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Questions and Answers
What do N and C refer to at the ends of polypeptide chains?
Which of the following is NOT a class of human antibodies?
What is the primary advantage of obinutuzumab over rituximab in treating B-cell malignancies?
What characteristic distinguishes the third-generation anti-CD20 mAbs from the second generation?
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What function do the heavy chain constant regions primarily serve in antibodies?
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What types of molecules can serve as antigens that bind to antibodies?
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What is the irreversible process that allows B cells to produce different antibody isotypes?
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The term clonal expansion specifically refers to which phenomenon in lymphocytes?
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What are linear epitopes of protein antigens composed of?
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Which statement accurately describes the interaction between antibodies and antigens?
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Which is a biological function mediated by the antibody C regions?
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What enhances the immune system's ability to respond to a previously encountered foreign antigen?
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What potential issue can arise from high concentrations of polyvalent antigens and antibodies?
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Which light chain isotype is NOT part of the human antibody structure?
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What purpose does glycoengineering serve in monoclonal antibodies like obinutuzumab?
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Which feature is common among second-generation anti-CD20 mAbs?
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What is the primary outcome of B cell activation following antigen engagement?
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What differentiates T-dependent antibody responses from T-independent responses?
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Which process involves the alteration of antibody isotype during an immune response?
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Which receptors play a crucial role in activating B cells?
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In the context of humoral immune responses, which term describes the qualitative and quantitative differences between primary and secondary antibody responses?
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The engagement of the B cell receptor (BCR) by multiple antigen types results in what effect on B cells?
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What is the role of memory cells in the humoral immune response?
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Which mechanism is primarily involved in the high affinity and specific recognition of antigens by antibodies?
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What is a primary challenge associated with the delivery of monoclonal antibodies?
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What response might occur if a mouse antibody is injected into a human?
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What is one notable advantage of the International Nonproprietary Names (INNs) system for monoclonal antibodies?
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What is a common limitation faced by therapeutic antibodies?
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What technology was used to develop Rituximab?
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Which of the following describes a potential outcome of immunogenicity in patients treated with monoclonal antibodies?
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What is the primary function of antibodies targeting vascular endothelial growth factor (VEGF)?
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What differentiates Ofatumumab from other monoclonal antibodies?
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What is the primary advantage of memory B lymphocytes compared to naïve B lymphocytes?
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Which of the following statements accurately describes monoclonal antibodies?
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In the context of humoral immune response, which change is not expected from memory T cells upon re-exposure to the same antigen?
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What role do monoclonal antibodies play in tumor identification?
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Which application of monoclonal antibodies is critical for the diagnosis of diseases?
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What is a noted therapeutic use of monoclonal antibodies?
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How do memory cells impact the overall immune response to subsequent exposures to antigens?
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Which statement about the differentiation of memory cells is true?
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Study Notes
Humoral Immune Responses
- The activation of B cells leads to their proliferation and differentiation into antibody-secreting plasma cells and memory cells.
T-dependent and T-independent antibody responses
- T-dependent antibody responses rely on the interaction between antigen-presenting cells, T helper cells and B cells.
- T-independent responses are triggered by antigens activating B cells without the involvement of T helper cells.
Primary and secondary humoral immune responses
- The initial exposure to an antigen results in a primary immune response.
- The secondary response occurs upon re-exposure to the same antigen and is characterized by a faster and more robust antibody production.
Pathways of antigen delivery to follicular B cells
- Antigens can reach follicular B cells via several pathways, including direct capture from the blood, interaction with macrophages, and transport through the lymphatic system.
Activation of B Cells by Antigens and Other Signals
- The activation of B cells depends on the interaction of B cell receptors (BCRs) with antigens and the engagement of other signaling receptors like Toll-like receptors and complement receptor type 2.
- The interaction between BCRs and antigens leads to signaling cascades resulting in B cell proliferation and differentiation.
Effects of B cell antigen receptor engagement
- The interaction between B cells and different types of antigens, such as multivalent structures or proteins, triggers B cell proliferation and differentiation.
Sequence of events in humoral immune responses
- The sequence of events in T-dependent antibody responses involves antigen processing and presentation by antigen-presenting cells (APCs), T helper cell activation, and B cell differentiation.
Obinutuzumab
- Obinutuzumab is a glycoengineered antibody that exhibits higher efficacy compared to rituximab in treating B-cell malignancies like chronic lymphocytic leukemia (CLL).
- Glycoengineering enhances the binding of monoclonal antibodies to immune cells.
Rituximab mechanisms of action
- Rituximab is a monoclonal antibody targeting the CD20 protein found on B cells.
- Rituximab mediates B cell depletion by inducing antibody-dependent cell-mediated cytotoxicity (ADCC).
Second- and third-generation anti-CD20 mAbs
- Second-generation anti-CD20 antibodies, such as ofatumumab, veltuzumab, and ocrelizumab, are humanized to minimize immunogenicity.
- Third-generation anti-CD20 antibodies, like AME-133v, PRO131921, and GA101, are further engineered with modifications in their Fc region to enhance binding affinity.
Antigens
- Antigens are substances specifically bound by antibodies or T lymphocyte antigen receptors.
- Antigens can be a variety of molecules including sugars, lipids, carbohydrates, proteins, and nucleic acids.
Antigenic Determinants
- Macromolecular antigens contain multiple epitopes or determinants, each recognized by a specific antibody.
- Epitopes can be linear sequences of amino acids or conformational structures formed by protein folding.
Antigen-Antibody Complexes
- The formation of immune complexes can occur when antigen-antibody ratios are favorable.
- While antibody binding to antigen is highly specific, cross-reactions are possible between similar structures.
Antibodies Characterization
- Antibodies are characterized by their molecular weight and structure, typically analyzed using gel electrophoresis.
Features of Immunoglobulin Binding Antigen
- Antibodies bind to antigens using a specific structure that allows for recognition and binding.
Human Immunoglobulin Repertoire
- Antibodies are classified into different isotypes: IgM, IgD, IgG, IgE, and IgA, based on differences in their heavy chain constant regions.
- The constant regions of the heavy chain define the antibody's isotype, while the variable regions are responsible for antigen binding.
- The light chains of an antibody can be either κ or λ.
Human Antibodies Isotypes
- The five antibody isotypes (IgG, IgM, IgD, IgA, and IgE) differ in their heavy chain constant regions and exhibit distinct biological functions.
- B cells can switch isotypes but it is an irreversible process.
- Most antibody effector functions are mediated through their constant regions.
Clonal Expansion
- Exposure to a specific antigen triggers a considerable proliferation of lymphocytes specific for that antigen, known as clonal expansion.
- This process increases the number of cells expressing identical receptors for the antigen, ensuring an effective adaptive immune response.
Memory
- Prior exposure to an antigen enhances the immune system's ability to respond to subsequent exposures, leading to a more rapid and vigorous response.
- Memory cells are generated during each exposure and are more efficient at eliminating the antigen than naïve lymphocytes.
- Memory B cells produce antibodies with higher affinities for the specific antigen.
- Memory T cells also exhibit a quicker and more potent reaction upon re-exposure to the antigen compared to naïve T cells.
Changes in antibody structure during humoral immune response
- Antibodies undergo structural changes during the humoral immune response, including affinity maturation and isotype switching, contributing to a more effective immune response.
Monoclonal antibodies
- Monoclonal antibodies are produced from a single clone of B cells and exhibit specificity towards a single antigenic determinant.
- They are used in various research, diagnostic, and therapeutic applications.
Monoclonal antibodies applications
- Monoclonal antibodies have numerous applications:
- Identification of cell-specific markers for classification of various cell types.
- Immunodiagnosis for detecting antigens or antibodies in biological samples.
- Tumor identification by staining histological tumor sections.
- Therapy for various diseases by targeting specific cells or molecules involved in disease development.
Therapeutic Antibodies
- Therapeutic antibodies are monoclonal antibodies specifically designed to target and neutralize specific disease-causing agents.
- They are used to treat a variety of diseases, including autoimmune conditions, cancers, and infectious diseases.
Monoclonal Antibodies in Clinical Use
- A wide range of monoclonal antibodies are currently being used to treat various diseases, showcasing their therapeutic potential.
International Nonproprietary Names (INNs) for Monoclonal Antibodies
- The INN system provides a standardized generic name for pharmaceutical substances to facilitate clear identification, safe dispensing, and global communication among healthcare professionals.
Revised monoclonal antibody (mAb) nomenclature scheme
- The World Health Organization (WHO) has established a revised nomenclature scheme for monoclonal antibodies to ensure clear and consistent naming of these important therapeutic agents.
Limitations of monoclonal antibodies
- Monoclonal antibodies have a few limitations, including:
- They are not orally available, requiring injection administration.
- Their delivery is challenging for intracellular targets and they cannot cross the blood-brain barrier.
- They are complex molecules produced by living cells, which makes controlling batch-to-batch variation and stability difficult.
- They can elicit the formation of anti-drug antibodies (ADA) in the recipient, potentially leading to reduced efficacy or adverse reactions.
Anti-Drug Antibodies (ADA) in Patients
- The formation of anti-drug antibodies (ADA) can occur in patients receiving monoclonal antibody therapy, potentially impacting the efficacy and safety of the treatment.
Recombinant Antibodies
- Recombinant antibodies are engineered to reduce their immunogenicity in humans, improving tolerability and efficacy.
Recombinant Antibodies: Anti-CD20
- Rituximab is a recombinant antibody targeting CD20 and is used to treat various B-cell malignancies.
- Ofatumumab is a fully humanized monoclonal antibody against CD20, specifically approved for treating previously untreated chronic lymphocytic leukemia (CLL).
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Description
Test your knowledge on humoral immune responses, including the activation and differentiation of B cells, T-dependent and T-independent antibody responses. Explore the nuances of primary and secondary immune responses and the pathways for antigen delivery to B cells. Prepare for an insightful challenge!
