key: cord-0778020-igv2wl97
authors: Dias da Silva, Wilmar; Tambourgi, Denise V.
title: IgY: A promising antibody for use in immunodiagnostic and in immunotherapy
date: 2010-06-15
journal: Vet Immunol Immunopathol
DOI: 10.1016/j.vetimm.2009.12.011
sha: faa10d20171fc79193c7b5b64da8448d34830765
doc_id: 778020
cord_uid: igv2wl97

Immunoglobulin IgY is the major antibody produced by chickens (Gallus domesticus). After their V-C gene is rearranged in B cells, IgY is continually synthesized, excreted into the blood and transferred to the egg yolk, where it is accumulated. IgY is produced by hens to provide their offspring with an effective humoral immunity against the commonest avian pathogens until full maturation of their own immune system. In this review we aim to give an overview about the generation, structure, properties of IgY, as well as the advantages of chicken antibodies use over mammalian antibodies in immunodiagnostics and immunotherapy.

B lymphocytes and their mature counterpart, plasmocytes, are highly specialized secretor type of cells whose exclusive products are glycoproteins, the immunoglobulins (Igs) or antibodies. These cells are found in several animal groups including mammals and birds. According to the ''clonal selection theory'' proposed by F. MacFarlane Burnet in the 1950s, which has now been demonstrated to be correct, an enormous number of antibody-producing cells are constantly differentiated and each one expresses on its surface an Ig specific for a unique antigen.

In the human immunoglobulin molecule, the protein prototype has two identical 25 kDa light (L) chains and also two identical 55-77 kDa heavy (H) chains. Two structurally distinct regions are found in both chains: in light Immunoglobulin Diversity Chicken IgY Egg Purification Immunodiagnostic Immunotherapy A B S T R A C T Immunoglobulin IgY is the major antibody produced by chickens (Gallus domesticus). After their V-C gene is rearranged in B cells, IgY is continually synthesized, excreted into the blood and transferred to the egg yolk, where it is accumulated. IgY is produced by hens to provide their offspring with an effective humoral immunity against the commonest avian pathogens until full maturation of their own immune system. In this review we aim to give an overview about the generation, structure, properties of IgY, as well as the advantages of chicken antibodies use over mammalian antibodies in immunodiagnostics and immunotherapy.

ß 2010 Elsevier B.V. All rights reserved.

chains, V L (110 amino acids) and C L (110 amino acids) and in heavy chains, V H (110 amino acids) and C H (330-440 amino acids). Therefore, the whole immunoglobulin molecule contains 1320-1540 amino acid residues (Edelman, 1991) . The L and H polypeptides are positioned in such way that V domains and C domains of L chains are in parallel with their counterpart of the H chain. Each HL monomer contains one antigen-binding site. Inter-chain disulfide bonds and non-covalent interactions associate each L chain with one H chain and the two H chains with the each other (Padlan, 1994; Ramsland and Farrugia, 2002) . The amino acid sequences in L and H chains, rather than being straight, are folded into regular segments by intrachain disulfide bonds forming globular regions, the molecular domains. L chains contain two domains, V L and C L , whereas the H chains have four to five domains, V H 1, C H 1, C H 2, C H 3 (or C H 4). In the tetrameric Ig molecule, H 2 L 2 , there are a total of 12-14 domains: 4V domains and 8-10C domains. Pairing of one entire L chain (L V L C ) with the first domain of the H chain (H V H C1 ) results in (L V L C ) (H V H C 1), called Fab, while pairing C H 2 and C H 3 from the two H chains results in the formation of (C H 2 C H 3) (C H 2 C H 3), called Fc portion (Padlan, 1994; Ramsland and Farrugia, 2002) . In most Igs there are, therefore, two Fabs and one Fc. The two Fab regions join the Fc region to form the Y-like structure at the hinge region. This region is rich in proline residues, providing flexibility to this region (Saphire et al., 2002) . Sites of carbohydrate attachments and regions for interactions with the complement component, C1, are located within the C H 2 domain of Igs with three C H domains, or in the C H 3 domain of the Igs with four C H domains (Davies and Metzger, 1983; Bengten et al., 2000) (Fig. 1A) .

Immunoglobulin IgY is the major antibody produced by chickens (Gallus domesticus). After their V-C gene is rearranged in B cells, IgY is continually synthesized, secreted into the blood and transferred to the egg yolk, where it is accumulated (Warr et al., 1995) . IgY is produced by hens to provide their offspring with an effective humoral immunity against the commonest avian pathogens until full maturation of their own immune system. In chickens, only three immunoglobulins classes have been well identified, IgM, IgA and IgY, and suggested but not yet proven are IgD and IgE (Chen et al., 1982; Burns and Maxwell, 1981) . IgY (167,250 kDa), although prevalent in circulating blood (5-7 mg/ml of serum) and in egg yolk (100 mg/egg yolk), is also found in duodenal contents, tracheal secretions and in seminal fluid (Leslie and Clem, 1969) .

IgY, like its mammalian counterpart IgG, is composed of two L and two H chains. Their L (18,660 kDa) and H (designated as upsilon, y, 65,105 kDa) chains are also composed of V and C regions (Sun et al., 2001) . The L chain contains one V and one C domain, and the y chain contains one V domain and four C domains (Cy1, Cy2, Cy3 and Cy4) (Zhao et al., 2000; Carlander, 2002) . The Fab regions, similar to mammalian immunoglobulins, contain the antigen-binding sites, whereas the Fc region contains domains responsible for complement activation, opsonization and mast cell sensitization for anaphylactic reactions (Fig. 1B) .

By the use of a recombinant fragment of IgY-Fc consisting of a dimmer of the Cy3/Cy4 domains, the putative common origin for mammalian and avian immunoglobulins was investigated. The Fcy3-4 was expressed, crystallized, and its X-ray structure determined. The presence of common features to both IgG-Fc and IgE-Fc in the obtained Fcy3-4 crystals reinforced such structural ancient commonality (Alexander et al., 2009 ). Although such common origin, marked structural differences distinguish mammalian IgG and avian IgY. 

The estimated diversity in antibody specificity is close to 10 11 and it is enough to cover the antigen repertoire. Effective production of antibodies for the existent antigenic repertoire requires rearrangement of the different immunoglobulin protein segments (Tonegawa, 1981; Alt et al., 1987) . In mammalian species, such as mouse and human, the presence in the genome of multiple functional V (variable), D (diversity) and J (joining) segments ensures rearrangement to form VDJ H and VJ L complexes, which encodes V H and V L domains, respectively for the heavy (H) and light (L) chains of the Ig molecule. For a Ig rearranged functional antibody molecule, some V segments are randomly selected to form the V L J and V H J(D) DNA segments (Fig. 2) . The estimated rearranging segment numbers in mammalian Ig loci are:

Mouse: V H , 100-200; V L kappa, 250-300; V L lambda, 3; D, 27 exclusively for heavy chain; J, 4 for both chains. Human: V H , 130; V L kappa, 75; V L lambda 75; D, 15 exclusively for heavy chain; J, 6 for heavy chain; 5 and 7 for the light kappa and lambda chains, respectively.

An additional mechanism that generates new diversity, throughout the already assembled Ig locus, is known as somatic hypermutation. Although somatic mutations occur in low frequency in all dividing cells, their frequency is higher in B cells at a rate of 10 3 mutations per nucleotide pair per cell division. This high rate of point mutation, approximately one million times higher than in other cells, is restricted to the rearranged Ig locus. Point mutations, besides assure such enormous increase in the antibody repertoire is responsible for the emergence of immunoglobulins with high affinity for their specific antigens. In mammalian the antibody diversity can be also generated through a ''multi-V(D)J'' mechanism. In sheep in which the Ig locus contains a limited number of different VJ L rearrangements, diversity is further created by the introduction of multiple point mutations into the rearranged segments (Reynaud et al., 1991; Weill et al., 1995) (Fig. 2) .

In chickens, both H and L chain gene loci consist of a single V gene (Reynaud et al., 1985; Weill and Reynaud, 1987) . This intrinsic deficiency in the capacity to generate antibody diversity by germ line rearrangement of V locus DNA segments is over passed by the gene hyper conversion Reynaud et al., 1987) , V-J flexible joining (McCormick et al., 1989) and somatic point mutation (Parvari et al., 1990) . Around days 15-17 of the embryonic development, immature B cells progenitors leave the bone marrow and migrate to bursa of Fabricius. After properly homing in special sites of bursa of Fabricius, blocks of DNA are transferred from pseudo-Vgenes to the recombined V regions of the Ig genes. Clones of mature competent B cells are produced and the immune humoral compartment is organized (Masteller et al., 1995) .

Three exons separated by two introns encode the y Hchain constant regions of IgY, IgA and IgM all located on chromosome E18C15W15. On this chromosome intervening DNA sequences of 18 and 15 kb separate the genes for IgA, IgY and IgM, respectively. The entire H Ig locus, V(D)Jagm comprises a DNA segment with, approximately, 67 kb (Zhao et al., 2000) . To construct the large number of V(D)J in chicken, equivalent to mammals, different mechanisms are used. First, by successive partial conversions of the rearranged V(D) containing the only V region and one of the 16 alternative D sequences available (Carlander, 2002) . Next, by successive partial conversions of the rearranged V(D) segments by templates located in an upstream array of pseudo-V(D) genes and the V(D)J is rearranged (Carlander, 2002; McCormick et al., 1993) (Fig. 3) . The mature competent immunoglobulin-producing B cells leave the bursa of Fabricius to populate the chicken's secondary immune system .

IgY secretion in the young chick starts 6 days after hatching. The IgY secreted by mature B cells is delivered directly into the circulation, attaining a constant concentration of 1.0-1.5 mg/ml of serum (Davies et al., 1995) . Along the hen's productive life, the serum IgY concentration is maintained stable due to an equilibrium resulting from its continued synthesis and transfer processes.

The IgY stored in egg yolk, at the time of incubation, is the antibody source produced by the hen to protect the young chick during the first days after hatching. The IgY antibody concentrations range from 50 to 100 mg per egg yolk. In contrast, IgM and IgA are present in egg-white but almost undetectable in egg yolk (Carlander, 2002) . These antibodies are first adhered in the yolk sac from days 7 to 18 of incubation, where they bind and fix in a domainspecific Fc receptors-pH-dependent manner (McCormick et al., 1993) . This association of IgY-Fc and yolk sac receptors is first mediated by low affinity sac receptors with K D of 3.4 Â 10 À7 (on the 8th day of incubation), and then by receptors of high affinity, with K D 3.4 Â 10 À8 (on the 18th day of incubation) (McCormick et al., 1993) . The IgY-Fc receptors continually attract and bind all IgY reaching the hen serum (Davies et al., 1995) .

Although IgY can be purified from serum or plasma, egg yolk is by far the indicated source for purification (Brambell, 1970; Rose et al., 1974) . Eggs can be collected daily from the same hen and processed either individually or, as desired, from hens belonging to a similar immunized group. Over 100 mg of purified IgY can be obtained from a single egg (Tressler and Roth, 1987) . As hens continue producing eggs along at least 10 months, it is possible to obtain enormous amounts of specific IgY directed to the Fig. 3 . The antibody diversification in chicken by gene conversion. During this process pseudo-derived genes sequences (left) replace homologous sequences in rearranged immunoglobulin genes (right), giving rise to rearranged complete IgG (IgY) functional gene (center). This process occurs in bursa of Fabricius resident B cells. Resulting IgY molecules are secreted into the blood circulation and subsequently stored on egg yolk. same or related antigens (Loeken and Roth, 1983; Polson et al., 1980) . Different methods are currently used to isolate IgY from egg yolk. A simple non-expensive method was published by Bhanushali et al. (1994) ; the egg yolk is diluted 10-fold with distilled water, pH 5.5 and the suspension incubated overnight at 4 8C. The supernatant containing the IgY is collected by centrifugation (10,000 Â g at 4 8C for 30 min), and the temperature adjusted to 20 8C and subjected to 29% ammonium sulfate. Precipitate proteins are recovered by centrifuging the solution (10,000 Â g at 4 8C for 30 min), re-dissolving in 0.15 M NaCl and dialyzing against this same solution. The material can be further purified by Q-Sepharose Fast Flow chromatography to remove nonimmunoglobulin proteins. The resulting IgY preparations are re-dissolved in 0.15 M NaCl and dialyzed against this same solution. When specific purified IgY antibodies are desired, immune-affinity chromatography can be used. The antibodies are applied, at neutral pH, to a column prepared with a matrix, where the antigen of interest is bound. After washing with isotonic phosphate-saline, pH 7.2, to remove non-specific antibodies, specific bound IgY antibodies are eluted with 0.1 M glycine, pH 2.2-2.8 (Akita and Nakai, 1992; Kim et al., 1999; Almeida et al., 1998 Almeida et al., , 2003 Almeida et al., , 2008 .

IgY, like mammalian IgG, is a reasonably stable protein. Diluted in saline-containing substances that preserve the protein structure, IgY antibody activity can be stored at 2-4 8C. When lyophilized, the IgY antibody activity is not diminished even after several months of storage at temperatures of À20 8C or less, or even for 1 month at 37 8C. IgY, however, is not very stable at temperatures of higher than 70 8C, and at pH below 4.0 (Shimitzu et al., 1994; Olovsson and Larsson, 1993; Larsson et al., 1999) . IgY can be stored for over 10 years in 0.15 M NaCl containing 0.02% NaN 3 at 4 8C (Shimitzu et al., 1994) . The IgY antibodies, such as mammalian IgG, can be labeled by routinely described methods with biotin or horseradish (Olovsson and Larsson, 1993; Larsson et al., 1999) .

Similar to mammalian IgG, IgY is bivalent, but its hinge region is more rigid due to a very different amino acid sequence (Warr et al., 1995) . This region is probably responsible for the particular behavior that occurs when the IgY antibody combines with the antigen.

The IgY antibodies are identified and quantified by the usual immunochemical methods. Reliable methods for characterizing or quantifying IgY antibodies include agglutination of particulate antigens, precipitation of soluble antigens, identification of cell-bound antigens by immunofluorescence techniques (Kim et al., 1999) and the blocking of some exposed active domains in wellcharacterized molecules, such as toxins, enzymes, hormones, or even other immunglobulins (Kubbo et al., 1973; Shimitzu et al., 1998; Akita et al., 1998; Hata et al., 1993) . Agglutination and precipitation of the antigens are particularly affected by the rigidity of IgY hinge region. The immune precipitin reaction, for instance, expresses better when performed in the presence of 1.5 M NaCl (Shimitzu et al., 1998) . IgY antibodies are, however, very effective at neutralizing toxins present in animal venoms (Almeida et al., 1998 (Almeida et al., , 2003 (Almeida et al., , 2008 Shimitzu et al., 1998; Akita et al., 1998; Hata et al., 1993) , and block some virulence factors such as BfpA, expressed by enteropathogenic Escherichia coli (Almeida et al., 2003) .

The IgY concentration in the serum of adult hens is approximately 5-7 mg/ml. One hen of a high egg-laying strain can produce around 20 eggs per month. Such amounts correspond to 2 g of IgY per month equivalent, therefore, to the IgY content of 300 ml of serum or 600 ml of total blood (Shimitzu et al., 1994) . Such amounts of blood only can be obtained from large mammals. Chicken antibodies, therefore, constitute a much less expensive vehicle for use in diagnostic proposals.

It is a well-known concept that the immune response is more potent when the distance between the antigen source and the immune system increases. Therefore, to obtain immunoreagents containing antibody titers against mammalian antigens, chickens are better and cheaper than mammals (Shimitzu et al., 1994; Olovsson and Larsson, 1993; Svendsen and Hau, 1996; Ericka, 1999; Larsson et al., 1999) . Furthermore, chicken antibodies recognize more epitopes when mammalian proteins are used as antigens, than the corresponding mammalian antibodies (Svendsen and Hau, 1996; Hadge and Anbrosuius, 1984; Horton et al., 1984; Song et al., 1985) . The absence of immunological cross-reactivity between chicken IgY and mammalian IgG (Hadge and Anbrosuius, 1984) , determined by the evolutionary distance, reinforces the advantages of using IgY over IgG as the first antibody in some types of immunological reactions. For instance, in immunohistochemical analysis the usually common cross-reactions observed between tissue IgG and epitopes, shared by the primary antibody and recognized by the secondary mammalian antibody, are not observed when IgY is used as the secondary antibody (Larsson and Lindahl, 1993) . Chicken antibodies exhibit high avidity (10 9 L/mol) even after the first immunization. In order to reach similar avidity values (10 10 L/mol), sheep must receive four boosters (Wooley and Landon, 1995) .

Despite the significant advantage of chickens over sheep as antibody producers, the antibody half-lives of chicken antibodies are approximately 36 h, while sheep antibodies half-lives are of about 15 days. Chickens can be immunized through different routes, as desired by the immunization protocols (Wooley and Landon, 1995) . The injection of the antigen by the intramuscular route results in higher antibody levels by day 28 after immunization, and the resulting antibodies also exhibit higher specificity, being over 10 times more specific when compared with chickens immunized with the same antigen but by the sub-cutaneous via (Wooley and Landon, 1995) . Chickens, immunized by the intramuscular via, continue producing specific antibodies during more than 200 days (Horton et al., 1984) . Chickens can also tolerate the use of common immunological adjuvants, such as Freund's adjuvant, Specol, Hunters TiterMax and lipopeptide Pam 3 -Cys-(lys) 4 (Losch et al., 1986) . The percentage of antigen specific antibodies in one egg yolk is close to 10% (Losch et al., 1986; Hass and Aspock, 1988; Thalley and Carrol, 1990; Akita et al., 1998) .

Effective protection against Salmonella enteritidis, Salmonella e. typhimurium, Campylobacter jejuni, Escherichia coli ETEC, murine and bovine rotavirus, and bovine corona virus infections in mice, pig and calves has been obtained with the use of passively-administered egg yolk-derived antibodies (Chalghoumi et al., 2009) .

Purified IgY preparations, obtained from hens immunized with C. jejuni, were able to induce both prophylactic and therapeutic effects in chickens. The prophylactic protection was analyzed by preincubating 0.5 g of IgY with 10 6 CFU of the bacteria, while the therapeutic effect was analyzed by administering the bacteria 4 days before the administration of 0.2 g IgY antibodies. Antibodies and bacteria were administered orally and protection against infection was followed by counting the bacteria in faeces. A decrease in the number of bacteria in faeces, as compared with controls, was observed. In the therapeutic experiment, a marked reduction of 80-95% was also observed. These observations suggest that oral passive immunization with anti-C. jejuni IgY may be a prophylactic and therapeutic tool to protect chickens against this bacterial infection (Tsubokura et al., 1997) .

Anti-S. enteritidis egg yolk antibodies, administered in powdered form in hens feed, were found to reduce the rate of S. enteritidis contaminated eggs (13.3% contaminated eggs), in comparison with the control group (26.0% contaminated eggs). Doses of 3 g of egg powder per day per hen ($2.5% of the feed) were ingested ad libitum for 23 or 26 days. The experimental group received egg powder from immunized hens. In contrast, the control group received egg powder from non-immunized hens (Gü rtler et al., 2004) .

The protective effect of feed supplementation with nonimmunized egg yolk powdered and immunized egg yolk powder (containing anti-S. enteritidis antibodies) on the elimination of S. enteritidis infection in laying hens was further investigated in a multi-trial study. Hens were orally infected with 10 9 CFU S. enteritidis. Four weeks after the bacterial challenge, hens were given daily a supplemented feed of 15% (w/w) of either non-immunized egg yolk powder or immunized egg yolk powder for 28 days. Oral administration of both powders resulted in a rapid decrease in the number of S. enteritidis in faeces and an elimination of the organism after 2 weeks of feeding (Brady et al., 2002; Sugita-Konishi et al., 2000) .

In order to investigate the specificity of the egg yolk IgY antibodies for protecting hens against S. e. typhimurium, C. jejuni, and E. coli infections, hens were given the nonimmunized egg yolk powder at concentrations ranging between 1 and 10% (w/w) for S. e. typhimurium and C. jejuni challenge tests, and between 5 and 10% (w/w) for the E. coli challenge test. Egg yolk powder, at a concentration of close to 5% (w/w) was able to eliminate S. e. typhimurium and significantly reduce the bacterial shedding after 2 weeks of feeding. Higher concentrations (7.5%, w/w) of egg yolk powder from non-immune hens were also able to reduce the colonization of C. jejuni and E. coli. Therefore, oral administration of non-immunized egg yolk powder can reduce colonization of the intestinal tract, indicating that the egg yolk may contain additional anti-infectious factors, besides IgY.

Among the non-specific antibacterial activities present in egg yolk, the lipoprotein-derived anti-microbial factor from hen-egg yolk (LDAMF) and egg plasma-derived sialyoligosaccharides (EPDS) have been identified. LDAMF inhibits Streptococcus strain growth, in vitro, while (EPDS) prevents Salmonella infection (Gü rtler et al., 2004; Sugita-Konishi et al., 2000 , 2002 .

Experiments to observe the effect of S. enteritidisspecific IgY administration on the bacterial fecal shedding have been performed recently (Sugita-Konishi et al., 2002; Schade et al., 2005; Rahimi et al., 2007) . Fifteen milliliters off yolk-containing antibody were mixed with 3.84 ml of drinking water on day one continuing for duration of the experiment. In comparison to control animals, who did not receive antibodies, the treated animals had significantly lower faecal shedding (0% versus 14%) and lower cecal concentrations of S. enteritidis (0.27 log 10 CFU versus 3.98 log 10 CFU). They also presented lower isolation of S. enteritidis from the liver, spleen and ileum. Under the conditions of this study, the use of S. enteritidis-specific IgY had a beneficial effect in reducing the colonization of Salmonella in market-aged broilers.

In experiments conducted in vitro, chicken IgY-specific antibodies directed against the E. coli enteropathogenic BfpA virulence factor have also been shown to block, in a dose-effect manner, the virulence factor-induced apoptosis of Vera cells (Melo et al., 2005) .

The use of chicken IgY, instead of IgG mammalian antibodies, to detect non-self or even self antigens, certainly may help lower costs of clinical or research immunological tests (Table 1 ). In addition, chicken antibodies do not activate the mammalian complement system nor interact with rheumatoid factors, or bacterial and human Fc receptors.

The advantages of chicken antibodies over mammalian antibodies include: (a) reduction in animal use, since chickens produce larger amounts of antibodies than laboratory animals; (b) the elimination of painful blood collections in animals; (c) the utility of IgY in many immunological assays without loss of specificity and sensitivity; (d) the considerably lower cost of feeding and handling of chickens than mammalians; (e) crude egg may be used as an antibody source. Items (a) and (b) meet the recommendations of the European Centre for the Validation of Alternative Methods (ECVAM), which specify that yolk antibodies should be used instead of mammalian antibodies for animal welfare reasons (Schade et al., 2005) . 

The crystal structure of an avian IgY-Fc fragment reveals conservation with both mammalian IgG and IgE

Neutralization of enterotoxogenic Escherichia coli heat-labile toxin by chicken egg yolk immunoglobulin Y and its antigen-binding fragments

Immunoglobulins from egg yolk. Isolation and purification

Egg yolk anti-BfpA antibodies as a tool for recognizing and identifying enteropathogenic Escherichia coli

Development of process to produce polyvalent IgY antibodies anti-African snake venom

Development of snake antivenom antibodies in chickens and their purification from yolk

Development of the primary antibody repertoire

Immunoglobulin isotypes: structure, function, and genetics

Simple method to purify chicken immunoglobulin G

A lipoprotein-derived anti-microbial factor from hen-egg yolk is active against Streptococcus species

The transmission of passive immunity from mother to young

A modification of Jerne's theory of antibody production using the concept of clonal selection

Probable occurrence of IgE in the adult domestic fowl (Gallus domesticus) after horse serum stimulation

Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala. Dissertation from the Faculty of Medicine 1119

Hen egg yolk antibodies (IgY), production and use for passive immunization against bacterial enteric infections in chicken

Evidence for an IgD homologue on chicken lymphocytes

Selection of a specific phage-display antibodies libraries derived from chicken immunoglobulin genes

Structural basis of antibody function

Human anti-animal antibody interferences in immunological assays

Antibody structure and molecular immunology

Effect of orally administered egg yolk antibodies on Salmonella enteritidis contamination of hen's eggs

Evolution of low molecular weight immunoglobulins-IV. IgY-like immunoglobulins of birds, reptiles and amphibians, precursors of mammalian IgA

Purification of egg yolk immunoglobulins. A two-step procedure using hydrophobic interaction chromatography and gel filtration

Productivity and some properties of egg yolk antibody (IgY) against human rotavirus compared with rabbit IgG

Exploitation of phylogenetic distance in cell surface immune labeling studies with b 2 -microglobulin

Reusability of avidin-biotinylated immunoglobulin Y columns in immunoaffinity chromatography

The Antigens

Chicken Antibodies: A Tool to Avoid Interference in Immunological Assays

Peroxidase labeling of chicken antibodies

Phylogen of immunoglobulin structure and function. Immunoglobulins of the chicken

Analysis of maternal IgG subpopulations which are transported into the chicken oocyte

The chicken egg, an antibody source

Expression of sialyl Lewis (x) and Lewis (x) defines distinct stages chicken B cell maturation

Selection for B cells with productive IgL gene rearrangements occurs in the bursa of Fabricius during chicken embryonic development

Immunoglobulin gene diversification by gene conversion

Expression of the virulence factor, BfpA, by enteropathogenic Escherichia coli, is essential for apoptosis signalling but not for NF-kB activation in host cells

Biotin labeling of chicken antibodies and their subsequent use in ELISA and immunohistochemistry

Anatomy of the antibody molecule

Somatic diversification of chicken immunoglobulin light chains by point mutations

Isolation of viral IgY antibodies from yolks of immunized hens

Prevention of Salmonella infection in poultry by specific egg-derived antibody

Crystal structures of human antibodies detailed and unfinished tapestry of immunoglobulins gene products

A single rearrangement event generates most of the chicken immunoglobulin light chain diversity

A hyper conversion mechanism generates the chicken light chain preimmune repertoire

The chicken D locus and its contribution to the immunoglobulin heavy chain repertoire

Immunoglobulin classes in the hens' egg, their segregation in yolk and white

Contrasting IgG structures reveal extreme asymmetry and flexibility

Chicken egg yolk antibodies (IgYtechnology). A review of progress in production and use in research and human and veterinary medicine

Egg yolk antibody (IgY) stability in aqueous solution with high sugar concentrations

Anti-E. coli immunoglobulin Y isolated from egg yolk of immunized chickens as potential food ingredient

Antibodies to the a-subunit of insulin receptor from eggs of immunized hens

Inhibition of bacterial adhesion and Salmonella infection in BALB/c mice by sialyoligosaccharides and their derivatives from chicken egg yolk

Blockade of Salmonella enteritidis passage across the basolateral barriers of human intestinal epithelial cells by specific antibody

Preparation and mass spectrometric study of egg yolk antibody (IgY) against rabies virus

Chicken eggs in polyclonal antibody production

Rattlesnake and scorpion antivenoms from the egg yolks of immunized hens

Somatic generation of antibody diversity

IgG receptors on the embryonic chick yolk sac

Oral administration of antibodies as prophylaxis and therapy in Campylobacter jejuni-infected chickens

IgY: clues to the origins of modern antibodies

Hypermutation generating the sheep immunoglobulin repertoire is an antigen-dependent process

The chicken B cell compartment

Comparison of antibody production to human interleukine-6 (I-L6) by sheep and chickens

Mapping of the chicken immunoglobulin heavy-chain constant region gene locus reveals an inverted alpha gene upstream of a condensed upsilon gene