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106-935: Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells , and transports metabolic waste products away from those same cells. Blood is composed of blood cells suspended in blood plasma . Plasma, which constitutes 55% of blood fluid, is mostly water (92% by volume), and contains proteins , glucose , mineral ions , and hormones . The blood cells are mainly red blood cells (erythrocytes), white blood cells (leukocytes), and (in mammals) platelets (thrombocytes). The most abundant cells are red blood cells. These contain hemoglobin , which facilitates oxygen transport by reversibly binding to it, increasing its solubility. Jawed vertebrates have an adaptive immune system , based largely on white blood cells. White blood cells help to resist infections and parasites. Platelets are important in

212-731: A blood bank . There are many different blood types in humans, the ABO blood group system , and the Rhesus blood group system being the most important. Transfusion of blood of an incompatible blood group may cause severe, often fatal, complications, so crossmatching is done to ensure that a compatible blood product is transfused. Other blood products administered intravenously are platelets, blood plasma, cryoprecipitate, and specific coagulation factor concentrates. Many forms of medication (from antibiotics to chemotherapy ) are administered intravenously, as they are not readily or adequately absorbed by

318-472: A "sandwich" shape, the immunoglobulin fold , held together by a disulfide bond. Secreted antibodies can occur as a single Y-shaped unit, a monomer . However, some antibody classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six units). IgG can also form hexamers, though no J chain

424-523: A B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a " naive B lymphocyte ." The naive B lymphocyte expresses both surface IgM and IgD. The co-expression of both of these immunoglobulin isotypes renders the B cell ready to respond to antigen. B cell activation follows engagement of

530-600: A Y shape. In humans and most other mammals , an antibody unit consists of four polypeptide chains ; two identical heavy chains and two identical light chains connected by disulfide bonds . Each chain is a series of domains : somewhat similar sequences of about 110 amino acids each. These domains are usually represented in simplified schematics as rectangles. Light chains consist of one variable domain V L and one constant domain C L , while heavy chains contain one variable domain V H and three to four constant domains C H 1, C H 2, ... Structurally an antibody

636-574: A blood transfusion, because the metabolism of transfused red blood cells does not restart immediately after a transfusion. In modern evidence-based medicine , bloodletting is used in management of a few rare diseases, including hemochromatosis and polycythemia . However, bloodletting and leeching were common unvalidated interventions used until the 19th century, as many diseases were incorrectly thought to be due to an excess of blood, according to Hippocratic medicine. English blood ( Old English blod ) derives from Germanic and has cognates with

742-441: A distinct epitope of an antigen. Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited by the size of the human genome. Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes. The chromosomal region that encodes an antibody

848-542: A given microbe – that is, the ability of the microbe to enter the body and begin to replicate (not necessarily to cause disease) – depends on sustained production of large quantities of antibodies, meaning that effective vaccines ideally elicit persistent high levels of antibody, which relies on long-lived plasma cells. At the same time, many microbes of medical importance have the ability to mutate to escape antibodies elicited by prior infections, and long-lived plasma cells cannot undergo affinity maturation or class switching. This

954-408: A huge number of antibodies, each with different paratopes , and thus different antigen specificities. The rearrangement of several subgenes (i.e. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells. RAG proteins play an important role with V(D)J recombination in cutting DNA at a particular region. Without

1060-440: A manifestation of immunological memory. In the course of an immune response, B cells can progressively differentiate into antibody-secreting cells or into memory B cells. Antibody-secreting cells comprise plasmablasts and plasma cells , which differ mainly in the degree to which they secrete antibody, their lifespan, metabolic adaptations, and surface markers. Plasmablasts are rapidly proliferating, short-lived cells produced in

1166-400: A mast cell, triggering its degranulation : the release of molecules stored in its granules. Binds to allergens and triggers histamine release from mast cells and basophils , and is involved in allergy . Humans and other animals evolved IgE to protect against parasitic worms , though in the present, IgE is primarily related to allergies and asthma. Although The antibody isotype of

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1272-423: A pH below 7.35 is too acidic , whereas blood pH above 7.45 is too basic. A pH below 6.9 or above 7.8 is usually lethal. Blood pH, partial pressure of oxygen (pO 2 ) , partial pressure of carbon dioxide (pCO 2 ) , and bicarbonate (HCO 3 ) are carefully regulated by a number of homeostatic mechanisms , which exert their influence principally through the respiratory system and the urinary system to control

1378-444: A part of a virus that is essential for its invasion). More narrowly, an antibody ( Ab ) can refer to the free (secreted) form of these proteins, as opposed to the membrane-bound form found in a B cell receptor. The term immunoglobulin can then refer to both forms. Since they are, broadly speaking, the same protein, the terms are often treated as synonymous. To allow the immune system to recognize millions of different antigens,

1484-462: A secondary immune response, undergoing class switching, affinity maturation, and differentiating into antibody-secreting cells. Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. herpes zoster ). Durable protection from infections caused by

1590-548: A similar range of meanings in all other Germanic languages (e.g. German Blut , Swedish blod , Gothic blōþ ). There is no accepted Indo-European etymology. Robin Fåhræus (a Swedish physician who devised the erythrocyte sedimentation rate ) suggested that the Ancient Greek system of humorism , wherein the body was thought to contain four distinct bodily fluids (associated with different temperaments), were based upon

1696-432: A specific antigen is present in the body and triggers B cell activation. The BCR is composed of surface-bound IgD or IgM antibodies and associated Ig-α and Ig-β heterodimers , which are capable of signal transduction . A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface. Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate

1802-429: A strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis . Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival allowing the average affinity of antibodies to increase over time. The process of generating antibodies with increased binding affinities

1908-402: A three-to-one ratio: the interstitial fluid volume is about 12 liters; the vascular volume is about 4 liters. The interstitial fluid compartment is divided into the lymphatic fluid compartment – about 2/3, or 8 (6–10) liters, and the transcellular fluid compartment (the remaining 1/3, or about 4 liters). The vascular volume is divided into the venous volume and the arterial volume; and

2014-423: Is blood plasma , a fluid that is the blood's liquid medium, which by itself is straw-yellow in color. The blood plasma volume totals of 2.7–3.0 liters (2.8–3.2 quarts) in an average human. It is essentially an aqueous solution containing 92% water, 8% blood plasma proteins , and trace amounts of other materials. Plasma circulates dissolved nutrients, such as glucose , amino acids , and fatty acids (dissolved in

2120-437: Is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses , including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens . Antigen literally means "antibody generator", as it

2226-522: Is also partitioned into two antigen-binding fragments (Fab), containing one V L , V H , C L , and C H 1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape. In between them is a hinge region of the heavy chains, whose flexibility allows antibodies to bind to pairs of epitopes at various distances, to form complexes ( dimers , trimers, etc.), and to bind effector molecules more easily. In an electrophoresis test of blood proteins , antibodies mostly migrate to

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2332-458: Is arterial or venous blood). Most of it (about 70%) is converted to bicarbonate ions HCO − 3 by the enzyme carbonic anhydrase in the red blood cells by the reaction CO 2 + H 2 O → H 2 CO 3 → H + HCO − 3 ; about 7% is dissolved in the plasma; and about 23% is bound to hemoglobin as carbamino compounds. Hemoglobin, the main oxygen-carrying molecule in red blood cells, carries both oxygen and carbon dioxide. However,

2438-418: Is associated with a large number of beliefs. One of the most basic is the use of blood as a symbol for family relationships through birth/parentage; to be "related by blood" is to be related by ancestry or descendence, rather than marriage. This bears closely to bloodlines , and sayings such as " blood is thicker than water " and " bad blood ", as well as " Blood brother ". Blood is given particular emphasis in

2544-440: Is bright red, because carbon monoxide causes the formation of carboxyhemoglobin . In cyanide poisoning, the body cannot use oxygen, so the venous blood remains oxygenated, increasing the redness. There are some conditions affecting the heme groups present in hemoglobin that can make the skin appear blue – a symptom called cyanosis . If the heme is oxidized, methemoglobin , which is more brownish and cannot transport oxygen,

2650-415: Is called affinity maturation . Affinity maturation occurs in mature B cells after V(D)J recombination, and is dependent on help from helper T cells . Isotype or class switching is a biological process occurring after activation of the B cell, which allows the cell to produce different classes of antibody (IgA, IgE, or IgG). The different classes of antibody, and thus effector functions, are defined by

2756-407: Is circulated around the body through blood vessels by the pumping action of the heart . In humans, blood is pumped from the strong left ventricle of the heart through arteries to peripheral tissues and returns to the right atrium of the heart through veins . It then enters the right ventricle and is pumped through the pulmonary artery to the lungs and returns to the left atrium through

2862-448: Is closer to human IgG2 than human IgG1 in terms of its function. The term humoral immunity is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from cell-mediated immunity , which generally describes the responses of T cells (especially cytotoxic T cells). In general, antibodies are considered part of

2968-544: Is compensated for through memory B cells: novel variants of a microbe that still retain structural features of previously encountered antigens can elicit memory B cell responses that adapt to those changes. It has been suggested that long-lived plasma cells secrete B cell receptors with higher affinity than those on the surfaces of memory B cells, but findings are not entirely consistent on this point. Antibodies are heavy (~150 k Da ) proteins of about 10 nm in size, arranged in three globular regions that roughly form

3074-478: Is dangerous to health, and severe hypoxia (saturations less than 30%) may be rapidly fatal. A fetus , receiving oxygen via the placenta , is exposed to much lower oxygen pressures (about 21% of the level found in an adult's lungs), so fetuses produce another form of hemoglobin with a much higher affinity for oxygen ( hemoglobin F ) to function under these conditions. CO 2 is carried in blood in three different ways. (The exact percentages vary depending whether it

3180-426: Is formed. In the rare condition sulfhemoglobinemia , arterial hemoglobin is partially oxygenated, and appears dark red with a bluish hue. Veins close to the surface of the skin appear blue for a variety of reasons. However, the factors that contribute to this alteration of color perception are related to the light-scattering properties of the skin and the processing of visual input by the visual cortex , rather than

3286-435: Is free to bind oxygen, and fewer oxygen molecules can be transported throughout the blood. This can cause suffocation insidiously. A fire burning in an enclosed room with poor ventilation presents a very dangerous hazard, since it can create a build-up of carbon monoxide in the air. Some carbon monoxide binds to hemoglobin when smoking tobacco. Blood for transfusion is obtained from human donors by blood donation and stored in

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3392-461: Is in equilibrium with lymph , which is continuously formed in tissues from blood by capillary ultrafiltration. Lymph is collected by a system of small lymphatic vessels and directed to the thoracic duct , which drains into the left subclavian vein , where lymph rejoins the systemic blood circulation. Blood circulation transports heat throughout the body, and adjustments to this flow are an important part of thermoregulation . Increasing blood flow to

3498-570: Is known as the Haldane effect , and is important in the transport of carbon dioxide from the tissues to the lungs. A rise in the partial pressure of CO 2 or a lower pH will cause offloading of oxygen from hemoglobin, which is known as the Bohr effect . Some oxyhemoglobin loses oxygen and becomes deoxyhemoglobin. Deoxyhemoglobin binds most of the hydrogen ions as it has a much greater affinity for more hydrogen than does oxyhemoglobin. In mammals, blood

3604-507: Is large and contains several distinct gene loci for each domain of the antibody—the chromosome region containing heavy chain genes ( IGH@ ) is found on chromosome 14 , and the loci containing lambda and kappa light chain genes ( IGL@ and IGK@ ) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences between

3710-511: Is oxygenated and dark red when it is deoxygenated . Medical terms related to blood often begin with hemo- , hemato- , haemo- or haemato- from the Greek word αἷμα ( haima ) 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

3816-458: Is present, ensuring that antibody levels to the antigen in question do not fall to 0, provided the plasma cell stays alive. The rate of antibody secretion, however, can be regulated, for example, by the presence of adjuvant molecules that stimulate the immune response such as TLR ligands. Long-lived plasma cells can live for potentially the entire lifetime of the organism. Classically, the survival niches that house long-lived plasma cells reside in

3922-493: Is produced predominantly by the liver , while hormones are produced by the endocrine glands and the watery fraction is regulated by the hypothalamus and maintained by the kidney . Healthy erythrocytes have a plasma life of about 120 days before they are degraded by the spleen , and the Kupffer cells in the liver. The liver also clears some proteins, lipids, and amino acids. The kidney actively secretes waste products into

4028-430: Is required. IgA tetramers and pentamers have also been reported. Antibodies also form complexes by binding to antigen: this is called an antigen-antibody complex or immune complex . Small antigens can cross-link two antibodies, also leading to the formation of antibody dimers, trimers, tetramers, etc. Multivalent antigens (e.g., cells with multiple epitopes) can form larger complexes with antibodies. An extreme example

4134-625: Is reversible, and the antibody's affinity towards an antigen is relative rather than absolute. Relatively weak binding also means it is possible for an antibody to cross-react with different antigens of different relative affinities. The main categories of antibody action include the following: More indirectly, an antibody can signal immune cells to present antibody fragments to T cells , or downregulate other immune cells to avoid autoimmunity . Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in

4240-410: Is the clumping, or agglutination , of red blood cells with antibodies in blood typing to determine blood groups : the large clumps become insoluble, leading to visually apparent precipitation . The membrane-bound form of an antibody may be called a surface immunoglobulin (sIg) or a membrane immunoglobulin (mIg). It is part of the B cell receptor (BCR), which allows a B cell to detect when

4346-463: Is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking

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4452-529: Is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue. Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens. It has been estimated that humans generate about 10 billion different antibodies, each capable of binding

4558-454: Is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment. Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called switch (S) regions , found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand

4664-548: The Islamic , Jewish , and Christian religions, because Leviticus 17:11 says "the life of a creature is in the blood." This phrase is part of the Levitical law forbidding the drinking of blood or eating meat with the blood still intact instead of being poured off. Body fluid The total body of water is divided into fluid compartments , between the intracellular fluid compartment (also called space, or volume) and

4770-527: The acid–base balance and respiration, which is called compensation. An arterial blood gas test measures these. Plasma also circulates hormones transmitting their messages to various tissues. The list of normal reference ranges for various blood electrolytes is extensive. Human blood is typical of that of mammals, although the precise details concerning cell numbers, size, protein structure , and so on, vary somewhat between species. In non-mammalian vertebrates, however, there are some key differences: Blood

4876-416: The adaptive immune system , though this classification can become complicated. For example, natural IgM, which are made by B-1 lineage cells that have properties more similar to innate immune cells than adaptive, refers to IgM antibodies made independently of an immune response that demonstrate polyreactivity- they recognize multiple distinct (unrelated) antigens. These can work with the complement system in

4982-405: The clotting of blood. 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, and venous blood carries carbon dioxide, a waste product of metabolism produced by cells, from the tissues to the lungs to be exhaled. Blood is bright red when its hemoglobin

5088-427: The erectile tissue in the penis and clitoris . Another example of a hydraulic function is the jumping spider , in which blood forced into the legs under pressure causes them to straighten for a powerful jump, without the need for bulky muscular legs. Hemoglobin is the principal determinant of the color of blood ( hemochrome ). Each molecule has four heme groups, and their interaction with various molecules alters

5194-420: The extracellular fluid (ECF) compartment (space, volume) in a two-to-one ratio: 28 (28–32) liters are inside cells and 14 (14–15) liters are outside cells. The ECF compartment is divided into the interstitial fluid volume – the fluid outside both the cells and the blood vessels – and the intravascular volume (also called the vascular volume and blood plasma volume) – the fluid inside the blood vessels – in

5300-736: The iota (ι) chain, are found in other vertebrates like sharks ( Chondrichthyes ) and bony fishes ( Teleostei ). In most placental mammals , the structure of antibodies is generally the same. Jawed fish appear to be the most primitive animals that are able to make antibodies similar to those of mammals, although many features of their adaptive immunity appeared somewhat earlier. Cartilaginous fish (such as sharks) produce heavy-chain-only antibodies (i.e., lacking light chains) which moreover feature longer chain pentamers (with five constant units per molecule). Camelids (such as camels, llamas, alpacas) are also notable for producing heavy-chain-only antibodies. The antibody's paratope interacts with

5406-482: The pulmonary veins . Blood then enters the left ventricle to be circulated again. Arterial blood carries oxygen from inhaled air to all of the cells of the body, and venous blood carries carbon dioxide, a waste product of metabolism by cells , to the lungs to be exhaled. However, one exception includes pulmonary arteries, which contain the most deoxygenated blood in the body, while the pulmonary veins contain oxygenated blood. Additional return flow may be generated by

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5512-477: The urine . About 98.5% of the oxygen in a sample of arterial blood in a healthy human breathing air at sea-level pressure is chemically combined with the hemoglobin . About 1.5% is physically dissolved in the other blood liquids and not connected to hemoglobin. The hemoglobin molecule is the primary transporter of oxygen in mammals and many other species. Hemoglobin has an oxygen binding capacity between 1.36 and 1.40 ml O 2 per gram hemoglobin, which increases

5618-437: The "classical" complement system. This results in the killing of bacteria in two ways. First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization ; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement system components form a membrane attack complex to assist antibodies to kill

5724-614: The BCRs from most other cell signaling receptors. These patches may improve the efficiency of the cellular immune response . In humans, the cell surface is bare around the B cell receptors for several hundred nanometers, which further isolates the BCRs from competing influences. Antibodies can come in different varieties known as isotypes or classes . In humans there are five antibody classes known as IgA, IgD, IgE, IgG, and IgM, which are further subdivided into subclasses such as IgA1, IgA2. The prefix "Ig" stands for immunoglobulin , while

5830-516: The CO 2 bound to hemoglobin does not bind to the same site as oxygen. Instead, it combines with the N-terminal groups on the four globin chains. However, because of allosteric effects on the hemoglobin molecule, the binding of CO 2 decreases the amount of oxygen that is bound for a given partial pressure of oxygen. The decreased binding to carbon dioxide in the blood due to increased oxygen levels

5936-513: The F V region. It is the subregion of Fab that binds to an antigen. More specifically, each variable domain contains three hypervariable regions – the amino acids seen there vary the most from antibody to antibody. When the protein folds, these regions give rise to three loops of β-strands , localized near one another on the surface of the antibody. These loops are referred to as the complementarity-determining regions (CDRs), since their shape complements that of an antigen. Three CDRs from each of

6042-458: The Fc region and influence interactions with effector molecules. The N-terminus of each chain is situated at the tip. Each immunoglobulin domain has a similar structure, characteristic of all the members of the immunoglobulin superfamily : it is composed of between 7 (for constant domains) and 9 (for variable domains) β-strands , forming two beta sheets in a Greek key motif . The sheets create

6148-489: The Fc region of an antibody, while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway . Another role of the Fc region is to selectively distribute different antibody classes across the body. In particular, the neonatal Fc receptor (FcRn) binds to the Fc region of IgG antibodies to transport it across

6254-491: The V, D and J gene segments exist, and are tandemly arranged in the genomes of mammals . In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates

6360-481: The actual color of the venous blood. Skinks in the genus Prasinohaema have green blood due to a buildup of the waste product biliverdin . Substances other than oxygen can bind to hemoglobin; in some cases, this can cause irreversible damage to the body. Carbon monoxide, for example, is extremely dangerous when carried to the blood via the lungs by inhalation, because carbon monoxide irreversibly binds to hemoglobin to form carboxyhemoglobin, so that less hemoglobin

6466-450: The adaptive immune system is regulated by interactions between idiotypes. The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen. Effector cells (such as macrophages or natural killer cells ) bind via their Fc receptors (FcR) to

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6572-410: The antibody (also known as effector functions), in addition to some other structural features. Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response. Between species, while classes and subclasses of antibodies may be shared (at least in name), their functions and distribution throughout the body may be different. For example, mouse IgG1

6678-686: The antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination discussed below. Somatic recombination of immunoglobulins, also known as V(D)J recombination , involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments. V, D and J segments are found in Ig heavy chains , but only V and J segments are found in Ig light chains . Multiple copies of

6784-562: The antigen's epitope. An antigen usually contains different epitopes along its surface arranged discontinuously, and dominant epitopes on a given antigen are called determinants. Antibody and antigen interact by spatial complementarity (lock and key). The molecular forces involved in the Fab-epitope interaction are weak and non-specific – for example electrostatic forces , hydrogen bonds , hydrophobic interactions , and van der Waals forces . This means binding between antibody and antigen

6890-421: The antigen-binding sites at both tips of the antibody come in an equally wide variety. The rest of the antibody structure is much less variable; in humans, antibodies occur in five classes , sometimes called isotypes : IgA , IgD , IgE , IgG , and IgM . Human IgG and IgA antibodies are also divided into discrete subclasses (IgG1, IgG2, IgG3, IgG4; IgA1 and IgA2). The class refers to the functions triggered by

6996-567: The arterial volume has a conceptually useful but unmeasurable subcompartment called the effective arterial blood volume . Clinical samples are generally defined as non-infectious human or animal materials including blood , saliva , excreta , body tissue and tissue fluids , and also FDA-approved pharmaceuticals that are blood products . In medical contexts, it is a specimen taken for diagnostic examination or evaluation, and for identification of disease or condition. Antibody An antibody ( Ab ) or immunoglobulin ( Ig )

7102-401: The bacterium directly (bacteriolysis). To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate . Since an antibody has at least two paratopes, it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against

7208-471: The blood or bound to plasma proteins), and removes waste products, such as carbon dioxide , urea , and lactic acid . Other important components include: The term serum refers to plasma from which the clotting proteins have been removed. Most of the proteins remaining are albumin and immunoglobulins . Blood pH is regulated to stay within the narrow range of 7.35 to 7.45, making it slightly basic (compensation). Extra-cellular fluid in blood that has

7314-434: The bloodstream, they are said to be part of the humoral immune system . Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Antibodies contribute to immunity in three ways: They prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating

7420-424: The body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures. At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in

7526-469: The body, including: Blood accounts for 7% of the human body weight, with an average density around 1060 kg/m, very close to pure water's density of 1000 kg/m. The average adult has a blood volume of roughly 5 litres (11 US pt) or 1.3 gallons, which is composed of plasma and formed elements . The formed elements are the two types of blood cell or corpuscle – the red blood cells , (erythrocytes) and white blood cells (leukocytes), and

7632-477: The bone marrow, though it cannot be assumed that any given plasma cell in the bone marrow will be long-lived. However, other work indicates that survival niches can readily be established within the mucosal tissues- though the classes of antibodies involved show a different hierarchy from those in the bone marrow. B cells can also differentiate into memory B cells which can persist for decades similarly to long-lived plasma cells. These cells can be rapidly recalled in

7738-420: The cell fragments called platelets that are involved in clotting. By volume, the red blood cells constitute about 45% of whole blood, the plasma about 54.3%, and white cells about 0.7%. Whole blood (plasma and cells) exhibits non-Newtonian fluid dynamics . One microliter of blood contains: 45 ± 7 (38–52%) for males 42 ± 5 (37–47%) for females Oxygenated: 98–99% Deoxygenated: 75% About 55% of blood

7844-430: The cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell . In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane -bound form. Some daughter cells of the activated B cells undergo isotype switching , a mechanism that causes the production of antibodies to change from IgM or IgD to

7950-423: The classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Antibodies are produced exclusively by B cells in response to antigens where initially, antibodies are formed as membrane-bound receptors, but upon activation by antigens and helper T cells, B cells differentiate to produce soluble antibodies. Many natural antibodies are directed against

8056-403: The constant (C) regions of the immunoglobulin heavy chain. Initially, naive B cells express only cell-surface IgM and IgD with identical antigen binding regions. Each isotype is adapted for a distinct function; therefore, after activation, an antibody with an IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from

8162-413: The digestive tract. After severe acute blood loss, liquid preparations, generically known as plasma expanders, can be given intravenously, either solutions of salts (NaCl, KCl, CaCl 2 etc.) at physiological concentrations, or colloidal solutions, such as dextrans, human serum albumin , or fresh frozen plasma. In these emergency situations, a plasma expander is a more effective life-saving procedure than

8268-410: The disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut. These antibodies undergo quality checks in the endoplasmic reticulum (ER), which contains proteins that assist in proper folding and assembly. Rejection of xenotransplantated organs

8374-414: The diversity of the antibody pool and impacts the antibody's antigen-binding affinity . Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a stronger interaction (high affinity). B cells that express high affinity antibodies on their surface will receive

8480-583: The earliest phases of an immune response to help facilitate clearance of the offending antigen and delivery of the resulting immune complexes to the lymph nodes or spleen for initiation of an immune response. Hence in this capacity, the function of antibodies is more akin to that of innate immunity than adaptive. Nonetheless, in general antibodies are regarded as part of the adaptive immune system because they demonstrate exceptional specificity (with some exception), are produced through genetic rearrangements (rather than being encoded directly in germline ), and are

8586-602: The early phases of the immune response (classically described as arising extrafollicularly rather than from the germinal center ) which have the potential to differentiate further into plasma cells. The literature is sloppy at times and often describes plasmablasts as just short-lived plasma cells- formally this is incorrect. Plasma cells, in contrast, do not divide (they are terminally differentiated ), and rely on survival niches comprising specific cell types and cytokines to persist. Plasma cells will secrete huge quantities of antibody regardless of whether or not their cognate antigen

8692-430: The exact color. Arterial blood and capillary blood are bright red, as oxygen imparts a strong red color to the heme group. Deoxygenated blood is a darker shade of red; this is present in veins, and can be seen during blood donation and when venous blood samples are taken. This is because the spectrum of light absorbed by hemoglobin differs between the oxygenated and deoxygenated states. Blood in carbon monoxide poisoning

8798-414: The genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation , by a process called somatic hypermutation (SHM). SHM results in approximately one nucleotide change per variable gene, per cell division. As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains. This serves to increase

8904-846: The heavy and light chains together form an antibody-binding site whose shape can be anything from a pocket to which a smaller antigen binds, to a larger surface, to a protrusion that sticks out into a groove in an antigen. Typically though, only a few residues contribute to most of the binding energy. The existence of two identical antibody-binding sites allows antibody molecules to bind strongly to multivalent antigen (repeating sites such as polysaccharides in bacterial cell walls , or other sites at some distance apart), as well as to form antibody complexes and larger antigen-antibody complexes . The structures of CDRs have been clustered and classified by Chothia et al. and more recently by North et al. and Nikoloudis et al. However, describing an antibody's binding site using only one single static structure limits

9010-769: The invading microbe. The activation of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity (ADCC) – this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer . The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens. Humans and higher primates also produce "natural antibodies" that are present in serum before viral infection. Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination , other foreign antigen exposure or passive immunization . These antibodies can activate

9116-462: The last, gamma globulin fraction. Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ . This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ (gamma) heavy chains which characterize the IgG class of antibodies. The variable domains can also be referred to as

9222-526: The lungs is still roughly 75% (70 to 78%) saturated. Increased oxygen consumption during sustained exercise reduces the oxygen saturation of venous blood, which can reach less than 15% in a trained athlete; although breathing rate and blood flow increase to compensate, oxygen saturation in arterial blood can drop to 95% or less under these conditions. Oxygen saturation this low is considered dangerous in an individual at rest (for instance, during surgery under anesthesia). Sustained hypoxia (oxygenation less than 90%),

9328-406: The movement of skeletal muscles , which can compress veins and push blood through the valves in veins toward the right atrium . The blood circulation was famously described by William Harvey in 1628. In vertebrates, the various cells of blood are made in the bone marrow in a process called hematopoiesis , which includes erythropoiesis , the production of red blood cells; and myelopoiesis ,

9434-462: The observation of blood clotting in a transparent container. When blood is drawn in a glass container and left undisturbed for about an hour, four different layers can be seen. A dark clot forms at the bottom (the "black bile"). Above the clot is a layer of red blood cells (the "blood"). Above this is a whitish layer of white blood cells (the "phlegm"). The top layer is clear yellow serum (the "yellow bile"). In general, Greek thinkers believed that blood

9540-557: The other antibody isotypes, IgE, IgA, or IgG, that have defined roles in the immune system. In mammals there are two types of immunoglobulin light chain , which are called lambda (λ) and kappa (κ). However, there is no known functional difference between them, and both can occur with any of the five major types of heavy chains. Each antibody contains two identical light chains: both κ or both λ. Proportions of κ and λ types vary by species and can be used to detect abnormal proliferation of B cell clones. Other types of light chains, such as

9646-417: The oxygen is consumed; afterwards, venules and veins carry deoxygenated blood back to the heart. Under normal conditions in adult humans at rest, hemoglobin in blood leaving the lungs is about 98–99% saturated with oxygen , achieving an oxygen delivery between 950 and 1150 ml/min to the body. In a healthy adult at rest, oxygen consumption is approximately 200–250 ml/min, and deoxygenated blood returning to

9752-587: The pathogen in cells that recognize their Fc region. Those cells that recognize coated pathogens have Fc receptors, which, as the name suggests, interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose , mast cells and neutrophils will degranulate , natural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of

9858-455: The pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway . Antibodies will also trigger vasoactive amine degranulation to contribute to immunity against certain types of antigens (helminths, allergens). Antibodies that bind to surface antigens (for example, on bacteria) will attract the first component of the complement cascade with their Fc region and initiate activation of

9964-603: The placenta, from the mother to the fetus. In addition to this, binding to FcRn endows IgG with an exceptionally long half-life relative to other plasma proteins of 3-4 weeks. IgG3 in most cases (depending on allotype) has mutations at the FcRn binding site which lower affinity for FcRn, which are thought to have evolved to limit the highly inflammatory effects of this subclass. Antibodies are glycoproteins , that is, they have carbohydrates (glycans) added to conserved amino acid residues. These conserved glycosylation sites occur in

10070-437: The presence of these proteins, V(D)J recombination would not occur. After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as allelic exclusion ) thus each B cell can produce antibodies containing only one kind of variable chain. Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells,

10176-504: The production of white blood cells and platelets. During childhood, almost every human bone produces red blood cells; as adults, red blood cell production is limited to the larger bones: the bodies of the vertebrae, the breastbone (sternum), the ribcage, the pelvic bones, and the bones of the upper arms and legs. In addition, during childhood, the thymus gland, found in the mediastinum , is an important source of T lymphocytes . The proteinaceous component of blood (including clotting proteins)

10282-437: The same activated B cell to produce antibodies of different isotypes. Only the constant region of the antibody heavy chain changes during class switching; the variable regions, and therefore antigen specificity, remain unchanged. Thus the progeny of a single B cell can produce antibodies, all specific for the same antigen, but with the ability to produce the effector function appropriate for each antigenic challenge. Class switching

10388-420: The second and the third most supplied organs, with 1100 ml/min and ~700 ml/min, respectively. Relative rates of blood flow per 100 g of tissue are different, with kidney, adrenal gland and thyroid being the first, second and third most supplied tissues, respectively. The restriction of blood flow can also be used in specialized tissues to cause engorgement, resulting in an erection of that tissue; examples are

10494-444: The suffix denotes the type of heavy chain the antibody contains: the heavy chain types α (alpha), γ (gamma), δ (delta), ε (epsilon), μ (mu) give rise to IgA, IgG, IgD, IgE, IgM, respectively. The distinctive features of each class are determined by the part of the heavy chain within the hinge and Fc region. The classes differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in

10600-489: The surface (e.g., during warm weather or strenuous exercise) causes warmer skin, resulting in faster heat loss. In contrast, when the external temperature is low, blood flow to the extremities and surface of the skin is reduced and to prevent heat loss and is circulated to the important organs of the body, preferentially. Rate of blood flow varies greatly between different organs. Liver has the most abundant blood supply with an approximate flow of 1350 ml/min. Kidney and brain are

10706-440: The table. For example, IgE antibodies are responsible for an allergic response consisting of histamine release from mast cells , often a sole contributor to asthma (though other pathways exist as do exist symptoms very similar to yet not technically asthma). The antibody's variable region binds to allergic antigen, for example house dust mite particles, while its Fc region (in the ε heavy chains) binds to Fc receptor ε on

10812-441: The total blood oxygen capacity seventyfold, compared to if oxygen solely were carried by its solubility of 0.03 ml O 2 per liter blood per mm Hg partial pressure of oxygen (about 100 mm Hg in arteries). With the exception of pulmonary and umbilical arteries and their corresponding veins, arteries carry oxygenated blood away from the heart and deliver it to the body via arterioles and capillaries , where

10918-430: The understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities. In the framework of the immune network theory , CDRs are also called idiotypes. According to immune network theory,

11024-412: The variable domains are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity-determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of

11130-491: Was discovered in the year 1900 by Karl Landsteiner . Jan Janský is credited with the first classification of blood into the four types (A, B, AB, and O) in 1907, which remains in use today. In 1907 the first blood transfusion was performed that used the ABO system to predict compatibility. The first non-direct transfusion was performed on 27 March 1914. The Rhesus factor was discovered in 1937. Due to its importance to life, blood

11236-460: Was made from food. Plato and Aristotle are two important sources of evidence for this view, but it dates back to Homer's Iliad . Plato thinks that fire in our bellies transform food into blood. Plato believes that the movements of air in the body as we exhale and inhale carry the fire as it transforms our food into blood. Aristotle believed that food is concocted into blood in the heart and transformed into our body's matter. The ABO blood group system

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