Chapter 21 - Part 2 (lecture slides)

ZOOL 2023 Chapter 21 – Immune System Overview
21.2 Barrier Defenses and the Innate Immune Response

  • First Line of Defense:

    • Skin and mucous membranes act as physical barriers to pathogens. The skin serves as a tough, impermeable barrier, while mucous membranes line the respiratory, gastrointestinal, and urogenital tracts, producing mucus that traps pathogens.

    • Functions:

      • Prevent entry of pathogens.

        • Examples: Tears and saliva flush microorganisms from surfaces like the eyes and urethra, containing lysozyme which breaks down bacterial cell walls and provides an additional layer of enzymatic defense.

    • Other Physical Barriers:

      • Ciliated cells in the respiratory tract trap and move pathogens out of the airways, while acidic environments in the stomach can kill ingested pathogens.

  • Second Line of Defense:

    • Consists of nonspecific internal defenses that come into play when barriers are breached.

    • Components:

      • Antimicrobial substances:

        • Interferons: Antiviral cytokines produced by virus-infected cells that signal neighboring cells to heighten their antiviral defenses.

        • Complement system: A series of proteins activated by microbes to promote pathogen destruction through opsonization and formation of membrane attack complexes that lyse pathogens.

        • Iron-binding proteins (e.g., transferrin, ferritin) limit sequester iron from pathogens, as iron is essential for bacterial growth, thereby limiting their proliferation.

        • Antimicrobial proteins such as defensins disrupt the membranes of pathogens, providing an additional level of chemical defense.

    • Cells:

      • Phagocytes: Include macrophages, neutrophils, monocytes, dendritic cells, and eosinophils that engulf and destroy pathogens.

      • Natural killer (NK) cells: Specialized lymphocytes that kill infected or cancerous cells by releasing perforins and granzymes, inducing apoptosis.

    • Physiological responses:

      • Inflammation: Involves vasodilation, increased vascular permeability, phagocyte emigration, and accumulation of fluids, causing redness, heat, swelling, and pain, which serve to limit the spread of pathogens.

      • Fever: Triggered by pyrogens (e.g., cytokines like IL-1), resetting the hypothalamus’s thermostat; beneficial in creating a less favorable environment for pathogens and enhancing the body’s repair processes during infections.

21.3 The Adaptive Immune Response: T Lymphocytes and Their Functional Types

  • Adaptive Immunity:

    • Types:

      • Cell-mediated immunity (T cells).

      • Humoral immunity (B cells).

    • Characteristics:

      • Specificity: Ability to target specific pathogens through recognition of unique antigens.

      • Memory: Immune system retains information about past infections, leading to quicker and more robust responses upon re-exposure to the same pathogen.

    • T Lymphocytes:

      • Different functional types:

        • CD4+ T helpers: Activate other immune cells, particularly B cells and macrophages, by releasing cytokines that enhance the immune response.

        • CD8+ T cytotoxic cells: Directly kill infected or cancerous cells through the recognition of abnormal antigens presented via MHC Class I molecules.

        • Mechanism of action: Activated through recognition of specific antigens presented in conjunction with MHC molecules, crucial for target identification.

21.4 The Adaptive Immune Response: B-Lymphocytes and Antibodies

  • B Lymphocytes (B cells):

    • Responsible for humoral immunity, producing key components in immune defense.

    • Function: Produce antibodies (immunoglobulins) that specifically bind to corresponding antigens, neutralizing or marking them for destruction.

    • Activation:

      • Directly recognize antigens through their B-cell receptors (BCRs) or indirectly through antigen presenting cells (APCs).

      • Following activation, B cells proliferate and differentiate into plasma cells that secrete antibodies or memory B cells that provide long-term immunity for secondary responses.

    • Antibody Structure:

      • Consist of four polypeptide chains (two heavy, two light), forming a Y-shaped structure, critical for their function in antigen recognition and neutralization.

      • Variable region: Highly specific for targeting unique antigens.

      • Constant region: Defines the class of antibody (IgG, IgA, IgM, IgE, or IgD) which tailors the immune response to different pathogens.

21.5 The Immune Response against Pathogens

  • Cooperation Between Innate and Adaptive Immunity:

    • The innate immune response enhances the effectiveness of adaptive responses by initially containing the infection and recruiting adaptive immune cells for a more directed attack.

  • Mechanisms of Action:

    • Antibodies neutralize pathogens, opsonize pathogens for phagocytosis by marking them for destruction, and activate complement pathways that lead to lysis of pathogens.

    • T cell-mediated responses effectively target infected host cells, supporting direct cellular immunity, which is critical for eliminating intracellular pathogens and tumor cells.

21.6 Diseases Associated with Depressed or Overactive Immune Responses

  • Autoimmune Diseases:

    • Occur when the immune system mistakenly attacks the body's own tissues, demonstrating loss of self-tolerance.

    • Examples include:

      • Celiac disease (attacks intestines): Triggered by an inappropriate immune response to gluten.

      • Diabetes mellitus type I (attacks pancreatic beta cells): Leads to insulin deficiency and hyperglycemia.

      • Graves' disease (hyperthyroidism due to antibody mimic): Results in excessive thyroid hormone production.

      • Hashimoto's thyroiditis (hypothyroidism due to antibody blockage): Leads to thyroid dysfunction and reduced hormone levels.

  • Hypersensitivity Reactions:

    • Overactive immune responses to harmless antigens can lead to tissue damage and various allergic reactions.

    • Types:

      • Immediate hypersensitivity (Type I): IgE mediated, results in allergy symptoms such as asthma, hives, or anaphylaxis upon exposure to allergens.

      • Cytotoxic hypersensitivity (Type II): Involves destruction of cells via IgG or IgM antibodies that bind to cell surface antigens.

      • Immune complex-mediated (Type III): Results from formation of immune complexes that deposit in tissues, causing inflammation and damage.

      • Delayed-type hypersensitivity (Type IV): T cells are involved, such as in contact dermatitis or reactions to certain infections (e.g., tuberculosis).

Important Concepts and Definitions:

  • Immunocompetence: The ability of the immune system to carry out adaptive responses effectively, including recognizing and responding to antigens.

  • Epitope: The specific part of an antigen to which an antibody attaches, crucial for the specificity of the immune response.

  • Hapten: A small substance that alone cannot trigger an immune response unless attached to a larger carrier molecule, from which an immune response can be generated, often seen in allergic reactions.

  • Antigen-presenting cells (APC): Cells that display antigen on their surface in combination with major histocompatibility complex (MHC) molecules, which is essential for T-cell recognition (e.g., on dendritic cells, macrophages, and B cells).

  • Major Histocompatibility Complex (MHC):

    • Class I MHC: Present on all nucleated cells; signals cytotoxic T cells, crucial for detecting infected or cancerous cells.

    • Class II MHC: Present on professional APCs; signals helper T cells and plays a key role in orchestrating the adaptive immune response.