)
* Tuberculosis
* Leprosy
* Sarcoidosis
* Rheumatoid arthritis
* Type 1 diabetes mellitus
* Multiple sclerosis
* Inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)

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.

Insulin resistance is a condition in which the body's cells become less responsive to insulin, a hormone produced by the pancreas that regulates blood sugar levels. In response to this decreased sensitivity, the pancreas produces more insulin to help glucose enter the cells. However, over time, the pancreas may not be able to keep up with the increased demand for insulin, leading to high levels of glucose in the blood and potentially resulting in type 2 diabetes, prediabetes, or other health issues such as metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease. Insulin resistance is often associated with obesity, physical inactivity, and genetic factors.

Interferon-gamma (IFN-γ) is a soluble cytokine that is primarily produced by the activation of natural killer (NK) cells and T lymphocytes, especially CD4+ Th1 cells and CD8+ cytotoxic T cells. It plays a crucial role in the regulation of the immune response against viral and intracellular bacterial infections, as well as tumor cells. IFN-γ has several functions, including activating macrophages to enhance their microbicidal activity, increasing the presentation of major histocompatibility complex (MHC) class I and II molecules on antigen-presenting cells, stimulating the proliferation and differentiation of T cells and NK cells, and inducing the production of other cytokines and chemokines. Additionally, IFN-γ has direct antiproliferative effects on certain types of tumor cells and can enhance the cytotoxic activity of immune cells against infected or malignant cells.

Immunoconjugates are biomolecules created by the conjugation (coupling) of an antibody or antibody fragment with a cytotoxic agent, such as a drug, radionuclide, or toxin. This coupling is designed to direct the cytotoxic agent specifically to target cells, usually cancer cells, against which the antibody is directed, thereby increasing the effectiveness and reducing the side effects of the therapy.

The antibody part of the immunoconjugate recognizes and binds to specific antigens (proteins or other molecules) on the surface of the target cells, while the cytotoxic agent part enters the cell and disrupts its function, leading to cell death. The linker between the two parts is designed to be stable in circulation but can release the cytotoxic agent once inside the target cell.

Immunoconjugates are a promising area of research in targeted cancer therapy, as they offer the potential for more precise and less toxic treatments compared to traditional chemotherapy. However, their development and use also pose challenges, such as ensuring that the immunoconjugate binds specifically to the target cells and not to normal cells, optimizing the dose and schedule of treatment, and minimizing the risk of resistance to the therapy.

CD86 is a type of protein found on the surface of certain immune cells called antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells. These proteins are known as co-stimulatory molecules and play an important role in activating T cells, a type of white blood cell that is crucial for adaptive immunity.

When APCs encounter a pathogen or foreign substance, they engulf it, break it down into smaller peptides, and display these peptides on their surface in conjunction with another protein called the major histocompatibility complex (MHC) class II molecule. This presentation of antigenic peptides to T cells is not sufficient to activate them fully. Instead, APCs must also provide a co-stimulatory signal through interactions between co-stimulatory molecules like CD86 and receptors on the surface of T cells, such as CD28.

CD86 binds to its receptor CD28 on T cells, providing a critical second signal that promotes T cell activation, proliferation, and differentiation into effector cells. This interaction is essential for the development of an effective immune response against pathogens or foreign substances. In addition to its role in activating T cells, CD86 also helps regulate immune tolerance by contributing to the suppression of self-reactive T cells that could otherwise attack the body's own tissues and cause autoimmune diseases.

Overall, CD86 is an important player in the regulation of the immune response, helping to ensure that T cells are activated appropriately in response to pathogens or foreign substances while also contributing to the maintenance of self-tolerance.

CD95 (also known as Fas or APO-1) is a type of cell surface receptor that can bind to specific proteins and trigger programmed cell death, also known as apoptosis. It is an important regulator of the immune system and helps to control the activation and deletion of immune cells. CD95 ligand (CD95L), the protein that binds to CD95, is expressed on activated T-cells and can induce apoptosis in other cells that express CD95, including other T-cells and tumor cells.

An antigen is any substance that can stimulate an immune response, leading to the production of antibodies or activation of immune cells. In the context of CD95, antigens may refer to substances that can induce the expression of CD95 on the surface of cells, making them susceptible to CD95L-mediated apoptosis. These antigens could include viral proteins, tumor antigens, or other substances that trigger an immune response.

Therefore, the medical definition of 'antigens, CD95' may refer to substances that can induce the expression of CD95 on the surface of cells and make them targets for CD95L-mediated apoptosis.

Sodium Chloride is defined as the inorganic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. It is commonly known as table salt or halite, and it is used extensively in food seasoning and preservation due to its ability to enhance flavor and inhibit bacterial growth. In medicine, sodium chloride is used as a balanced electrolyte solution for rehydration and as a topical wound irrigant and antiseptic. It is also an essential component of the human body's fluid balance and nerve impulse transmission.

Salt-tolerant plants, also known as halophytes, are plants that can grow and complete their life cycle in saline environments. These plants have specialized adaptations that allow them to survive and reproduce in the presence of high concentrations of salt, particularly sodium chloride (NaCl), which is toxic to most plants.

Salt tolerance in plants is a complex trait that involves various physiological and biochemical mechanisms, such as:

1. Exclusion: Preventing the uptake of excess salt by the roots or excluding it from entering the plant cells.
2. Compartmentalization: Storing excess salt in vacuoles or older leaves that can be shed to reduce the overall salt load.
3. Tissue tolerance: Adapting to high salt concentrations within the plant tissues without experiencing toxicity or osmotic stress.
4. Osmoregulation: Maintaining water balance and cell turgor by synthesizing and accumulating compatible solutes, such as proline and glycine betaine, which help to lower the osmotic potential of the cells.
5. Ion homeostasis: Regulating the uptake and distribution of essential ions, like potassium (K+), while minimizing the accumulation of toxic ions, such as sodium (Na+) and chloride (Cl-).

Examples of salt-tolerant plants include mangroves, sea grasses, cordgrass, glasswort, and certain species of cacti and succulents. These plants have significant ecological and agricultural importance in coastal areas and arid regions, where salinity is a major environmental constraint.

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.

Immunomodulation is the process of modifying or regulating the immune system's response. It can involve either stimulating or suppressing various components of the immune system, such as white blood cells, antibodies, or cytokines. This can be achieved through various means, including medications (such as immunosuppressive drugs used in organ transplantation), vaccines, and other therapies.

The goal of immunomodulation is to restore balance to an overactive or underactive immune system, depending on the specific medical condition being treated. It can help to prevent or treat diseases that result from abnormal immune responses, such as autoimmune disorders, allergies, and infections.

Coculture techniques refer to a type of experimental setup in which two or more different types of cells or organisms are grown and studied together in a shared culture medium. This method allows researchers to examine the interactions between different cell types or species under controlled conditions, and to study how these interactions may influence various biological processes such as growth, gene expression, metabolism, and signal transduction.

Coculture techniques can be used to investigate a wide range of biological phenomena, including the effects of host-microbe interactions on human health and disease, the impact of different cell types on tissue development and homeostasis, and the role of microbial communities in shaping ecosystems. These techniques can also be used to test the efficacy and safety of new drugs or therapies by examining their effects on cells grown in coculture with other relevant cell types.

There are several different ways to establish cocultures, depending on the specific research question and experimental goals. Some common methods include:

1. Mixed cultures: In this approach, two or more cell types are simply mixed together in a culture dish or flask and allowed to grow and interact freely.
2. Cell-layer cultures: Here, one cell type is grown on a porous membrane or other support structure, while the second cell type is grown on top of it, forming a layered coculture.
3. Conditioned media cultures: In this case, one cell type is grown to confluence and its culture medium is collected and then used to grow a second cell type. This allows the second cell type to be exposed to any factors secreted by the first cell type into the medium.
4. Microfluidic cocultures: These involve growing cells in microfabricated channels or chambers, which allow for precise control over the spatial arrangement and flow of nutrients, waste products, and signaling molecules between different cell types.

Overall, coculture techniques provide a powerful tool for studying complex biological systems and gaining insights into the mechanisms that underlie various physiological and pathological processes.

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.

Autoimmune encephalomyelitis (EAE) is a model of inflammatory demyelinating disease used in medical research to study the mechanisms of multiple sclerosis (MS) and develop new therapies. It is experimentally induced in laboratory animals, typically mice or rats, through immunization with myelin antigens or T-cell transfer. The resulting immune response leads to inflammation, demyelination, and neurological dysfunction in the central nervous system (CNS), mimicking certain aspects of MS.

EAE is a valuable tool for understanding the pathogenesis of MS and testing potential treatments. However, it is essential to recognize that EAE is an experimental model and may not fully recapitulate all features of human autoimmune encephalomyelitis.

Peripheral Vascular Diseases (PVD) refer to a group of medical conditions that affect the blood vessels outside of the heart and brain. These diseases are characterized by a narrowing or blockage of the peripheral arteries, which can lead to reduced blood flow to the limbs, particularly the legs.

The primary cause of PVD is atherosclerosis, a buildup of fats, cholesterol, and other substances in and on the walls of the arteries, forming plaques that restrict blood flow. Other risk factors include smoking, diabetes, hypertension, high cholesterol levels, and a family history of vascular disease.

Symptoms of PVD can vary depending on the severity of the condition but may include leg pain or cramping during exercise (claudication), numbness or tingling in the legs, coldness or discoloration of the feet, sores or wounds that heal slowly or not at all, and in severe cases, gangrene.

PVD can increase the risk of heart attack and stroke, so it is essential to diagnose and treat the condition as early as possible. Treatment options include lifestyle changes such as quitting smoking, exercising regularly, and maintaining a healthy diet, medications to control symptoms and reduce the risk of complications, and surgical procedures such as angioplasty or bypass surgery to restore blood flow.

Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.

Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.

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.

Immunophenotyping is a medical laboratory technique used to identify and classify cells, usually in the context of hematologic (blood) disorders and malignancies (cancers), based on their surface or intracellular expression of various proteins and antigens. This technique utilizes specific antibodies tagged with fluorochromes, which bind to the target antigens on the cell surface or within the cells. The labeled cells are then analyzed using flow cytometry, allowing for the detection and quantification of multiple antigenic markers simultaneously.

Immunophenotyping helps in understanding the distribution of different cell types, their subsets, and activation status, which can be crucial in diagnosing various hematological disorders, immunodeficiencies, and distinguishing between different types of leukemias, lymphomas, and other malignancies. Additionally, it can also be used to monitor the progression of diseases, evaluate the effectiveness of treatments, and detect minimal residual disease (MRD) during follow-up care.

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).

"Freezing" is a term used in the medical field to describe a phenomenon that can occur in certain neurological conditions, most notably in Parkinson's disease. It refers to a sudden and temporary inability to move or initiate movement, often triggered by environmental factors such as narrow spaces, turning, or approaching a destination. This can increase the risk of falls and make daily activities challenging for affected individuals.

Freezing is also known as "freezing of gait" (FOG) when it specifically affects a person's ability to walk. During FOG episodes, the person may feel like their feet are glued to the ground, making it difficult to take steps forward. This can be very distressing and debilitating for those affected.

It is important to note that "freezing" has different meanings in different medical contexts, such as in the field of orthopedics, where it may refer to a loss of joint motion due to stiffness or inflammation. Always consult with a healthcare professional for accurate information tailored to your specific situation.

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.

Analgesics, opioid are a class of drugs used for the treatment of pain. They work by binding to specific receptors in the brain and spinal cord, blocking the transmission of pain signals to the brain. Opioids can be synthetic or natural, and include drugs such as morphine, codeine, oxycodone, hydrocodone, hydromorphone, fentanyl, and methadone. They are often used for moderate to severe pain, such as that resulting from injury, surgery, or chronic conditions like cancer. However, opioids can also produce euphoria, physical dependence, and addiction, so they are tightly regulated and carry a risk of misuse.

Fas Ligand Protein (FasL or CD95L) is a type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily. It plays a crucial role in programmed cell death, also known as apoptosis. The FasL protein binds to its receptor, Fas (CD95 or APO-1), which is found on the surface of various cells including immune cells. This binding triggers a signaling cascade that leads to apoptosis, helping to regulate the immune response and maintain homeostasis in tissues.

FasL can also be produced as a soluble protein (sFasL) through alternative splicing or proteolytic cleavage of the membrane-bound form. Soluble FasL may have different functions compared to its membrane-bound counterpart, and its role in physiology and disease is still under investigation.

Dysregulation of the Fas/FasL system has been implicated in various pathological conditions, including autoimmune diseases, neurodegenerative disorders, and cancer.

"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.

Genetically modified plants (GMPs) are plants that have had their DNA altered through genetic engineering techniques to exhibit desired traits. These modifications can be made to enhance certain characteristics such as increased resistance to pests, improved tolerance to environmental stresses like drought or salinity, or enhanced nutritional content. The process often involves introducing genes from other organisms, such as bacteria or viruses, into the plant's genome. Examples of GMPs include Bt cotton, which has a gene from the bacterium Bacillus thuringiensis that makes it resistant to certain pests, and golden rice, which is engineered to contain higher levels of beta-carotene, a precursor to vitamin A. It's important to note that genetically modified plants are subject to rigorous testing and regulation to ensure their safety for human consumption and environmental impact before they are approved for commercial use.

Salinity is not a term that has a specific medical definition. However, in general terms, salinity refers to the level of salt or sodium content in a substance, usually measured in parts per thousand (ppt). In a medical context, salinity might be discussed in relation to things like the body's fluid balance or the composition of certain bodily fluids, such as sweat or tears.

It is worth noting that in some cases, high salinity levels can have negative effects on health. For example, consuming water with very high salt content can lead to dehydration and electrolyte imbalances, which can be dangerous. Similarly, exposure to high-salinity environments (such as seawater) can cause skin irritation and other problems in some people. However, these are not direct medical definitions of salinity.

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.

Inbred A mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings. This results in a high degree of genetic similarity among individuals within the strain, making them useful for research purposes where a consistent genetic background is desired. The Inbred A strain is maintained through continued brother-sister mating. It's important to note that while these mice are called "Inbred A," the designation does not refer to any specific medical condition or characteristic. Instead, it refers to the breeding practices used to create and maintain this particular strain of laboratory mice.

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.

Gene expression regulation in plants refers to the processes that control the production of proteins and RNA from the genes present in the plant's DNA. This regulation is crucial for normal growth, development, and response to environmental stimuli in plants. It can occur at various levels, including transcription (the first step in gene expression, where the DNA sequence is copied into RNA), RNA processing (such as alternative splicing, which generates different mRNA molecules from a single gene), translation (where the information in the mRNA is used to produce a protein), and post-translational modification (where proteins are chemically modified after they have been synthesized).

In plants, gene expression regulation can be influenced by various factors such as hormones, light, temperature, and stress. Plants use complex networks of transcription factors, chromatin remodeling complexes, and small RNAs to regulate gene expression in response to these signals. Understanding the mechanisms of gene expression regulation in plants is important for basic research, as well as for developing crops with improved traits such as increased yield, stress tolerance, and disease resistance.

Immunization is defined medically as the process where an individual is made immune or resistant to an infectious disease, typically through the administration of a vaccine. The vaccine stimulates the body's own immune system to recognize and fight off the specific disease-causing organism, thereby preventing or reducing the severity of future infections with that organism.

Immunization can be achieved actively, where the person is given a vaccine to trigger an immune response, or passively, where antibodies are transferred to the person through immunoglobulin therapy. Immunizations are an important part of preventive healthcare and have been successful in controlling and eliminating many infectious diseases worldwide.

Transforming Growth Factor-beta (TGF-β) is a type of cytokine, which is a cell signaling protein involved in the regulation of various cellular processes, including cell growth, differentiation, and apoptosis (programmed cell death). TGF-β plays a critical role in embryonic development, tissue homeostasis, and wound healing. It also has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.

TGF-β exists in multiple isoforms (TGF-β1, TGF-β2, and TGF-β3) that are produced by many different cell types, including immune cells, epithelial cells, and fibroblasts. The protein is synthesized as a precursor molecule, which is cleaved to release the active TGF-β peptide. Once activated, TGF-β binds to its receptors on the cell surface, leading to the activation of intracellular signaling pathways that regulate gene expression and cell behavior.

In summary, Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine involved in various cellular processes, including cell growth, differentiation, apoptosis, embryonic development, tissue homeostasis, and wound healing. It has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.

Immunologic cytotoxicity refers to the damage or destruction of cells that occurs as a result of an immune response. This process involves the activation of immune cells, such as cytotoxic T cells and natural killer (NK) cells, which release toxic substances, such as perforins and granzymes, that can kill target cells.

In addition, antibodies produced by B cells can also contribute to immunologic cytotoxicity by binding to antigens on the surface of target cells and triggering complement-mediated lysis or antibody-dependent cellular cytotoxicity (ADCC) by activating immune effector cells.

Immunologic cytotoxicity plays an important role in the body's defense against viral infections, cancer cells, and other foreign substances. However, it can also contribute to tissue damage and autoimmune diseases if the immune system mistakenly targets healthy cells or tissues.

'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.

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.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that can affect almost any organ or system in the body. In SLE, the immune system produces an exaggerated response, leading to the production of autoantibodies that attack the body's own cells and tissues, causing inflammation and damage. The symptoms and severity of SLE can vary widely from person to person, but common features include fatigue, joint pain, skin rashes (particularly a "butterfly" rash across the nose and cheeks), fever, hair loss, and sensitivity to sunlight.

Systemic lupus erythematosus can also affect the kidneys, heart, lungs, brain, blood vessels, and other organs, leading to a wide range of symptoms such as kidney dysfunction, chest pain, shortness of breath, seizures, and anemia. The exact cause of SLE is not fully understood, but it is believed to involve a combination of genetic, environmental, and hormonal factors. Treatment typically involves medications to suppress the immune system and manage symptoms, and may require long-term management by a team of healthcare professionals.

Mononuclear leukocytes are a type of white blood cells (leukocytes) that have a single, large nucleus. They include lymphocytes (B-cells, T-cells, and natural killer cells), monocytes, and dendritic cells. These cells play important roles in the body's immune system, including defending against infection and disease, and participating in immune responses and surveillance. Mononuclear leukocytes can be found in the bloodstream as well as in tissues throughout the body. They are involved in both innate and adaptive immunity, providing specific and nonspecific defense mechanisms to protect the body from harmful pathogens and other threats.

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.

Immunotherapy is a type of medical treatment that uses the body's own immune system to fight against diseases, such as cancer. It involves the use of substances (like vaccines, medications, or immune cells) that stimulate or suppress the immune system to help it recognize and destroy harmful disease-causing cells or agents, like tumor cells.

Immunotherapy can work in several ways:

1. Activating the immune system: Certain immunotherapies boost the body's natural immune responses, helping them recognize and attack cancer cells more effectively.
2. Suppressing immune system inhibitors: Some immunotherapies target and block proteins or molecules that can suppress the immune response, allowing the immune system to work more efficiently against diseases.
3. Replacing or enhancing specific immune cells: Immunotherapy can also involve administering immune cells (like T-cells) that have been genetically engineered or modified to recognize and destroy cancer cells.

Immunotherapies have shown promising results in treating various types of cancer, autoimmune diseases, and allergies. However, they can also cause side effects, as an overactive immune system may attack healthy tissues and organs. Therefore, careful monitoring is necessary during immunotherapy treatment.

A peptide fragment is a short chain of amino acids that is derived from a larger peptide or protein through various biological or chemical processes. These fragments can result from the natural breakdown of proteins in the body during regular physiological processes, such as digestion, or they can be produced experimentally in a laboratory setting for research or therapeutic purposes.

Peptide fragments are often used in research to map the structure and function of larger peptides and proteins, as well as to study their interactions with other molecules. In some cases, peptide fragments may also have biological activity of their own and can be developed into drugs or diagnostic tools. For example, certain peptide fragments derived from hormones or neurotransmitters may bind to receptors in the body and mimic or block the effects of the full-length molecule.

Immunosuppressive agents are medications that decrease the activity of the immune system. They are often used to prevent the rejection of transplanted organs and to treat autoimmune diseases, where the immune system mistakenly attacks the body's own tissues. These drugs work by interfering with the immune system's normal responses, which helps to reduce inflammation and damage to tissues. However, because they suppress the immune system, people who take immunosuppressive agents are at increased risk for infections and other complications. Examples of immunosuppressive agents include corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus.

An epitope is a specific region on the surface of an antigen (a molecule that can trigger an immune response) that is recognized by an antibody, B-cell receptor, or T-cell receptor. It is also commonly referred to as an antigenic determinant. Epitopes are typically composed of linear amino acid sequences or conformational structures made up of discontinuous amino acids in the antigen. They play a crucial role in the immune system's ability to differentiate between self and non-self molecules, leading to the targeted destruction of foreign substances like viruses and bacteria. Understanding epitopes is essential for developing vaccines, diagnostic tests, and immunotherapies.

"Cold temperature" is a relative term and its definition can vary depending on the context. In general, it refers to temperatures that are lower than those normally experienced or preferred by humans and other warm-blooded animals. In a medical context, cold temperature is often defined as an environmental temperature that is below 16°C (60.8°F).

Exposure to cold temperatures can have various physiological effects on the human body, such as vasoconstriction of blood vessels near the skin surface, increased heart rate and metabolic rate, and shivering, which helps to generate heat and maintain body temperature. Prolonged exposure to extreme cold temperatures can lead to hypothermia, a potentially life-threatening condition characterized by a drop in core body temperature below 35°C (95°F).

It's worth noting that some people may have different sensitivities to cold temperatures due to factors such as age, health status, and certain medical conditions. For example, older adults, young children, and individuals with circulatory or neurological disorders may be more susceptible to the effects of cold temperatures.

Glucose is a simple monosaccharide (or single sugar) that serves as the primary source of energy for living organisms. It's a fundamental molecule in biology, often referred to as "dextrose" or "grape sugar." Glucose has the molecular formula C6H12O6 and is vital to the functioning of cells, especially those in the brain and nervous system.

In the body, glucose is derived from the digestion of carbohydrates in food, and it's transported around the body via the bloodstream to cells where it can be used for energy. Cells convert glucose into a usable form through a process called cellular respiration, which involves a series of metabolic reactions that generate adenosine triphosphate (ATP)—the main currency of energy in cells.

Glucose is also stored in the liver and muscles as glycogen, a polysaccharide (multiple sugar) that can be broken down back into glucose when needed for energy between meals or during physical activity. Maintaining appropriate blood glucose levels is crucial for overall health, and imbalances can lead to conditions such as diabetes mellitus.

Muramidase, also known as lysozyme, is an enzyme that hydrolyzes the glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycan, a polymer found in bacterial cell walls. This enzymatic activity plays a crucial role in the innate immune system by contributing to the destruction of invading bacteria. Muramidase is widely distributed in various tissues and bodily fluids, such as tears, saliva, and milk, and is also found in several types of white blood cells, including neutrophils and monocytes.

Lymphoid tissue is a specialized type of connective tissue that is involved in the immune function of the body. It is composed of lymphocytes (a type of white blood cell), which are responsible for producing antibodies and destroying infected or cancerous cells. Lymphoid tissue can be found throughout the body, but it is particularly concentrated in certain areas such as the lymph nodes, spleen, tonsils, and Peyer's patches in the small intestine.

Lymphoid tissue provides a site for the activation, proliferation, and differentiation of lymphocytes, which are critical components of the adaptive immune response. It also serves as a filter for foreign particles, such as bacteria and viruses, that may enter the body through various routes. The lymphatic system, which includes lymphoid tissue, helps to maintain the health and integrity of the body by protecting it from infection and disease.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

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.

Diabetes Mellitus, Type 2 is a metabolic disorder characterized by high blood glucose (or sugar) levels resulting from the body's inability to produce sufficient amounts of insulin or effectively use the insulin it produces. This form of diabetes usually develops gradually over several years and is often associated with older age, obesity, physical inactivity, family history of diabetes, and certain ethnicities.

In Type 2 diabetes, the body's cells become resistant to insulin, meaning they don't respond properly to the hormone. As a result, the pancreas produces more insulin to help glucose enter the cells. Over time, the pancreas can't keep up with the increased demand, leading to high blood glucose levels and diabetes.

Type 2 diabetes is managed through lifestyle modifications such as weight loss, regular exercise, and a healthy diet. Medications, including insulin therapy, may also be necessary to control blood glucose levels and prevent long-term complications associated with the disease, such as heart disease, nerve damage, kidney damage, and vision loss.

T-lymphocytes, also known as T-cells, are a type of white blood cell that plays a key role in the immune response. They help to protect the body from infection and disease by identifying and attacking foreign substances such as viruses and bacteria.

Helper-inducer T-lymphocytes, also known as CD4+ T-cells or Th0 cells, are a specific subset of T-lymphocytes that help to coordinate the immune response. They do this by activating other immune cells, such as B-lymphocytes (which produce antibodies) and cytotoxic T-lymphocytes (which directly attack infected cells). Helper-inducer T-lymphocytes also release cytokines, which are signaling molecules that help to regulate the immune response.

Helper-inducer T-lymphocytes can differentiate into different subsets of T-cells, depending on the type of cytokines they are exposed to. For example, they can differentiate into Th1 cells, which produce cytokines that help to activate cytotoxic T-lymphocytes and macrophages; or Th2 cells, which produce cytokines that help to activate B-lymphocytes and eosinophils.

It is important to note that helper-inducer T-lymphocytes play a crucial role in the immune response, and dysfunction of these cells can lead to immunodeficiency or autoimmune disorders.

A lymphocyte count is a laboratory test that measures the number of white blood cells called lymphocytes in a sample of blood. Lymphocytes are a vital part of the immune system and help fight off infections and diseases. A normal lymphocyte count ranges from 1,000 to 4,800 cells per microliter (µL) of blood for adults.

An abnormal lymphocyte count can indicate an infection, immune disorder, or blood cancer. A low lymphocyte count is called lymphopenia, while a high lymphocyte count is called lymphocytosis. The cause of an abnormal lymphocyte count should be investigated through further testing and clinical evaluation.

Desiccation is a medical term that refers to the process of extreme dryness or the state of being dried up. It is the removal of water or moisture from an object or tissue, which can lead to its dehydration and preservation. In medicine, desiccation may be used as a therapeutic technique for treating certain conditions, such as drying out wet wounds or preventing infection in surgical instruments. However, desiccation can also have harmful effects on living tissues, leading to cell damage or death.

In a broader context, desiccation is also used to describe the process of drying up of an organ, tissue, or body part due to various reasons such as exposure to air, heat, or certain medical conditions that affect moisture regulation in the body. For example, diabetic patients may experience desiccation of their skin due to decreased moisture production and increased evaporation caused by high blood sugar levels. Similarly, people living in dry climates or using central heating systems may experience desiccation of their mucous membranes, leading to dryness of the eyes, nose, and throat.

Membrane proteins are a type of protein that are embedded in the lipid bilayer of biological membranes, such as the plasma membrane of cells or the inner membrane of mitochondria. These proteins play crucial roles in various cellular processes, including:

1. Cell-cell recognition and signaling
2. Transport of molecules across the membrane (selective permeability)
3. Enzymatic reactions at the membrane surface
4. Energy transduction and conversion
5. Mechanosensation and signal transduction

Membrane proteins can be classified into two main categories: integral membrane proteins, which are permanently associated with the lipid bilayer, and peripheral membrane proteins, which are temporarily or loosely attached to the membrane surface. Integral membrane proteins can further be divided into three subcategories based on their topology:

1. Transmembrane proteins, which span the entire width of the lipid bilayer with one or more alpha-helices or beta-barrels.
2. Lipid-anchored proteins, which are covalently attached to lipids in the membrane via a glycosylphosphatidylinositol (GPI) anchor or other lipid modifications.
3. Monotopic proteins, which are partially embedded in the membrane and have one or more domains exposed to either side of the bilayer.

Membrane proteins are essential for maintaining cellular homeostasis and are targets for various therapeutic interventions, including drug development and gene therapy. However, their structural complexity and hydrophobicity make them challenging to study using traditional biochemical methods, requiring specialized techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and single-particle cryo-electron microscopy (cryo-EM).

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Down-regulation is a process that occurs in response to various stimuli, where the number or sensitivity of cell surface receptors or the expression of specific genes is decreased. This process helps maintain homeostasis within cells and tissues by reducing the ability of cells to respond to certain signals or molecules.

In the context of cell surface receptors, down-regulation can occur through several mechanisms:

1. Receptor internalization: After binding to their ligands, receptors can be internalized into the cell through endocytosis. Once inside the cell, these receptors may be degraded or recycled back to the cell surface in smaller numbers.
2. Reduced receptor synthesis: Down-regulation can also occur at the transcriptional level, where the expression of genes encoding for specific receptors is decreased, leading to fewer receptors being produced.
3. Receptor desensitization: Prolonged exposure to a ligand can lead to a decrease in receptor sensitivity or affinity, making it more difficult for the cell to respond to the signal.

In the context of gene expression, down-regulation refers to the decreased transcription and/or stability of specific mRNAs, leading to reduced protein levels. This process can be induced by various factors, including microRNA (miRNA)-mediated regulation, histone modification, or DNA methylation.

Down-regulation is an essential mechanism in many physiological processes and can also contribute to the development of several diseases, such as cancer and neurodegenerative disorders.

A plant root is not a medical term per se, but it is a term from botany, which is the study of plants. However, I can certainly provide a definition for you.

Plant roots are the underground organs of a plant that typically grow downward into the soil. They serve several important functions, including:

1. Anchorage: Roots help to stabilize the plant and keep it upright in the ground.
2. Absorption: Roots absorb water and nutrients from the soil, which are essential for the plant's growth and development.
3. Conduction: Roots conduct water and nutrients up to the above-ground parts of the plant, such as the stem and leaves.
4. Vegetative reproduction: Some plants can reproduce vegetatively through their roots, producing new plants from root fragments or specialized structures called rhizomes or tubers.

Roots are composed of several different tissues, including the epidermis, cortex, endodermis, and vascular tissue. The epidermis is the outermost layer of the root, which secretes a waxy substance called suberin that helps to prevent water loss. The cortex is the middle layer of the root, which contains cells that store carbohydrates and other nutrients. The endodermis is a thin layer of cells that surrounds the vascular tissue and regulates the movement of water and solutes into and out of the root. The vascular tissue consists of xylem and phloem, which transport water and nutrients throughout the plant.

CD3 antigens are a group of proteins found on the surface of T-cells, which are a type of white blood cell that plays a central role in the immune response. The CD3 antigens are composed of several different subunits (ε, δ, γ, and α) that associate to form the CD3 complex, which is involved in T-cell activation and signal transduction.

The CD3 complex is associated with the T-cell receptor (TCR), which recognizes and binds to specific antigens presented by antigen-presenting cells. When the TCR binds to an antigen, it triggers a series of intracellular signaling events that lead to T-cell activation and the initiation of an immune response.

CD3 antigens are important targets for immunotherapy in some diseases, such as certain types of cancer. For example, monoclonal antibodies that target CD3 have been developed to activate T-cells and enhance their ability to recognize and destroy tumor cells. However, CD3-targeted therapies can also cause side effects, such as cytokine release syndrome, which can be serious or life-threatening in some cases.

Inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is characterized by the following signs: rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio laesa (loss of function). The process involves the activation of the immune system, recruitment of white blood cells, and release of inflammatory mediators, which contribute to the elimination of the injurious stimuli and initiation of the healing process. However, uncontrolled or chronic inflammation can also lead to tissue damage and diseases.

In immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in ... Tregs are the central mediators of immune suppression and they play a key role in maintaining peripheral tolerance. The master ... Dependence of a particular antigen on either central or peripheral tolerance is determined by its abundance in the organism. B ... were shown to play a role in peripheral tolerance. Both of those populations are able to induce CD8 T cell tolerance by the ...
Xing Y, Hogquist KA (June 2012). "T-cell tolerance: central and peripheral". Cold Spring Harbor Perspectives in Biology. 4 (6 ... In a process known as "Central Tolerance", T-cells are exposed to cortical epithelial cells that express a variety of different ... Tolerance to self-protein is crucial for overall wellbeing; when the body erroneously identifies self-proteins as "non-self", ... factor allows the medullary epithelial cells of the thymus to express proteins would normally be present in peripheral tissue ...
Tolerogenic DCs are essential in maintenance of central and peripheral tolerance through induction of T cell clonal deletion, T ... Tol-DCs promotes central and peripheral tolerance. These tolerogenic properties are executed by deletion of T cells, induction ... "Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4" (PDF). Nature Immunology. 6 (3): 280-6 ... Moreover, Ag-specific tolerance in humans can be induced in vivo via vaccination with Ag-pulsed ex vivo generated tolerogenic ...
Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced-in ... Central tolerance is the main way the immune system learns to discriminate self from non-self. Peripheral tolerance is key to ... Immune tolerance is formally differentiated into central or peripheral; however, alternative terms such as "natural" or " ... These two methods of categorization are sometimes confused, but are not equivalent-central or peripheral tolerance may be ...
Metzger, T.C. (2011). "Control of Central and Peripheral Tolerance by Aire". Immunological Reviews. 241 (1): 89-103. doi: ...
Both cTEC and mTEC participate in imposing central and peripheral tolerance. cTECs play a key role in the positive selection ... Type 1 diabetes is a result of the absence of self-tolerance, which is characterized by a decreased expression of Insulin 1 and ... TECs, as a component of the thymus, play a key role in thymocyte development and self-tolerance, so their dysfunction causes ... Medulla is also important for implementation of self tolerance, which is mediated by CD4+CD25+Foxp3 nTreg cells. Foxp3 Treg ...
"Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance". Immunity. 36 (3): 438- ... Two processes of central tolerance take place in thymic medulla, namely clonal deletion (recessive tolerance) and T Regulatory ... The most efficient subset in TRA presentation and both modes of central tolerance was found to be CD8α+ thymic-derived DCs ( ... Indispensability of DCs for the establishment of central tolerance was further verified by recent analysis, which revealed that ...
The first type of tolerance is central tolerance, that occurs in the thymus. T cells that bind (via their T cell receptor) to ... The second type of immunological tolerance is peripheral tolerance. Some self reactive T cells escape the thymus for a number ... This process is called tolerance. Dendritic cells also promote immunological tolerance, which stops the body from attacking ... When immunological tolerance fails, autoimmune diseases can follow. Phagocytes of humans and other jawed vertebrates are ...
... is not perfect, so peripheral tolerance exists as a secondary mechanism to ensure that T and B cells are not ... Peripheral tolerance is distinct from central tolerance in that it occurs once developing immune cells exit primary lymphoid ... mount an immune response against self if not killed or inactivated by central tolerance mechanisms. Therefore, without central ... Central tolerance is essential to proper immune cell functioning because it helps ensure that mature B cells and T cells do not ...
Immune tolerance Central tolerance Peripheral tolerance regulatory T cells Immune response Immune tolerance in pregnancy ... Infectious tolerance is a term referring to a phenomenon where a tolerance-inducing state is transferred from one cell ... The goal is to achieve long-term tolerance of the transplant through short-term therapy. The term "infectious tolerance" was ... "Induction of tolerance in peripheral T cells with monoclonal antibodies". European Journal of Immunology. 20 (12): 2737-2745. ...
Cross-presenting dendritic cells have a significant impact on the promotion of central and peripheral immune tolerance. In ... In regard to peripheral tolerance, peripheral tissue resting dendritic cells are able to promote self tolerance against ... Lutz, Manfred B.; Kurts, Christian (2009-09-01). "Induction of peripheral CD4+ T-cell tolerance and CD8+ T-cell cross-tolerance ... Although the function of dendritic cells in central tolerance is still relatively unknown, it appears that thymic dendritic ...
The expression of peripheral antigens in mimetic cells strongly implies a function in establishing central immune tolerance. ... Since its discovery in 2001, AIRE (Autoimmune regulator) has been the main focus of studies of thymic (central) immune ... AIRE induces the expression of many antigens specific to differentiated cells not found in the thymus (termed peripheral tissue ... "Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self". Nature Immunology. 2 (11): 1032- ...
When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the ... which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cells are the immune ... Peripheral membrane proteins, Oncogenes, Apoptosis, Programmed cell death). ...
Kanta H, Mohan C (July 2009). "Three checkpoints in lupus development: central tolerance in adaptive immunity, peripheral ... Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system. The American College of ... B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation ... West SG (September 1996). "Lupus and the central nervous system". Current Opinion in Rheumatology. 8 (5): 408-414. doi:10.1097/ ...
Therefore, one of the most important roles of the thymus is the induction of central tolerance. However, the thymus is not ... The secondary (or peripheral) lymphoid organs, which include lymph nodes and the spleen, maintain mature naive lymphocytes and ... The primary (or central) lymphoid organs generate lymphocytes from immature progenitor cells. The thymus and the bone marrow ... As a major lymphoid organ and a central player in the reticuloendothelial system, the spleen retains the ability to produce ...
... have been conducted in attempts to create a general model for the mechanical tolerance of neurons within the Central Nervous ... One such in vitro model has found that CNS neurons have a lower threshold for stress and strain loads than Peripheral Nervous ...
... is a process specific to the thymus that plays a pivotal role in the establishment of central tolerance. This phenomenon ... PGE is distinct from the expression of TRAs in the peripheral tissues also by its monoalelic or bialelic course. On the other ... their importance for the establishment of central tolerance remains elusive. It is assumed however, that B cells in the thymus ... plays role in different physiological processes than central tolerance, e.g. development of the brain, and acts as a classical ...
Immune tolerance is maintained by central and peripheral tolerance. During central tolerance, T-cells are selected in the ... While autoimmunity is thought to result from the breakdown of central and peripheral tolerance, undesirable immune responses ... A short, 5-day course of FcR-binding, anti-CD3 antibody treatment was able to re-establish peripheral tolerance in animal ... These strategies employed the use of soluble peptide tolerance and oral peptide tolerance to great efficacy in experimental ...
Peripheral tolerance is a mechanism controlling such autoreactive T cells in secondary lymphoid organs, blood circulation and ... not controlled by the central tolerance mechanism in the thymus or better eliminate such self-reactive T cells on the other ... Activation-dependent T cell revision process is part of peripheral tolerance mechanisms if the new TCR specificity loses its ... are eliminated in the thymus immediately in a process of central tolerance, however it is not 100% effective again. As a result ...
... but also peripheral tolerance by allowing homing of tolerogenic dendritic cells to lymph nodes. CCR7 is expressed by various ... disruption and insufficient T cell receptor stimulation It must however be noted that CCR7 affects not only central tolerance, ... Their activation in peripheral tissues induces CCR7 expression on the cell's surface, which recognize CCL19 and CCL21 produced ... June 2001). "Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor ...
Diamond's primary interests are in the mechanisms of central and peripheral tolerance of autoreactive B cells, and the defects ... the mosaic of central nervous system involvement in lupus". BMC Medicine. 11 (1): 90. doi:10.1186/1741-7015-11-90. ISSN 1741- ...
... and CTLs will not be activated in response to them due to central and peripheral tolerance mechanisms. When a cell expresses ... PirB is expressed in the central nervous system and diminishes ocular dominance plasticity in the developmental critical period ...
Alloimmunity Cross-reactivity Tolerance Central tolerance Peripheral tolerance Clonal anergy Clonal deletion Tolerance in ... BioMed Central:Immunology is an open access journal publishing original peer-reviewed research articles. Nature Reviews ... Neuroimmune system in the Central nervous system Ocularimmunology - Ocular immune system in the Eye Cancer immunology/ ...
Dominant and recessive tolerance are forms of a peripheral tolerance (the other tolerance beside peripheral is a central ... and consists of a direct induction of peripheral lymphocyte tolerance. An individual in a state of anergy often indicates that ... Similarly to recessive tolerance, unopposed NFAT signalling is also important for T-reg induction. In this case, the NFAT ... Many viruses (HIV being the most extreme example) seem to exploit the immune system's use of tolerance induction to evade the ...
December 2003). "An immunologically privileged retinal antigen elicits tolerance: major role for central selection mechanisms ... April 2007). "Limited peripheral T cell anergy predisposes to retinal autoimmunity". Journal of Immunology. 178 (7): 4276-83. ... Failure of this mechanism leads to neutrophil and other leukocyte recruitment from the peripheral blood through IL-17 secretion ...
This process forms part of central tolerance to attempt to change the specificity of the antigen receptor of self reactive ... It is thought that 20-50% of all peripheral naive B cells have undergone receptor editing making it the most common method of ... Halverson R, Torres RM, Pelanda R (2004). "Receptor editing is the main mechanism of B cell tolerance toward membrane antigens ... Meffre, E; Wardemann, H (2008). "B-cell tolerance checkpoints in health and autoimmunity". Current Opinion in Immunology. 20 (6 ...
Tolerance can also be differentiated into "central" and "peripheral" tolerance, on whether or not the above-stated checking ... Loss of tolerance by T cells has been extremely hard to demonstrate, and where there is evidence for an abnormal T cell ... "Tolerance and Autoimmunity". Archived from the original on 2011-01-01. Retrieved 2007-03-19. Edwards JC, Cambridge G, Abrahams ... A puzzling feature of the documented loss of tolerance seen in spontaneous human autoimmunity is that it is almost entirely ...
Rocha, B. and von Boehmer, H.: Peripheral selection of the T cell repertoire. Science 251, 1225 (1991). Peripheral tolerance by ... Nature 351, 150 (1991). Central tolerance by deletion of immature T cells in TCR transgenic mice. Teho H. S., Kisielow, P., ... Kisielow, P., Blüthmann, H., Staerz, U. D., Steinmetz, M. and von Boehmer, H.: Tolerance in T cell receptor transgenic mice: ... Tolerance to histocompatibility determinants in tetraparental bone marrow chimeras. J. Exp. Med. 141, 322 (1975). Graft-versus- ...
... s enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, ... The reasons for the short-term mood-improving effects of stimulants are unclear, but may relate to rapid tolerance. Tolerance ... In addition, tolerance to the mood-lifting effects of amphetamine has led to dose escalation and dependence. Although the ... Abuse of central nervous system (CNS) stimulants is common. Addiction to some CNS stimulants can quickly lead to medical, ...
This is caused by a loss of tolerance to proteins in the body, resulting in immune cells recognising these as 'foreign' and ... The spinal cord is protected by vertebrae and connects the peripheral nervous system to the brain, and it acts as a "minor" ... Central nervous system diseases, also known as central nervous system disorders, are a group of neurological disorders that ... Central nervous system tumors are the most common forms of pediatric cancer. Brain tumors are the most frequent and have the ...
Tolerance is generally accepted to be an active process and, in essence, a learning experience for T cells. ... Immunologic tolerance is a state of immune unresponsiveness specific to a particular antigen or set of antigens induced by ... Central (Intrathymic) Mechanisms of Tolerance. The chief mechanism of T-cell tolerance is the deletion of autoreactive T cells ... donor-specific tolerance has been termed prope tolerance [33] (from Latin prope "near") or minimal immunosuppression tolerance. ...
This phenomenon is known as self-tolerance. It refers to the lack of responsiveness to the individuals self-antigens. Hence ... Difference Between Central Tolerance and Peripheral Tolerance - Introduction Normally our immune system shows a response ... Deficits in central and peripheral tolerance also cause auto-immune disease resulting in syndromes like systemic lupus ... This immune tolerance is of 2types central tolerance which occurs in the primary lymphoid organs (thymus and bone marrow) where ...
In immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in ... Tregs are the central mediators of immune suppression and they play a key role in maintaining peripheral tolerance. The master ... Dependence of a particular antigen on either central or peripheral tolerance is determined by its abundance in the organism. B ... were shown to play a role in peripheral tolerance. Both of those populations are able to induce CD8 T cell tolerance by the ...
Expression of the Autoimmune Regulator Gene and Its Relevance to the Mechanisms of Central and Peripheral Tolerance. Roberto ...
It is important that disease tolerance is not confused with the equally important concept of immune tolerance in which immune ... the possibility that immune tolerance and disease tolerance can operate in a complementary fashion within the same setting of ... This latter strategy is referred to as disease tolerance and involves coordination between immune cells and tissue-specific ... T-cell tolerance: central and peripheral. Cold Spring Harb Perspect Biol. (2012) 4:a006957. doi: 10.1101/cshperspect.a006957 ...
5). Furthermore, B cell stimulation assays reveal defects in central and peripheral B cell tolerance (see Supplementary Figs. ... Furthermore, B cell stimulation assays identified defects in central and peripheral B cell tolerance (Supplementary Results and ... 4c), as well as inflammatory cytokines and chemokines in peripheral blood (Fig. 4d). Temporary discontinuation of dasatinib ... fenestrated endothelial cells that play a central role in liver homeostasis by regulating intrahepatic vascular tone, immune ...
Interaction of Central and Peripheral Benzodiazepine Sites in Benzodiazepine Tolerance and Discontinuation. Prog Neuro- ... Hvam T. Central stimulation under valiumbehandling. [A Central Stimulating Effect of Valium.] Ugeskrift for Laeger 1964; 126: ... Depression of Central Respiratory Drive by Nitrazepam. Thorax 1978; 33: 97-100. Rufino-Ruiz J et al. Apnea and Retarded ... Rapid Development of Tolerance to the Sedative Effects of Lorazepam and Triazolam in Rats. Psychopharmacology 1981; 73: 240-245 ...
IgA immunity and oral tolerance. Thus, impaired antigen-specific Ab responses in aged animals and the elderly have been ... Aging also impairs oral tolerance, which may be of central importance for maintaining GI homeostasis. Thus, as early as 6-8- ... mediated immune responses are more susceptible to aging than are lymphoid tissues involved in peripheral immunity. ... Mucosal immunity and tolerance in the elderly Mech Ageing Dev. 2004 Dec;125(12):889-98. doi: 10.1016/j.mad.2004.05.009. ...
... of peripheral Tregs and during induction of mucosal tolerance they seem to have a central role in maintenance of tolerance [101 ... Mucosal tolerance induction of gluten is another potential strategy in reducing the risk of T1D but this also needs further ... Mucosal Tolerance Induction by Gliadin. A study showed that BB rats fed wheat gluten neonatally versus at weaning were ... These studies show that a possible strategy in the prevention of T1D may be induction of mucosal tolerance against gluten, but ...
We suggest that a high-tolerance capacity of the alloreactive transplacentally acquired maternal lymphocytes represents a ... the possible inability of the thymus to delete these abnormal clones due to compromise of both central and peripheral tolerance ... R. Somech, A. J. Simon, A. Lev et al., "Reduced central tolerance in Omenn syndrome leads to immature self-reactive oligoclonal ... and peripheral (FOXP3+ deficiency) tolerance mechanisms [3]. For example, Omenn syndrome, a typical case of impaired T-cell ...
Because of their central role in initiating an immune response while maintaining tolerance, impaired function of these cells ... might lead to the break of peripheral tolerance and initiation of immune responses to self-antigens. This review will focus on ...
... are the central component of peripheral immune tolerance. Whereas a dysregulated Treg cytokine signature has been observed in ...
The area of Tolerance is reviewed in a very up-to-date chapter. Recent elucidation of the role of central tolerance in ... generation of a variety of peripheral regulatory cells to control self-reactive cells that escape the thymus. Tolerance is ... Of recurrent interest is the extent to which central mechanisms contribute to T cell tolerance toward the abundance of tissue- ... The central phenomenon at issue in immunology is resistance to infection: the fact that we do not passively succumb to microbes ...
... controls systemic inflammation and tissue responses via central regulation of peripheral tolerance in multiple organs. ... GDF15 Is an Inflammation-Induced Central Mediator of Tissue ToleranceLuan HH, Wang A, Hilliard B, Carvalho F, Rosen CE, Ahasic ... GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance Cell 2019, 178: 1231-1244.e11. PMID: 31402172, PMCID: ... that that immune events in the lung could be monitored in the peripheral blood in many forms of human pulmonary fibrosis. We ...
... a central role in the development and maintenance of immunological tolerance by promoting the ectopic expression of peripheral ... which has a central function in maintaining immunological tolerance. A number of conditions with proven or likely autoimmune ...
T cells with low avidity for a tissue-restricted antigen routinely evade central and peripheral tolerance and cause ... Reduced functional avidity promotes central and effector memory CD4+ T cell responses to tumor-associated antigens.54 The ... Reduced functional avidity promotes central and effector memory CD4 T cell responses to tumor-associated antigens. J Immunol ... Immune checkpoints are inhibitory pathways crucial for the maintenance of self-tolerance and protection of tissues from overt ...
... opioid tolerance, hyperalgesic states, central pain syndromes, etc.). As-needed rescue opioids may be necessary for adequate ... Peripheral Nerve Blocks. Peripheral nerve blockade is an effective and safe technique for providing post-operative analgesia ... The theory that certain medications may help reduce the up-regulation of nociceptors at peripheral or central locations when ... Peripheral nerve catheters may be left in for several days, although it should be noted the risk of abscesses requiring ...
Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity. October 4, 2017. Central ... Autoimmune regulator (Aire) is a regulator of central tolerance that is expressed predominantly in medullary thymic epithelial ... and peripheral blood of six patients with hepatocellular carcinoma (HCC). From the... ... tolerance is essential for protection against autoimmune reactions, but cancers being so similar to "self", this protective ...
... cells that initiate adaptive immunity by the activation of naïve lymphocytes and induce central and peripheral tolerance by ... IL-12 plays a central role in the pathogenesis of inflammation and several reports suggest that IL-12 is the critical decisive ... into the mechanism of action of SFA and into its potential clinical use as a novel immunosuppressive agent for tolerance ...
How DCs initiate immunity against foreign antigens while maintaining tolerance to self-antigens is both a paradox and central ... the ability of DCs to induce peripheral tolerance likely represents a major constraint against the generation of antitumor ... DCs are thus paradoxically important in cancer, generating both immunity and tolerance. Given their central role in controlling ... 1). Such signals may enhance the DCs ability to present self-antigen to promote tolerance and elicit the production of Tregs; ...
Central and peripheral tolerance, type-1 diabetes (example of autoimmune disease), and Treg biogenesis and function.. 00:34:33 ... It covers two important mechanisms that prevent autoimmunity (central and peripheral tolerance) and characterizes the ... APS-1 Syndrome, AIRE protein role in T cell tolerance, AIRE expression/localization, and importance of Tregs for APS-1. 00:37: ... Xenotransplantation, 𝛼1,3-Gal, genetically engineered pigs for organ transplants, xenograft rejection, tolerance induction, ...
The thymus plays a pivotal role in the establishment of immune central tolerance by producing a diverse repertoire of non- ... CONTEXT: The thymus plays a pivotal role in the establishment of immune central tolerance by producing a diverse repertoire of ... the effect of these TFs on self-tolerance induction will be evaluated by analyzing signs of autoimmunity in peripheral tissues. ... Beyond this fundamental understanding of central tolerance, the SelfExpress project will help in designing novel therapeutic ...
Margiana, R., Kzar, H. H., Hussam, F., Hameed, N. M., Al-qaim, Z. H., Al-Gazally, M. E., Kandee, M., Saleh, M. M., Toshbekov, B. B. U., Tursunbaev, F., Karampoor, S. & Mirzaei, R., Aug 2023, In: Pathology Research and Practice. 248, 154705.. Research output: Contribution to journal › Review article › peer-review ...
It behaves central and peripheral nervous system stimulator leading to systemic effects, tolerance, dependence and poisoning. ... A tabulação dos dados ocorreu por meio da utilização de três figuras metodológicas: ideia central, expressões chave e o ... The tabulation of the data occurred through the use of three methodological figures: central idea, key expressions and ... Comporta-se como um estimulador do sistema nervoso central e periférico levando a efeitos sistêmicos, tolerância, dependência e ...
It is called as central tolerance. Tolerance acquired outside thymus is called peripheral tolerance. Because some self-reactive ... Tolerance Tolerance is unresponsiveness for certain specific antigens. Antigens present during embryonic life are considered " ... Tolerance is maintained best if the antigen is constantly present.. *A most important step in autoimmune disease is the ... T-cells are not killed in thymus peripheral tolerance is required. This is called as Clonal Anergy. This is the functional ...
Autoimmunity results from a breakdown in one or more central or peripheral mechanisms of lymphocyte tolerance induction or ... In the case of T cells, central tolerance is imposed within the thymus, key orchestrators being medullary thymic epithelial ... Intramural Directions for Submitting to PubMed Central via NIHMS. *NIH Publishing Agreement Forms*Procedures for Non-Peer- ... 2) To understand how the two major medullary tolerance mechanisms - induction of misplaced transcripts and differentiation of ...
... the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to ... Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, ...
... epithelial cells results in peripheral but not central CD8 T cell tolerance. Tissue Antigens, 66 (5), 475-476. ... epithelial cells results in peripheral but not central CD8 T cell tolerance ... Narayan, S., Fernando, G., Frazer, I. H. and Leggatt, G. (2005). A model of peripheral CD8(+) T cell tolerance against skin ... A model of peripheral CD8(+) T cell tolerance against skin antigen. ...
Nemazee D (October 2006). "Receptor editing in lymphocyte development and central tolerance". Nature Reviews. Immunology. 6 (10 ...
GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. We conclude that WASp plays an ... important role in the establishment and maintenance of B cell tolerance in humans and that restoration of WASp by GT is able to ...
  • Immune tolerance or immunological tolerance is the state of unresponsiveness of the immune system to the substances or tissues that are capable to induce an immune response. (tutorialspoint.com)
  • In immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. (wikipedia.org)
  • Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the autoimmune regulator (AIRE) gene, which has a central function in maintaining immunological tolerance. (ersjournals.com)
  • The AIRE protein is a transcriptional regulator expressed mainly in the thymus and plays a central role in the development and maintenance of immunological tolerance by promoting the ectopic expression of peripheral tissue-restricted antigens in medullary epithelial cells of the thymus 2 . (ersjournals.com)
  • We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. (tokushima-u.ac.jp)
  • The mechanisms by which these forms of tolerance are established are distinct but the resultant effect is similar. (tutorialspoint.com)
  • Some of the mechanisms for peripheral tolerance involve the T regulatory cells (subsets of CD4 and CD8). (tutorialspoint.com)
  • These cells can trigger an autoimmune response, and there are several mechanisms of peripheral tolerance to prevent their activation. (wikipedia.org)
  • Antigen-specific mechanisms of peripheral tolerance include persistent of T cell in quiescence, ignorance of antigen and direct inactivation of effector T cells by either clonal deletion, conversion to regulatory T cells (Tregs) or induction of anergy. (wikipedia.org)
  • Dendritic cells (DCs) participate in the negative selection of autoreactive T cells in the thymus, but they also mediate peripheral immune tolerance through several mechanisms. (wikipedia.org)
  • This Frontiers Research Topic entitled "Evolving mechanisms of disease tolerance" aims to demonstrate how the research and our understanding of this concept is leading to, what we consider, a new golden age of infectious disease research and discovery. (frontiersin.org)
  • Paudel and Sanfaçon return to the roots of disease tolerance by describing the mechanisms by which plants tolerate viral infection. (frontiersin.org)
  • Although immunity is extensively impaired in such cases, regulatory tolerance mechanisms are not known to be affected [ 2 ]. (hindawi.com)
  • These cells expand in the periphery, causing tissue infiltration and damage due to breakdown of both central (e.g., autoimmune regulator, AIRE protein dysfunction) and peripheral (FOXP3 + deficiency) tolerance mechanisms [ 3 ]. (hindawi.com)
  • The suggested mechanism for this phenomenon is the possible inability of the thymus to delete these abnormal clones due to compromise of both central and peripheral tolerance mechanisms [ 5 ]. (hindawi.com)
  • Dendritic cells (DCs) are professional antigen presenting cells that initiate adaptive immunity by the activation of naïve lymphocytes and induce central and peripheral tolerance by mechanisms that include deletion, anergy and induction of regulatory T lymphocytes. (rotrf.org)
  • This session showcases the generation of antibody diversity (via V, D, J recombination), and the mechanisms that ensure the proper function of B cells (pre-BCR signaling and tolerance). (ibiology.org)
  • Autoimmunity results from a breakdown in one or more central or peripheral mechanisms of lymphocyte tolerance induction or maintenance. (nih.gov)
  • 2) To understand how the two major medullary tolerance mechanisms - induction of misplaced transcripts and differentiation of misplaced cells - integrate to provide a strong safety net. (nih.gov)
  • Mechanisms in CD4 antibody-mediated transplantation tolerance: kinetics of induction, antigen dependency and role of regulatory T cells. (ox.ac.uk)
  • Immunologic tolerance is a state of immune unresponsiveness specific to a particular antigen or set of antigens induced by previous exposure to that antigen or set. (medscape.com)
  • Due to random genetic recombinations, immune cells genetically express receptors for the specific self and foreign antigens in the central lymphoid organs. (tutorialspoint.com)
  • Not all self-antigens are expressed in the central lymphoid organs where the negative selection occurs. (tutorialspoint.com)
  • In the thymus, the thymocytes which have a high affinity for self-antigens undergo apoptosis leading to their death, whereas the thymocytes with a low and moderate affinity towards the self-antigens cross the barrier and enter the periphery during negative selection hence we need peripheral tolerance as well. (tutorialspoint.com)
  • Peripheral tolerance prevents immune response to harmless food antigens and allergens, too. (wikipedia.org)
  • iTregs are enriched in the gut to establish tolerance to commensal microbiota and harmless food antigens. (wikipedia.org)
  • iDCs perform endocytosis and phagocytosis of foreign antigens and apoptotic cells, which occurs physiologically in peripheral tissues. (wikipedia.org)
  • Both of those populations are able to induce CD8 T cell tolerance by the presentation of the endogenous antigens on MHCI molecules. (wikipedia.org)
  • Because of their central role in initiating an immune response while maintaining tolerance, impaired function of these cells might lead to the break of peripheral tolerance and initiation of immune responses to self-antigens. (nih.gov)
  • Historical perspective of the study of immunology, antigens/antibodies, side chain hypothesis, clonal selection hypothesis, antibody structure & function, generation of antibody diversity via VDJ recombination, and tolerance. (ibiology.org)
  • A unique feature of mTECs is expression of thousands of loci encoding antigens typically associated with fully differentiated peripheral parenchymal cells (peripheral-tissue antigens or PTAs). (nih.gov)
  • On the other hand, the discovery that the thymus contains a broad representation of self-antigens and that this depends on the expression of the product of the gene [[AIRE]] by the medullary thymic epithelial cells opens the possibility of manipulating central tolerance. (transhumanist.ru)
  • Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). (tokushima-u.ac.jp)
  • Tolerance can be classified into 2 types depending on where this state is originally induced in the thymus or bone marrow or in other tissues and lymph nodes. (tutorialspoint.com)
  • Further, it has been shown that gut-associated lymphoreticular tissue (GALT) mediated immune responses are more susceptible to aging than are lymphoid tissues involved in peripheral immunity. (nih.gov)
  • For example, Omenn syndrome, a typical case of impaired T-cell differentiation with abnormal self-reactive cells, is invariably characterized by autoimmune features such as generalized scaly exudative erythroderma, enlarged lymphoid tissues, and peripheral expansion of oligoclonal T-cells, in addition to increased susceptibility for severe infections [ 3 , 4 ]. (hindawi.com)
  • CTLA-4 affects central tolerance, while PD1/PD-L1 modulates immune responses in peripheral tissues. (endocrinologyadvisor.com)
  • Central tolerance processes of negative selection and receptor editing work to eliminate many auto-reactive T cells in the thymus and auto-reactive B cells in bone marrow respectively. (tutorialspoint.com)
  • CONTEXT: The thymus plays a pivotal role in the establishment of immune central tolerance by producing a diverse repertoire of non-autoreactive T lymphocytes. (anr.fr)
  • This lack of knowledge leaves considerable gaps in our understanding of how the "self" is expressed in the thymus and how immune central tolerance is established. (anr.fr)
  • In the case of T cells, central tolerance is imposed within the thymus, key orchestrators being medullary thymic epithelial cells (mTECs), which play critical roles in both negative selection of T effector cells and positive selection of T regulatory cells. (nih.gov)
  • Given the central role of the thymus in tolerance, these facts have stimulated the interest in the biology of the thymus in humans. (transhumanist.ru)
  • Aside from dendritic cells, additional cell populations were identified that are able to induce antigen-specific T cell tolerance. (wikipedia.org)
  • LNSCs can drive the CD4 T cell tolerance by the presentation of the peptide-MHCII complexes, which they acquired from the DCs. (wikipedia.org)
  • GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. (thinkbeforeyouclickca.org)
  • If antibody therapy is continued for the full 5 weeks, T cell tolerance can still be established, suggesting that antibody therapy does not prevent lymphocytes from registering the presence of antigen. (ox.ac.uk)
  • 2006. Regulation of B-cell tolerance by the lupus susceptibility gene Ly108. (uh.edu)
  • Recently, the role of inflammation in the central nervous system, particularly the hypothalamus in diet-induced IR progress, has been noted in rodent models and human (Posey et al. (deepdyve.com)
  • it affects the peripheral nervous system but also the central nervous system. (medscape.com)
  • Alcohol Toxicity and Withdrawal Alcohol (ethanol) is a central nervous system depressant. (msdmanuals.com)
  • 5. Patients with a previous history of demyelinating or inflammatory diseases of the Central Nervous System (CNS) or Peripheral (SNP). (who.int)
  • 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)
  • We suggest that a high-tolerance capacity of the alloreactive transplacentally acquired maternal lymphocytes represents a toleration advantage, yet still associated with severe immunodeficiency. (hindawi.com)
  • However, during the study of achieving immune tolerance, ways in which to induce states of "partial tolerance" have been discovered, in which lower-than-conventional amounts of ongoing pharmacologic immunosuppression are needed. (medscape.com)
  • However, immature DCs (iDCs) are able to induce both CD4 and CD8 tolerance. (wikipedia.org)
  • In fact, it has also been demonstrated that peripheral alterations in the insulin pathway observed in patients with T2DM contribute to alterations in brain insulin, leading to an increase of Aβ accumulation and a decrease of its clearance, which induce neuronal damage and, therefore, cognitive decline, creating a vicious cycle of pathogenesis [ 19 ]. (biomedcentral.com)
  • Nonetheless, immune tolerance remains the holy grail of transplantation immunology and clinical transplantation. (medscape.com)
  • Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire. (tokushima-u.ac.jp)
  • Once the tolerant state is established, it is difficult to break that tolerance by lymphocyte infusions from normal donors. (ox.ac.uk)
  • Some investigators also recently verified that the molecular signalling pathways of DC-T lymphocyte interaction might be novel targets for induction of transplant tolerance or handling of allograft immunity. (reninsignaling.com)
  • Given their central role in controlling the immune response in patients with cancer, DCs are emerging as a critical cell type that must be considered as we come to understand basic cancer immunobiology. (aacrjournals.org)
  • We have shown a reduction in the number and functional activity of T-reg in peripheral blood of patients with multiple sclerosis in the acute stage, the increase in their number during remission, duration of the relationship of the autoimmune process and the degree of disability of patients with the contents of T-reg. (spr-journal.ru)
  • Common presentations of diabetic peripheral neuropathy are loss of sensation or distal to proximal numbness that can be "so severe patients can't feel their feet," said Feldman. (medscape.com)
  • Peripheral stigmata of lipid abnormalities and atherosclerosis, such as premature arcus cornealis, xanthelasma, eruptive (skin) xanthomata, tendon xanthomata, and lipemia retinalis, may be found in some patients. (medscape.com)
  • La présente analyse récapitule les facteurs pathologiques majeurs liant l'obésité au diabète, en se concentrant sur les données épidémiologiques actuelles relatives aux patients diabétiques obèses dans le monde arabe, l'étiologie de la maladie et les déterminants génétiques du diabète et de l'obésité. (who.int)
  • 2. Patients who have not received the standard 1st line treatment (recombinant IFN a2), due to non-tolerance or contraindication. (who.int)
  • Induction of immunologic tolerance has been achieved and studied in numerous laboratory animal models, but it remains an elusive goal in clinical organ transplantation and in the management of autoimmune disease in humans. (medscape.com)
  • Considering the relevance of disease tolerance across the kingdoms of life and throughout the evolution of mammals, we have assembled exciting reviews detailing how this defense strategy is conserved from plants to humans against diverse forms of infection. (frontiersin.org)
  • Transplantation tolerance could eliminate many of the adverse events associated with immunosuppressive agents. (medscape.com)
  • We expect to gain novel insights into the mechanism of action of SFA and into its potential clinical use as a novel immunosuppressive agent for tolerance induction in solid organ transplantation. (rotrf.org)
  • Therefore, there are many signs indicating that a period of translational research applying the principles of thymic biology and central tolerance to transplantation has already started. (transhumanist.ru)
  • DCs are thus paradoxically important in cancer, generating both immunity and tolerance. (aacrjournals.org)
  • Understanding the paradoxical importance of dendritic cells in immunity and tolerance will inform the development of successful cancer immunotherapies. (aacrjournals.org)
  • However, the possibility that immune tolerance and disease tolerance can operate in a complementary fashion within the same setting of infection or inflammation is certainly not excluded. (frontiersin.org)
  • Finally, in very recent work, we have collaborated with investigators in Yale's School of Immunobiology to describe a new innate immune process by which the inflammation associated hormone GDF15 (also called macrophage inhibitory cytokine 1) controls systemic inflammation and tissue responses via central regulation of peripheral tolerance in multiple organs. (yale.edu)
  • IL-12 plays a central role in the pathogenesis of inflammation and several reports suggest that IL-12 is the critical decisive factor switching tolerogenic DCs into immunogenic DCs. (rotrf.org)
  • 2017). The inhibition of hypothalamic inflammation by intracerebroventricular (ICV) administration of IKK2 inhibitor (IMD-0354) rectified PM2.5-induced glucose intolerance, IR, energy metabolism dysfunction, and attenuated peripheral inflammation in response to PM2.5 exposure (Song et al. (deepdyve.com)
  • Safe, reliable strategies for the induction of full tolerance have not yet been developed. (medscape.com)
  • Indeed, the frequencies of naive CD4+ T cells and dendritic cells (DCs) in Peyer's patches of aged mice were reduced and this led to a lack of essential cytokine synthesis for the induction of either S-IgA immunity or oral tolerance. (nih.gov)
  • The ability to mentalize, or theory of mind (ToM), is sexually Foxp3+ regulatory T cells (Treg cells) are the central component of peripheral immune tolerance. (neurosciencenews.com)
  • Moreover, Wu and coworkers have proven the existence of peripheral metabolic changes in plasma and liver of AD mice models, suggesting that AD development is not only caused by alterations in the brain but also that systemic impairment plays a key role in the pathology [ 18 ]. (biomedcentral.com)
  • Specifically, they demonstrated that genetic variation in mice can delineate host resistance vs. disease tolerance following malaria infection ( 8 ). (frontiersin.org)
  • When tolerant cells were "parked" in T cell-depleted mice, tolerance and "resistance" were eventually lost by 6 months. (ox.ac.uk)
  • In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). (biomedcentral.com)
  • Central IKK2 Inhibition Ameliorates Air Pollution-Mediated Hepatic Glucose and Lipid Metabolism. (deepdyve.com)
  • 2007). Emerging evidence from both epidemiological and experimental studies indicates the adverse consequences of PM2.5 exposure on diabetes, including worsening of whole-body insulin sensitivity, glucose tolerance impairment, lipid accumulation, and glucose metabolism dysfunction (Hwang et al. (deepdyve.com)
  • 2017). Whether central inhibition of IKK2 could reverse the dysfunction of glucose and lipid metabolism remains unknown. (deepdyve.com)
  • immature cell is then subjected to negative selection to delete grouped based on their previously defined pheno- self-reactive cells before it leaves the BM to enter peripheral typic features, and a gene expression pattern for lymphoid organs, where it becomes a mature B cell [9]. (lu.se)
  • In this context, the association between T2DM and AD is very complex where several molecular pathways are interlinked such as insulin resistance, peripheral inflammatory response, and endoplasmic reticulum stress, among others [ 13 ]. (biomedcentral.com)
  • Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease. (wikipedia.org)
  • Agreement and Reliability of Fasted and Oral Glucose Tolerance Test-Derived Indices of Insulin Sensitivity and Beta Cell Function in Boys. (exeter.ac.uk)
  • This latter strategy is referred to as disease tolerance and involves coordination between immune cells and tissue-specific structural cells to maximize host fitness in the face of disruption to homeostatic conditions ( 4 ). (frontiersin.org)
  • The concept of disease tolerance was introduced in 1894 by Nathan Augustus Cobb, an American plant pathologist. (frontiersin.org)
  • Following Cobb's seminal observations, plant biologists rebranded the concept of endurance to disease tolerance ( 7 ). (frontiersin.org)
  • In the same year, Ayres and Schneider demonstrated that simple organisms such as the fruit fly Drosophila melanogaster can also use disease tolerance as a host defense mechanism in the context of gram-positive and gram-negative bacterial infections ( 10 , 11 ). (frontiersin.org)
  • Collectively, these studies have provided the impetus for investigating disease tolerance as an alternative and/or complementary form of host defense not only in the context of infection but also in settings of non-communicable diseases such as autoimmunity, asthma, and atherosclerosis. (frontiersin.org)
  • Budischak and Cressler provide an ecological perspective on how environmental resources contribute to disease tolerance across the evolutionary spectrum. (frontiersin.org)
  • These methods can be categorized into neuraxial local analgesics and opioids, peripheral nerve blocks, and wound infiltration. (medscape.com)
  • Tolerance is generally accepted to be an active process and, in essence, a learning experience for T cells. (medscape.com)
  • Among those, only fibroblastic reticular cells and lymphatic endothelial cells (LECs) were shown to play a role in peripheral tolerance. (wikipedia.org)
  • Normal cells do not express Neoantigens and therefore, neoantigen-specific immune reactions are not subjected to central and peripheral tolerance. (patent-art.com)
  • 1998). Genetic dissection of SLE pathogenesis: Sle1 on murine chromosome 1 leads to selective loss of tolerance to chromatin components. (uh.edu)
  • however, the effect of central and peripheral factors on exercise tolerance remains unclear. (bvsalud.org)
  • Dependence of a particular antigen on either central or peripheral tolerance is determined by its abundance in the organism. (wikipedia.org)
  • B cell peripheral tolerance is much less studied and is largely mediated by B cell dependence on T cell help. (wikipedia.org)
  • Anand KJS, Ingraham J. Tolerance, Dependence, and Strategies for Compassionate Withdrawal of Analgesics and Anxiolytics in the Pediatric ICU. (benzo.org.uk)
  • Current protocols inducing microchimerism to generate tolerance to solid organ grafts suggest that this could be a feasible therapeutic goal. (transhumanist.ru)
  • In particular we are interested in the central interaction of the adiposity hormones leptin and insulin, which appears crucial for the maintenance of energy and glucose homeostasis. (otago.ac.nz)
  • A patient may have central adiposity in spite of a normal BMI. (medscape.com)
  • Aging also impairs oral tolerance, which may be of central importance for maintaining GI homeostasis. (nih.gov)
  • Transplant tolerance is defined as a state of donor-specific unresponsiveness without a need for ongoing pharmacologic immunosuppression. (medscape.com)
  • Alcohol Use Disorder and Rehabilitation Alcohol use disorder involves a pattern of alcohol use that typically includes craving and manifestations of tolerance and/or withdrawal along with adverse psychosocial consequences. (msdmanuals.com)
  • Mitochondria is the central site of cellular energy production and plays an important role in cell survival and death. (biomed.news)
  • Neurologists can play an important role in addressing the alarming increase in diabetic peripheral neuropathy (DPN), a troubling result of the obesity and type 2 diabetes pandemics. (medscape.com)
  • Symptoms can include peripheral neuropathy, a pellagra-like. (msdmanuals.com)
  • We established that a loss of central leptin action during obesity leads to impaired insulin action, which might explain the striking correlation of obesity and type 2 diabetes. (otago.ac.nz)
  • We show that the maintenance of both tolerance and "resistance" requires a continuous supply of antigen. (ox.ac.uk)
  • Finally, we wished to establish whether "resistance" was peculiar to this form of peripheral tolerance, or whether it might also be present in tolerance considered to be classically central. (ox.ac.uk)