Humoral immunity
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Questions and Answers

The process that leads to the development of B cells is divided into three stages. What are these three stages?

Maturation, activation, and differentiation

What is the primary location for the development of B lymphocytes in most vertebrates?

  • Bone marrow (correct)
  • Lymph nodes
  • Thymus
  • Spleen

    • Which of the following processes involves the transformation of activated B cells into a different cell type that produces antibodies?

  • Proliferation
  • Differentiation (correct)
  • Maturation
  • Activation

    • In response to an antigen, which type of cell do B lymphocytes differentiate into that serves as a long-term immune response mechanism?

    <p>Memory B cells</p> Signup and view all the answers

    What specific event marks the activation of B lymphocytes?

    <p>Contact with specific antigens</p> Signup and view all the answers

    What is the end result of the maturation process of B lymphocytes?

    <p>Generation of immunocompetent B cells</p> Signup and view all the answers

    Plasma cells secrete ______ specific for a given antigen

    <p>Plasma cells secrete immunoglobulins (antibodies) specific for a given antigen</p> Signup and view all the answers

    Which statement accurately describes the fate of naive B cells that do not engage an antigen?

    <p>They die within a few weeks.</p> Signup and view all the answers

    What is required for the activation of B cells by thymus-dependent antigens?

    <p>Helper T cells (CD4+).</p> Signup and view all the answers

    Which of the following is a characteristic of thymus-independent antigens in B cell activation?

    <p>Directly activate naive B cells without prior exposure.</p> Signup and view all the answers

    What is the primary outcome of B cell activation?

    <p>Proliferation into plasma cells and memory B cells.</p> Signup and view all the answers

    What is the role of plasma cells in the immune response following B cell activation?

    <p>They produce and secrete antibodies specific to antigens.</p> Signup and view all the answers

    What type of antigens are known to be polyclonal activators of B cells?

    <p>TI-1 antigens</p> Signup and view all the answers

    Which immunoglobulin is predominantly produced in response to stimulation by TI antigens?

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

    How do TI-2 antigens primarily activate B cells?

    <p>By extensively cross-linking multiple membrane Ig receptors</p> Signup and view all the answers

    What is a characteristic feature of the immune response induced by TI antigens?

    <p>It is usually weak and lacks memory cells</p> Signup and view all the answers

    Which statement accurately describes TI-1 antigens?

    <p>They are recognized by both the B cell receptor and TLRs</p> Signup and view all the answers

    Which component is primarily responsible for signal transduction in B cell receptor activation?

    <p>Igα and Igβ chains</p> Signup and view all the answers

    What is the characteristic motif found within the cytoplasmic region of Igα and Igβ chains?

    <p>Immunoreceptor tyrosine based activation motif (ITAM)</p> Signup and view all the answers

    Why are the cytoplasmic tails of the BCRs, such as IgM and IgD, inadequate for signal transduction?

    <p>They are too short to initiate signaling cascades.</p> Signup and view all the answers

    Which of the following statements correctly describes the function of B cell receptors (BCRs)?

    <p>BCRs bind antigens but do not transduce signals.</p> Signup and view all the answers

    What are the structural features of Igα and Igβ that facilitate their function in signal transduction?

    <p>They possess long cytoplasmic tails with ITAMs.</p> Signup and view all the answers

    What factor does NOT affect the kinetics of a primary immune response?

    <p>Species of the antigen</p> Signup and view all the answers

    Which statement accurately describes the primary immune response?

    <p>It involves clonal selection and expansion.</p> Signup and view all the answers

    During the lag time of the primary immune response, which event occurs first?

    <p>Clonal selection of B cells</p> Signup and view all the answers

    What type of immunoglobulin is primarily produced during the initial stages of the primary immune response?

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

    Which of the following statements is true regarding memory B cells?

    <p>They are essential for immediate antibody production upon re-exposure to antigen.</p> Signup and view all the answers

    What distinguishes the secondary humoral immune response from the primary immune response?

    <p>It shows higher levels of IgG compared to IgM.</p> Signup and view all the answers

    Which factor contributes to the rapid generation of the secondary immune response?

    <p>The presence of memory B and T cells.</p> Signup and view all the answers

    How does the strength of the secondary immune response compare to the primary immune response?

    <p>It is stronger due to memory B and T cells.</p> Signup and view all the answers

    What is a primary characteristic of antibodies secreted during the secondary immune response?

    <p>They exhibit a higher affinity to antigens.</p> Signup and view all the answers

    Which statement accurately describes the duration of the secondary immune response compared to the primary immune response?

    <p>It is known to last longer than the primary immune response.</p> Signup and view all the answers

    What is the primary type of antibody that dominates in the primary humoral response?

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

    What is the typical lag time observed after antigen administration for the secondary humoral response?

    <p>3-4 days</p> Signup and view all the answers

    Which statement accurately describes the affinity of antibodies produced during the primary and secondary responses?

    <p>Primary response antibodies have low affinity while secondary response antibodies have high affinity.</p> Signup and view all the answers

    Which of the following best describes the magnitude of the secondary humoral response compared to the primary response?

    <p>It is 100 to 1000 times greater.</p> Signup and view all the answers

    What type of antigens primarily induce the secondary humoral response?

    <p>T dependent antigens only</p> Signup and view all the answers

    What is the primary lymphoid organ where blood-borne antigens become concentrated?

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

    Which sequence describes the correct initial steps in a humoral immune response toward protein antigens?

    <p>Recognition of antigens by B cells and T cells, followed by migration and interaction.</p> Signup and view all the answers

    What triggers the proliferation and differentiation of B cells during humoral immune responses?

    <p>Interaction of activated T cells with B cells.</p> Signup and view all the answers

    Where do antigens from external surfaces concentrate before initiating a humoral immune response?

    <p>Lymph nodes</p> Signup and view all the answers

    In the context of humoral immunity, which cells initially recognize and bind to the antigens?

    <p>B cells and CD4+ T cells</p> Signup and view all the answers

    What is the primary role of CD4+ T cells in T cell–dependent humoral immune responses?

    <p>Providing co-stimulatory signals to activate B cells</p> Signup and view all the answers

    What is the outcome of the interaction between activated B cells and helper T cells in extrafollicular sites?

    <p>Short-lived plasma cell generation and early isotype switching</p> Signup and view all the answers

    Which two signals are necessary for the co-stimulation of B cells by activated CD4+ T cells?

    <p>Antigen engagement and binding of CD40L to CD40</p> Signup and view all the answers

    What occurs during the late events in the germinal centers of T cell–dependent immune responses?

    <p>Selection for high-affinity antibody-producing cells</p> Signup and view all the answers

    Which statement accurately describes the process of isotype switching in B cells?

    <p>It allows the generation of diverse antibody responses through class switching.</p> Signup and view all the answers

    What is the main function of germinal centers in secondary lymphoid tissues?

    <p>To generate long-lived plasma cells and memory B cells</p> Signup and view all the answers

    Which of the following best describes the environment of germinal centers?

    <p>A location that enhances B cell mutation and selection</p> Signup and view all the answers

    What differentiates the long-lived plasma cells produced in germinal centers from other B cells?

    <p>They secrete antibodies that persist in the body.</p> Signup and view all the answers

    Which outcome is specifically associated with the formation of germinal centers?

    <p>Production of diverse antibody specificities</p> Signup and view all the answers

    What type of immune response is greatly enhanced by the action of germinal centers?

    <p>The humoral immune response to antigens</p> Signup and view all the answers

    What structural features differentiate the dark zone from the light zone within a germinal center?

    <p>The dark zone consists of proliferating B cells and the light zone contains follicular dendritic cells.</p> Signup and view all the answers

    During the germinal center reaction, which processes occur concurrently with the migration of B cells?

    <p>Affinity maturation, somatic mutation, and migration into the germinal center occur concurrently.</p> Signup and view all the answers

    What is the primary purpose of follicular dendritic cells located in the light zone of germinal centers?

    <p>To facilitate the selection of high-affinity B cells.</p> Signup and view all the answers

    Which of the following statements regarding the formation of high-affinity antibody-secreting cells is true?

    <p>High-affinity antibody-secreting cells arise from B cells that have undergone affinity maturation and isotype switching.</p> Signup and view all the answers

    What characterizes the overall function of germinal centers in secondary lymphoid organs?

    <p>They orchestrate the processes of B cell proliferation and somatic mutation enhancing antibody affinity.</p> Signup and view all the answers

    Which cytokine is responsible for inducing the production of IgG2b in B cells during isotype switching?

    <p>TGF-beta</p> Signup and view all the answers

    What change occurs in B cells during heavy chain isotype switching in response to specific cytokines?

    <p>B cells stop producing IgM and produce IgG, IgA or IgE.</p> Signup and view all the answers

    Which factor primarily regulates Ig class switching in B cells during T-dependent responses?

    <p>Cytokines produced by activated helper T cells</p> Signup and view all the answers

    During isotype switching, which heavy chain class is induced by the cytokine IL-1?

    <p>IgG1</p> Signup and view all the answers

    Which of the following classes of antibodies is produced when B cells undergo isotype switching as a response to LPS?

    <p>IgG1</p> Signup and view all the answers

    What is the primary mechanism by which clonal expansion occurs?

    <p>Proliferation of a single T cell of a specific antigen specificity</p> Signup and view all the answers

    Which aspect of clonal selection indicates the activation of lymphocytes?

    <p>Binding of antigen to specific receptors on B cells</p> Signup and view all the answers

    In the context of lymphocyte activation, what is the role of antigen binding?

    <p>It triggers cell activation and proliferation.</p> Signup and view all the answers

    What hypothesis explains the specificity of lymphocyte receptors prior to antigen interaction?

    <p>Clonal selection hypothesis</p> Signup and view all the answers

    What ensures that a given lymphocyte expresses the correct receptor prior to antigen exposure?

    <p>Gene rearrangement processes during lymphocyte development</p> Signup and view all the answers

    What is the primary function of follicular dendritic cells in the immune response?

    <p>Present antigen for interaction with B cells</p> Signup and view all the answers

    Which of the following correctly describes the outcome of high-affinity B cell selection?

    <p>They are selected to survive while low-affinity cells are clonal deleted</p> Signup and view all the answers

    Which statement accurately represents the role of memory B cells?

    <p>They recirculate between blood and lymphoid organs for long-term immunity</p> Signup and view all the answers

    What criterion is essential for effective vaccines targeting microbes?

    <p>Promoting affinity maturation and memory B cell generation</p> Signup and view all the answers

    What distinguishes plasma cells from other B cells in terms of function?

    <p>They begin producing antibodies and lose their BCR</p> Signup and view all the answers

    What characterizes the variable region of antibodies?

    <p>It shows significant variability in amino acid sequences.</p> Signup and view all the answers

    Which statement accurately describes the structure of antibodies?

    <p>Each antibody comprises two light chains and two heavy chains.</p> Signup and view all the answers

    What is the function of the Fc fragment derived from antibody digestion?

    <p>It does not bind antigens but crystallizes at low temperature.</p> Signup and view all the answers

    Which type of light chains can antibodies possess?

    <p>Either kappa or lambda chains exclusively.</p> Signup and view all the answers

    Which class of immunoglobulins corresponds to the heavy chain type mu (μ)?

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

    What is the primary role of IgG subclasses in relation to the placenta during pregnancy?

    <p>They provide protection to the fetus.</p> Signup and view all the answers

    Which statement is true about the structure of IgG?

    <p>It possesses two gamma heavy chains and two light chains.</p> Signup and view all the answers

    Which subclass of IgG is known for its ability to activate the complement system?

    <p>IgG3</p> Signup and view all the answers

    How do the IgG subclasses differ among various animal species?

    <p>Some species may have unique subclasses not present in humans.</p> Signup and view all the answers

    What enhances the process of opsonization and phagocytosis involving IgG3?

    <p>Interaction with Fc receptors on macrophages.</p> Signup and view all the answers

    What is the primary role of secretory IgA in the body?

    <p>To protect mucosal surfaces from pathogens</p> Signup and view all the answers

    Which structural feature distinguishes secretory IgA from other immunoglobulins?

    <p>It has a secretory component that protects it from digestion</p> Signup and view all the answers

    How is secretory IgA formed during its transport across epithelial cells?

    <p>Through the cleavage of the poly-Ig receptor</p> Signup and view all the answers

    What type of receptor is associated with the transport of IgA across mucosal epithelium?

    <p>Poly-Ig receptor</p> Signup and view all the answers

    What percentage of total serum immunoglobulin is attributed to IgA?

    <p>10-15%</p> Signup and view all the answers

    What is a notable structural characteristic of IgM in its free form?

    <p>It is a pentamer arranged in a star-like configuration.</p> Signup and view all the answers

    How does IgM primarily differ from IgG in terms of complement activation?

    <p>IgM activates complement more effectively than IgG.</p> Signup and view all the answers

    What factor limits the stable binding capacity of IgM for large antigens?

    <p>The requirement for small antigens to occupy all ten binding sites.</p> Signup and view all the answers

    What is the primary function of the joining chain associated with IgM?

    <p>To connect the individual subunits of IgM.</p> Signup and view all the answers

    Which statement best describes the antigen binding properties of IgM?

    <p>IgM can bind to multiple large antigens simultaneously.</p> Signup and view all the answers

    What role does IgE play in the immune response?

    <p>Mediating allergic reactions through binding to mast cells</p> Signup and view all the answers

    What is the primary characteristic of IgD?

    <p>It serves as a B cell receptor alongside IgM</p> Signup and view all the answers

    How does antigen binding influence IgE molecules?

    <p>Antigen cross-linking of IgE triggers degranulation of mast cells</p> Signup and view all the answers

    What percentage of total immunoglobulin in serum is IgD?

    <p>0.2%</p> Signup and view all the answers

    Which of the following statements about IgE is incorrect?

    <p>IgE is abundant in serum and serves multiple roles in immunity</p> Signup and view all the answers

    What differentiates allotypic determinants from isotypic determinants in immunoglobulins?

    <p>Isotypic determinants are species-specific, while allotypic determinants account for differences within a species.</p> Signup and view all the answers

    Which statement accurately reflects the role of idiotypic determinants in immunoglobulin function?

    <p>Idiotypic determinants influence the immune response by determining antibody specificity.</p> Signup and view all the answers

    How are allotypic antibodies generally produced within a species?

    <p>By injecting immunoglobulin from one member of a species into another member of the same species.</p> Signup and view all the answers

    What would likely induce an immune response if introduced to a different species?

    <p>Isotypic immunoglobulin from one species.</p> Signup and view all the answers

    Which statement accurately characterizes isotypic antigenic determinants?

    <p>They are constant regions and are species-specific, relating to heavy-chain and light-chain types.</p> Signup and view all the answers

    What roles do antibodies perform apart from binding to antigens?

    <p>They induce effector activity of other immune components.</p> Signup and view all the answers

    Which part of the antibody is responsible for binding to antigens?

    <p>The variable region.</p> Signup and view all the answers

    How do antibodies contribute to the immune response if they do not kill pathogens directly?

    <p>By recruiting immune cells through their constant region.</p> Signup and view all the answers

    Which statement correctly describes the relationship between antibodies and pathogens?

    <p>Antibodies facilitate the immune response through other components.</p> Signup and view all the answers

    What is true about the effector functions induced by antibodies?

    <p>They are initiated by the antibody's constant region interacting with other immune cells.</p> Signup and view all the answers

    Which function is primarily associated with opsonization in the immune response?

    <p>Enhances phagocytosis of antigens</p> Signup and view all the answers

    Which receptor is specifically involved in transporting IgG through the placenta?

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

    What is the main biological function of Fc receptors on cell surfaces?

    <p>Facilitating diverse antibody functions</p> Signup and view all the answers

    Which type of antibody is capable of initiating antibody-dependent cellular cytotoxicity (ADCC)?

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

    Which of the following statements best describes the characteristic of serum generated from polyclonal antibody responses?

    <p>It consists of antibodies from multiple B cell clones with diverse specificities.</p> Signup and view all the answers

    What is a key distinction between polyclonal and monoclonal antibodies?

    <p>Monoclonal antibodies are specific for a single antigenic epitope.</p> Signup and view all the answers

    Which method was developed by Köhler and Milstein to produce monoclonal antibodies?

    <p>Fusion of normal plasma cells with myeloma cells.</p> Signup and view all the answers

    Why are polyclonal antibodies considered unsuitable for therapeutic procedures?

    <p>They lack specificity for single antigens.</p> Signup and view all the answers

    What characteristic feature do hybrid cells produced through the fusion process exhibit?

    <p>They have the ability to replicate indefinitely.</p> Signup and view all the answers

    What is a fundamental limitation in the purification of polyclonal antibodies?

    <p>There is no feasible way to purify them to create monoclonal antibodies.</p> Signup and view all the answers

    Study Notes

    B Cell Development

    • B lymphocytes, a type of white blood cell, are responsible for humoral immunity, which involves the production of antibodies.
    • B cell development, also known as B cell maturation, is the process by which these cells become mature and capable of mounting an immune response.
    • This process occurs primarily in the bone marrow, a spongy tissue found within bones, particularly in humans and mice.
    • The bone marrow provides a unique microenvironment conducive to B cell development.
    • Immature B cells undergo a series of developmental stages within the bone marrow, resulting in mature B cells that are capable of recognizing and responding to specific antigens.

    B Cell Activation and Differentiation

    • Mature B cells reside in the lymph nodes and spleen, where they encounter antigens.
    • Activation of B cells occurs when a B cell receptor (BCR) on the surface of the B cell binds to a specific antigen.
    • This binding event triggers a cascade of intracellular signaling events.
    • Activated B cells differentiate into plasma cells and memory B cells.
    • Plasma cells, which are antibody-producing factories, are responsible for producing and secreting antibodies that target the specific antigen encountered by the B cell.
    • Memory B cells are long-lived cells that remain in the body after an infection, providing immunological memory.
    • These memory B cells quickly differentiate into antibody-producing plasma cells if the body encounters the same antigen again, providing a faster and more robust immune response upon re-exposure.

    B Cell Activation

    • B cell activation is triggered by antigen presence.
    • Activated B cells proliferate and differentiate into plasma cells and memory B cells.
    • Naive B cells that don't encounter antigens die within a few weeks.
    • B cell activation can occur via two pathways: thymus-dependent (TD) antigens and thymus-independent (TI) antigens.
    • Activation by TD antigens requires the presence of helper T cells (CD4+).

    T-dependent vs T-independent Antigens

    • T-independent antigens (TI) can directly activate B cells without the help of T cells.

    T-independent Antigen Types

    • TI-1 antigens: Polyclonal activators of B cells. Act as mitogens.
      • Recognized by B cell receptors (BCRs) or Toll-like receptors (TLRs).
    • TI-2 antigens: Activate B cells by extensively cross-linking to multiple membrane immunoglobulin receptors.

    T-independent Response Characteristics

    • Weak immune response: Not as strong as T-dependent responses.
    • No memory cell differentiation: No long-term memory immune cells formed.
    • Dominant immunoglobulin: IgM is the primary antibody produced.

    B Cell Receptor Structure and Signaling

    • B cell receptors (BCRs) are composed of immunoglobulin molecules, primarily IgM and IgD, which bind antigens.
    • BCRs have a short cytoplasmic tail, insufficient for signal transduction.
    • Signal transduction is accomplished by Igα and Igβ chains, which are associated with the BCR.
    • Igα and Igβ chains have longer cytoplasmic tails containing Immunoreceptor Tyrosine-based Activation Motifs (ITAMs).
    • ITAMs are crucial for initiating intracellular signaling cascades upon antigen binding.

    Humoral Immune Response

    • Initial exposure to an antigen triggers the primary immune response
    • The primary immune response involves antibody production by plasma cells and the generation of memory B cells
    • The kinetics of the primary immune response are influenced by several factors:
      • Nature of the antigen
      • Administration route (vaccine or infection route)
      • Presence or absence of an adjuvant (vaccines)
      • Species of infected or immunized individuals
    • The primary immune response is characterized by a lag time
    • During the lag time, the following events occur:
      • Clonal selection: B cells with specificity for foreign antigens are selected
      • Clonal expansion: The number of antigen-specific B cells increases
      • Differentiation: Plasma cells and memory cells develop
      • Antibody production: Mostly IgM is produced, with lesser amounts of IgG

    Primary Immune Response

    • Characterized by low antibody levels.

    Secondary Humoral Immune Response

    • Occurs upon subsequent exposure to the same antigen.
    • Dependent on memory B and T helper cells.
    • Generated rapidly compared to the primary response.
    • Stronger than the primary response due to memory B and T cells.
    • Lasts longer than the primary response.
    • Antibodies secreted have a higher affinity to antigens.
    • Characterized by higher levels of IgG than IgM.

    Primary vs. Secondary Humoral Responses

    • Responding B Cells:
      • Primary Response: Naive B Cells
      • Secondary Response: Memory B Cells
    • Lag Time: Time between antigen administration and the start of the immune response
      • Primary Response: 4-7 days
      • Secondary Response: 3-4 days
    • Peak of Response: Time when the immune response is at its highest
      • Primary Response: 7-10 days
      • Secondary Response: 3-5 days
    • Magnitude of Response:
      • Primary Response: Varies depending on the antigen
      • Secondary Response: 100 to 1000 times stronger than the primary response
    • Isotype and Antibody Production:
      • Primary Response: IgM is the dominant antibody
      • Secondary Response: IgG is the dominant antibody
    • Type of Antigen Inducing Response:
      • Primary Response: Both T-dependent and T-independent antigens
      • Secondary Response: Primarily T-dependent antigens
    • Antibody Affinity:
      • Primary Response: Low affinity
      • Secondary Response: High affinity

    Sites of humoral immunity induction

    • Antigens from external surfaces concentrate in lymph nodes.
    • Bloodborne antigens concentrate in the spleen.

    Sequence of events in humoral immune responses to T cell– dependent protein antigens

    • B cells and CD4+ T cells initiate immune responses by recognizing antigens.
    • Activated lymphocytes migrate towards B cells.
    • B cell proliferation and differentiation occur through interactions between activated lymphocytes.

    Humoral Immune Responses to T Cell–Dependent Protein Antigens

    • The immune system is initiated by the recognition of antigens by B cells and CD4+ T cells.
    • Activated lymphocytes migrate towards B cells, leading to B cell proliferation and differentiation.
    • Helper T cell stimulation in extrafollicular sites produces short-lived plasma cells and early isotype switching.
    • Activation of T cells by B cells induces follicular helper T cells.
    • Late events occur in germinal centers, including:
      • Selection of high-affinity cells (affinity maturation)
      • Additional isotype switching
      • Memory B cell generation
      • Generation of long-lived plasma cells
    • B cell activation requires two signals:
      • Signal 1: Antigen engagement (TCR + Ag on MHC II of B cells)
      • Signal 2: Binding of CD40 on the B cell and CD40L on the activated Th cell, inducing B7 which interacts with CD28 (co-stimulatory signals)

    Germinal Centers

    • Germinal centers (GC) form in secondary lymphoid tissues, like lymph nodes and spleen.
    • B cells in GC are activated by specific antigens, and undergo rapid proliferation.
    • GCs are essential for the production of long-lived antibody-secreting plasma cells and memory B cells.
    • Plasma cells produce antibodies, which are proteins that can bind to and neutralize specific antigens.
    • Memory B cells can quickly respond to reinfection with the same antigen, providing protection against reinfection.

    Germinal Centers

    • Germinal centers are located within the follicles of secondary lymphoid organs.
    • Each germinal center has two distinct zones: a dark zone and a light zone.
    • The dark zone is characterized by proliferating B cells.
    • The light zone contains follicular dendritic cells which display antigens for B cell selection.

    Germinal Center Reaction

    • B cells activated by antigen migrate to the germinal center.
    • Activated B cells undergo rapid proliferation in the dark zone.
    • During proliferation, B cells undergo somatic hypermutation, allowing for affinity maturation.
    • The B cells also switch their immunoglobulin isotype.
    • High affinity antibody-secreting cells and memory cells exit the germinal center.

    Ig class switching

    • B cells undergo heavy chain isotype switching in response to different types of microbes by changing the class of antibody produced
    • This occurs by recombining the VH DH JH unit with C regions of any heavy chain
    • The result of this is that B cells can produce different classes of antibody with different functions
      • For example, switching from IgM to IgG leads to the production of antibodies that can activate complement or bind to Fc receptors on other cells
    • Isotype switching is regulated by cytokines produced by helper T cells
      • Interleukin-4 can induce isotype switching to IgG1
      • Interferon gamma can induce isotype switching to IgG3 or IgG2a
      • TGF-beta can induce isotype switching to IgG2b
      • Interferon alpha can induce isotype switching to IgG2a
    • LPS induces IL-4

    Clonal Expansion

    • Proliferation of T cells originating from a single T cell with a specific antigen recognition site is known as clonal expansion.
    • This expansion occurs after the T cell encounters its specific antigen.

    Clonal Selection

    • The clonal selection hypothesis explains how the immune system generates a diverse repertoire of B cells, each with unique antigen specificity.
    • B cells express receptors specific for a particular antigen before encountering it.
    • Binding of the antigen to the B cell's receptor activates the cell.
    • This activation triggers proliferation of the B cell, creating a clone of daughter cells with the same antigen specificity.
    • These daughter cells are responsible for producing antibodies against the specific antigen that triggered their expansion.

    Affinity Maturation

    • Somatic mutations (point mutations, deletions, and insertions) of Ig genes occur in germinal centers leading to increased antibody affinity
    • B cells with high affinity for foreign antigens are selected to survive, while those with low affinity are eliminated through clonal deletion
    • Follicular dendritic cells (FDCs) play a crucial role in clonal selection by presenting antigens on their cell surface for B cell interaction
    • T CD4+ cells are essential for the selection process, recognizing antigens presented by B cells (centrocytes) in the context of MHC class II
    • After selection, B cells differentiate into plasma cells, which lose their BCR and produce antibodies, and memory B cells

    Generation of Memory B Cells

    • Memory B cells are generated during germinal center reactions, enabling rapid responses to subsequent antigen encounters
    • They can survive for extended periods without continuous antigenic stimulation
    • Memory B cells can reside in lymphoid organs or circulate between the blood and lymphoid organs
    • Effective vaccines against microbes and their toxins must induce both affinity maturation and memory B cell formation

    Antibodies

    • Antibodies are proteins produced by B cells in response to antigens.
    • Found in serum, milk, tears, saliva, mucus, and bile.
    • Composed of four chains: two light (L) and two heavy (H) chains.
    • Light chains have a molecular weight of 22,000 daltons each.
    • Heavy chains have a molecular weight of 55,000 daltons each.
    • L and H chains are associated by disulfide bonds and non-covalent interactions.
    • Two L-H dimers associate via disulfide bonds to form a heterodimer (antibody).
    • The first 110 amino acids of the L and H chains are highly variable, called the variable region (VL and VH).
    • The region below the variable region is constant, called the constant region (CL and CH).
    • Papain digestion of IgG produces three fragments: two Fab fragments and one Fc fragment.
    • Fab fragments bind antigens.
    • Fc fragment does not bind antigens but crystallizes at low temperatures.
    • Two types of L chains: kappa (κ) and lambda (λ).
    • Antibodies have only one type of L chain (κ or λ).
    • Five types of H chains: alpha (α), gamma (γ), delta (δ), epsilon (ε), and mu (μ).
    • The type of H chain determines the immunoglobulin class (IgA, IgG, IgD, IgE, or IgM).
    • Immunoglobulins with different heavy chains are called isotypes.

    Immunoglobulin Subclasses

    • Immunoglobulin subclasses are determined by small differences in the amino acid sequences of heavy chains.
    • IgG is the most abundant immunoglobulin in serum, accounting for approximately 80%.
    • IgG molecules consist of two γ heavy chains and two light chains, which can be either κ or λ.
    • The number of IgG subclasses varies across different animal species.
    • In humans, IgG1, IgG3, and IgG4 can cross the placenta to protect the developing fetus.
    • IgG3 activates the complement system, which enhances the immune response.
    • IgG3 binds to Fc receptors on macrophages, promoting opsonization and phagocytosis.

    What is IgA?

    • IgA makes up 10-15% of total immunoglobulins in serum.
    • It is the dominant immunoglobulin in body secretions like milk, tears, and mucous in mucosal linings of the respiratory, digestive, and reproductive tracts.
    • IgA exists mostly as a monomer but can be found as a dimer, trimer, or tetramer.

    Secretory IgA (sIgA)

    • The IgA found in external secretions is a dimer called secretory IgA.
    • Two units of this IgA dimer are connected by Fc, a joining chain, and a secretory component.
    • Plasma cells producing secretory IgA are found in the submucosal of the mucous membranes.
    • Secretory IgA is formed during translocation through epithelial cells of the mucosal.

    How is Secretory IgA Formed?

    • IgA dimer binds to the poly-Ig receptor on the epithelial cell surface.
    • This receptor is present on the basolateral surface of many mucosal epithelia, including the digestive tract and mammary, salivary, and lacrimal glands.
    • IgA is transported through endocytosis with the poly-Ig receptor across the cell to the opposite side of the cell surface (luminal side, e.g., intestines).
    • The poly-Ig receptor is cleaved enzymatically and becomes part of the secretory IgA dimer.

    Function of Secretory IgA

    • The secretory component protects the hinge regions of IgA from digestion by proteolytic enzymes.
    • High IgA levels are maintained at surfaces rich in proteolytic enzymes.
    • IgA protects against pathogens (bacteria, viruses) entering the body through mucosal surfaces.
    • Antigen-antibody complexes formed at these surfaces are removed by local mechanisms like ciliated epithelial cells in the respiratory tract or peristalsis in the digestive tract.

    IgM Properties

    • 5-10% of total immunoglobulin in serum
    • Free IgM is a pentamer
    • Monomeric IgM is found as a receptor on B cells
    • Molecular weight: 900,000 daltons
    • Five subunits arranged in a star-like fashion, connected through the Fc region and a joining chain
    • 10 antigen-binding regions (Fab fragments)
    • First immunoglobulin synthesized by newborns
    • First immunoglobulin produced during a primary humoral immune response

    IgM Function

    • Can only bind 5 large antigens due to its structure
    • Effective in binding antigens with repetitive epitopes (e.g., viruses, red blood cells)
    • More effective in activating complement than IgG
    • Two Fc fragments in close proximity are required for complement activation

    IgE

    • Found in small amounts in serum
    • Plays a critical role in triggering allergic reactions
    • Binds to Fc receptors on basophils and mast cells
    • When an antigen binds to two IgE molecules, mast cell granules move to the cell surface and release their contents
    • These granules contain mediators of inflammation, contributing to allergic responses

    IgD

    • Accounts for approximately 0.2% of total serum immunoglobulins
    • Alongside IgM, IgD acts as a B cell receptor (BCR) on the surface of naive B lymphocytes
    • No known biological effector function has been identified for IgD

    Antigenic Determinants on Immunoglobulins

    • Immunoglobulins (Ig) are themselves antigens, meaning they can induce an immune response when introduced to other species.
    • This immune response produces anti-Ig antibodies which are useful for studying B lymphocyte development and for diagnostic purposes.

    Categories of Antigenic Determinants

    • Isotypic determinants distinguish the different isotypes of immunoglobulins.
      • These determinants are found in the constant regions of heavy and light chains.
      • Each species has different isotypes, making antibodies from one species foreign antigens to another, triggering an immune reaction.
    • Allotypic determinants distinguish between different alleles of isotype genes within a single species.
      • These determinants are encoded by alleles that cause small amino acid sequence variations within isotypes.
      • Allotypic antibodies are produced by injecting immunoglobulin from one member of a species into another member of the same species.
    • Idiotypic determinants are found in the variable regions of both light and heavy chains of a given antibody.
      • They determine the unique specificity of an individual antibody.

    Antibody Functions

    • Antibodies do not directly kill or remove pathogens.
    • Antibodies bind antigens using their variable region, and interact with other cells via their constant region (Fc).
    • Antibody binding to an antigen triggers effector functions in other immune cells, leading to pathogen removal.

    Antibody Functions

    • Antibodies bind to foreign antigens recognized within the host.
    • Antibodies mediate effector functions that lead to the elimination of foreign antigens, such as infectious agents.

    Opsonization

    • Antibodies coat antigens, facilitating phagocytosis by macrophages and neutrophils.
    • Macrophages and neutrophils have Fc receptors on their cell surfaces.
    • Phagocytosis is initiated when Fc receptors engage with Fc fragments on antibodies.

    Antibody-Dependent Cellular Cytotoxicity (ADCC)

    • Target cells are recognized through CD16 only when antibodies are present.

    Fc Receptors

    • Glycoproteins found on the surface of many cells.
    • Responsible for various biological functions of antibodies:
      • Induce regulatory signals that affect cell activation or inhibition.
      • Transcytosis.
      • Mediation of phagocytosis.
      • Antibody-dependent cell cytotoxicity.
    • Antibodies bound to Fc receptors on cell surfaces can:
      • Induce regulatory signals that affect activation or inhibition of cells bearing the Fc receptors.
      • Participate in transcytosis (transport).
      • Mediate phagocytosis.
      • Initiate Antibody-Dependent Cell Cytotoxicity (ADCC).

    Types of Fc Receptors

    • Poly-Ig receptors transport IgA and IgM through epithelial cells.
    • FcRn (neonatal Fc receptor) transports IgG through the placenta to the blood circulation of the fetus and regulates serum IgG levels.
    • FcαR binds IgA.
    • FcεR binds IgE.
    • FcγR exists in multiple forms (RI, II-A, RII-B1, RII-B2, RIII) and binds IgG and its subclasses.

    Monoclonal Antibodies

    • Most antigens have multiple antigenic epitopes, inducing the proliferation and differentiation of distinct B cell clones producing different antibodies.
    • This creates heterogeneous serum containing a mixture of antibodies specific to different antigens.
    • These antibodies are called polyclonal antibodies.
    • Polyclonal antibodies are suitable for various effector functions, such as mediating phagocytosis and activating complement.
    • Polyclonal antibodies are not suitable for diagnostic or therapeutic procedures.
    • Monoclonal antibodies are produced by a single clone and are specific for a single antigenic epitope.
    • Köhler and Milstein developed a method to produce monoclonal antibodies by fusing normal plasma cells with myeloma cells.
    • The hybrid cells are immortal and continuously produce antibodies of single specificity.

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    Understand humoral immunity

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