ANTIBODY

'Antibodies' are Y-shaped 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. They are made of a few basic structural units called ''chains''; each antibody has two large heavy chains and two small light chains. 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. 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.Eleonora Market, F. Nina Papavasiliou (2003) ''V(D)J Recombination and the Evolution of the Adaptive Immune System'' PLoS Biology1(1): e16.
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. Each of these variants can bind to a different target, known as an antigen. Immunobiology., Janeway CA, Jr ''et al'', , , Garland Publishing, 2001, 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. These epitopes fit precisely with their antibody, similar to a key fitting into a lock, in a highly specific interaction 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. 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. Human Physiology, Rhoades RA, Pflanzer RG, , , Thomson Learning, 2002,
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. Somatic immunoglobulin hypermutation, Diaz M, Casali P, , , Curr Opin Immunol, 2002 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. This allows a single antibody to be used by several different parts of the immune system.
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). The BCR allows a B cell to detect when a specific antigen is present in the body and triggers B cell activation.^[1] 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.^[2] Antibodies are, therefore, an essential component of the adaptive immune system that learns, adapts and remembers responses to invading pathogens. Production of antibodies is the main function of the humoral immune system. Immunology, Infection, and Immunity, Pier GB, Lyczak JB, Wetzler LM, , , ASM Press, 2004,

Contents

Isotypes

Structure

Immunoglobulin domains

Heavy chain

Light chain

Fab and Fc Regions

Function

Neutralization

Activation of complement

Activation of effector cells

Affinity versus avidity

Immunoglobulin diversity

V(D)J recombination

Somatic hypermutation and affinity maturation

Class switching

Medical applications

Disease diagnosis

Disease therapy

Prenatal therapy

Research applications

Use

History

See also

References

External links

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 their colonization by pathogens.[3]	Some antibodies form complexes that bind to multiple antigen molecules.
IgD	1	Functions mainly as an antigen receptor on B cells. The riddle of the dual expression of IgM and IgD, Geisberger R, Lamers M, Achatz G, , , Immunology, 2006 Its function is less defined than other isotypes.
IgE	1	Binds to allergens and triggers histamine release from mast cells, and is involved in allergy. Also protects against parasitic worms.
IgG	4	In its four forms, provides the majority of antibody-based immunity against invading pathogens.
IgM	1	Expressed on the surface of B cells and in a secreted form with very high avidity. Eliminates pathogens in the early stages of B cell mediated immunity before there is sufficient IgG.

Antibodies can come in different forms known as isotypes or classes. In mammals there are five antibody isotypes known as IgA, IgD, IgE,IgG and IgM. 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. Human antibody-Fc receptor interactions illuminated by crystal structures, Woof J, Burton D, , , Nat Rev Immunol, 2004
The antibody isotype of a B cell changes during the cell's development and activation. 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. Allotypes of IgM and IgD receptors in the mouse: a probe for lymphocyte differentiation, Goding J, , , Contemp Top Immunobiol, 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 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 antiodies to change from IgM or IgD to the other antibody isotypes, IgE, IgA or IgG, that have defined roles in the immune system.

Structure

Antibodies are heavy globular plasma proteins that are also known as immunoglobulins. They have sugar chains added to some of their amino acid residues.^[4] In other words, antibodies are ''glycoproteins''. 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. Immunoglobulin structure and function as revealed by electron microscopy, Roux K, , , Int Arch Allergy Immunol, 1999
, and thus different antigen specificities.
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.^[14]

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. Following activation with antigen, B cells begin to proliferate rapidly. 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). 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.
Somatic hypermutation serves to increase the diversity of the antibody pool and impacts the antibody’s antigen-binding affinity.^[15] 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). Recirculation of germinal center B cells: a multilevel selection strategy for antibody maturation, Or-Guil M, Wittenbrink N, Weiser AA, Schuchhardt J, , , Immunol. Rev., 2007 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. Thus, B cells expressing higher affinity antibodies for 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.^[16]

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). 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.^[17]
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 is broken by the activity of a series of enzymes at two selected S-regions.^[18][19] The variable domain exon is rejoined through a process called non-homologous end joining (NHEJ) to the desired constant region (γ, α or ε). This process results in an immunoglobulin gene that encodes an antibody of a different isotype.^[20]

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.^[21] For example, in biochemical assays for disease diagnosis,^[22] a titer of antibodies directed against Epstein-Barr virus or Lyme disease is estimated from the blood. 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.^[23] Elevations in different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients whom the diagnosis is unclear. 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. Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia are detected with the Coombs test. Blood Groups and Red Cell Antigens, , Laura, Dean, National Library of Medicine (US),, 2005, The Coombs test is also used for antibody screening in blood transfusion preparation and also for antibody screening in antenatal women.
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.

Disease therapy

"Targeted" monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis,^[24] multiple sclerosis,^[25] psoriasis,^[26] and many forms of cancer including non-Hodgkin's lymphoma,^[27] colorectal cancer, head and neck cancer and breast cancer.^[28]
Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia, result in partial or complete lack of antibodies.^[29] These diseases are often treated by inducing a short term form of immunity called passive immunity. 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. Immunization Ghaffer A

Prenatal therapy

''Rho(D) Immune Globulin'' antibodies are specific for human Rhesus D antigen, also known as Rhesus factor. Prevention of Rh alloimmunization, Fung Kee Fung K, Eason E, Crane J, Armson A, De La Ronde S, Farine D, Keenan-Lindsay L, Leduc L, Reid G, Aerde J, Wilson R, Davies G, Désilets V, Summers A, Wyatt P, Young D, , , J Obstet Gynaecol Can, 2003 These antibodies are known under several brand names, including RhoGAM. 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.
During normal childbirth, delivery trauma or complications during pregnancy, blood from a fetus can enter the mother's system. In the case of an Rh-incompatible mother and child, consequential blood mixing may sensitize an Rh- mother to the Rh antigen, putting the remainder of the pregnancy, and any subsequent pregnancies, at risk for hemolytic disease of the newborn.^[30] RhoGAM is administered as part of a prenatal treatment regimen to prevent sensitization that may occur when a Rhesus-negative mother has a Rhesus-positive
fetus.
Treatment of a mother with RhoGAM 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. Therefore, her humoral immune system will not make anti-Rh antibodies, and will not attack the Rhesus antigens of the current or subsequent baby. RhoGAM treatment prevents sensitization that can lead to Rh disease, but does not prevent or treat the underlying disease itself.

Research applications

Immunofluorescence image of the eukaryotic cytoskeleton. Actin filaments are shown in red, microtubules in green, and the nuclei in blue.

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. 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. Antigens are also injected into chickens for generation of polyclonal antibodies in egg yolk.^[31] 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. The fused cells are called hybridomas, and will continually grow and secrete antibody in culture. Single hybridoma cells are isolated by dilution cloning to generate cell clones that all produce the same antibody; these antibodies are called ''monoclonal antibodies''.^[32]
Generated polyclonal and monoclonal antibodies are often purified using Protein A/G or antigen-affinity chromatography.^[33]

Use

In research, purified antibodies are used in many applications. They are most commonly used to identify and locate intracellular and extracellular proteins. 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. Single-cell microbiology: tools, technologies, and applications, Brehm-Stecher B, Johnson E, , , Microbiol Mol Biol Rev, 2004 They are also used in immunoprecipitation to separate proteins and anything bound to them (co-immunoprecipitation) from other molecules in a cell lysate,^[34] in Western blot analyses to identify proteins separated by electrophoresis,^[35] and in immunohistochemistry or immunofluorescence to examine protein expression in tissue sections or to locate proteins within cells with the assistance of a microscope.^[36] Proteins can also be detected and quantified with antibodies, using ELISA and ELISPOT techniques.^[37][38]

History

The study of antibodies began in 1890 when Emil von Behring and Shibasaburo Kitasato described antibody activity against diphtheria and tetanus toxins. Behring and Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen.^[39][40] 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.^[41] 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.^[42]
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.^[43] The biochemical properties of antigen-antibody binding interactions were examined in more detail in the late 1930s by John Marrack.^[44] 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.^[45] In 1948, Astrid Fagreaus discovered that B cells, in the form of plasma cells, were responsible for generating antibodies.^[46]
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,^[47] and their realization that this protein was the same as the Bence-Jones protein described in 1845 by Henry Bence Jones.^[48] Edelman went on to discover that antibodies are composed of disulphide bond-linked heavy and light chains. Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized by Rodney Porter. The Nobel chronicles. 1972: Gerald M Edelman (b 1929) and Rodney R Porter (1917-85), Raju TN, , , Lancet, 1999 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. 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) ^[49] and David Rowe and John Fahey identified IgD,^[50] and IgE was identified by Kikishige Ishizaka and Teruki Ishizaka as a class of antibodies involved in allergic reactions.^[51]
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.^[52]

See also

★ Anti-mitochondrial antibodies

★ Anti-nuclear antibodies

★ ELISA

★ Humoral immunity

★ Immunology

★ Immunosuppressive drug

★ Monoclonal antibody

★ Nanobodies

★ Secondary antibodies

References

1. T cell-dependent B cell activation, Parker D, , , Annu Rev Immunol, 1993
2. From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion, Borghesi L, Milcarek C, , , Immunol Res, 2006
3. Immunoglobulin A: strategic defense initiative at the mucosal surface, Underdown B, Schiff J, , , Annu Rev Immunol, 1986
4. The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N-glycosylation on Fc alpha receptor interactions, Mattu T, Pleass R, Willis A, Kilian M, Wormald M, Lellouch A, Rudd P, Woof J, Dwek R, , , J Biol Chem, 1998
5. Membrane proteins with immunoglobulin-like domains--a master superfamily of interaction molecules, Barclay A, , , Semin Immunol, 2003
6. Spatial structure of immunoglobulin molecules, Huber R, , , Klin Wochenschr, 1980
7. Complement and Fc-receptors in regulation of the antibody response, Heyman B, , , Immunol Lett, 1996
8. Venoms, antivenoms and immunotherapy, Chippaux J, Goyffon M, , , Toxicon, 1998
9. The role of the complement system in innate immunity, Rus H, Cudrici C, Niculescu F, , , Immunol Res, 2005
10. In vitro affinity maturation of human IgM antibodies reactive with tumor-associated antigens, Pancook J, Beuerlein G, Pecht G, Tang Y, Nie Y, Wu H, Huse W, Watkins J, , , Hybrid Hybridomics, 2001
11. The role of antibody concentration and avidity in antiviral protection, Bachmann MF, Kalinke U, Althage A, ''et al'', , , Science, 1997
12. Structure, function and properties of antibody binding sites, Mian I, Bradwell A, Olson A, , , J Mol Biol, 1991
13. Development of the immunoglobulin repertoire, Fanning LJ, Connor AM, Wu GE, , , Clin. Immunol. Immunopathol., 1996
14. A stepwise epigenetic process controls immunoglobulin allelic exclusion, Bergman Y, Cedar H, , , Nat Rev Immunol, 2004
15. Origin of immune diversity: genetic variation and selection, Honjo T, Habu S, , , Annu Rev Biochem, 1985
16.
17. Evolution of isotype switching, Stavnezer J, Amemiya CT, , , Semin. Immunol., 2004
18. Activation-induced cytidine deaminase: a dual role in class-switch recombination and somatic hypermutation, Durandy A, , , Eur. J. Immunol., 2003
19. Class switching and Myc translocation: how does DNA break?, Casali P, Zan H, , , Nat. Immunol., 2004
20. Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations, Lieber MR, Yu K, Raghavan SC, , , DNA Repair (Amst.), 2006
21. Animated depictions of how antibodies are used in ELISA assays
22. Animated depictions of how antibodies are used in ELISPOT assays
23. Current possibilities of turbidimetry and nephelometry, Stern P, , , Klin Biochem Metab, 2006
24. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?, Feldmann M, Maini R, , , Annu Rev Immunol, 2001
25. Is natalizumab a breakthrough in the treatment of multiple sclerosis?, Doggrell S, , , Expert Opin Pharmacother, 2003
26.
27. Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia, Plosker G, Figgitt D, , , Drugs, 2003
28. First-line Herceptin monotherapy in metastatic breast cancer, Vogel C, Cobleigh M, Tripathy D, Gutheil J, Harris L, Fehrenbacher L, Slamon D, Murphy M, Novotny W, Burchmore M, Shak S, Stewart S, , , Oncology, 2001
29. Fates of human B-cell precursors, LeBien TW, , , Blood, 2000
30. RhD haemolytic disease of the fetus and the newborn, Urbaniak S, Greiss M, , , Blood Rev, 2000
31. Generation and application of chicken egg-yolk antibodies, Tini M, Jewell UR, Camenisch G, Chilov D, Gassmann M, , , Comp. Biochem. Physiol., Part A Mol. Integr. Physiol., 2002
32. Human monoclonal antibodies, Cole SP, Campling BG, Atlaw T, Kozbor D, Roder JC, , , Mol. Cell. Biochem., 1984
33. Immunoglobulin purification by affinity chromatography using protein A mimetic ligands prepared by combinatorial chemical synthesis, Kabir S, , , Immunol Invest, 2002
34. Immunoprecipitation procedures, Williams N, , , Methods Cell Biol, 2000
35. Western blotting, Kurien B, Scofield R, , , Methods, 2006
36. Immunohistochemical staining of fixed tissues, Scanziani E, , , Methods Mol Biol,
37. Enzyme-linked immunosorbent assay (ELISA)., Reen DJ., , , Methods Mol Biol., 1994
38. Chemistry and biology of the ELISPOT assay, Kalyuzhny AE, , , Methods Mol Biol., 2005
39. Emil von Behring - Biography
40. The Late Baron Shibasaburo Kitasato, AGN, , , Canadian Medical Association Journal, 1931
41. Paul Ehrlich--in search of the magic bullet, Winau F, Westphal O, Winau R, , , Microbes Infect., 2004
42. Cellular versus humoral immunology: a century-long dispute, Silverstein AM, , , Nat. Immunol., 2003
43. Michael Heidelberger and the demystification of antibodies, Van Epps HL, , , J. Exp. Med., 2006
44. Chemistry of antigens and antibodies, , JR, Marrack, His Majesty's Stationery Office, 1938,
45. The Linus Pauling Papers: How Antibodies and Enzymes Work
46. Labeled antigens and antibodies: the evolution of magic markers and magic bullets, Silverstein AM, , , Nat. Immunol., 2004
47. The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins, Edelman GM, Gally JA, , , J. Exp. Med., 1962
48. Bence Jones proteins: a powerful tool for the fundamental study of protein chemistry and pathophysiology, Stevens FJ, Solomon A, Schiffer M, , , Biochemistry, 1991
49. The discovery of secretory IgA and the mucosal immune system, Tomasi TB, , , Immunol. Today, 1992
50. Structural and functional properties of membrane and secreted IgD, Preud'homme JL, Petit I, Barra A, Morel F, Lecron JC, Lelièvre E, , , Mol. Immunol., 2000
51. The discovery of immunoglobulin E, Johansson SG, , , Allergy and asthma proceedings : the official journal of regional and state allergy societies, 2006
52. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions, Hozumi N, Tonegawa S, , , Proc. Natl. Acad. Sci. U.S.A., 1976

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.com

★ research antibody review based on open-source, peer-reviewed publications at exactantigen.com

★ Antibody database, search by reactivity, host species, applications and conjugate at biocompare.com