12-Cell__Mediated_Effector_Responses_Chpt._14_2023__5_

Effector Responses

Overview of Cell-Mediated Immune Response

  • Definition: A critical component of the adaptive immune system where T cells and other immune cells respond to infected or abnormal cells.

  • Targets:

    • Virus-infected cells

    • Tumor cells

    • Grafted tissues

    • Fungi

    • Intracellular parasites

    • Some intracellular bacteria (e.g., tuberculosis)

Types of Effector T Cells

  • CD4+ T cells (Helper T cells): Subtypes include TH1, TH2, etc.

  • CD8+ T cells (Cytotoxic T cells): Subtypes include Tc1 and Tc2.

Activation and Characteristics

  • Differences Between Naïve and Effector T Cells:

    • Activation:

      • Naïve T cells require co-stimulation, whereas effector T cells need minimal co-stimulation.

      • Effector T cells have higher expression of adhesion molecules.

    • Cell Adhesion:

      • CD2 and LFA-1 molecules are expressed 2-4 fold higher on effectors.

      • These molecules interact with LFA-3 and ICAM on antigen-presenting cells (APCs).

Role of CD45 in T Cell Activation

  • CD45 Structure:

    • A large transmembrane protein expressed by all leukocytes, including T cells.

    • Functional role in TCR signaling.

  • Isoforms:

    • CD45RA: Present on naïve T cells.

    • CD45RO: Present on effector T cells, enhances signaling.

Mechanism of Helper T Cell Action

  • Activated Helper T Cells:

    • Stimulate cytotoxic T cells via IL-2 secretion.

    • Stimulate B cells with specific interleukins (IL-2, IL-4, IL-5, IL-6).

    • Activate macrophages and help further stimulate other helper T cells.

Activation of CD8+ Cytotoxic T Cells

  • Process:

    1. Recognition of MHC I-antigen complex on target cells.

    2. Activation through multiple signals including costimulatory interactions (CD28-B7).

    3. IL-2 interaction with receptors.

Mechanisms of Cytotoxic T Cell Killing

  • Killing Methods:

    • Perforin/Granzyme Pathway:

      • Perforin creates pores in target cell membranes, allowing granzymes to enter and induce apoptosis.

    • Fas-FasL Interaction:

      • The engagement of Fas on target cells by FasL on cytotoxic T cells also leads to apoptosis.

Role of Natural Killer (NK) Cells

  • Characteristics:

    • Comprise 5-10% of lymphocytes, lack antigen-specific receptors.

    • Recognize and kill infected or tumor cells by detecting the absence of MHC class I molecules.

  • Mechanisms of Action:

    • Utilize perforin/granzyme and Fas-FasL pathways similarly to cytotoxic T cells.

Overview of Antibody-Mediated Immunity

  • B Lymphocytes:

    • Develop in bone marrow and acquire receptors specific for antigens.

    • Activation results in clonal proliferation and differentiation into plasma or memory cells.

  • Antibody Functions:

    • Neutralization of pathogens, agglutination of antigens, precipitation of soluble antigens.

    • Complement activation leading to opsonization and inflammation.

Summary of Immunological Functions

  • Cytotoxic T Cells:

    • Directly attack infected or cancer cells and initiate apoptosis through several pathways.

  • NK Cells:

    • Act as early responders in immune defense, regulate both innate and adaptive immunity.

  • NKT Cells:

    • Bridge the innate and adaptive immune responses, recognize lipid antigens.

Importance of Cell-Mediated Immunity

  • Implications in Disease:

    • Cell-mediated immunity is crucial for combating intracellular infections.

    • Conditions like DiGeorge Syndrome illustrate the role of T cells in managing intracellular pathogens.