Effector mechanisms of activated lymphocytes

Introduction

This comprehensive and structured course delves into the critical role of effector mechanisms carried out by activated lymphocytes. These immune cells are crucial in defending the host against various pathogens, tumors, and other foreign entities. The course aims to provide a detailed understanding of the diverse strategies employed by lymphocytes upon activation.

Activation of Lymphocytes

T-cell Activation

1. Antigen Recognition: T cells recognize antigens presented on Major Histocompatibility Complex (MHC) molecules on antigen-presenting cells.
2. Co-stimulatory Signals: The interaction between CD28 on the T cell and CD80/CD86 on the APC triggers intracellular signaling cascades, leading to activation.
3. Cytokine Responses: Interleukin (IL)-2, IL-4, and Interferon-γ (IFN-γ) are crucial cytokines produced during T cell activation that regulate their functions.

B-cell Activation

1. Antigen Recognition: B cells recognize antigens via surface receptors, known as immunoglobulins or antibodies.
2. Co-stimulatory Signals: CD40 on the B cell interacts with CD40L on T helper cells, leading to intracellular signaling and activation.
3. Cytokine Responses: IL-6, IL-10, and IFN-γ are significant cytokines involved in B cell activation.

Effector Mechanisms of Activated T Cells

Cytotoxic T Lymphocytes (CTL)

1. Granule Exocytosis: Upon encountering an infected or malignant cell, CTL release cytoplasmic granules containing perforins and granzymes into the intercellular space.
2. Apoptosis Induction: Perforins form pores in the target cell membrane, leading to granzyme entry and activation of caspases, ultimately triggering apoptosis.
3. Fas/FasL Interaction: CTL can also induce apoptosis through the Fas-Fas ligand (FasL) pathway, which leads to intrinsic apoptotic signaling in the target cell.

Helper T Cells

1. Cytokine Production: Upon activation, helper T cells secrete cytokines such as IL-2, IL-4, and IFN-γ that recruit and activate other immune cells.
2. B Cell Activation: Helper T cells aid in B cell activation by providing co-stimulatory signals and producing cytokines like IL-4 and IL-5 that promote B cell proliferation and differentiation into antibody-secreting plasma cells.
3. Th1/Th2 Polarization: The polarization of the T helper response towards either a Th1 (IFN-γ dominant) or Th2 (IL-4 dominant) phenotype dictates the type of immune response mounted against the pathogen or tumor.

Effector Mechanisms of Activated B Cells

Antibody Production and Function

1. Immunoglobulin Class Switching: Activated B cells undergo class switching, allowing them to produce various immunoglobulin isotypes (IgG, IgA, IgM, IgE) with distinct functions.
2. Complement Fixation: The binding of antibodies to antigens triggers the complement system, leading to opsonization and lysis of pathogens or targeted cells.
3. Antibody-dependent Cellular Cytotoxicity (ADCC): Activated effector cells like Natural Killer (NK) cells bind to antibody-coated target cells via Fc receptors, causing their destruction.

Memory and Regulatory Responses

Memory T and B Cells

1. Long-lived Survival: Memory T and B cells exhibit prolonged survival compared to naïve or activated effector cells, allowing for rapid responses upon re-exposure to the same antigen.
2. Enhanced Responses: Memory cells demonstrate increased proliferative capacity and cytokine production in comparison to naive cells, contributing to more robust immunity.

Regulatory T Cells (Tregs) and B Regulatory Cells (Bregs)

1. Immune Suppression: Tregs and Bregs play crucial roles in maintaining immune homeostasis by suppressing overactive immune responses, preventing autoimmunity, and modulating allergic reactions.
2. Mechanisms of Suppression: Tregs and Bregs exert their effects through a variety of mechanisms, including cell-cell contact, secretion of immunosuppressive cytokines (IL-10, TGF-β), and production of anti-inflammatory mediators.