Gamma globulins are a class of globulins, identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins, although some immunoglobulins are not gamma globulins, some gamma globulins are not immunoglobulins. Gamma globulin injections are given in an attempt to temporarily boost a patient's immunity against disease. Being a product derived from bone marrow and lymph gland cells, gamma globulin injections, along with blood transfusions and intravenous drug use, can pass along hepatitis C to their recipients. Once hepatitis C was identified in 1989, blood banks began screening all blood donors for the presence of the virus in their bloodstream. However, since hepatitis C is known to have been present since at least the 1940s, a gamma globulin shot received prior to the early 1990s put the recipient at risk of being infected. Injections are most used on patients having been exposed to hepatitis A or measles, or to make a kidney donor and a recipient compatible regardless of blood type or tissue match.
Injections are used to boost immunity in patients unable to produce gamma globulins because of an immune deficiency, such as X-linked agammaglobulinemia and hyper IgM syndrome. Such injections are less common in modern medical practice than they were and injections of gamma globulin recommended for travelers have been replaced by the use of hepatitis A vaccine. Gamma globulin infusions are used to treat some immunological diseases, such as idiopathic thrombocytopenia purpura, a disease in which the platelets are being attacked by antibodies, leading to low platelet counts, it appears that gamma globulin causes the spleen to ignore the antibody-tagged platelets, thus allowing them to survive and function. A recent clinical trial of gamma globulin in chronic fatigue syndrome patients had no recognizable benefit, while an older trial showed improvement; the success of this treatment remains uncertain. Another theory on how gamma globulin administration works in autoimmune disease is by overloading the mechanisms that degrade gamma globulins.
Overloading the degradation mechanism causes the harmful gamma globulins to have a much shorter halflife in sera. Intravenous immunoglobulin may be used in Kawasaki disease. Intravenous gamma globulin was FDA-approved in 2004 to reduce antibodies in a patient with kidney failure to allow that person to accept a kidney from a donor with a different blood type, or, an unacceptable tissue match. Stanley Jordan at Cedars-Sinai Medical Center in Los Angeles pioneered this treatment. An excess is known as hypergammaglobulinemia. A deficiency is known as hypogammaglobulinemia. A disease of gamma globulins is called a "gammopathy". Gamma-Globulins at the US National Library of Medicine Medical Subject Headings
Blood is a body fluid in humans and other animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells. In vertebrates, it is composed of blood cells suspended in blood plasma. Plasma, which constitutes 55% of blood fluid, is water, contains proteins, mineral ions, carbon dioxide, blood cells themselves. Albumin is the main protein in plasma, it functions to regulate the colloidal osmotic pressure of blood; the blood cells are red blood cells, white blood cells and platelets. The most abundant cells in vertebrate blood are red blood cells; these contain hemoglobin, an iron-containing protein, which facilitates oxygen transport by reversibly binding to this respiratory gas and increasing its solubility in blood. In contrast, carbon dioxide is transported extracellularly as bicarbonate ion transported in plasma. Vertebrate blood is bright red when its hemoglobin is oxygenated and dark red when it is deoxygenated.
Some animals, such as crustaceans and mollusks, use hemocyanin to carry oxygen, instead of hemoglobin. Insects and some mollusks use a fluid called hemolymph instead of blood, the difference being that hemolymph is not contained in a closed circulatory system. In most insects, this "blood" does not contain oxygen-carrying molecules such as hemoglobin because their bodies are small enough for their tracheal system to suffice for supplying oxygen. Jawed vertebrates have an adaptive immune system, based on white blood cells. White blood cells help to resist parasites. Platelets are important in the clotting of blood. Arthropods, using hemolymph, have hemocytes as part of their immune system. Blood is circulated around the body through blood vessels by the pumping action of the heart. In animals with lungs, arterial blood carries oxygen from inhaled air to the tissues of the body, venous blood carries carbon dioxide, a waste product of metabolism produced by cells, from the tissues to the lungs to be exhaled.
Medical terms related to blood begin with hemo- or hemato- from the Greek word αἷμα for "blood". In terms of anatomy and histology, blood is considered a specialized form of connective tissue, given its origin in the bones and the presence of potential molecular fibers in the form of fibrinogen. Blood performs many important functions within the body, including: Supply of oxygen to tissues Supply of nutrients such as glucose, amino acids, fatty acids Removal of waste such as carbon dioxide and lactic acid Immunological functions, including circulation of white blood cells, detection of foreign material by antibodies Coagulation, the response to a broken blood vessel, the conversion of blood from a liquid to a semisolid gel to stop bleeding Messenger functions, including the transport of hormones and the signaling of tissue damage Regulation of core body temperature Hydraulic functions Blood accounts for 7% of the human body weight, with an average density around 1060 kg/m3 close to pure water's density of 1000 kg/m3.
The average adult has a blood volume of 5 litres, composed of plasma and several kinds of cells. These blood cells consist of erythrocytes and thrombocytes. By volume, the red blood cells constitute about 45% of whole blood, the plasma about 54.3%, white cells about 0.7%. Whole blood exhibits non-Newtonian fluid dynamics. If all human hemoglobin were free in the plasma rather than being contained in RBCs, the circulatory fluid would be too viscous for the cardiovascular system to function effectively. One microliter of blood contains: 4.7 to 6.1 million, 4.2 to 5.4 million erythrocytes: Red blood cells contain the blood's hemoglobin and distribute oxygen. Mature red blood cells lack a nucleus and organelles in mammals; the red blood cells are marked by glycoproteins that define the different blood types. The proportion of blood occupied by red blood cells is referred to as the hematocrit, is about 45%; the combined surface area of all red blood cells of the human body would be 2,000 times as great as the body's exterior surface.
4,000–11,000 leukocytes: White blood cells are part of the body's immune system. The cancer of leukocytes is called leukemia. 200,000 -- 500,000 thrombocytes: Also called platelets. Fibrin from the coagulation cascade creates a mesh over the platelet plug. About 55% of blood is blood plasma, a fluid, the blood's liquid medium, which by itself is straw-yellow in color; the blood plasma volume totals of 2.7–3.0 liters in an average human. It is an aqueous solution containing 92% water, 8% blood plasma proteins, trace amounts of other materials. Plasma circulates dissolved nutrients, such as glucose, amino acids, fatty acids, removes waste products, such as carbon dioxide and lactic acid. Other important components include: Serum albumin Blood-clotting factors Immunoglobulins lipoprotein particles Various
Alpha-1-antitrypsin or α1-antitrypsin is a protein belonging to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. A protease inhibitor, it is known as alpha1–proteinase inhibitor or alpha1-antiproteinase because it inhibits various proteases. In older biomedical literature it was sometimes called serum trypsin inhibitor, because its capability as a trypsin inhibitor was a salient feature of its early study; as a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells neutrophil elastase, has a reference range in blood of 0.9–2.3 g/L, but the concentration can rise manyfold upon acute inflammation. When the blood contains inadequate amounts of A1AT or functionally defective A1AT, neutrophil elastase is excessively free to break down elastin, degrading the elasticity of the lungs, which results in respiratory complications, such as chronic obstructive pulmonary disease, in adults. A1AT leaves its site of origin, the liver, joins the systemic circulation.
A1PI is an exogenous one used as medication. The pharmaceutical form is purified from human donor blood and is sold under the nonproprietary name alpha1–proteinase inhibitor and under various trade names. Recombinant versions are available but are used in medical research more than as medication. A1AT is a 52-kDa serpin and, in medicine, it is considered the most prominent serpin. Most serpins inactivate enzymes by binding to them covalently, requiring high levels to perform their function. In the acute phase reaction, a further elevation is required to "limit" the damage caused by activated neutrophil granulocytes and their enzyme elastase, which breaks down the connective tissue fiber elastin. Like all serine protease inhibitors, A1AT has a characteristic secondary structure of beta sheets and alpha helices. Mutations in these areas can lead to non-functional proteins that can polymerise and accumulate in the liver. Disorders of this protein include alpha-1 antitrypsin deficiency, an autosomal codominant hereditary disorder in which a deficiency of alpha-1 antitrypsin leads to a chronic uninhibited tissue breakdown.
This causes the degradation of lung tissue and leads to characteristic manifestations of pulmonary emphysema. Evidence has shown that cigarette smoke can result in oxidation of methionine 358 of α1-antitrypsin, a residue essential for binding elastase; because A1AT is expressed in the liver, certain mutations in the gene encoding the protein can cause misfolding and impaired secretion, which can lead to liver cirrhosis. An rare form of Pi, termed PiPittsburgh, functions as an antithrombin, due to a mutation. One person with this mutation has been reported to have died of a bleeding diathesis. A liver biopsy will show abundant PAS-positive globules within periportal hepatocytes. Patients with rheumatoid arthritis have been found to make autoantibodies toward the carbamylated form of A1AT in the synovial fluid; this suggests that A1AT may play an tissue-protecting role outside the lungs. These antibodies are associated with a more severe disease course, can be observed years before disease onset, may predict the development of RA in arthralgia patients.
Carbamylated A1AT is being developed as an antigenic biomarker for RA. The protein was named "antitrypsin" because of its ability to bind and irreversibly inactivate the enzyme trypsin in vitro covalently. Trypsin, a type of peptidase, is a digestive enzyme active in elsewhere; the term alpha-1 refers to the protein's behavior on protein electrophoresis. On electrophoresis, the protein component of the blood is separated by electric current. There are several clusters, the first being albumin, the second being the alpha, the third beta and the fourth gamma; the non-albumin proteins are referred to as globulins. The alpha region can be further divided into two sub-regions, termed "1" and "2". Alpha-1 antitrypsin is the main protein of the alpha-globulin 1 region. Another name used is alpha-1 proteinase inhibitor; the gene is located on the long arm of the fourteenth chromosome. Over 100 different variants of α1-antitrypsin have been described in various populations. North-Western Europeans are most at risk for carrying one of the most common mutant forms of A1AT, the Z mutation.
A1AT is a single-chain glycoprotein consisting of 394 amino acids in the mature form and exhibits many glycoforms. The three N-linked glycosylations sites are equipped with so-called diantennary N-glycans. However, one particular site shows a considerable amount of heterogeneity since tri- and tetraantennary N-glycans can be attached to the Asparagine 107; these glycans carry different amounts of negatively charged sialic acids. The fucosylated triantennary N-glycans were shown to have the fucose as part of a so-called Sialyl
An antibody known as an immunoglobulin, is a large, Y-shaped protein produced by plasma cells, used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen, via the fragment antigen-binding variable region; each tip of the "Y" of an antibody contains a paratope, specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly. Depending on the antigen, the binding may impede the biological process causing the disease or may activate macrophages to destroy the foreign substance; the ability of an antibody to communicate with the other components of the immune system is mediated via its Fc region, which contains a conserved glycosylation site involved in these interactions. The production of antibodies is the main function of the humoral immune system.
Antibodies are secreted by B cells of the adaptive immune system by differentiated B cells called plasma cells. Antibodies can occur in two physical forms, a soluble form, secreted from the cell to be free in the blood plasma, a membrane-bound form, attached to the surface of a B cell and is referred to as the B-cell receptor; the BCR is found only on the surface of B cells and facilitates the activation of these cells and their subsequent differentiation into either antibody factories called plasma cells or memory B cells that will survive in the body and remember that same antigen so the B cells can respond faster upon future exposure. In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, antibody generation following antigen binding. Soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms. Antibodies are glycoproteins belonging to the immunoglobulin superfamily.
They constitute most of the gamma globulin fraction of the blood proteins. They are made of basic structural units—each with two large heavy chains and two small light chains. There are several different types of antibody heavy chains that define the five different types of crystallisable fragments that may be attached to the antigen-binding fragments; the five different types of Fc regions allow antibodies to be grouped into five isotypes. Each Fc region of a particular antibody isotype is able to bind to its specific Fc Receptor, thus allowing the antigen-antibody complex to mediate different roles depending on which FcR it binds; the ability of an antibody to bind to its corresponding FcR is further modulated by the structure of the glycan present at conserved sites within its Fc region. The ability of antibodies to bind to FcRs helps to direct the appropriate immune response for each different type of foreign object they encounter. For example, IgE is responsible for an allergic response consisting of mast cell degranulation and histamine release.
IgE's Fab paratope binds to allergic antigen, for example house dust mite particles, while its Fc region binds to Fc receptor ε. The allergen-IgE-FcRε interaction mediates allergic signal transduction to induce conditions such as asthma. Though the general structure of all antibodies is similar, a small region at the tip of the protein is variable, allowing millions of antibodies with different tip structures, or antigen-binding sites, to exist; this region is known as the hypervariable region. Each of these variants can bind to a different antigen; this enormous diversity of antibody paratopes on the antigen-binding fragments allows the immune system to recognize an wide variety of antigens. The large and diverse population of antibody paratope is generated by random recombination events of a set of gene segments that encode different antigen-binding sites, followed by random mutations in this area of the antibody gene, which create further diversity; this recombinational process that produces clonal antibody paratope diversity is called VJ or VJ recombination.
The antibody paratope is polygenic, made up of three genes, V, D, J. Each paratope locus is polymorphic, such that during antibody production, one allele of V, one of D, one of J is chosen; these gene segments are joined together using random genetic recombination to produce the paratope. The regions where the genes are randomly recombined together is the hyper variable region used to recognise different antigens on a clonal basis. Antibody genes re-organize in a process called class switching that changes the one type of heavy chain Fc fragment to another, creating a different isotype of the antibody that retains the antigen-specific variable region; this allows a single antibody to be used by different types of Fc receptors, expressed on different parts of the immune system. The first use of the term "antibody" occurred in a text by Paul Ehrlich; the term Antikörper appears in the conclusion of his article "Experimental Studies on Immunity", published in October 1891, which states that, "if two substances give rise to two different Antikörper they themselves must be different".
However, the term was not accepted and several other terms for antibody were proposed.
A polymer is a large molecule, or macromolecule, composed of many repeated subunits. Due to their broad range of properties, both synthetic and natural polymers play essential and ubiquitous roles in everyday life. Polymers range from familiar synthetic plastics such as polystyrene to natural biopolymers such as DNA and proteins that are fundamental to biological structure and function. Polymers, both natural and synthetic, are created via polymerization of many small molecules, known as monomers, their large molecular mass relative to small molecule compounds produces unique physical properties, including toughness, a tendency to form glasses and semicrystalline structures rather than crystals. The terms polymer and resin are synonymous with plastic; the term "polymer" derives from the Greek word πολύς and μέρος, refers to a molecule whose structure is composed of multiple repeating units, from which originates a characteristic of high relative molecular mass and attendant properties. The units composing polymers derive or conceptually, from molecules of low relative molecular mass.
The term was coined in 1833 by Jöns Jacob Berzelius, though with a definition distinct from the modern IUPAC definition. The modern concept of polymers as covalently bonded macromolecular structures was proposed in 1920 by Hermann Staudinger, who spent the next decade finding experimental evidence for this hypothesis. Polymers are studied in the fields of biophysics and macromolecular science, polymer science. Products arising from the linkage of repeating units by covalent chemical bonds have been the primary focus of polymer science. Polyisoprene of latex rubber is an example of a natural/biological polymer, the polystyrene of styrofoam is an example of a synthetic polymer. In biological contexts all biological macromolecules—i.e. Proteins, nucleic acids, polysaccharides—are purely polymeric, or are composed in large part of polymeric components—e.g. Isoprenylated/lipid-modified glycoproteins, where small lipidic molecules and oligosaccharide modifications occur on the polyamide backbone of the protein.
The simplest theoretical models for polymers are ideal chains. Polymers are of two types: occurring and synthetic or man made. Natural polymeric materials such as hemp, amber, wool and natural rubber have been used for centuries. A variety of other natural polymers exist, such as cellulose, the main constituent of wood and paper; the list of synthetic polymers in order of worldwide demand, includes polyethylene, polystyrene, polyvinyl chloride, synthetic rubber, phenol formaldehyde resin, nylon, polyacrylonitrile, PVB, many more. More than 330 million tons of these polymers are made every year. Most the continuously linked backbone of a polymer used for the preparation of plastics consists of carbon atoms. A simple example is polyethylene. Many other structures do exist. Oxygen is commonly present in polymer backbones, such as those of polyethylene glycol, DNA. Polymerization is the process of combining many small molecules known as monomers into a covalently bonded chain or network. During the polymerization process, some chemical groups may be lost from each monomer.
This happens in the polymerization of PET polyester. The monomers are terephthalic acid and ethylene glycol but the repeating unit is —OC—C6H4—COO—CH2—CH2—O—, which corresponds to the combination of the two monomers with the loss of two water molecules; the distinct piece of each monomer, incorporated into the polymer is known as a repeat unit or monomer residue. Laboratory synthetic methods are divided into two categories, step-growth polymerization and chain-growth polymerization; the essential difference between the two is that in chain growth polymerization, monomers are added to the chain one at a time only, such as in polyethylene, whereas in step-growth polymerization chains of monomers may combine with one another directly, such as in polyester. Newer methods, such as plasma polymerization do not fit neatly into either category. Synthetic polymerization reactions may be carried out without a catalyst. Laboratory synthesis of biopolymers of proteins, is an area of intensive research. There are three main classes of biopolymers: polysaccharides and polynucleotides.
In living cells, they may be synthesized by enzyme-mediated processes, such as the formation of DNA catalyzed by DNA polymerase. The synthesis of proteins involves multiple enzyme-mediated processes to transcribe genetic information from the DNA to RNA and subsequently translate that information to synthesize the specified protein from amino acids; the protein may be modified further following translation in order to provide appropriate structure and functioning. There are other biopolymers such as rubber, suberin and lignin. Occurring polymers such as cotton and rubber were familiar materials for years before synthetic polymers such as polyethene and perspex appeared on the market. Many commercially important polymers are synthesized by chemical modification of occurring polymers. Prominent examples inclu
The albumins are a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, experience heat denaturation. Albumins are found in blood plasma and differ from other blood proteins in that they are not glycosylated. Substances containing albumins, such as egg white, are called albuminoids. A number of blood transport proteins are evolutionarily related, including serum albumin, alpha-fetoprotein, vitamin D-binding protein and afamin. Albumin binds to the cell surface receptor albondin. Serum albumin is the main protein of human blood plasma, it binds water, fatty acids, bilirubin and pharmaceuticals: its main function is to regulate the oncotic pressure of blood. Alpha-fetoprotein is a fetal plasma protein that binds fatty acids and bilirubin. Vitamin D-binding protein binds to its metabolites, as well as to fatty acids; the isoelectric point of albumin is 4.9. The 3D structure of human serum albumin has been determined by X-ray crystallography to a resolution of 2.5 ångströms.
Albumin is a 65–70 kDa protein. Albumin comprises three homologous domains; each domain is a product of two subdomains. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. Structurally, the serum albumins are similar, each domain containing five or six internal disulfide bonds, as shown schematically below: Serum albumin is the most abundant blood plasma protein and is produced in the liver and forms a large proportion of all plasma protein; the human version is human serum albumin, it constitutes about 50% of human plasma protein. Serum albumins are important in regulating blood volume by maintaining the oncotic pressure of the blood compartment, they serve as carriers for molecules of low water solubility this way isolating their hydrophobic nature, including lipid-soluble hormones, bile salts, unconjugated bilirubin, free fatty acids, calcium and some drugs like warfarin, clofibrate & phenytoin.
For this reason, it is sometimes referred as a molecular "taxi". Competition between drugs for albumin binding sites may cause drug interaction by increasing the free fraction of one of the drugs, thereby affecting potency. Specific types include: human serum albumin bovine serum albumin or BSA used in medical and molecular biology labs; the normal range of human serum albumin in adults is 3.5 to 5 g/dL. For children less than three years of age, the normal range is broader, 2.9–5.5 g/dL. Low albumin may be caused by liver disease, nephrotic syndrome, protein-losing enteropathy, malnutrition, late pregnancy, genetic variations and malignancy. High albumin is always caused by dehydration. In some cases of retinol deficiency, the albumin level can be elevated to high-normal values; this is. This swelling likely occurs during treatment with 13-cis retinoic acid, a pharmaceutical for treating severe acne, amongst other conditions. In lab experiments it has been shown that all-trans retinoic acid down regulates human albumin production.
Other albumin types include the storage protein ovalbumin in egg white, different storage albumins in the seeds of some plants, including hemp. Note that the protein "albumin" is spelled with an "i", while "albumen" with an "e", is the white of an egg, which contains several dozen types of albumin ovalbumin. For patients with low blood volume, there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as normal saline, or that albumin reduces mortality in patients with burns and low albumin levels. Therefore, the Cochrane Collaboration recommends. In acoustic droplet vaporization, albumin is sometimes used as a surfactant. ADV has been proposed as a cancer treatment by means of occlusion therapy. Human serum albumin may be used to reverse drug/chemical toxicity by binding to free drug/agent. Worldwide, certain traditional Chinese medicines contain wild bear bile, banned under CITES legislation. Dip sticks, similar to common pregnancy tests, have been developed to detect the presence of bear albumin in traditional medicine products, indicating that bear bile had been used in their creation.
Cohn process Serum albumin Bovine serum albumin Human serum albumin Albumins at the US National Library of Medicine Medical Subject Headings The Albumin website Albumin binding prediction
Bence Jones protein
A Bence Jones protein is a monoclonal globulin protein or immunoglobulin light chain found in the urine, with a molecular weight of 22-24 kDa. Detection of Bence Jones protein may be suggestive of multiple myeloma or Waldenström's macroglobulinemia. Bence Jones proteins are diagnostic of multiple myeloma in the context of target organ manifestations such as renal failure, lytic bone lesions, anemia, or large numbers of plasma cells in the bone marrow of patients. Bence Jones proteins are present in 2/3 of multiple myeloma cases; the proteins are produced by neoplastic plasma cells. They can be lambda; the light chains can be single homogeneous immunoglobulins. They are found in urine as a result of decreased kidney filtration capabilities due to renal failure, sometimes induced by hypercalcemia from the calcium released as the bones are destroyed or from the light chains themselves; the light chains have been detected by heating a urine specimen and now by electrophoresis of concentrated urine.
More serum free light chain assays have been utilised in a number of published studies which have indicated superiority over the urine tests for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma and AL amyloidosis. The Bence Jones protein was described by the English physician Henry Bence Jones in 1847 and published in 1848