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Questions and Answers
What is the outcome of B cell activation?
How do primary and secondary humoral immune responses differ?
What is the role of complement receptor type 2 in B cell activation?
What triggers B cell proliferation and differentiation?
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How do antigen-activated helper T cells interact with B cells?
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What happens to protein antigens recognized by membrane Ig on B cells?
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What is the primary mechanism by which halothane causes life-threatening hepatitis?
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Which event is NOT characteristic of the germinal center reaction?
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What is the process by which activated B cells undergo genetic diversification called?
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What is the function of secreted antibodies in the immune system?
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What role do membrane-bound antibodies serve in B lymphocytes?
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Which of the following is an immediate biological effector function triggered by antigen-bound antibodies?
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In the context of B cell activation, what does isotype switching refer to?
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Which of the following descriptions best describes antibodies?
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What do the light chains of an immunoglobulin molecule have in common?
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What defines the five different isotypes of human antibodies?
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What is the significance of clonal expansion in lymphocytes?
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What role do memory cells play in the immune response?
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How are monoclonal antibodies characterized?
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What happens to the quality of the immune response upon repeated exposure to the same antigen?
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What is the primary reason individuals can produce millions of different antibodies?
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What do the three hypervariable regions of antibodies primarily contribute to?
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What is true about the basic structure of all antibodies?
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What is the classification of antibodies based on?
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Which of the following is NOT an isotype of antibodies?
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What features are retained within the Ig domains of antibodies?
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How do the hypervariable regions of antibodies relate to their function?
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Why are different antibody isotypes significant in the immune response?
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What characterizes the N-terminal domains of antibody molecules?
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What are complementarity-determining regions responsible for in an antibody's function?
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Study Notes
Humoral Immune Responses
- B cell activation leads to proliferation and differentiation into plasma cells (antibody secreting) and memory cells
- T cells assist in B cell activation in T-dependent antibody responses
- T-independent responses are less conventional, and involve B cell activation directly by certain antigens
Primary and Secondary Humoral Immune Responses
- Responses to protein antigens differ in magnitude and quality between primary and secondary exposures
- Primary responses are slower and less effective
- Secondary responses are faster, more robust, and involve higher affinity antibodies due to memory cells
Antibody Delivery to Follicular B Cells
- Antigens can reach follicular B cells via direct entry, transport by antigen presenting cells, or through lymph nodes
- Follicular B cells are specialized for antigen capture and processing
B Cell Activation
- B cells are activated by antigen binding to the B cell receptor (BCR)
- BCR triggering can be augmented by complement receptor 2 (CR2) and Toll-like receptors (TLRs)
- These receptors recognize specific molecular patterns present on pathogens
Effects of BCR Engagement
- BCR engagement initiates B cell proliferation and differentiation
- Multivalent antigens trigger stronger signals, leading to rapid division
- Protein antigens require T cell help for effective activation
Humoral Immune Response to T-dependent Protein Antigens
- B cells internalize protein antigens and process them into peptides
- Peptides are presented to helper T cells via MHC class II molecules
- Helper T cells recognize the MHC-peptide complexes and activate specific B cells
Antigen Presentation to Helper T Cells
- B cells present processed antigens to helper T cells, initiating a T-dependent response
- Hapten-carrier conjugates involve B cell recognition of the hapten and T cell recognition of the carrier protein
- Certain haptens can trigger autoimmune reactions, such as hydralazine (causing drug-induced lupus), halothane (inducing hepatitis), and penicillin analogs (leading to autoimmune hemolytic anemia)
Role of CD40L:CD40 Interaction in T-dependent B Cell Activation
- CD40 ligand (CD40L) on helper T cells binds to CD40 on B cells
- This interaction provides essential costimulatory signal for optimal B cells activation
Germinal Center Reaction
- Germinal centers form within lymph nodes during T-dependent responses
- They are specialized structures where B cells undergo affinity maturation, isotype switching, and generate memory cells and long-lived plasma cells
- The germinal center reaction is a complex process of B cell diversification and selection for the most effective immune response
Heavy Chain Isotype Switching
- Activated B cells undergo isotype switching to produce different antibody classes (IgG, IgA, IgE)
- Switching involves DNA recombination and changes in the constant region of the antibody heavy chain
- Each isotype has specialized functions
Affinity Maturation
- B cells undergo somatic mutations in their variable regions, leading to increased affinity for a specific antigen
- This occurs within germinal centers
- B cells with higher affinity antibodies gain a survival advantage
B Cell Selection in Germinal Centers
- B cells compete for limited resources and survival signals
- B cells with the highest affinity for antigens receive better survival signals
- This process shapes the immune repertoire towards high-affinity antibody producers
Membrane and Secreted µ Chains
- Early B cell development involves the production of both membrane-bound and secreted forms of the µ chain of IgM
- This allows B cells to express IgM as a receptor and later secrete it as a soluble antibody
Antibodies (Immunoglobulins)
- Antibodies are glycoproteins produced by B cells
- They bind to specific antigens and trigger effector functions
- Effector functions include neutralization, inflammation, phagocytosis, complement activation, and direct cell killing
Antibody Structure
- Antibodies have a basic structure of two identical heavy chains and two identical light chains
- Light chains are either kappa (κ) or lambda (λ)
- Each chain contains Ig domains, folded units responsible for structure and function
- Each antibody has a variable region (V region) and a constant region (C region)
Hypervariable Region of Immunoglobulins
- The V region is responsible for antigen binding
- It contains hypervariable regions called complementarity-determining regions (CDRs)
- CDRs are crucial for antigen recognition and specificity
Antigen-Antibody Binding
- CDRs on the antibody interact with the antigen through shape and chemical complementarity
- This interaction is highly specific
General Features of Antibody Structure
- All antibodies share a core structure of two heavy chains and two light chains
- Heavy and light chains have domains
- Domains are independently folded units of about 110 amino acids, containing conserved sequences and disulfide bonds
Antibodies Characterization
- Antibodies can be analyzed using gel electrophoresis
- Under non-reducing conditions, antibodies migrate as intact molecules
- Under reducing conditions, the disulfide bonds are broken, separating the heavy and light chains
Features of Immunoglobulin Binding Antigen
- Antibody binding is specific and saturable
- Antibody binding follows the law of mass action
- Antibody binding can be affected by pH and temperature
Human Immunoglobulin Repertoire
- Humans produce a vast array of antibodies, each with unique antigen specificity
- Antibodies are classified into isotypes based on their C region of the heavy chain
- The five main antibody isotypes in humans are IgM, IgD, IgG, IgE, and IgA
Human Antibody Isotypes
- Antibodies can switch isotypes through genetic recombination
- Switching is irreversible and changes the effector functions of the antibody
- The isotype switch is triggered by external signals, such as cytokines
Clonal Expansion
- Lymphocytes exposed to their specific antigen undergo clonal expansion
- This increases the number of antigen-specific cells, allowing the immune system to keep pace with rapidly dividing pathogens
Memory
- Repeated exposure to an antigen generates memory cells
- Memory cells are more efficient at responding to the antigen than naïve lymphocytes
- Memory cells produce antibodies with higher affinity than those produced in the primary response
Changes in Antibody Structure during Immune Response
- Antibodies undergo changes in structure during the immune response
- These changes lead to increased affinity and altered effector functions
- Antibody structure can reflect the history of exposure to antigens
Monoclonal Antibodies
- Monoclonal antibodies are produced from a single clone of B cells
- They recognize a single antigenic determinant
- Used in research, diagnostics, and therapeutics
Revised Monoclonal Antibody Nomenclature
- A revised nomenclature scheme for monoclonal antibodies was developed in 2017
- This scheme helps to standardize the naming of monoclonal antibodies
Limitations of Monoclonal Antibodies
- Not orally bioavailable, requiring injection for administration
- Difficult to target intracellular targets due to barriers
- Can elicit anti-drug antibodies (ADA) if recognized as foreign by the immune system
- Manufacturing can be challenging due to the complexity of the molecules
Anti-Drug Antibodies (ADA)
- ADA can neutralize monoclonal antibodies and reduce their effectiveness
- ADA can also lead to side effects
- ADA can occur in patients receiving monoclonal antibody therapies
Recombinant Antibodies
- Recombinant antibodies are produced using genetic engineering techniques
- They are designed to reduce immunogenicity
- Often used as therapeutic antibodies
Recombinant Antibodies: Anti-CD20
- Rituximab is a chimeric antibody targeting CD20 on B cells used in non-Hodgkin lymphoma
- Ofatumumab is a fully humanized anti-CD20 antibody used in chronic lymphocytic leukemia (CLL)
- Obinutuzumab is a glycoengineered anti-CD20 antibody with improved efficacy compared to rituximab
Second and Third Generation Anti-CD20 mAbs
- Second-generation anti-CD20 antibodies are humanized to reduce immunogenicity
- Third-generation anti-CD20 antibodies have engineered Fc regions to increase their binding affinity for FcγRIIIa receptors
- Third-generation antibodies are under development for improved cancer treatment
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Description
Explore the intricate processes of humoral immune responses, including B cell activation, proliferation, and the differences between primary and secondary immune responses. This quiz delves into the roles of T cells, antigens, and how antibodies are delivered to follicular B cells.
