Humoral Immune Responses in Immunology
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Questions and Answers

What is the outcome of B cell activation?

  • B cells undergo apoptosis.
  • B cells only secrete antibodies without differentiation.
  • B cells become solely memory cells.
  • B cells proliferate and differentiate into plasma cells and memory cells. (correct)

    • How do primary and secondary humoral immune responses differ?

  • They differ only in the time it takes to respond.
  • Primary responses are triggered by T-independent antigens only.
  • Secondary responses do not involve memory cells.
  • They differ qualitatively and quantitatively in response to protein antigens. (correct)

    • What is the role of complement receptor type 2 in B cell activation?

  • It serves as an exclusive receptor for T cells.
  • It inhibits B cell proliferation.
  • It enhances the activation response of B cells to antigens. (correct)
  • It directly binds to antibodies.

    • What triggers B cell proliferation and differentiation?

    <p>The binding of antigens and signals from other immune cells.</p> Signup and view all the answers

    How do antigen-activated helper T cells interact with B cells?

    <p>They move towards B cells in response to chemokine signals.</p> Signup and view all the answers

    What happens to protein antigens recognized by membrane Ig on B cells?

    <p>They are endocytosed and processed for MHC presentation.</p> Signup and view all the answers

    What is the primary mechanism by which halothane causes life-threatening hepatitis?

    <p>Induction of an autoimmune response</p> Signup and view all the answers

    Which event is NOT characteristic of the germinal center reaction?

    <p>Production of T cells</p> Signup and view all the answers

    What is the process by which activated B cells undergo genetic diversification called?

    <p>Germinal center reaction</p> Signup and view all the answers

    What is the function of secreted antibodies in the immune system?

    <p>Engagement of effector mechanisms against antigens</p> Signup and view all the answers

    What role do membrane-bound antibodies serve in B lymphocytes?

    <p>Function as receptors mediating B cell activation</p> Signup and view all the answers

    Which of the following is an immediate biological effector function triggered by antigen-bound antibodies?

    <p>Inflammation activation</p> Signup and view all the answers

    In the context of B cell activation, what does isotype switching refer to?

    <p>Change in antibody structure without altering specificity</p> Signup and view all the answers

    Which of the following descriptions best describes antibodies?

    <p>Highly diverse glycoproteins with multiple functions</p> Signup and view all the answers

    What do the light chains of an immunoglobulin molecule have in common?

    <p>They are of the same light chain isotype.</p> Signup and view all the answers

    What defines the five different isotypes of human antibodies?

    <p>The heavy chain constant regions.</p> Signup and view all the answers

    What is the significance of clonal expansion in lymphocytes?

    <p>It increases the number of cells with identical receptors.</p> Signup and view all the answers

    What role do memory cells play in the immune response?

    <p>They respond more rapidly to subsequent exposures.</p> Signup and view all the answers

    How are monoclonal antibodies characterized?

    <p>They originate from a single B cell clone.</p> Signup and view all the answers

    What happens to the quality of the immune response upon repeated exposure to the same antigen?

    <p>The response is typically larger and more rapid.</p> Signup and view all the answers

    What is the primary reason individuals can produce millions of different antibodies?

    <p>Highly variable antigen-binding regions</p> Signup and view all the answers

    What do the three hypervariable regions of antibodies primarily contribute to?

    <p>Formation of the antigen-combining site</p> Signup and view all the answers

    What is true about the basic structure of all antibodies?

    <p>They consist of two identical heavy chains and two identical light chains</p> Signup and view all the answers

    What is the classification of antibodies based on?

    <p>Differences in heavy chain C regions</p> Signup and view all the answers

    Which of the following is NOT an isotype of antibodies?

    <p>IgH</p> Signup and view all the answers

    What features are retained within the Ig domains of antibodies?

    <p>Conserved sequences and intrachain disulfide bonds</p> Signup and view all the answers

    How do the hypervariable regions of antibodies relate to their function?

    <p>They contribute to the antigen specificity of antibodies</p> Signup and view all the answers

    Why are different antibody isotypes significant in the immune response?

    <p>They perform distinct functions based on their structures</p> Signup and view all the answers

    What characterizes the N-terminal domains of antibody molecules?

    <p>They create variability among antibodies of different specificities</p> Signup and view all the answers

    What are complementarity-determining regions responsible for in an antibody's function?

    <p>Determining the binding specificity of the antibody</p> Signup and view all the answers

    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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    Humoral Immune Responses PDF

    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.

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