Adaptive Immune Response to Extracellular Bacterial Infection

Adaptive Immune Response to Extracellular Bacterial Infection

Diagram of Adaptive Immune Response Events

  • Antigen Presentation:

    • Extracellular bacteria are phagocytosed by antigen-presenting cells (APCs) such as macrophages or dendritic cells.

    • Inside the APC, the bacteria are broken down into peptide fragments.

    • These peptide fragments are loaded onto MHC class II molecules.

    • The MHC class II molecules, with the bound peptide, are transported to the cell surface.

  • T Cell Activation:

    • T helper cells (specifically, CD4+ T cells) recognize the peptide-MHC class II complex on the APC via their T cell receptor (TCR).

    • Co-stimulatory molecules (e.g., B7 on the APC binding to CD28 on the T cell) are also required for full T cell activation.

    • Once activated, the T helper cell proliferates and differentiates into different subsets, such as Th1 or Th2 cells, depending on the cytokines present in the environment.

  • B Cell Activation:

    • B cells recognize the extracellular bacteria via their B cell receptor (BCR), which is a membrane-bound antibody.

    • The bacteria are internalized, processed, and presented as peptides on MHC class II molecules.

    • The activated T helper cells (particularly Th2 cells) recognize the peptide-MHC class II complex on the B cell.

    • T cell help, provided through CD40L on the T cell binding to CD40 on the B cell and through the release of cytokines (e.g., IL-4, IL-5), is essential for B cell activation.

  • Antibody Production:

    • Activated B cells undergo clonal expansion and differentiate into plasma cells.

    • Plasma cells are specialized for producing and secreting large amounts of antibody.

    • Some activated B cells differentiate into memory B cells, which provide long-lasting immunity.

Explanation of Key Events

  • Antigen Presentation by APCs: APCs engulf and process the extracellular bacteria, presenting bacterial peptides on MHC class II molecules to activate T helper cells. This is essential for initiating the adaptive immune response.

  • T Cell Activation and Differentiation: T helper cells, once activated by APCs, orchestrate the immune response by releasing cytokines and providing help to B cells. The differentiation into Th1 or Th2 subsets depends on the cytokines present during activation, influencing the type of immune response.

  • B Cell Activation and Antibody Production: B cells recognize the bacteria via their BCR and require T cell help to become fully activated. Activated B cells differentiate into plasma cells, which produce and secrete antibodies that target the bacteria.

Antibody Production and Function

  • Antibody Production Process:

    • B cells are activated by binding to their specific antigen (the extracellular bacteria). This is facilitated by the BCR.

    • Internalization and presentation of processed antigen on MHC class II molecules.

    • Interaction with T helper cells, specifically Th2 cells, that recognize the same antigen. This interaction involves CD40L-CD40 binding and cytokine release (e.g., IL-4).

    • Activated B cells undergo clonal expansion, affinity maturation (where the antibody becomes more specific and has a higher affinity for the antigen), and class switching (where the antibody changes its isotype, e.g., from IgM to IgG).

    • Differentiation into plasma cells, which are antibody-secreting factories.

  • Functions of Antibodies in Fighting Infection:

    • Neutralization: Antibodies bind to the bacteria and prevent them from infecting host cells. The antibody physically blocks the binding of the bacteria to host cell receptors.

    • Opsonization: Antibodies coat the bacteria, making them more easily recognized and phagocytosed by phagocytes (e.g., macrophages, neutrophils). Phagocytes have receptors for the Fc region of antibodies, which enhances phagocytosis.

    • Complement Activation: Antibodies can activate the complement system, leading to the formation of the membrane attack complex (MAC) and lysis of the bacteria. The classical pathway of complement activation is initiated by antibody binding to the bacterial surface.

    • Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Antibodies bind to the bacteria, and then natural killer (NK) cells recognize the antibody-coated bacteria via their Fc receptors. This triggers the NK cell to release cytotoxic granules, killing the bacteria.

Relevance to Previous Lectures (Q6 & Q7) and B Cell Lecture

  • Referring to previous questions, the initial steps of the innate immune response (e.g., phagocytosis by macrophages) are crucial for controlling the infection before the adaptive immune response is activated.

  • The B cell lecture provides detailed information about B cell development, activation, and differentiation, which are essential for understanding antibody production.

The adaptive immune response to extracellular bacterial infections is a complex process initiated by antigen-presenting cells (APCs) that phagocytose and process bacteria, presenting bacterial peptides on MHC class II molecules to activate T helper cells. Upon activation, T helper cells orchestrate the immune response by releasing cytokines and assisting in B cell activation. B cells recognize the bacteria via their B cell receptor (BCR) and, with the help of T helper cells, differentiate into plasma cells. These plasma cells produce and secrete antibodies that neutralize pathogens, facilitate opsonisation for enhanced phagocytosis, activate the complement system for bacterial lysis, and mediate antibody-dependent cell-mediated cytotoxicity (ADCC). The antibodies' functions include neutralization (blocking infection), opsonization (enhancing phagocytosis), complement activation (leading to bacterial