Chapter 21: The Immune System – Innate Immunity

Chapter 21: The Immune System – Innate Immunity

Overview of the Immune System

The immune system is a functional system, not a discrete organ system, responsible for defending the body against potentially harmful invaders and abnormal cells. It consists of a network of cells, tissues, and molecules that work together to provide immunity.

• Immunity: The body's ability to resist or eliminate potentially harmful foreign invaders or abnormal cells.

• Functions:

  • Defending against invading pathogens (e.g., bacteria, viruses, fungi, parasites)

  • Removing worn-out cells and damaged tissue

  • Immune surveillance: identifying and destroying abnormal cancer cells

Organization of Immune Defenses

• Innate (Nonspecific) Immunity: Present at birth; provides immediate, rapid, but nonselective defense against pathogens.

• Adaptive (Specific) Immunity: Develops after exposure; customizes defenses for specific pathogens and provides memory for future responses.

Lines of Defense

• First Line of Defense (Innate): Surface barriers (skin and mucous membranes) and their secretions.

• Second Line of Defense (Innate): Internal defenses including phagocytes, natural killer cells, inflammation, antimicrobial proteins, and fever.

• Third Line of Defense (Adaptive): Lymphocytes (B and T cells) and antibodies.

Innate Immunity: First Line of Defense

Surface Barriers

Surface barriers provide the initial protection against pathogens by forming physical and chemical shields.

• Skin: Keratinized epithelium forms a tough barrier; resistant to weak acids, bases, bacterial enzymes, and toxins.

• Mucous Membranes: Line all body cavities open to the exterior; trap and remove pathogens.

• Cilia: Sweep dust and bacteria-laden mucus away from the respiratory tract.

• Chemical Barriers:

  • Acid Mantle: Acidity of skin and secretions inhibits microbial growth.

  • Enzymes: Lysozyme in saliva, respiratory mucus, and tears destroys bacteria; stomach enzymes kill microorganisms.

  • Mucus: Traps microorganisms in respiratory and digestive tracts.

Table: The First Line of Defense – Surface Membrane Barriers

Category/Associated Elements	Protective Mechanism
Intact skin epidermis	Forms mechanical barrier; acid mantle inhibits bacterial growth; keratin resists acids, alkalis, and enzymes
Intact mucosa membranes	Mechanical barrier; mucus traps microorganisms; nasal hairs filter; cilia propel debris away
Gastric juice	Hydrochloric acid and protein-digesting enzymes destroy pathogens in stomach
Lacrimal secretion (tears), saliva	Continuously lubricate and cleanse eyes/mouth; contain lysozyme, an enzyme that destroys bacteria
Urine	Acidic pH inhibits bacterial growth; flushes microbes from urinary tract

Innate Immunity: Second Line of Defense

Internal Defenses

When pathogens breach surface barriers, the second line of defense is activated, involving cellular and chemical responses.

A) Phagocytosis

• Phagocytes: Leukocytes that ingest and digest foreign invaders.

• Neutrophils: Most abundant phagocytes; target bacteria; become phagocytic upon exposure to infectious material; die after fighting.

• Macrophages: Develop from monocytes; reside in tissues; chief and most robust phagocytic cells; live longer than neutrophils.

• Opsonization: The process by which pathogens are coated with opsonins (antibodies or complement proteins) to enhance phagocytosis.

Phagocytosis Steps:

1. Phagocyte adheres to pathogen/debris.

2. Phagocyte forms pseudopods to engulf particles, forming a phagosome.

3. Lysosome fuses with phagosome, forming a phagolysosome.

4. Lysosomal enzymes digest pathogens.

5. Exocytosis removes indigestible material.

B) Natural Killer (NK) Cells

• Large lymphocytes that police blood and lymph.

• Nonphagocytic; attack cells lacking "self" cell-surface receptors (e.g., MHC proteins).

• Induce apoptosis (programmed cell death) in cancer and virus-infected cells.

• Secrete chemicals that enhance the inflammatory response.

• Deficiency in NK cells is associated with increased risk of blood cancers.

C) Inflammation

Inflammation is a general response to tissue injury, aiming to inactivate invaders, remove debris, and prepare for healing.

• Goals of Inflammation:

  1. Inactivate invaders

  2. Remove debris

  3. Prepare for healing and repair

• Key Events:

  • Resident macrophages secrete chemotactic factors and cytokines.

  • Mast cells release histamine, increasing capillary permeability and causing edema.

  • Neutrophils and monocytes migrate to the site (diapedesis).

  • Clotting factors form a fibrin mesh to isolate the area.

• Benefits of Edema: Sweeps foreign material into lymphatics, delivers clotting proteins, and isolates injured area.

• Chronic Inflammation: Occurs when the trigger persists; associated with many chronic diseases (e.g., arthritis, cardiovascular disease).

Table: The Second Line of Defense – Innate Cellular and Chemical Defenses

Category/Associated Elements	Protective Mechanism
Phagocytes	Engulf and destroy pathogens; macrophages also contribute to adaptive immune responses
Natural Killer (NK) cells	Promote apoptosis in virus-infected/cancerous cells; recognize general abnormalities
Inflammatory response	Prevents spread of agents, disposes of debris, sets stage for repair; releases inflammatory chemicals
Antimicrobial proteins	Include interferons and complement proteins; interfere with microbial replication, enhance phagocytosis, and intensify inflammation
Fever	Systemic response; high temperature inhibits microbes and enhances repair

D) Antimicrobial Proteins

• Complement System: ~20 blood proteins circulating in inactive form; activation enhances inflammation, directly destroys bacteria, and enhances both innate and adaptive defenses.

• Activation Pathways: Classical (antibody-mediated), Lectin, and Alternative (pathogen surface-mediated).

• Membrane Attack Complex (MAC): Forms pores in target cell membranes, leading to cell lysis.

• Interferons: Proteins released by virus-infected cells; warn neighboring cells, stimulate production of antiviral proteins, and degrade viral RNA.

E) Fever

• Abnormally high body temperature; systemic response to infection.

• Leukocytes and macrophages secrete pyrogens in response to foreign substances.

• Pyrogens act on the hypothalamus to raise body temperature.

• Benefits of Moderate Fever:

  • Liver and spleen sequester iron and zinc (needed by microorganisms).

  • Increases metabolic rate, accelerating tissue repair.

Summary Table: Innate Immune Defenses

Defense	Main Components	Function
First Line	Skin, mucous membranes, secretions	Physical and chemical barriers to entry
Second Line	Phagocytes, NK cells, inflammation, antimicrobial proteins, fever	Internal cellular and chemical defenses

Key Terms

• Phagocytosis: Cellular process of engulfing and digesting pathogens.

• Opsonins: Molecules (antibodies, complement proteins) that enhance phagocytosis.

• Apoptosis: Programmed cell death induced by NK cells.

• Pyrogens: Substances that induce fever by acting on the hypothalamus.

• Diapedesis: Movement of leukocytes out of blood vessels to sites of inflammation.

Example: When a splinter introduces bacteria under the skin, the innate immune system responds first with surface barriers, then with phagocytes and inflammation, and finally with fever and antimicrobial proteins if the infection persists.

Additional info: Chronic inflammation is implicated in diseases such as arthritis, cardiovascular disease, and cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are commonly used to suppress inflammation.