Podcast
Questions and Answers
What is the primary function of antibodies in the immune response?
What is the primary function of antibodies in the immune response?
What distinguishes the variable region of immunoglobulins?
What distinguishes the variable region of immunoglobulins?
Which component is NOT part of the antigen-binding receptor on B cells?
Which component is NOT part of the antigen-binding receptor on B cells?
How many identical heavy chains comprise a monomer of antibodies?
How many identical heavy chains comprise a monomer of antibodies?
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Which immunoglobulin class does not typically have a flexible hinge region?
Which immunoglobulin class does not typically have a flexible hinge region?
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What role does glycosylation play in antibodies?
What role does glycosylation play in antibodies?
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What type of bonds hold the heavy and light chains of antibodies together?
What type of bonds hold the heavy and light chains of antibodies together?
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Which part of the antibody is involved in enhancing phagocytosis?
Which part of the antibody is involved in enhancing phagocytosis?
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What mediates the biological effector function of antibodies?
What mediates the biological effector function of antibodies?
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What is the result of papain-mediated digestion of an IgG molecule?
What is the result of papain-mediated digestion of an IgG molecule?
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Which type of epitopes varies from individual to individual?
Which type of epitopes varies from individual to individual?
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What is the main function of IgA in the context of transcytosis?
What is the main function of IgA in the context of transcytosis?
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Which immunoglobulin class is primarily involved in mast cell degranulation?
Which immunoglobulin class is primarily involved in mast cell degranulation?
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Which function is attributed to antibody-mediated activation of complement?
Which function is attributed to antibody-mediated activation of complement?
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What defines isotypic epitopes in antibodies?
What defines isotypic epitopes in antibodies?
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Which components are found in a human IgG molecule?
Which components are found in a human IgG molecule?
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Which immunoglobulin subclass is most abundant in serum and has the ability to cross the placenta during pregnancy?
Which immunoglobulin subclass is most abundant in serum and has the ability to cross the placenta during pregnancy?
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What is the primary class of immunoglobulin produced first by newborns?
What is the primary class of immunoglobulin produced first by newborns?
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Which immunoglobulin is characterized by existing as a dimer in mucosal secretions and is protected by a secretory component?
Which immunoglobulin is characterized by existing as a dimer in mucosal secretions and is protected by a secretory component?
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What is a unique role of IgE in the immune system?
What is a unique role of IgE in the immune system?
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Which immunoglobulin subclass has a low concentration in fluid between cells due to its large size?
Which immunoglobulin subclass has a low concentration in fluid between cells due to its large size?
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What is a major function of dimeric IgA in mucosal secretions?
What is a major function of dimeric IgA in mucosal secretions?
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Which immunoglobulin subclass primarily activates basophils and mast cells?
Which immunoglobulin subclass primarily activates basophils and mast cells?
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Which immunoglobulin is least abundant in serum and is primarily found on the surface of B cells?
Which immunoglobulin is least abundant in serum and is primarily found on the surface of B cells?
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What distinguishes monoclonal antibodies from polyclonal antibodies?
What distinguishes monoclonal antibodies from polyclonal antibodies?
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Which regions of antibodies are primarily responsible for their effector functions?
Which regions of antibodies are primarily responsible for their effector functions?
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What is the role of hybridoma cells in the production of monoclonal antibodies?
What is the role of hybridoma cells in the production of monoclonal antibodies?
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Which antibody class is primarily involved in mast cell degranulation?
Which antibody class is primarily involved in mast cell degranulation?
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Which statement about the immunoglobulin superfamily is true?
Which statement about the immunoglobulin superfamily is true?
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What do complementarity determining regions of antibodies contribute to?
What do complementarity determining regions of antibodies contribute to?
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How are hybridoma cells selected during monoclonal antibody production?
How are hybridoma cells selected during monoclonal antibody production?
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Which is NOT a function associated with antibodies?
Which is NOT a function associated with antibodies?
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Study Notes
Antibodies
- Glycoproteins on the surface of B cells and secreted by plasma cells
- Found in blood serum and secreted fluids like saliva and milk
- Activate the classical complement pathway
- Act as opsonins to enhance phagocytosis
- Neutralize toxins and viruses
- Function as antigen receptors for B cells
B Cell Receptor
- Membrane-bound immunoglobulin (mIg) molecules have short cytoplasmic tails, incapable of interacting with intracellular signaling molecules
- Antigen-binding receptor on B cells consists of mIg and the disulfide-linked Ig-α/Ig-β heterodimer
- Cytoplasmic tails of Ig-α and Ig-β interact with intracellular signaling molecules like tyrosine kinases
Immunoglobulin Structure
- Monomers (IgA, IgD, IgE, IgG, and IgM) composed of 2 identical heavy chains (5 classes: α, δ, ε, γ, µ) and 2 identical light chains (2 classes: κ and λ) held together by disulfide bonds and noncovalent interactions
- Globular domains of ~110 amino acids formed by intrachain disulfide bonds
- V region of heavy and light chains has variable amino acid sequences, defining antigen specificity
- C regions of heavy and light chains have relatively constant amino acid sequences, determining effector functions
- Glycosylation influences antibody stability and interactions with other proteins
Immunoglobulin Domains
- Light chains contain 1 VL and 1 CL domain
- Heavy chains contain 1 VH domain and 3 or 4 constant domains, designated CH1-4
- V region domains at the amino-terminal portion of heavy and light chains form the antigen-binding site
- Three hypervariable regions within the V region show greater amino acid sequence variability, forming the antigen-binding site
- Framework regions outside of the hypervariable regions exhibit less amino acid variability
Hinge Region
- Proline-rich amino acid sequences between the CH1 and CH2 domains form a flexible hinge region in IgA, IgD, and IgG molecules
- CH2 domain of IgM and IgE has hinge region-like properties
Immunoglobulin Structure-Function
- C region domains at the carboxyl-terminal portion of the heavy chain mediate biological effector function
- Differences in heavy chain constant region domains determine antibody half-life, distribution, complement-fixing ability, and Fc receptor binding
- Carboxyl terminal domain of membrane-bound and secreted antibody differs in both structure and function
- Different classes of membrane-bound immunoglobulin molecules are expressed by B cells at different stages of their development
- Proteolysis of IgG by enzymes (papain, pepsin) can cleave IgG molecules into specific fragments
Immunoglobulin Epitopes
- Antibodies are immunogenic
- Isotypic epitopes are located in constant regions, defining heavy chain classes/subclasses and light chain types/subtypes within a species
- Allotypic epitopes are located in constant regions and may vary from individual to individual
- Idiotypic epitopes are located within heavy and light chain variable regions, defining specificity
Immunoglobulin Effector Functions
- Opsonization: Interactions of antibodies with Fc receptors on phagocytes promote phagocytosis
- Complement Activation: Antibody-mediated activation of complement is responsible for inactivation/removal/killing of pathogens
- Antibody-dependent cell-mediated cytotoxicity (ADCC): Antibody (IgG) acts as a receptor to enable recognition and killing of target cells by natural killer (NK) cells with Fc receptors (CD16)
- Transcytosis: Passage of antibodies across epithelial layers delivers certain classes of antibody (primarily IgA) to mucosal surfaces
- Induction of mast cell degranulation: Initiated by Fc receptors for IgE
Human Ig Classes
- IgG: Most abundant immunoglobulin in serum and extravascular spaces; neutralizes viruses/toxins, opsonizes microbes, activates classical complement pathway, mediates ADCC reactions, and crosses the placenta during pregnancy
- IgM: First immunoglobulin class made by newborns and in a primary immune response; efficient agglutinator of particulate antigens and activator of the classical complement pathway; concentration is low in fluid between cells due to its large size; J chain allows transport across epithelial mucosa
- IgA: Present as a monomer in serum and as a dimer in mucosal secretions; dimeric IgA is formed by the addition of a J chain and secretory component; protects the secreted IgA molecule from proteolysis; defends mucosal surfaces from microbial attack
- IgE: Binds high affinity Fcε receptors on mast cells and basophils; crosslinking membrane-bound IgE causes mast cell and basophil degranulation, leading to acute inflammation and atopic (Type I) allergic responses; plays a role in host defense against certain parasitic worms
- IgD: Primarily on the surface of B cells; activates basophils (and mast cells); mainly present in the airways, saliva, and tear fluid
Immunoglobulin Superfamily
- Many molecules associated with immune function exhibit the immunoglobulin-fold domain structure
- Members include antibody, Ig-α/Ig-β, the T cell receptor, Fc receptors, CD4, major histocompatibility complex molecules, and various cell adhesion molecules
- This family of genes is thought to have originated through mutation and duplication from a single primordial gene encoding a polypeptide of 110 amino acids
Monoclonal Antibodies
- Derived from a single B cell clone and are therefore specific for a single epitope
- Produced by immortal hybridoma cells created by fusing an antigen-specific B cell with a transformed (cancerous) myeloma cell
- Hybrid cells are selected by growth in tissue culture medium that allows only the hybridoma cells to grow
- Hybridoma clones that produce a monoclonal antibody with the desired antigenic specificity are propagated in tissue culture for use as diagnostic, imaging and therapeutic agents
Production of a mouse monoclonal antibody
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- Immunize a mouse with the antigen
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- Extract B cells producing antibodies to the antigen
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- Fuse the B cells with myeloma cells to create hybridomas (immortalized cells)
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- Select for hybridomas that produce the antibody of interest
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- Grow selected hybridoma cells in culture for large-scale production
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- Purification of the monoclonal antibody
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- Use of the monoclonal antibody for diagnosis, imaging, or therapy
Monoclonal antibodies as treatments for disease
- Monoclonal antibodies are increasingly used as therapeutic agents for a wide range of diseases, including cancer, autoimmune diseases, and infectious diseases.
- They target specific antigens on cells or tissues and can block cell signaling, deliver toxins to cancer cells, recruit immune cells to the site of disease, or prevent the body from rejecting transplanted organs.
- Examples of monoclonal antibodies used in therapy include rituximab (treating rheumatoid arthritis and non-Hodgkin's lymphoma), trastuzumab (treating HER2-positive breast cancer), and infliximab (treating inflammatory bowel disease).
Learning Objectives:
- Describe and draw the structure of all the antibody classes including heavy and light chains
- Explain which regions of antibodies are responsible for antigen specificity and effector functions
- Describe the complementarity determining regions, Fc, Fab, and hinge regions of antibodies
- Differentiate isotypic, allotypic and idiotypic determinants/epitopes of antibodies
- Paraphrase the effector functions of antibodies (opsonization, ADCC, complement activation, transcytosis, and mast cell degranulation), and which antibody class contributes to each of them
- Recall that antibodies are part of a greater protein family encompassing many molecules regulating the immune system (Immunoglobulin family)
- Describe how monoclonal antibodies are produced in the laboratory
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Description
Test your knowledge on antibodies and B cell receptors, focusing on their structure and function. This quiz covers the immunoglobulin types and their roles in the immune response, including details about B cell receptors. Dive into the details of glycoproteins, complementation, and antigen binding.
