Immunoglobulin Subunits
Immunoglobulins
Immunoglobulin G
Immunoglobulin A
Immunoglobulin M
Protein Subunits
Selection of anti-double-stranded DNA B cells in autoimmune MRL-lpr/lpr mice. (1/12)
Abs to DNA and nucleoproteins are expressed in systemic autoimmune diseases, whereas B cells producing such Abs are edited, deleted, or inactivated in healthy individuals. Why autoimmune individuals fail to regulate is not well understood. In this study, we investigate the sources of anti-dsDNA B cells in autoimmune transgenic MRL-lpr/lpr mice. These mice are particularly susceptible to lupus because they carry a site-directed transgene, H76R that codes for an anti-DNA H chain. Over 90% of the B cells are eliminated in the bone marrow of these mice, and the few surviving B cells are associated with one of two Vkappa editors, Vkappa38c and Vkappa21D. Thus, it appears that negative selection by deletion and editing are intact in MRL-lpr/lpr mice. However, a population of splenic B cells in the H76R MRL-lpr/lpr mice produces IgG anti-nuclear Abs, and these mice have severe autoimmune organ damage. These IgG Abs are not associated with editors but instead use a unique Vkappa gene, Vkappa23. The H76R/Vkappa23 combination has a relatively high affinity for dsDNA and an anti-nuclear Ab pattern characteristic of lupus. Therefore, this Vkappa gene may confer a selective advantage to anti-DNA Abs in diseased mice. (+info)Human domain antibodies against virulence traits of Candida albicans inhibit fungus adherence to vaginal epithelium and protect against experimental vaginal candidiasis. (2/12)
Antibody variable domains (domain antibodies [DAbs]) are genetically engineered antibody fragments that include individual heavy-chain (VH) or kappa-chain (Vkappa) variable domains and lack the Fc region. Human DAbs against the 65-kDa mannoprotein (MP65) or the secretory aspartyl proteinase (SAP)-2 of Candida albicans (monospecific DAbs) or against both fungal antigens (heterodimeric, bispecific DAbs) were generated from phage expression libraries. Both monospecific and bispecific DAbs inhibited fungus adherence to the epithelial cells of rat vagina and accelerated the clearance of vaginal infection with the fungus. When heterodimeric DAbs were used, the clearance of infection was at least equivalent to treatment with fluconazole. The in vivo protective effects of DAbs were demonstrated by both pre- and postchallenge schedules of DAb administration and with both fluconazole-susceptible and fluconazole-resistant strains of C. albicans. This is the first demonstration that human DAbs lacking the Fc constituent can efficiently control an infection and can act largely by inhibiting adherence. (+info)Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. (3/12)
PURPOSE: Passive immunotherapy with antitumor antibodies has the potential to induce active tumor immunity via the opsonic enhancement of immunogenicity of tumor antigen. We have assessed whether immune sensitization to the HER-2/neu tumor antigen occurs during treatment with the anti-HER-2/neu monoclonal antibody trastuzumab. EXPERIMENTAL DESIGN: Twenty-seven patients treated with trastuzumab and chemotherapy were assessed for the induction of HER-2/neu-specific immunity. Sera and peripheral blood mononuclear cells obtained before and after trastuzumab therapy were compared for the presence of anti-HER-2/neu endogenous Iglambda antibodies and HER-2/neu-specific CD4 responses by ELISA and enzyme-linked immunospot, respectively. RESULTS: Anti-HER-2/neu antibodies were detectable in 8 of 27 (29%) patients before trastuzumab treatment and in 15 of 27 (56%) patients during trastuzumab treatment. In the overall study population, anti-HER-2/neu humoral responses significantly increased during therapy (P < 0.001) and were not associated with development of an anti-idiotypic response. In 10 evaluable individuals, 6 showed augmented HER-2/neu-specific CD4 T-cell responses during therapy. Of the 22 individuals treated for metastatic disease, those patients showing objective clinical responses exhibited more frequent (P = 0.004) and larger (P = 0.006) treatment-associated anti-HER-2/neu humoral responses. CONCLUSION: Humoral immune sensitization occurs during treatment with chemotherapy and trastuzumab. Further studies are warranted to investigate whether augmented anti-HER-2/neu humoral and cellular immunity contributes mechanistically to clinical outcome. (+info)Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization. (4/12)
The Ig superfamily (IgSF) intercellular adhesion molecule-1 (ICAM-1) equilibrates between monomeric and dimeric forms on the cell surface, and dimerization enhances cell adhesion. A crystal structure of ICAM-1 IgSF domains (D) 3-5 revealed a unique dimerization interface in which D4s of two protomers fuse through edge beta-strands to form a single super beta-sandwich domain. Here, we describe a crystal structure at 2.7-A resolution of monomeric ICAM-1 D3-D5, stabilized by the monomer-specific Fab CA7. CA7 binds to D5 in a region that is buried in the dimeric interface and is distal from the dimerization site in D4. In monomeric ICAM-1 D3-D5, a 16-residue loop in D4 that is disordered in the dimeric structure could clearly be traced as a BC loop, a short C strand, and a CE meander with a cis-Pro followed by a solvent-exposed, flexible four-residue region. Deletions of 6 or 10 residues showed that the C-strand is essential for monomer stability, whereas a distinct six-residue deletion showed little contribution of the CE meander. Mutation of two inward-pointing Leu residues in edge beta-strand E to Lys increased monomer stability, confirming the hypothesis that inward-pointing charged side chains on edge beta-strands are an important design feature to prevent beta-supersheet formation. Overall, the studies reveal that monomer-dimer transition is associated with a surprisingly large, physiologically relevant, IgSF domain rearrangement. (+info)A focused antibody library for selecting scFvs expressed at high levels in the cytoplasm. (5/12)
BACKGROUND: Intrabodies are defined as antibody molecules which are ectopically expressed inside the cell. Such intrabodies can be used to visualize or inhibit the targeted antigen in living cells. However, most antibody fragments cannot be used as intrabodies because they do not fold under the reducing conditions of the cell cytosol and nucleus. RESULTS: We describe the construction and validation of a large synthetic human single chain antibody fragment library based on a unique framework and optimized for cytoplasmic expression. Focusing the library by mimicking the natural diversity of CDR3 loops ensured that the scFvs were fully human and functional. We show that the library is highly diverse and functional since it has been possible to isolate by phage-display several strong binders against the five proteins tested in this study, the Syk and Aurora-A protein kinases, the alphabeta tubulin dimer, the papillomavirus E6 protein and the core histones. Some of the selected scFvs are expressed at an exceptional high level in the bacterial cytoplasm, allowing the purification of 1 mg of active scFv from only 20 ml of culture. Finally, we show that after three rounds of selection against core histones, more than half of the selected scFvs were active when expressed in vivo in human cells since they were essentially localized in the nucleus. CONCLUSION: This new library is a promising tool not only for an easy and large-scale selection of functional intrabodies but also for the isolation of highly expressed scFvs that could be used in numerous biotechnological and therapeutic applications. (+info)Anti-DNA Ig peptides promote Treg cell activity in systemic lupus erythematosus patients. (6/12)
(+info)Exclusion of natural autoantibody-producing B cells from IgG memory B cell compartment during T cell-dependent immune responses. (7/12)
(+info)Determinism and stochasticity during maturation of the zebrafish antibody repertoire. (8/12)
(+info)Immunoglobulins, also known as antibodies, are glycoprotein molecules that play a crucial role in the immune response. They are produced by B cells and are composed of two heavy chains and two light chains, which are held together by disulfide bonds to form a Y-shaped structure.
The heavy chains and light chains are made up of constant (C) regions and variable (V) regions. The variable regions are responsible for recognizing and binding to specific antigens, while the constant regions determine the class and effector functions of the immunoglobulin.
Immunoglobulin subunits refer to the individual heavy and light chains that make up the immunoglobulin molecule. There are five classes of heavy chains (alpha, delta, gamma, epsilon, and mu) and two classes of light chains (kappa and lambda). Each class of heavy chain combines with a specific class of light chain to form different types of immunoglobulins, such as IgA, IgD, IgE, IgG, and IgM.
Therefore, the medical definition of 'Immunoglobulin Subunits' refers to the individual heavy and light chains that make up the immunoglobulin molecule, which are responsible for recognizing and binding to specific antigens, and determining the class and effector functions of the immunoglobulin.
Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by the immune system's B cells in response to the presence of foreign substances, such as bacteria, viruses, and toxins. These Y-shaped proteins play a crucial role in identifying and neutralizing pathogens and other antigens, thereby protecting the body against infection and disease.
Immunoglobulins are composed of four polypeptide chains: two identical heavy chains and two identical light chains, held together by disulfide bonds. The variable regions of these chains form the antigen-binding sites, which recognize and bind to specific epitopes on antigens. Based on their heavy chain type, immunoglobulins are classified into five main isotypes or classes: IgA, IgD, IgE, IgG, and IgM. Each class has distinct functions in the immune response, such as providing protection in different body fluids and tissues, mediating hypersensitivity reactions, and aiding in the development of immunological memory.
In medical settings, immunoglobulins can be administered therapeutically to provide passive immunity against certain diseases or to treat immune deficiencies, autoimmune disorders, and other conditions that may benefit from immunomodulation.
Immunoglobulin G (IgG) is a type of antibody, which is a protective protein produced by the immune system in response to foreign substances like bacteria or viruses. IgG is the most abundant type of antibody in human blood, making up about 75-80% of all antibodies. It is found in all body fluids and plays a crucial role in fighting infections caused by bacteria, viruses, and toxins.
IgG has several important functions:
1. Neutralization: IgG can bind to the surface of bacteria or viruses, preventing them from attaching to and infecting human cells.
2. Opsonization: IgG coats the surface of pathogens, making them more recognizable and easier for immune cells like neutrophils and macrophages to phagocytose (engulf and destroy) them.
3. Complement activation: IgG can activate the complement system, a group of proteins that work together to help eliminate pathogens from the body. Activation of the complement system leads to the formation of the membrane attack complex, which creates holes in the cell membranes of bacteria, leading to their lysis (destruction).
4. Antibody-dependent cellular cytotoxicity (ADCC): IgG can bind to immune cells like natural killer (NK) cells and trigger them to release substances that cause target cells (such as virus-infected or cancerous cells) to undergo apoptosis (programmed cell death).
5. Immune complex formation: IgG can form immune complexes with antigens, which can then be removed from the body through various mechanisms, such as phagocytosis by immune cells or excretion in urine.
IgG is a critical component of adaptive immunity and provides long-lasting protection against reinfection with many pathogens. It has four subclasses (IgG1, IgG2, IgG3, and IgG4) that differ in their structure, function, and distribution in the body.
Immunoglobulin A (IgA) is a type of antibody that plays a crucial role in the immune function of the human body. It is primarily found in external secretions, such as saliva, tears, breast milk, and sweat, as well as in mucous membranes lining the respiratory and gastrointestinal tracts. IgA exists in two forms: a monomeric form found in serum and a polymeric form found in secretions.
The primary function of IgA is to provide immune protection at mucosal surfaces, which are exposed to various environmental antigens, such as bacteria, viruses, parasites, and allergens. By doing so, it helps prevent the entry and colonization of pathogens into the body, reducing the risk of infections and inflammation.
IgA functions by binding to antigens present on the surface of pathogens or allergens, forming immune complexes that can neutralize their activity. These complexes are then transported across the epithelial cells lining mucosal surfaces and released into the lumen, where they prevent the adherence and invasion of pathogens.
In summary, Immunoglobulin A (IgA) is a vital antibody that provides immune defense at mucosal surfaces by neutralizing and preventing the entry of harmful antigens into the body.
Immunoglobulin M (IgM) is a type of antibody that is primarily found in the blood and lymph fluid. It is the first antibody to be produced in response to an initial exposure to an antigen, making it an important part of the body's primary immune response. IgM antibodies are large molecules that are composed of five basic units, giving them a pentameric structure. They are primarily found on the surface of B cells as membrane-bound immunoglobulins (mlgM), where they function as receptors for antigens. Once an mlgM receptor binds to an antigen, it triggers the activation and differentiation of the B cell into a plasma cell that produces and secretes large amounts of soluble IgM antibodies.
IgM antibodies are particularly effective at agglutination (clumping) and complement activation, which makes them important in the early stages of an immune response to help clear pathogens from the bloodstream. However, they are not as stable or long-lived as other types of antibodies, such as IgG, and their levels tend to decline after the initial immune response has occurred.
In summary, Immunoglobulin M (IgM) is a type of antibody that plays a crucial role in the primary immune response to antigens by agglutination and complement activation. It is primarily found in the blood and lymph fluid, and it is produced by B cells after they are activated by an antigen.
A protein subunit refers to a distinct and independently folding polypeptide chain that makes up a larger protein complex. Proteins are often composed of multiple subunits, which can be identical or different, that come together to form the functional unit of the protein. These subunits can interact with each other through non-covalent interactions such as hydrogen bonds, ionic bonds, and van der Waals forces, as well as covalent bonds like disulfide bridges. The arrangement and interaction of these subunits contribute to the overall structure and function of the protein.
Immunoglobulin heavy chains are proteins that make up the framework of antibodies, which are Y-shaped immune proteins. These heavy chains, along with light chains, form the antigen-binding sites of an antibody, which recognize and bind to specific foreign substances (antigens) in order to neutralize or remove them from the body.
The heavy chain is composed of a variable region, which contains the antigen-binding site, and constant regions that determine the class and function of the antibody. There are five classes of immunoglobulins (IgA, IgD, IgE, IgG, and IgM) that differ in their heavy chain constant regions and therefore have different functions in the immune response.
Immunoglobulin heavy chains are synthesized by B cells, a type of white blood cell involved in the adaptive immune response. The genetic rearrangement of immunoglobulin heavy chain genes during B cell development results in the production of a vast array of different antibodies with unique antigen-binding sites, allowing for the recognition and elimination of a wide variety of pathogens.