Adaptive Immunity 2

Lecture Overview

  • Topic: Adaptive Immunity - Humoral Immunity

  • Key Topics:

    • Humoral immunity

    • B lymphocytes

    • Antibody classes

    • T helper lymphocytes

    • Antigen Presenting Cells (APC)

    • MHC II

  • Source Material: Openstax Microbiology Textbook

    • Chapter 18, Adaptive Immune Responses (MMG2010, 2025)

Adaptive Immunity

  • Definition: Based on the activity of lymphocytes.

  • Referenced Source: Talaro and Talaro. (2001). Foundations in Microbiology: Basic Principles. Edition 4. McGraw-Hill Companies, Inc. Permission required for reproduction or display.

  • Distinction Between Antigens:

    • Extracellular Antigens: Associated with MHC II-epitope complexes.

    • Intracellular Antigens: Associated with MHC I-epitope complexes.

B Cells and Humoral Immunity

  • B Cells: Fundamental units of humoral immunity.

  • Functions of B Cells:

    • Possess approximately 100,000 identical B Cell Receptor (BCR) molecules per B cell.

    • Differentiate into plasma cells that secrete antibodies.

    • Antibodies are the secreted form of BCR, also known as immunoglobulins (Ig).

  • Antigen Presenting Cells (APC): Express MHC II molecules.

Antibody Structure

  • Structure of Immunoglobulin (Ig):

    • Y-shaped molecule consisting of:

    • 2 heavy chains

    • 2 light chains

    • Variable (V) Region:

    • Contains the antigen-binding site.

    • Two binding sites present on every Ig.

    • Constant (C) Region:

    • Determines the antibody class.

Functions of Antibodies

  • Ig Functions:

    • Neutralization:

    • Binds pathogens, blocking their ability to attach to target cells.

    • Agglutination:

    • Clumps antigens by binding them together.

    • Opsonization:

    • Enhances phagocytosis by tagging pathogens.

    • Complement Activation:

    • Triggers classical pathway for complement activation.

    • ADCC (Antibody-Dependent Cell Mediated Cytotoxicity):

    • Uses antibodies to recruit NK cells to destroy large pathogens that cannot be phagocytosed.

Detailed Ig Functions

  • Neutralization Details:

    • Specific antibodies bind to bacterial, viral antigens and toxins, preventing attachment to target cells.

  • Opsonization Details:

    • Antibodies function as opsonins, facilitating recognition and destruction by macrophages, dendritic cells, and neutrophils through Fc receptors.

  • Agglutination Function:

    • IgM antibodies agglutinate bacteria by binding multiple epitopes from different bacteria simultaneously, forming aggregates.

  • ADCC Function:

    • Antibodies bind large pathogenic cells and then interact with NK cells, allowing the NK cell to release cytotoxins that kill the pathogen.

B Cell Activation

  • Types of Activation:

    • T Cell Dependent Activation:

    • Antigen binds to BCR.

    • B cell internalizes and presents antigen via MHC II.

    • Helper T cell (TH2) provides costimulation with cytokines.

    • B cell proliferates into plasma cells and memory B cells.

    • T Cell Independent Activation:

    • BCR binds a free epitope.

    • B cell proliferates into plasma cells and memory B cells without T cell interaction.

T Cell-Dependent Activation Mechanism

  • The B cell recognizes and internalizes an antigen.

  • B cell presents the antigen to a specific T helper cell.

    • Interaction triggers T cell activation.

    • Cytokines are released to activate the B cell, leading to proliferation and differentiation into plasma cells.

T Cell-Independent Activation Mechanism

  • T-Independent Antigens: Have repeating epitopes that induce B cell recognition.

  • Activation requires an additional signal, often from TLRs interacting with pathogen-associated molecular patterns (PAMPs).

  • Once activated, B cells proliferate and differentiate into antibody-secreting plasma cells.

Memory Cells and Plasma Cells

  • Once activated, B lymphocytes:

    • Proliferate and differentiate into plasma and memory cells.

    • Only B cells that successfully bind the antigen can proliferate further.

    • Memory Cells: Long-lived, remain in lymphatic tissues, mount a rapid response upon re-exposure.

Plasma Cells and Class Switching

  • Plasma Cells: Can produce more than one type of antibody through:

    • Class Switching: Alters the structure of the antibody based on cytokine signals, while specificity for the epitope remains unchanged.

  • Different antibody classes predominate in various body areas.

Classes of Antibodies (Immunoglobulins)

  • Five Major Classes:

    • IgG, IgA, IgM, IgD, IgE

  • Characteristics and Functions:

    • IgG: Most abundant, highest opsonization and neutralization activities, can cross the placenta.

    • IgM: First produced upon antigen invasion, forms pentamers.

    • IgA: Found in mucosal tissues, forms dimers, helps prevent pathogen adherence in mucosal surfaces.

    • IgD: Unknown function, found on B cell surfaces.

    • IgE: Involved in allergy responses.

Immune Memory and Antibody Responses

  • Primary Antibody Response:

    • Initial exposure results in short-lived plasma cells producing mostly IgM.

  • Secondary Antibody Response:

    • Subsequent exposures lead to quicker responses, memory cells facilitate rapid production of higher antibody concentrations (10-100 times more IgG).

    • Somatic Hypermutation: Changes in binding affinity strengthen antibody binding as the immune response progresses.

Overview of Immune Responses

  • Innate Immune Responses: include cytokines, phagocytosis, inflammation, and complement activation, facilitated by dendritic cells and macrophages.

  • Adaptive Immune Responses: involve the activation of T helper cells leading to B cell stimulation, proliferation, differentiation, and antibody production.

Major Histocompatibility Complex (MHC)

  • MHC Class II:

    • Found only on APCs (macrophages, dendritic cells, B cells).

    • Presents exogenous antigens (from phagocytosed pathogens) processed in vesicles.

    • Recognized by CD4+ T helper cells.

    • Importance: Crucial for linking innate and adaptive immunity; required for full immune activation.

Comparison of MHC Class I and II

  • MHC I: Found on all nucleated cells; presents endogenous (intracellular) antigens; recognized by CD8+ T cytotoxic cells.

  • MHC II: Found on APCs; presents exogenous (extracellular) antigens; recognized by CD4+ T helper cells.

Learning Objectives for Students

  • Understand and describe the sequence of events for antigen processing and presentation for intracellular and extracellular antigens.

  • Describe the role of APCs in humoral immunity, listing the three main APC types.

  • Compare T Cell Receptors (TCR) and B Cell Receptors (BCR) regarding epitope binding sites and interaction with MHC molecules.

  • Describe four mechanisms by which antibodies eliminate specific pathogens.

  • Explain how T helper cells and B cells are activated, leading to destruction of extracellular pathogens.

  • Distinguish specific characteristics of IgA, IgM, IgG, and IgE.

  • Understand the concept of antibody class switching.

  • Differentiate between MHC I and MHC II.

  • Contrast T helper cells and T cytotoxic cells in terms of co-receptors, activation signals, functions, and antigen elimination.

  • Compare and contrast cell-mediated and humoral immunity.