1E87 , 1E8I , 1FM5 , 3CCK , 3HUP
50-444: 969 12515 ENSG00000110848 ENSMUSG00000030156 Q07108 P37217 NM_001781 NM_001033122 NP_001772 NP_001028294 CD69 ( C luster of D ifferentiation 69) is a human transmembrane C-Type lectin protein encoded by the CD69 gene . It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in
100-422: A Wright's stained peripheral blood smear , a normal lymphocyte has a large, dark-staining nucleus with little to no eosinophilic cytoplasm. In normal situations, the coarse, dense nucleus of a lymphocyte is approximately the size of a red blood cell (about 7 μm in diameter). Some lymphocytes show a clear perinuclear zone (or halo) around the nucleus or could exhibit a small clear zone to one side of
150-562: A slow cooker , will not remove all the lectins. Some studies have found that lectins may interfere with absorption of some minerals, such as calcium , iron , phosphorus , and zinc . The binding of lectins to cells in the digestive tract may disrupt the breakdown and absorption of some nutrients, and as they bind to cells for long periods of time, some theories hold that they may play a role in certain inflammatory conditions such as rheumatoid arthritis and type 1 diabetes , but research supporting claims of long-term health effects in humans
200-533: A T cell is activated in a lymphoid organ through cytokine and TCR signaling, CD69 is expressed and forms a complex with S1PR1 (not S1PR3 or S1PR5). This association is dependent on the interaction between the CD69 transmembrane domain and helix-4 of S1PR1. Following formation of this complex, S1PR1 is internalized and is destroyed within the cell, inhibiting its ability to bind S1P and initiate downstream signaling. This in turn results in temporary lymphocyte retention in
250-843: A decrease in the entry of lymphocytes into lymph nodes, which can lead to a condition known as lymphocytosis, with a complete lymphocyte count of over 4000 per μl in adults or over 8000 per μl in children. This is unique in that many bacterial infections illustrate neutrophil-predominance instead. Lymphoproliferative disorders (LPD) encompass a diverse group of diseases marked by uncontrolled lymphocyte production, leading to issues like lymphocytosis, lymphadenopathy, and bone marrow infiltration. These disorders are common in immunocompromised individuals and involve abnormal proliferation of T and B cells, often resulting in immunodeficiency and immune system dysfunction. Various gene mutations, both iatrogenic and acquired, are implicated in LPD. One subtype, X-linked LPD,
300-482: A deeper understanding of their numerous biological functions, the plant lectins, also known as phytohemagglutinins , were noted for their particularly high specificity for foreign glycoconjugates (e.g., those of fungi and animals) and used in biomedicine for blood cell testing and in biochemistry for fractionation . Although they were first discovered more than 100 years ago in plants, now lectins are known to be present throughout nature. The earliest description of
350-914: A function. Several plant lectins have been found to recognize noncarbohydrate ligands that are primarily hydrophobic in nature, including adenine , auxins , cytokinin , and indole acetic acid , as well as water-soluble porphyrins . These interactions may be physiologically relevant, since some of these molecules function as phytohormones . Lectin receptor kinases (LecRKs) are believed to recognize damage associated molecular patterns (DAMPs), which are created or released from herbivore attack. In Arabidopsis , legume-type LecRKs Clade 1 has 11 LecRK proteins. LecRK-1.8 has been reported to recognize extracellular NAD molecules and LecRK-1.9 has been reported to recognize extracellular ATP molecules. Extraction of proteins and lectins can be extracted via similar processes, also with their analysis, and discovery. For example cottonseed contains compounds of interest within
400-417: A hierarchical fashion as well as in a more plastic fashion. The formation of lymphocytes is known as lymphopoiesis . In mammals , B cells mature in the bone marrow , which is at the core of most bones . In birds , B cells mature in the bursa of Fabricius , a lymphoid organ where they were first discovered by Chang and Glick, (B for bursa) and not from bone marrow as commonly believed. T cells migrate to
450-585: A lectin is believed to have been given by Peter Hermann Stillmark in his doctoral thesis presented in 1888 to the University of Dorpat . Stillmark isolated ricin, an extremely toxic hemagglutinin, from seeds of the castor plant ( Ricinus communis ). The first lectin to be purified on a large scale and available on a commercial basis was concanavalin A , which is now the most-used lectin for characterization and purification of sugar-containing molecules and cellular structures. The legume lectins are probably
500-453: A lectin-free diet in his book The Plant Paradox (2017). It excludes a large range of commonplace foods including whole grains , legumes, and most fruit, as well as the nightshade vegetables : tomatoes, potatoes, eggplant, bell peppers, and chili peppers. Gundry's claims about lectins are considered pseudoscience . His book cites studies that have nothing to do with lectins, and some that show—contrary to his own recommendations—that avoiding
550-488: A major family of protein antinutrients , which are specific sugar-binding proteins exhibiting reversible carbohydrate-binding activities. Lectins are similar to antibodies in their ability to agglutinate red blood cells. Many legume seeds have been proven to contain high lectin activity, termed hemagglutination . Soybean is the most important grain legume crop in this category. Its seeds contain high activity of soybean lectins ( soybean agglutinin or SBA). Long before
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#1732772934163600-443: A manner similar to Treg differentiation. Most lymphocytes express sphingosine-1-phosphate receptors (S1P1-5), which are G protein-coupled receptors located in the cell membrane that bind to the ligand sphingosine-1-phosphate (S1P) . S1P is a sphingolipid metabolite that is abundant in the bloodstream and, upon binding to S1PR1 , promotes lymphocyte egress from lymphoid organs so they can travel to affected tissues. However, when
650-741: A role in recognition at the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins. Lectins also mediate attachment and binding of bacteria , viruses , and fungi to their intended targets. Lectins are found in many foods. Some foods, such as beans and grains, need to be cooked, fermented or sprouted to reduce lectin content. Some lectins are beneficial, such as CLEC11A , which promotes bone growth, while others may be powerful toxins such as ricin . Lectins may be disabled by specific mono- and oligosaccharides , which bind to ingested lectins from grains, legumes, nightshade plants, and dairy; binding can prevent their attachment to
700-577: A signal-transmitting receptor in lymphocytes, including natural killer (NK) cells, and platelets (Cambiaggi et al., 1992) [supplied by OMIM]. The gene encoding CD69 is located in the NK gene complex on chromosome 6 and chromosome 12 in mice and humans respectively. Activation signaling pathways in lymphocytes, NK cells, dendritic cells and other cell types upregulate transcription factors, such as NF-κB , ERG-1 (erythroblast transformation-specific related gene-1), and AP-1 (activator protein), in order to promote
750-433: A strong and rapid response if the same pathogen is detected again; this is known as acquired immunity . NK cells are a part of the innate immune system and play a major role in defending the host from tumors and virally infected cells. NK cells modulate the functions of other cells, including macrophages and T cells, and distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of
800-421: A surface molecule called major histocompatibility complex (MHC) class I . NK cells are activated in response to a family of cytokines called interferons . Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered cells. They are named "natural killer cells" because they do not require prior activation in order to kill cells which are missing MHC class I. The X lymphocyte
850-463: A wide array of disorders involving B-cell (e.g., chronic lymphocytic leukemia) and T-cell (e.g., Sezary syndrome) abnormalities, each presenting distinct challenges in diagnosis and management. A low normal to low absolute lymphocyte concentration is associated with increased rates of infection after surgery or trauma . One basis for low T cell lymphocytes occurs when the human immunodeficiency virus (HIV) infects and destroys T cells (specifically,
900-403: Is a reported cell type expressing both a B-cell receptor and T-cell receptor and is hypothesized to be implicated in type 1 diabetes. Its existence as a cell type has been challenged by two studies. However, the authors of original article pointed to the fact that the two studies have detected X cells by imaging microscopy and FACS as described. Additional studies are required to determine
950-659: Is in greater abundance, it results in the removal of S1PR1 from the membrane as mentioned above. However, if S1PR1 is more abundant than CD69, as would be the case in mature T cells, CD69 membrane localization is reduced. In this manner, regulation of CD69 and S1PR1 expression and localization jointly impact lymphocyte egress and migration. Lectin Lectins are carbohydrate -binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides . Lectins have
1000-698: Is limited and most existing studies have focused on developing countries where malnutrition may be a factor, or dietary choices are otherwise limited. The first writer to advocate a lectin-free diet was Peter J. D'Adamo, a naturopathic physician best known for promoting the Blood type diet . He argued that lectins may damage a person's blood type by interfering with digestion, food metabolism, hormones, insulin production—and so should be avoided. D'Adamo provided no scientific evidence nor published data for his claims, and his diet has been criticized for making inaccurate statements about biochemistry. Steven Gundry proposed
1050-405: Is linked to mutations in the X chromosome, predisposing individuals to natural killer cell LPD and T-cell LPD. Additionally, conditions like common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), and certain viral infections elevate the risk of LPD. Treatment methods, such as immunosuppressive drugs and tissue transplantation, can also increase susceptibility. LPDs encompass
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#17327729341631100-402: Is still uncertain. Once thought to be necessary for rhizobia binding, this proposed function was ruled out through lectin-knockout transgene studies. The large concentration of lectins in plant seeds decreases with growth, and suggests a role in plant germination and perhaps in the seed's survival itself. The binding of glycoproteins on the surface of parasitic cells also is believed to be
1150-585: Is used to trace the path of efferent axons with PHA-L , a lectin from the kidney bean . A lectin ( BanLec ) from bananas inhibits HIV-1 in vitro . Achylectins, isolated from Tachypleus tridentatus , show specific agglutinating activity against human A-type erythrocytes. Anti-B agglutinins such as anti-BCJ and anti-BLD separated from Charybdis japonica and Lymantria dispar , respectively, are of value both in routine blood grouping and research. Lectins from legume plants, such as PHA or concanavalin A , have been used widely as model systems to understand
1200-568: The CD4 subgroup of T lymphocytes, which become helper T cells). Without the key defense that these T cells provide, the body becomes susceptible to opportunistic infections that otherwise would not affect healthy people. The extent of HIV progression is typically determined by measuring the percentage of CD4 T cells in the patient's blood – HIV ultimately progresses to acquired immune deficiency syndrome (AIDS). The effects of other viruses or lymphocyte disorders can also often be estimated by counting
1250-471: The ELISPOT or secretion assay techniques can be used. In the circulatory system , they move from lymph node to lymph node. This contrasts with macrophages , which are rather stationary in the nodes. A lymphocyte count is usually part of a peripheral complete blood cell count and is expressed as the percentage of lymphocytes to the total number of white blood cells counted. A general increase in
1300-467: The Paramyxoviridae family, use this mechanism to bind and gain entry to target cells. Purified lectins are important in a clinical setting because they are used for blood typing . Some of the glycolipids and glycoproteins on an individual's red blood cells can be identified by lectins. Non blood-group antigens can be identified by lectins: In neuroscience, the anterograde labeling method
1350-434: The antigen, either by releasing antibodies (in the case of B cells), cytotoxic granules ( cytotoxic T cells ) or by signaling to other cells of the immune system ( helper T cells ). Memory T cells remain in the peripheral tissues and circulation for an extended time ready to respond to the same antigen upon future exposure; they live weeks to several years, which is very long compared to other leukocytes. Microscopically, in
1400-480: The blood stream and mature in a distinct primary organ, called the thymus . Following maturation, the lymphocytes enter the circulation and peripheral lymphoid organs (e.g. the spleen and lymph nodes ) where they survey for invading pathogens and/or tumor cells. The lymphocytes involved in adaptive immunity (i.e. B and T cells) differentiate further after exposure to an antigen ; they form effector and memory lymphocytes. Effector lymphocytes function to eliminate
1450-463: The carbohydrates within the cell membrane. The selectivity of lectins means that they are useful for analyzing blood type , and they have been researched for potential use in genetically engineered crops to transfer pest resistance. branched α-mannosidic structures (high α-mannose type, or hybrid type and biantennary complex type N-Glycans) R2-GlcNAcβ1-4(Fucα1-6)GlcNAc-R1 William C. Boyd alone and then together with Elizabeth Shapleigh introduced
1500-458: The cell interior. CD69 lacks the characteristic Ca binding residues in CTLDs, indicating that it might bind to proteins rather than carbohydrates, the usual ligand of CTLDs. It has been shown that CD69 binds to Gal-1 , a carbohydrate binding protein located on some dendritic cells and macrophages, in addition to Myl9/12 . Other ligands have yet to be identified. However, it is known that binding of
1550-506: The development of pest. Concanavalin A and other commercially available lectins have been used widely in affinity chromatography for purifying glycoproteins. In general, proteins may be characterized with respect to glycoforms and carbohydrate structure by means of affinity chromatography , blotting , affinity electrophoresis , and affinity immunoelectrophoreis with lectins, as well as in microarrays , as in evanescent -field fluorescence-assisted lectin microarray. One example of
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1600-445: The immune response, while other T cells, called cytotoxic T cells , produce toxic granules that contain powerful enzymes which induce the death of pathogen-infected cells. Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form of memory cells . Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and are able to mount
1650-416: The immune system. It is also implicated in T cell differentiation as well as lymphocyte retention in lymphoid organs. The activation of T lymphocytes and Natural Killer (NK) cells, both in vivo and in vitro, induces expression of CD69. This molecule, which appears to be the earliest inducible cell surface glycoprotein acquired during lymphoid activation, is involved in lymphocyte proliferation and functions as
1700-589: The ligands initiates the Jak/Stat signaling pathway as well as the mTOR / HIF1-α pathway. CD69 is also known to interact with and mediate S1P and LAT1 receptors, which influence lymphocyte egress in lymphoid organs among other responses. More work must be done to fully characterize CD69-ligand interactions as well as CD69's method of transducing intracellular signals. CD69 expression has been associated with both regulatory T cell (Treg), memory T cell and Bcl6 CD69 LZ GC B plasmablast precursors. Treg precursors exit
1750-424: The lymph organs. It is thought that retention of lymphocytes in the lymph nodes may increase the chance of successful lymphocyte activation, especially if the initial activation signal was weak. Similarly, CD69 expressed in thymocytes following positive selection may ensure that T cells fully mature in the thymus prior to entering circulation. Some research has shown that S1PR1 and CD69 co-regulate so that when CD69
1800-532: The main type of cell found in lymph , which prompted the name "lymphocyte" (with cyte meaning cell). Lymphocytes make up between 18% and 42% of circulating white blood cells. The three major types of lymphocyte are T cells , B cells and natural killer (NK) cells. They can also be classified as small lymphocytes and large lymphocytes based on their size and appearance. Lymphocytes can be identified by their large nucleus. T cells ( thymus cells) and B cells ( bone marrow - or bursa -derived cells ) are
1850-745: The major cellular components of the adaptive immune response. T cells are involved in cell-mediated immunity , whereas B cells are primarily responsible for humoral immunity (relating to antibodies ). The function of T cells and B cells is to recognize specific "non-self" antigens, during a process known as antigen presentation . Once they have identified an invader, the cells generate specific responses that are tailored maximally to eliminate specific pathogens or pathogen-infected cells. B cells respond to pathogens by producing large quantities of antibodies which then neutralize foreign objects like bacteria and viruses . In response to pathogens some T cells, called T helper cells , produce cytokines that direct
1900-401: The molecular basis of how proteins recognize carbohydrates, because they are relatively easy to obtain and have a wide variety of sugar specificities. The many crystal structures of legume lectins have led to a detailed insight of the atomic interactions between carbohydrates and proteins. Legume seed lectins have been studied for their insecticidal potential and have shown harmful effects for
1950-558: The most well-studied lectins. Lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates . Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity ), B cells (for humoral , antibody -driven adaptive immunity ), and innate lymphoid cells (ILCs; "innate T cell-like" cells involved in mucosal immunity and homeostasis), of which natural killer cells are an important subtype (which functions in cell-mediated , cytotoxic innate immunity ). They are
2000-416: The nature and properties of X cells (also called dual expressers). Mammalian stem cells differentiate into several kinds of blood cell within the bone marrow . This process is called haematopoiesis . All lymphocytes originate, during this process, from a common lymphoid progenitor before differentiating into their distinct lymphocyte types. The differentiation of lymphocytes follows various pathways in
2050-478: The nucleus. Polyribosomes are a prominent feature in the lymphocytes and can be viewed with an electron microscope . The ribosomes are involved in protein synthesis , allowing the generation of large quantities of cytokines and immunoglobulins by these cells. It is impossible to distinguish between T cells and B cells in a peripheral blood smear. Normally, flow cytometry testing is used for specific lymphocyte population counts. This can be used to determine
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2100-505: The number of lymphocytes is known as lymphocytosis , whereas a decrease is known as lymphocytopenia . An increase in lymphocyte concentration is usually a sign of a viral infection (in some rare case, leukemias are found through an abnormally raised lymphocyte count in an otherwise normal person). A high lymphocyte count with a low neutrophil count might be caused by lymphoma . Pertussis toxin (PTx) of Bordetella pertussis , formerly known as lymphocytosis-promoting factor, causes
2150-423: The onset of an immune response. A prolonged immune response is then maintained by the non-canonical NF-κB pathway, which in turn is associated with Treg differentiation. In addition to Treg differentiation, CD69 is a common marker of precursor and mature resident memory T cells (TRMs) that are localized in peripheral tissues. TGF-β is also responsible for the development of TRMs, thus promoting TRM differentiation in
2200-402: The percentage of lymphocytes that contain a particular combination of specific cell surface proteins, such as immunoglobulins or cluster of differentiation (CD) markers or that produce particular proteins (for example, cytokines using intracellular cytokine staining (ICCS)). In order to study the function of a lymphocyte by virtue of the proteins it generates, other scientific techniques like
2250-558: The powerful biological attributes of lectins is the biochemical warfare agent ricin. The protein ricin is isolated from seeds of the castor oil plant and comprises two protein domains . Abrin from the jequirity pea is similar: Lectins are widespread in nature, and many foods contain the proteins. Some lectins can be harmful if poorly cooked or consumed in great quantities. They are most potent when raw as boiling, stewing or soaking in water for several hours can render most lectins inactive. Cooking raw beans at low heat, though, such as in
2300-557: The studies of extraction and purification of proteins Some hepatitis C viral glycoproteins may attach to C-type lectins on the host cell surface (liver cells) to initiate infection. To avoid clearance from the body by the innate immune system , pathogens (e.g., virus particles and bacteria that infect human cells) often express surface lectins known as adhesins and hemagglutinins that bind to tissue-specific glycans on host cell-surface glycoproteins and glycolipids . Multiple viruses, including influenza and several viruses in
2350-530: The term "lectin" in 1954 from the Latin word lectus , "chosen" (from the verb legere , to choose or pick out). Lectins may bind to a soluble carbohydrate or to a carbohydrate moiety that is a part of a glycoprotein or glycolipid . They typically agglutinate certain animal cells and/or precipitate glycoconjugates . Most lectins do not possess enzymatic activity. Lectins have these functions in animals: The function of lectins in plants ( legume lectin )
2400-471: The thymus expressing CD69 and complete differentiation into Treg cells in peripheral tissues when they encounter antigens and other cytokines, like IL-2 . Through the JAK/STAT signaling pathway, CD69 activation also induces the production of TGF-β as well as IL-2, which contribute to the differentiation of Treg cells as mentioned above. Furthermore, CD69 is also known to be upregulated by NF-κB signaling at
2450-429: The transcription of the CD69 gene. The CD69 protein is subject to post-translational modifications. Namely, it is differentially glycosylated to produce either a 28 kDa peptide or a 32 kDa peptide. Two of these peptides randomly combine to form a homodimer linked by a disulfide bond. These subunits have a C-type lectin domain (CTLD) that binds ligands, a transmembrane domain, and a cytoplasmic tail that relays signals to
2500-511: The whole grains wheat , barley , and rye will allow increase of harmful bacteria while diminishing helpful bacteria. Lectins are one of many toxic constituents of many raw plants that are inactivated by proper processing and preparation (e.g., cooking with heat, fermentation). For example, raw kidney beans naturally contain toxic levels of lectin (e.g. phytohaemagglutinin ). Adverse effects may include nutritional deficiencies , and immune ( allergic ) reactions. Lectins are considered
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