HAP_12e_Lecture_Ch 21_Accessible_Spring2025

Chapter 21: The Immune System: Innate and Adaptive Body Defenses

Introduction

• The immune system provides resistance to disease-causing microorganisms (microbes) such as bacteria, fungi, and viruses.

• It is a functional system, encompassing a variety of molecules and immune cells (especially lymphocytes) residing in lymphoid tissues and circulating in body fluids.

Analogies

• The body can be likened to a medieval castle with multiple defense lines working both independently and cooperatively against invasion.

Three Lines of Defense Against Pathogens

1. Surface Barriers

   • First line of defense consisting of intact skin and mucosae, acting as structural barriers to prevent pathogen entry.

2. Innate Internal Defenses

   • Second line of defense activated when surface barriers are breached, relying on inflammation and internal defenses (e.g., antimicrobial proteins, phagocytes).

3. Adaptive (Specific) Defense System

   • Third line of defense that functions like an elite fighting force, takes longer to mount and involves specific pathogen recognition.

Integration of Innate and Adaptive Defenses

• Innate and adaptive defenses are integrated, releasing and recognizing many of the same molecules. This relationship enhances the overall immune response.

Overview of the Immune System

• The immune system effectively protects the body from most infectious microbes, cancer cells, and even transplanted tissues and organs.

Part 1—Innate Defenses

Surface Barriers: First Line of Defense

• Physical Barriers

  • Skin and mucous membranes provide durable mechanical barriers.

  • Keratinized epidermis is resistant to weak acids, bases, enzymes, and toxins.

• Chemical Barriers

  • Produce protective chemicals inhibiting or destroying microbes:

    • Acid: Creates an acid mantle on skin and mucosae to inhibit bacterial growth.

    • Enzymes: Lysozyme found in saliva and other secretions kills many microbes.

    • Mucin: Traps microbes in digestive and respiratory tracts.

    • Defensins: Broad-spectrum antimicrobial peptides secreted during inflammation.

    • Other Chemicals: Sebum and dermcidin in sweat show toxicity to bacteria.

• Respiratory Modifications

  • Mucus-coated hairs trap particles in the nose, and cilia sweep mucus toward the mouth.

• Triggers for Internal Innate Defense

  • Breaches, such as cuts or nicks in the skin, activate internal defenses to protect deeper tissues.

21.1: Surface Barriers

21.2: Innate Internal Defenses

• Cells and Chemicals: Phagocytes (like neutrophils and macrophages), NK cells, antimicrobial proteins, inflammation, and fever act as the second line of defense.

• Pattern Recognition Receptors: Recognize specific microbes, activating immune responses. Toll-like receptors (TLRs) play a significant role.

Phagocytes

Types of Phagocytes:

• Neutrophils

  • Most abundant and phagocytize infectious materials in tissues.

• Macrophages

  • Voracious and can be free or fixed.

  • Free macrophages wander in tissues (e.g., alveolar macrophages), while fixed macrophages are stationary (e.g., in the liver).

Phagocytosis Process

1. Pathogen adherence via receptors.

2. Formation of pseudopods to engulf the particles, forming a phagosome.

3. Fusing of phagosome with lysosome forms a phagolysosome.

4. Destruction of pathogens through toxic compounds and lysosomal enzymes.

5. Exocytosis may remove indigestible materials.

Natural Killer (NK) Cells

• Large granular lymphocytes that patrol blood and lymph for abnormalities (like lack of MHC).

• Induces apoptosis in cancer and virus-infected cells without prior sensitization.

Inflammation: Tissue Response to Injury

• Causes: Trauma, heat, chemicals, or infection.

• Benefits: Prevents pathogen spread, disposes of debris, alerts adaptive systems, and sets the stage for repair.

• Cardinal Signs: Redness, heat, swelling, pain (and potential impaired function).

Phagocyte Mobilization

1. Leukocytosis: Increase in white blood cells.

2. Margination: Phagocytes cling to blood vessel walls.

3. Diapedesis: Neutrophils exit capillaries.

4. Chemotaxis: Attraction of leucocytes to the site of injury.

Antimicrobial Proteins

Types

• Interferons: Proteins produced in response to viral infection, spreading defense; activate NK and macrophages.

• Complement: Group of plasma proteins that amplify the inflammatory response and kill pathogens directly.

• Activation Pathways: Classic, lectin, and alternative pathways lead to an amplified response and pathogen destruction.

Fever

• Systemic response caused by pyrogens.

• Benefits include enhanced T lymphocyte activity, increased metabolic rate, and toughened defenses against bacterial growth.

Part 2—Adaptive Defenses

• Adaptive immunity is specific to pathogens and involves two arms:

  • Humoral Immunity: Involves B cells producing antibodies targeting extracellular targets (bacteria, toxins).

  • Cellular Immunity: Involves T cells targeting infected or cancerous cells directly.

Antigens

• Antigens are substances that provoke immune responses, typically large and complex molecules foreign to the body.

• Complete Antigens: Have immunogenicity and reactivity.

• Haptens: Small molecules that only become immunogenic when attached to a protein carrier.

Lymphocytes

• B Cells: Provide humoral immunity and produce antibodies.

• T Cells: Provide cellular immunity.

Mechanisms of Action of Antibodies

• Neutralization: Blocking pathogens from entering cells.

• Agglutination: Clumping pathogens for easier removal.

• Precipitation: Forming immune complexes from soluble antigens.

• Complement Activation: Triggers a cascade leading to cell lysis.

Cell-Mediated Immunity with T Cells

• T cells directly kill infected cells or cancerous cells and regulate immune responses.

• CD4 Cells: Helper T cells that facilitate the immune response.

• CD8 Cells: Cytotoxic T cells that attack infected cells directly.

Development and Education of T Cells

• T and B lymphocytes undergo a selection process for immunocompetence and self-tolerance.

Organ Transplants

• Compatibility in tissue matching (ABO and MHC antigens) is crucial for transplant success; immunosuppressive therapy may be needed.

Immune Response Issues

• Immunodeficiencies: Disorders impairing immune responses can be congenital (SCID) or acquired (AIDS).

• Autoimmune Diseases: Body's immune system mistakenly targets its own cells (e.g., rheumatoid arthritis).

• Hypersensitivities: Exaggerated immune responses to harmless substances (e.g., allergies).

Developmental Aspects of the Immune System

• The efficiency of the immune system declines with age, making older adults more susceptible to infection and autoimmune conditions.