Each antibody binds to a specific antigen; an interaction similar to a lock and key.

Antibodies (also known as immunoglobulins^[1]) are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. Gamma globulins, or Ig's are a class of Proteins in the blood identified by their position after Serum protein electrophoresis. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products Bodily fluids listed below are found in the bodies of men and/or women Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable They are typically made of basic structural units - each with two large heavy chains and two small light chains - to form, for example, monomers with one unit, dimers with two units or pentamers with five units. A heavy chain is the large Polypeptide subunit of a Protein complex, such as a Motor protein (e A monomer (from Greek mono "one" and meros "part" is a small Molecule that may become chemically bonded to other A dimer is a Chemical or Biological entity consisting of two subunits called Monomers which are held together by either Intramolecular forces A polymer is a large Molecule ( Macromolecule) composed of repeating Structural units typically connected by Covalent Chemical bonds Antibodies are produced by a kind of white blood cell called a B cell. B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by There are several different types of antibody heavy chain, and several different kinds of antibodies, which are grouped into different isotypes based on which heavy chain they possess. In Immunology, the "immunoglobulin isotype" refers to the genetic variations or differences in the constant regions of the heavy and light chains of the Ig (immunoglobulinsclasses Five different antibody isotypes are known in mammals, which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter. ^[2]

Although the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures to exist. This region is known as the hypervariable region. Each of these variants can bind to a different target, known as an antigen. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response ^[3] This huge diversity of antibodies allows the immune system to recognize an equally wide diversity of antigens. The unique part of the antigen recognized by an antibody is called an epitope. An epitope, also known as antigenic determinant, is the part of a Macromolecule that is recognized by the Immune system, specifically by antibodies These epitopes bind with their antibody in a highly specific interaction, called induced fit, that allows antibodies to identify and bind only their unique antigen in the midst of the millions of different molecules that make up an organism. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Recognition of an antigen by an antibody tags it for attack by other parts of the immune system. Antibodies can also neutralize targets directly by, for example, binding to a part of a pathogen that it needs to cause an infection. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious ^[4]

The large and diverse population of antibodies is generated by random combinations of a set of gene segments that encode different antigen binding sites (or paratopes), followed by random mutations in this area of the antibody gene, which create further diversity. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism ^[2][5] Antibody genes also re-organize in a process called class switching that changes the base of the heavy chain to another, creating a different isotype of the antibody that retains the antigen specific variable region. Immunoglobulin class switching (or isotype switching or isotypic commutation or class switch recombination) is a biological mechanism that changes This allows a single antibody to be used by several different parts of the immune system. Production of antibodies is the main function of the humoral immune system. The Humoral Immune Response (HIR is the aspect of immunity that is mediated by secreted Antibodies (as opposed to Cell-mediated immunity which involves ^[6]

Antibody forms

Antibodies occur in two forms: a soluble form secreted into the blood and tissue fluids, and a membrane-bound form attached to the surface of a B cell that is called the B cell receptor (BCR). Solubility is the characteristic Physical property referring to the ability of a given substance the Solute, to dissolve in a Solvent. Secretion is the process of segregating elaborating and releasing chemicals from a cell, or a secreted Chemical substance or amount of substance Tissue is a cellular organizational level intermediate between cells and a complete organism The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by The BCR allows a B cell to detect when a specific antigen is present in the body and triggers B cell activation. ^[7] Activated B cells differentiate into either antibody generating factories called plasma cells that secrete soluble antibody, or into memory cells that survive in the body for years afterwards to allow the immune system to remember an antigen and respond faster upon future exposures. In Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. Plasma cells (also called plasma B cells or plasmocytes) are cells of the Immune system that secrete large amounts of antibodies. Memory B cells are a B cell sub-type that are formed following primary infection ^[8] Antibodies are, therefore, an essential component of the adaptive immune system that learns, adapts and remembers responses to invading pathogens. Immune system|Passive immunity|Innate immune system The adaptive immune system is composed of highly specialized systemic cells and processes that eliminate or prevent Pathogenic

Isotypes

Antibody isotypes of mammals

Name	Types	Description	Antibody Complexes
IgA	2	Found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents colonization by pathogens. Immunoglobulin A ( IgA) is an Antibody playing a critical role in mucosal immunity The mucous membranes (or mucosae; singular mucosa) are linings of mostly endodermal origin covered in Epithelium, which are involved in In humans the respiratory tract is the part of the Anatomy that has to do with the process of respiration. In Anatomy, the genitourinary system is the Organ system of all the Reproductive organs and the Urinary system. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious [9] Also found in saliva, tears, and breast milk.
IgD	1	Functions mainly as an antigen receptor on B cells that have not been exposed to antigens. Immunoglobulin D ( IgD) is an Antibody isotype that makes up about 1% of Proteins in the Plasma membranes of immature B-lymphocytes [10] Its function is less defined than other isotypes.
IgE	1	Binds to allergens and triggers histamine release from mast cells and basophils, and is involved in allergy. In Biology, Immunoglobulin E ( IgE) is a class of Antibody (or Immunoglobulin " Isotype " that has only been found in An allergen is a nonparasitic Antigen capable of stimulating a Type-I hypersensitivity reaction in atopic individuals Histamine is a Biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a Neurotransmitter A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin Allergy is a disorder of the Immune system often also referred to as Atopy. Also protects against parasitic worms. See also Parasitic worm (disambiguation Parasitic worms or helminths are a division of eukaroytic Parasites that unlike external parasites such [6]
IgG	4	In its four forms, provides the majority of antibody-based immunity against invading pathogens. Immunoglobulin G ( IgG) is a Monomeric Immunoglobulin, built of two heavy chains γ and two light chains. [6] The only antibody capable of crossing the placenta to give passive immunity to fetus.
IgM	1	Expressed on the surface of B cells and in a secreted form with very high avidity. Immunoglobulin M, or IgM for short is a basic Antibody that is present on B cells It is the primary antibody against A and B Eliminates pathogens in the early stages of B cell mediated (humoral) immunity before there is sufficient IgG. [6][10]

Antibodies can come in different varieties known as isotypes or classes. In Immunology, the "immunoglobulin isotype" refers to the genetic variations or differences in the constant regions of the heavy and light chains of the Ig (immunoglobulinsclasses In placental mammals there are five antibody isotypes known as IgA, IgD, IgE,IgG and IgM. See also Evolution of mammals Eutheria ("true beast" are a group of Mammals consisting of Placental mammals plus all extinct Mammals They are each named with an "Ig" prefix that stands for immunoglobulin, another name for antibody, and differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table. ^[11]

The antibody isotype of a B cell changes during cell development and activation. B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by Immature B cells, which have never been exposed to antigen, are known as naïve B cells and express only the IgM isotype in a cell surface bound form. B cells begin to express both IgM and IgD when they reach maturity - the co-expression of both these immunoglobulin isotypes renders the B cell 'mature' and ready to respond to antigen. ^[12] B cell activation follows engagement of 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 Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. Plasma cells (also called plasma B cells or plasmocytes) are cells of the Immune system that secrete large amounts of antibodies. In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane-bound form. Secretion is the process of segregating elaborating and releasing chemicals from a cell, or a secreted Chemical substance or amount of substance The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer 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 the other antibody isotypes, IgE, IgA or IgG, that have defined roles in the immune system. Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. Immunoglobulin class switching (or isotype switching or isotypic commutation or class switch recombination) is a biological mechanism that changes

Structure

Antibodies are heavy (~150kDa) globular plasma proteins that are also known as immunoglobulins. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express Globular proteins, or spheroproteins are one of the two main Protein classes comprising "globe" -like proteins that are more or less soluble in Blood proteins, also called serum proteins, are Proteins found in Blood plasma. They have sugar chains added to some of their amino acid residues. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this ^[13] In other words, antibodies are glycoproteins. Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM. A monomer (from Greek mono "one" and meros "part" is a small Molecule that may become chemically bonded to other A dimer is a Chemical or Biological entity consisting of two subunits called Monomers which are held together by either Intramolecular forces A tetramer is a Protein with four subunits (tetrameric There are homo-tetramers (all Subunits are identical such as Glutathione S-transferase or Teleostei is one of three infraclasses in class Actinopterygii, the ray-finned fishes A polymer is a large Molecule ( Macromolecule) composed of repeating Structural units typically connected by Covalent Chemical bonds ^[14]

Several immunoglobulin domains make up the two heavy chains (red and blue) and the two light chains (green and yellow) of an antibody. The immunoglobulin domains are composed of between 7 (IgC) and 9 (IgV) β-strands. See also: [1]

Immunoglobulin domains

The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino In Chemistry, a disulfide bond is a single Covalent bond derived from the coupling of Thiol groups ^[11] Each chain is composed of structural domains called Ig domains. A protein domain is a part of protein sequence and structure that can evolve, function and exist independently of the rest of the protein chain These domains contain about 70-110 amino acids and are classified into different categories (for example, variable or IgV, and constant or IgC) according to their size and function. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this ^[15] They have a characteristic immunoglobulin fold in which two beta sheets create a “sandwich” shape, held together by interactions between conserved cysteines and other charged amino acids. An immunoglobulin fold is a common All-β protein fold that consists of a 2-layer sandwich of ~7 antiparallel β-strands arranged in two β-sheets. The β sheet (also β-pleated sheet) is the second form of regular Secondary structure in Proteins consisting of beta strands connected laterally Not to be confused with Cystine, its oxidized dimer Cysteine (abbreviated as Cys or C) is an α- Amino acid with

Heavy chain

For more details on this topic, see heavy chain. A heavy chain is the large Polypeptide subunit of a Protein complex, such as a Motor protein (e

There are five types of mammalian Ig heavy chain denoted by the Greek letters: α, δ, ε, γ, and μ. A heavy chain is the large Polypeptide subunit of a Protein complex, such as a Motor protein (e The Greek alphabet (Ελληνικό αλφάβητο is a set of twenty-four letters that has been used to write the Greek language since the late 9th or early ^[3] The type of heavy chain present defines the class of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively. ^[4] Distinct heavy chains differ in size and composition; α and γ contain approximately 450 amino acids, while μ and ε have approximately 550 amino acids. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this ^[3]

1. Fab region
2. The fragment antigen binding (Fab fragment is a region on an Antibody which binds to Antigens. Fc region
3. The fragment crystallizable region (Fc region is the tail region of an Antibody that interacts with cell surface receptors called Fc receptors and some proteins Heavy chain with one variable (V_H) domain followed by a constant domain (C_H1), a hinge region, and two more constant (C_H2 and C_H3) domains. A heavy chain is the large Polypeptide subunit of a Protein complex, such as a Motor protein (e
4. Light chain with one variable (V_L) and one constant (C_L) domain
5. Antigen binding site (paratope)
6. Hinge regions.

Each heavy chain has two regions, the constant region and the variable region. The constant region is identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α and δ have a constant region composed of three tandem (in a line) Ig domains, and a hinge region for added flexibility;^[11] heavy chains μ and ε have a constant region composed of four immunoglobulin domains. A protein domain is a part of protein sequence and structure that can evolve, function and exist independently of the rest of the protein chain ^[3] The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The process of immunological B-cell maturation involves transformation from an undifferentiated B cell to one that secretes antibodies with particular specificity The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain.

Light chain

For more details on this topic, see light chain.

In mammals there are two types of light chain, which are called lambda (λ) and kappa (κ). ^[3] A light chain has two successive domains: one constant domain and one variable domain. The approximate length of a light chain is 211 to 217 amino acids. ^[3] Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals. Other types of light chains, such as the iota (ι) chain, are found in lower vertebrates like Chondrichthyes and Teleostei. Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes Chondrichthyes or cartilaginous fishes are jawed Fish with paired fins paired nostrils scales two-chambered hearts and skeletons made of Cartilage rather Teleostei is one of three infraclasses in class Actinopterygii, the ray-finned fishes

Fab and Fc Regions

Some parts of an antibody have unique functions. The tips of the Y, for example, contain the site that bind antigen and, therefore, recognize specific foreign objects. This region of the antibody is called the Fab (fragment, antigen binding) region. The fragment antigen binding (Fab fragment is a region on an Antibody which binds to Antigens. It is composed of one constant and one variable domain from each heavy and light chain of the antibody. ^[16] The paratope is shaped at the amino terminal end of the antibody monomer by the variable domains from the heavy and light chains. The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or A monomer (from Greek mono "one" and meros "part" is a small Molecule that may become chemically bonded to other

The base of the Y plays a role in modulating immune cell activity. This region is called the Fc (Fragment, crystallizable) region, and is composed of two heavy chains that contribute two or three constant domains depending on the class of the antibody. The fragment crystallizable region (Fc region is the tail region of an Antibody that interacts with cell surface receptors called Fc receptors and some proteins ^[3] By binding to specific proteins the Fc region ensures that each antibody generates an appropriate immune response for a given antigen. ^[17] The Fc region also binds to various cell receptors, such as Fc receptors, and other immune molecules, such as complement proteins. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling An Fc receptor is a protein found on the surface of certain cells - including Natural killer cells Macrophages Neutrophils and Mast cells - that The complement system is a Biochemical cascade that helps clear Pathogens from an organism By doing this, it mediates different physiological effects including opsonization, cell lysis, and degranulation of mast cells, basophils and eosinophils. Physiology (from Greek grc φύσις physis, "nature origin" and grc -λογία -logia) is the study of the mechanical physical An opsonin is any molecule that acts as a binding Enhancer for the process of Phagocytosis, for example by coating the negatively-charged molecules on the membrane Lysis ( Greek, lysis from lyein = to separate refers to the death of a cell by breaking of the cellular membrane often by viral or osmotic Degranulation is a cellular process that releases Antimicrobial Cytotoxic molecules from secretory vesicles called granules found inside A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin Eosinophil granulocytes, usually called eosinophils (or less commonly acidophils) are White blood cells that are one of the Immune System components ^[11][18]

Function

Further information: Immune system

Since antibodies exist freely in the bloodstream, they are said to be part of the humoral immune system. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor The Humoral Immune Response (HIR is the aspect of immunity that is mediated by secreted Antibodies (as opposed to Cell-mediated immunity which involves Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen, a virus hull protein fragment, for example. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable For the leaf bug see Miridae. A capsid is the protein shell of a virus. Antibodies contribute to immunity in three main ways: they can prevent pathogens from entering or damaging cells by binding to them; they can stimulate removal of a pathogen by macrophages and other cells by coating the pathogen; and they can trigger direct pathogen destruction by stimulating other immune responses such as the complement pathway. Immunity is a material term that describes a state of having sufficient biological defenses to avoid Infection, Disease, or other unwanted biological invasion Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor The complement system is a Biochemical cascade that helps clear Pathogens from an organism ^[19]

Activation of complement

Antibodies that bind to surface antigens on, for example a bacterium, attract the first component of the complement cascade with their Fc region and initiate activation of the "classical" complement system. The complement system is a Biochemical cascade that helps clear Pathogens from an organism Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily ^[19] This results in the killing of bacteria in two ways. ^[6] 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. An opsonin is any molecule that acts as a binding Enhancer for the process of Phagocytosis, for example by coating the negatively-charged molecules on the membrane Secondly, some complement system components form a membrane attack complex to assist antibodies to kill the bacterium directly. membrane attack complex ( MAC) is typically formed on the surface of intruding Pathogenic Bacterial cells as a result of the activation of the ^[20]

Activation of effector cells

To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate. Agglutination is the clumping of particles The word agglutination comes from the Latin agglutinare, meaning "to glue to 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 the pathogen in cells that recognize their Fc region. ^[6]

Those cells which recognize coated pathogens have Fc receptors which, as the name suggests, interacts with the Fc region of IgA, IgG, and IgE antibodies. The fragment crystallizable region (Fc region is the tail region of an Antibody that interacts with cell surface receptors called Fc receptors and some proteins 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 the invading microbe. Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of White blood cells in humans and form an essential part of the Degranulation is a cellular process that releases Antimicrobial Cytotoxic molecules from secretory vesicles called granules found inside Natural killer cells (or NK cells) are a type of Cytotoxic Lymphocyte that constitute a major component of the Innate immune system. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Cytotoxicity is the quality of being toxic to cells Examples of toxic agents are a Chemical substance, an Immune cell or some types of Venom The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens. ^[3]

The secreted mammalian IgM has five Ig units. Immunoglobulin M, or IgM for short is a basic Antibody that is present on B cells It is the primary antibody against A and B Each Ig unit (labeled 1) has two epitope binding Fab regions, so IgM is capable of binding up to 10 epitopes. The fragment antigen binding (Fab fragment is a region on an Antibody which binds to Antigens.

Immunoglobulin diversity

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. ^[21] It has been estimated that humans generate about 10 billion different antibodies, each capable of binding a distinct epitope of an antigen. ^[22] Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance 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. ^[23]

Domain variability

The hypervariable regions of the heavy chain is shown in red, PDB 1IGT

The region (locus) of a chromosome that encodes an antibody is large and contains several distinct genes for each domain of the antibody - the locus 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. Immunoglobulin heavy locus, also known as IGH@, is a region on human Chromosome 14 that contains Gene for the Heavy chains of human antibodies Chromosome 14 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome Immunoglobulin lambda locus, also known as IGL@, is a region on human Chromosome 22 that contains Genes for the lambda Light chains of Immunoglobulin kappa locus, also known as IGK@, is a region on human Chromosome 2 that contains Genes for the kappa Light chains of antibodies Chromosome 22 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of Chromosome 22 Chromosome 2 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome 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 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). A complementarity determining region (CDR is a short Amino acid sequence found in the variable domains of Antigen receptor (e 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 the antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination discussed below. ^[24]

V(D)J recombination

For more details on this topic, see V(D)J recombination. V(DJ recombination is a mechanism of Genetic recombination that occurs in Vertebrates which randomly selects and assembles segments of Genes encoding

Simplistic overview of V(D)J recombination of immunoglobulin heavy chains

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. These segments are called variable (V), diversity (D) and joining (J) segments. ^[23] V, D and J segments are found in Ig heavy chains, but only V and J segments are found in Ig light chains. A heavy chain is the large Polypeptide subunit of a Protein complex, such as a Motor protein (e Multiple copies of the V, D and J gene segments exist, and are tandemly arranged in the genomes of mammals. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands 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 a huge number of antibodies, each with different paratopes, and thus different antigen specificities. ^[2]

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. Humans and many other organisms are Diploid, ie they have two copies of each Chromosome (one inherited from each parent in all their Somatic cells. ^[25][3]

Somatic hypermutation and affinity maturation

For more details on this topic, see Somatic hypermutation and Affinity maturation

Another mechanism that generates antibody diversity occurs in the mature B cell. Somatic hypermutation (or SHM is a mechanism inside cells that is part of the way the immune system adapts to the new foreign elements which confront it (for example In Immunology, affinity maturation is the process by which B-cells produce Antibodies with increased affinity for Antigen during the course of Following activation with antigen, B cells begin to proliferate rapidly. Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. In these rapidly dividing cells, 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). A point mutation, or single base substitution, is a type of Mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic SHM results in approximately one nucleotide change per variable gene, per cell division. Nucleotides are Organic compounds that consist of three joined structures a nitrogenous base a Sugar, and a Phosphate group ^[5] As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this

Somatic hypermutation serves to increase the diversity of the antibody pool and impacts the antibody’s antigen-binding affinity. In Chemical physics and Physical chemistry, chemical affinity can be defined as electronic properties by which dissimilar Chemical species are capable of ^[26] 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). ^[27] B cells that express high affinity antibodies on their surface will receive a strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis. ^[27] Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival. The process of generating antibodies with increased binding affinities 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. T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or ^[28]

Mechanism of class switch recombination that allows isotype switching in activated B cells

Class switching

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). Immunoglobulin class switching (or isotype switching or isotypic commutation or class switch recombination) is a biological mechanism that changes A biological process is a process of a living Organism (either plant or animal ^[2] The different classes of antibody, and thus effector functions, are defined by the constant (C) regions of the immunoglobulin heavy chain. Initially, naïve 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 a IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from 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 is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment. ^[29]

Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a 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). Nucleotides are Organic compounds that consist of three joined structures a nitrogenous base a Sugar, and a Phosphate group Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known The DNA strand is broken by the activity of a series of enzymes at two selected S-regions. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins ^[30][31] The variable domain exon is rejoined through a process called non-homologous end joining (NHEJ) to the desired constant region (γ, α or ε). An exon is a Nucleic acid sequence that is represented in the mature form of an RNA molecule after a portions of a precursor RNA Introns have been Non-homologous end joining ( NHEJ) is a pathway that repairs double-strand breaks in DNA This process results in an immunoglobulin gene that encodes an antibody of a different isotype. ^[32]

Medical applications

Disease diagnosis

Detection of particular antibodies is a very common form of medical diagnostics, and applications such as serology depend on these methods. Diagnosis is the identification by Process of elimination, of the nature of anything Serology is the scientific study of blood serum. In practice the term usually refers to the Diagnostic identification of antibodies in the serum ^[33] For example, in biochemical assays for disease diagnosis,^[34] a titer of antibodies directed against Epstein-Barr virus or Lyme disease is estimated from the blood. A titer (or titre) is a measure of concentration Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure The Epstein-Barr Virus ( EBV) also called Human herpesvirus 4 (HHV-4 is a Virus of the herpes family (which includes Herpes Lyme disease, or borreliosis, is an Emerging infectious disease caused by at least three Species of Bacteria belonging to the Genus If those antibodies are not present, either the person is not infected, or the infection occurred a very long time ago, and the B cells generating these specific antibodies have naturally decayed. In clinical immunology, levels of individual classes of immunoglobulins are measured by nephelometry (or turbidimetry) to characterize the antibody profile of patient. Immunology is a broad branch of biomedical Science that covers the study of all aspects of the Immune system in all Organisms It deals with Nephelometry is a technique used in Immunology to determine levels of IgM, IgG, and IgA. ^[35] Elevations in different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients whom the diagnosis is unclear. The liver is a vital organ in the human body and is present in Vertebrates and some other animals ^[4] For example, elevated IgA indicates alcoholic cirrhosis, elevated IgM indicates viral hepatitis and primary biliary cirrhosis, while IgG is elevated in viral hepatitis, autoimmune hepatitis and cirrhosis. Cirrhosis is a consequence of chronic Liver Disease characterized by replacement of liver tissue by fibrous Scar tissue as well as regenerative Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of Primary biliary cirrhosis is an Autoimmune disease of the Liver marked by the slow progressive destruction of the small bile ducts ( Bile canaliculi) within Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of Anomalous presentation of Human leukocyte antigen (HLA class II on the surface of Hepatocytes possibly due to Genetic predisposition or Acute liver infection Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues An epitope, also known as antigenic determinant, is the part of a Macromolecule that is recognized by the Immune system, specifically by antibodies A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia are detected with the Coombs test. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood Hemolytic anemia is Anemia due to Hemolysis, the abnormal breakdown of Red blood cells (RBCs either in the Blood vessels (intravascular hemolysis Coombs test (also known as Coombs' test, antiglobulin test or AGT) refers to two Clinical Blood tests used in Immunohematology ^[36] The Coombs test is also used for antibody screening in blood transfusion preparation and also for antibody screening in antenatal women. Blood transfusion is the process of transferring Blood or blood-based products from one person into the Circulatory system of another Pregnancy ( Latin graviditas) is the carrying of one or more offspring known as a Fetus or Embryo, inside the Uterus of a Female ^[36] Practically, several immunodiagnostic methods based on detection of complex antigen-antibody are used to diagnose infectious diseases, for example ELISA, immunofluorescence, Western blot, immunodiffusion, and immunoelectrophoresis. Enzyme-Linked ImmunoSorbent Assay, also called ELISA, Enzyme ImmunoAssay or EIA, is a biochemical technique used mainly in Immunology Immunofluorescence is the labeling of antibodies or Antigens with fluorescent Dyes This technique is often used to visualize the subcellular The western blot (alternatively immunoblot) is an Analytical technique used to detect specific Proteins in a given sample of tissue homogenate or Immunodiffusion is a diagnostic test which involves diffusion through a substance such as Agar. Immunoelectrophoresis ( IES) is the Electrophoresis of a determined Antigen mixture in an Agarose gel that allows the separation of different

Disease therapy

"Targeted" monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis,^[37] multiple sclerosis,^[38] psoriasis,^[39] and many forms of cancer including non-Hodgkin's lymphoma,^[40] colorectal cancer, head and neck cancer and breast cancer. Monoclonal antibodies ( mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune cell Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Psoriasis (səˈraɪəsɪs ( suh-RI-uh-sus) is a non-contagious disorder which affects the Skin and Joints It commonly causes red scaly Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled The non-Hodgkin lymphomas are a diverse group of hematologic cancers which encompass any Lymphoma other than Hodgkin lymphoma. Colorectal cancer, also called colon cancer or large bowel cancer, includes Cancerous growths in the colon, Rectum and The term head and neck cancer refers to a group of biologically similar cancers originating from the upper aerodigestive tract including the Lip, Oral cavity ( Breast cancer is a Cancer that starts in the cells of the Breast in women and men ^[41] Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia, result in partial or complete lack of antibodies. X-linked agammaglobulinemia (also called X-linked hypogammaglobulinemia XLA, Bruton type agammaglobulinemia) is a rare X-linked genetic disorder Hypogammaglobulinemia is a type of Immune disorder characterized by a reduction in all types of Gamma globulins It is distinguished from Dysgammaglobulinemia ^[42] These diseases are often treated by inducing a short term form of immunity called passive immunity. Immunity is a material term that describes a state of having sufficient biological defenses to avoid Infection, Disease, or other unwanted biological invasion Passive immunity is the transfer of active Humoral immunity in the form of readymade antibodies from one individual to another Passive immunity is achieved through the transfer of ready-made antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the affected individual. Blood plasma is the Liquid component of Blood, in which the Blood cells are suspended ^[43]

Prenatal therapy

For more details on this topic, see Rho(D) Immune Globulin. Rho(D Immune Globulin is a medicine given by intramuscular injection which is used to prevent the immunological condition known as Rhesus disease (or Hemolytic

Rho(D) Immune Globulin antibodies are specific for human Rhesus D (RhD) antigen, also known as Rhesus factor. The term Rhesus (Rh blood group system refers to the 5 main Rhesus Antigens (C c D E and e as well as the many other less frequent Rhesus antigens ^[44] These anti-RhD antibodies are known under several brand names, including RhoGAM, BayRHo-D, Gamulin Rh, HypRho-D, and WinRho SDF. A brand is a collection of Images and ideas representing an economic producer more specifically it refers to the descriptive verbal attributes and concrete symbols such as a Rhesus factor is an antigen found on red blood cells; individuals that are Rhesus-positive (Rh+) have this antigen on their red blood cells and individuals that are Rhesus-negative (Rh–) do not. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood During normal childbirth, delivery trauma or complications during pregnancy, blood from a fetus can enter the mother's system. Childbirth (also called labour, birth, partus or parturition) is the culmination of a Human Pregnancy or A fetus (or foetus or fœtus) is a developing Mammal or other Viviparous Vertebrate, after the Embryonic stage and In the case of an Rh-incompatible mother and child, consequential blood mixing may sensitize an Rh- mother to the Rh antigen on the blood cells of the Rh+ child, putting the remainder of the pregnancy, and any subsequent pregnancies, at risk for hemolytic disease of the newborn. Pregnancy ( Latin graviditas) is the carrying of one or more offspring known as a Fetus or Embryo, inside the Uterus of a Female Haemolytic disease of the newborn, also known as Haemolytic disease of the fetus and newborn, HDN, HDFN, or Erythroblastosis fetalis, is an ^[45] Anti-RhD antibodies are administered as part of a prenatal treatment regimen to prevent sensitization that may occur when a Rhesus-negative mother has a Rhesus-positive fetus. Prenatal care refers to the medical care recommended for women before and during Pregnancy. Treatment of a mother with Anti-RhD antibodies prior to and immediately after trauma and delivery destroys Rh antigen in the mother's system from the fetus. Importantly, this occurs before the antigen can stimulate maternal B cells to "remember" Rh antigen by generating memory B cells. Memory B cells are a B cell sub-type that are formed following primary infection Therefore, her humoral immune system will not make anti-Rh antibodies, and will not attack the Rhesus antigens of the current or subsequent baby. The Humoral Immune Response (HIR is the aspect of immunity that is mediated by secreted Antibodies (as opposed to Cell-mediated immunity which involves Rho(D) Immune Globulin treatment prevents sensitization that can lead to Rh disease, but does not prevent or treat the underlying disease itself. Rh disease (also known as Rh (D disease, Rhesus disease, RhD Hemolytic Disease of the Newborn, Rhesus D Hemolytic Disease of the Newborn or ^[44]

Research applications

Immunofluorescence image of the eukaryotic cytoskeleton. Immunofluorescence is the labeling of antibodies or Antigens with fluorescent Dyes This technique is often used to visualize the subcellular cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. Actin filaments are shown in red, microtubules in green, and the nuclei in blue. Actin is a globular roughly 42-kDa Protein found in all eukaryotic cells (except for Nematode sperm where it may be present at concentrations of Microtubules are one of the components of the Cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed

Specific antibodies are produced by injecting an antigen into a mammal, such as a mouse, rat or rabbit for small quantities of antibody, or goat, sheep, or horse for large quantities of antibody. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands A mouse (plural mice) is a small Animal that belongs to one Rats are various medium sized long-tailed Rodents of the superfamily Muroidea Rabbits are small Mammals in the family Leporidae of the order Lagomorpha, found in several parts of the world The domestic goat ( Capra aegagrus hircus) is a subspecies of goat Domesticated from the Wild goat of Southwest Asia and Eastern Europe The horse ( Equus caballus) is a hoofed ( Ungulate) Mammal, one of eight living species of the family Equidae. Blood isolated from these animals contains polyclonal antibodies — multiple antibodies that bind to the same antigen — in the serum, which can now be called antiserum. Polyclonal antibodies (or antisera are antibodies that are derived from different B cell lines Blood plasma is the Liquid component of Blood, in which the Blood cells are suspended This short article on antiserum deals exclusively with its applications Antigens are also injected into chickens for generation of polyclonal antibodies in egg yolk. The chicken ( Gallus gallus, sometimes G gallus domesticus) is a domesticated Fowl which is traditionally believed to have descended from An egg yolk is the part of an egg which serves as the Food source for the developing Embryo inside ^[46] To obtain antibody that is specific for a single epitope of an antigen, antibody-secreting lymphocytes are isolated from the animal and immortalized by fusing them with a cancer cell line. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. Biological Immortality can be defined as the absence of a sustained increase in rate of mortality as a function of chronological age The fused cells are called hybridomas, and will continually grow and secrete antibody in culture. Hybridoma are cells that have been engineered to produce a desired Antibody in large amounts Single hybridoma cells are isolated by dilution cloning to generate cell clones that all produce the same antibody; these antibodies are called monoclonal antibodies. Dilution cloning describes the process of obtaining a Monoclonal cell population starting from a polyclonal mass of cells Cloning in Biology is the process of producing populations of genetically-identical individuals that occurs in nature when organisms such as Bacteria, Insects Monoclonal antibodies ( mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune cell ^[47] Generated polyclonal and monoclonal antibodies are often purified using Protein A/G or antigen-affinity chromatography. Protein A/G is a recombinant fusion protein that combines IgG binding domains of both Protein A and Protein G. Affinity chromatography is a chromatographic method of separating biochemical mixtures based on a highly specific biologic interaction such as that between Antigen ^[48]

Use

In research, purified antibodies are used in many applications. They are most commonly used to identify and locate intracellular and extracellular proteins. Not to be confused with Intercellular, meaning "between cells" In Cell biology, Molecular biology and related fields the word extracellular (or sometimes extracellular space) means "outside the cell Antibodies are used in flow cytometry to differentiate cell types by the proteins they express; different types of cell express different combinations of cluster of differentiation molecules on their surface, and produce different intracellular and secretable proteins. Flow cytometry is a technique for counting examining and sorting microscopic particles suspended in a stream of fluid The cluster of differentiation (often abbreviated as CD) is a protocol used for the identification and investigation of Cell surface molecules present on Leukocytes ^[49] They are also used in immunoprecipitation to separate proteins and anything bound to them (co-immunoprecipitation) from other molecules in a cell lysate,^[50] in Western blot analyses to identify proteins separated by electrophoresis,^[51] and in immunohistochemistry or immunofluorescence to examine protein expression in tissue sections or to locate proteins within cells with the assistance of a microscope. Immunoprecipitation (IP is the technique of precipitating a protein Antigen out of solution using an Antibody that specifically binds to that particular Lysis ( Greek, lysis from lyein = to separate refers to the death of a cell by breaking of the cellular membrane often by viral or osmotic The western blot (alternatively immunoblot) is an Analytical technique used to detect specific Proteins in a given sample of tissue homogenate or Electrophoresis is the most well-known electrokinetic phenomenon. Immunohistochemistry or IHC refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibodies binding specifically Immunofluorescence is the labeling of antibodies or Antigens with fluorescent Dyes This technique is often used to visualize the subcellular A microscope ( Greek: ( micron) = small + ( skopein) = to look or see is an instrument for viewing objects that are ^[52][49] Proteins can also be detected and quantified with antibodies, using ELISA and ELISPOT techniques. Enzyme-Linked ImmunoSorbent Assay, also called ELISA, Enzyme ImmunoAssay or EIA, is a biochemical technique used mainly in Immunology The Enzyme-linked immunosorbent spot ( ELISPOT) assay is a common method for monitoring immune responses in humans and animals ^[53][54]

History

See also: History of immunology

The study of antibodies began in 1890 when Emil von Behring and Shibasaburo Kitasato described antibody activity against diphtheria and tetanus toxins. Timeline of immunology: 1718 - Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople observed the positive effects of Variolation Emil Adolf von Behring ( March 15, 1854 &ndash March 31, 1917) was a German Physiologist who received the 1901 was a Japanese Physician and bacteriologist. He is remembered as the co-discoverer of the infectious agent of Bubonic plague in Hong Kong in Diphtheria ( Greek διφθερα ( diphthera)—“pair of leather scrolls" is an upper respiratory tract illness characterized by sore Tetanospasmin is the Neurotoxin produced by the vegetative Spore of Clostridium tetani in anaerobic conditions causing Behring and Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen. The Humoral Immune Response (HIR is the aspect of immunity that is mediated by secreted Antibodies (as opposed to Cell-mediated immunity which involves ^[55][56] Their idea prompted Paul Ehrlich to propose the side chain theory for antibody and antigen interaction in 1897, when he hypothesized that receptors (described as “side chains”) on the surface of cells could bind specifically to toxins – in a "lock-and-key" interaction – and that this binding reaction was the trigger for the production of antibodies. Paul Ehrlich ( March 14, 1854 &ndash August 20, 1915) was a German Scientist who won the 1908 Nobel Side-chain theory ( German, Seitenkettentheorie) is a Theory proposed by Paul Ehrlich (1854&ndash1915 to explain the Immune response A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low ^[57] Other researchers believed that antibodies existed freely in the blood and, in 1904, Almroth Wright suggested that soluble antibodies coated bacteria to label them for phagocytosis and killing; a process that he named opsoninization. Sir Almroth Edward Wright, KBE, CB (1861-1947 was a British Bacteriologist and Immunologist. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole An opsonin is any molecule that acts as a binding Enhancer for the process of Phagocytosis, for example by coating the negatively-charged molecules on the membrane ^[58]

In the 1920s, Michael Heidelberger and Oswald Avery observed that antigens could be precipitated by antibodies and went on to show that antibodies were made of protein. Michael Heidelberger ( April 29, 1888 &ndash June 25, 1991) was an American Immunologist who is regarded as the father Oswald Theodore Avery ( October 21, 1877 &ndash 2 February, 1955) was a Canadian -born American Physician and ^[59] The biochemical properties of antigen-antibody binding interactions were examined in more detail in the late 1930s by John Marrack. ^[60] The next major advance was in the 1940s, when Linus Pauling confirmed the lock-and-key theory proposed by Ehrlich by showing that the interactions between antibodies and antigens depended more on their shape than their chemical composition. Linus Carl Pauling (February 28 1901 – August 19 1994 was an American Scientist, Peace activist, Author and educator. ^[61] In 1948, Astrid Fagreaus discovered that B cells, in the form of plasma cells, were responsible for generating antibodies. Plasma cells (also called plasma B cells or plasmocytes) are cells of the Immune system that secrete large amounts of antibodies. ^[62]

Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain,^[63] and their realization that this protein was the same as the Bence-Jones protein described in 1845 by Henry Bence Jones. Gerald Maurice Edelman (born July 1, 1929) is an American biologist who won the 1972 Nobel Prize in Physiology or Medicine for his A Bence Jones protein is a monoclonal Globulin Protein found in the Blood or Urine. Henry Bence Jones ( December 31, 1813 - April 20, 1873) English Physician and Chemist, was born at Thorington ^[64] Edelman went on to discover that antibodies are composed of disulfide bond-linked heavy and light chains. In Chemistry, a disulfide bond is a single Covalent bond derived from the coupling of Thiol groups Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized by Rodney Porter. Rodney Robert Porter, FRS ( 8 October 1917 &ndash 7 September 1985) was an English Biochemist. ^[65] Together, these scientists deduced the structure and complete amino acid sequence of IgG, a feat for which they were jointly awarded the 1972 Nobel prize in Physiology or Medicine. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this The Nobel Prize (Nobelpriset (Nobelprisen is a Swedish prize established in the 1895 will of Swedish chemist Alfred Nobel; it was first awarded in Peace, Literature Physiology (from Greek grc φύσις physis, "nature origin" and grc -λογία -logia) is the study of the mechanical physical Medicine is the art and science of healing It encompasses a range of Health care practices evolved to maintain and restore Human Health by the ^[65] While most of these early studies focused on IgM and IgG, other immunoglobulin isotypes were identified in the 1960s: Thomas Tomasi discovered secretory antibody (IgA)^[66] and David Rowe and John Fahey identified IgD,^[67] and IgE was identified by Kikishige Ishizaka and Teruki Ishizaka as a class of antibodies involved in allergic reactions. Immunoglobulin A ( IgA) is an Antibody playing a critical role in mucosal immunity David Rowe is the name of several people David E Rowe, American science historian David C John Fahey may refer to John Fahey (musician (1939–2001 American guitarist and composer John Fahey (politician (b In Biology, Immunoglobulin E ( IgE) is a class of Antibody (or Immunoglobulin " Isotype " that has only been found in ^[68]

Genetic studies revealed the basis of the vast diversity of these antibody proteins when somatic recombination of immunoglobulin genes was identified by Susumu Tonegawa in 1976. Susumu Tonegawa (利根川 進 Tonegawa Susumu, born September 6, 1939) is a Japanese Scientist who won the Nobel Prize for Physiology ^[69]

See also

References

External links

• Mike's Immunoglobulin Structure/Function Page at University of Cambridge
• Antibodies as the PDB molecule of the month Discussion of the structure of antibodies at Protein Data Bank
• Microbiology and Immunology On-line Textbook at University of South Carolina
• A hundred years of antibody therapy History and applications of antibodies in the treatment of disease at University of Oxford
• How Lymphocytes Produce Antibody from Cells Alive!
• Antibody applications Fluorescent antibody image library, University of Birmingham
• Images produced using antibodies at antibodypatterns. The University of Cambridge (often Cambridge University) located in Cambridge, England, is the second-oldest university in the The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography This article is about the University of South Carolina in Columbia The University of Oxford (informally "Oxford University" or simply "Oxford" located in the city of Oxford, Oxfordshire, England is the The University of Birmingham (informally Birmingham University) is a British red brick University located in the city of Birmingham com