Innate Immunity: The Body’s First and Second Lines of Defense

Chapter 15: Innate Immunity – The Body’s First and Second Lines of Defense

Overview of Host Defenses

The human body employs a multi-layered defense system against pathogens, organized into three lines of defense. This chapter focuses on the first two lines, which are part of innate (nonspecific) immunity. These defenses act rapidly and broadly against a wide range of invaders, providing immediate protection before the adaptive immune response is activated.

First Line of Defense: Physical and Chemical Barriers

The first line of defense consists of physical and chemical barriers that prevent pathogens from entering the body.

• Skin

  • Epidermis: The outermost layer, containing tightly packed cells and epidermal dendritic cells that help detect pathogens.

  • Dermis: The deeper layer, rich in collagen fibers that provide structural strength and resist penetration.

  • Chemicals: The skin secretes antimicrobial peptides (defensins), lysozyme (an enzyme that destroys bacterial cell walls), and sebum (an oily substance that lowers skin pH and inhibits microbial growth).

• Mucous Membranes

  • Epithelium: Thin, living cells that line body cavities open to the environment and secrete mucus to trap pathogens.

  • Connective Layer: Supports the epithelium and contains immune cells.

• Lacrimal Apparatus

  • Produces and drains tears, which contain lysozyme that destroys bacteria on the surface of the eye.

• Microbiome

  • Consists of resident and transient microorganisms that compete with pathogens for nutrients and space, making it difficult for pathogens to establish infection.

• Secretions and Activities (See Table 15.2)

  • Various body systems (digestive, urinary, reproductive, cardiovascular) produce secretions (e.g., saliva, urine, vaginal secretions) that flush out or destroy pathogens.

Second Line of Defense: Internal Innate Responses

If pathogens breach the first line, the second line of defense is activated. This includes cellular and chemical responses found in the blood and tissues.

Defense Components of Blood

• Plasma

  • Contains complement proteins (involved in pathogen destruction) and antibodies (produced during adaptive immunity).

• Leukocytes (White Blood Cells)

  • Granulocytes:

    • Basophils: Release histamine and other mediators of inflammation.

    • Eosinophils: Attack parasitic worms (helminths) and participate in allergic responses.

    • Neutrophils: Most abundant; phagocytize pathogens and release chemicals to kill invaders.

  • Agranulocytes:

    • Lymphocytes: Key players in adaptive immunity (covered in Chapter 16).

    • Monocytes: Differentiate into macrophages that phagocytize pathogens and debris.

Phagocytic and Non-Phagocytic Killing

• Phagocytic Killing

  • Carried out mainly by macrophages in a six-stage process: chemotaxis, adherence, ingestion, maturation, killing, and elimination.

• Non-Phagocytic Killing

  • Eosinophils: Secrete toxins to kill helminths.

  • Natural Killer (NK) Cells: Secrete toxins to destroy virus-infected or tumor cells.

  • Neutrophils: Release chemicals (e.g., reactive oxygen species) that kill nearby invaders.

Nonspecific Chemical Defenses Against Pathogens

• Toll-like Receptors (TLRs): Proteins on immune cells that recognize Pathogen-Associated Molecular Patterns (PAMPs) (e.g., bacterial cell wall components), triggering immune responses.

• PAMPs: Molecular structures common to groups of pathogens; recognition leads to secretion of inflammatory mediators, stimulation of adaptive immunity, and sometimes apoptosis (programmed cell death).

• Interferons:

  • Type I (e.g., IFN-α, IFN-β): Produced by infected cells; induce antiviral states in neighboring cells.

  • Type II (IFN-γ): Produced by lymphocytes; activates macrophages and enhances immune responses.

• Complement Proteins: A group of plasma proteins that enhance phagocytosis, lyse pathogens, and promote inflammation via three pathways:

  • Classical Pathway: Triggered by antibodies bound to pathogens.

  • Alternative Pathway: Activated directly by pathogen surfaces.

  • Lectin Pathway: Initiated by mannose-binding lectin binding to pathogen carbohydrates.

Defense by Physiological Processes

• Inflammation

  • Acute Inflammation: Rapid, short-term response characterized by vasodilation (widening of blood vessels), increased vascular permeability, migration of phagocytes, and tissue repair. Mediators include bradykinins, prostaglandins, leukotrienes, and histamine.

  • Chronic Inflammation: Long-lasting; can result in tissue damage and contribute to disease.

• Fever

  • Systemic response where pyrogens (e.g., bacterial toxins, cytoplasmic contents of bacteria, antibody-antigen complexes) trigger the hypothalamus to raise body temperature, inhibiting pathogen growth and enhancing immune activity.

Table: Examples of First Line Secretions and Activities (Adapted from Table 15.2)

Body System	Secretion/Activity	Antimicrobial Effect
Digestive	Saliva, stomach acid, bile, digestive enzymes	Flushes microbes, destroys pathogens, inhibits growth
Urinary	Urine flow	Washes out microbes from urinary tract
Reproductive	Vaginal secretions, mucus	Acidic pH inhibits pathogens, traps microbes
Cardiovascular	Blood flow, clotting	Removes pathogens, prevents spread

Example: The Role of Lysozyme

Lysozyme is an enzyme found in tears, saliva, and mucus. It breaks down the peptidoglycan in bacterial cell walls, leading to cell lysis and death of the bacteria. This is a key chemical defense in the first line of immunity.

Additional info: The adaptive immune response (third line of defense) is covered in Chapter 16 and involves highly specific responses mediated by lymphocytes (B and T cells).