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

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

Overview of Host Defenses

Innate immunity provides the body’s immediate, nonspecific defense against pathogens. It consists of physical barriers, cellular responses, and chemical mediators that act rapidly to prevent and control infections.

The Body’s First Line of Defense

Physical and Chemical Barriers

• Skin and mucous membranes are the primary barriers preventing pathogen entry.

• These barriers are supported by antimicrobial chemicals and physiological processes.

The Role of Skin in Innate Immunity

• The epidermis consists of multiple layers of tightly packed cells, making it difficult for pathogens to penetrate. Shedding of dead skin cells removes attached microorganisms.

• Epidermal dendritic cells phagocytize pathogens.

• The dermis contains collagen fibers that provide resistance to abrasions.

• Skin secretions include:

  • Perspiration: Contains salt (inhibits microbial growth), antimicrobial peptides, and lysozyme (destroys bacterial cell walls).

  • Sebum: Maintains pliability and lowers skin pH, inhibiting many bacteria.

The Role of Mucous Membranes in Innate Immunity

• Line all body cavities open to the environment (respiratory, digestive, urinary, reproductive tracts).

• Composed of:

  • Epithelium: Thin, living, tightly packed cells that are continually shed, removing microbes. Goblet and ciliated cells help trap and remove invaders.

  • Deeper connective tissue: Supports the epithelium and produces antimicrobial chemicals.

Comparison of Skin and Mucous Membranes

Feature	Skin	Mucous Membrane
Number of Cell Layers	Many	One to a few
Cells Tightly Packed?	Yes	Yes
Cells Dead or Alive?	Outer: dead; Inner: alive	Alive
Mucus Present?	No	Yes
Lysozyme Present?	Yes	With some
Sebum Present?	Yes	No
Cilia Present?	No	Trachea, uterine tubes
Constant Shedding?	Yes	Yes

The Role of the Lacrimal Apparatus

• Produces and drains tears, washing the surface of the eye.

• Tears contain lysozyme, which destroys bacteria.

The Role of the Microbiome

• Microbial antagonism: Normal microbiota compete with pathogens for nutrients and attachment sites, create unfavorable environments, and stimulate the immune system.

• Some microbiota produce antimicrobial compounds and vitamins, and modulate immunity.

Other First-Line Defenses

• Antimicrobial peptides: Present in skin, mucous membranes, and neutrophils; act against a variety of microbes.

• Other organs secrete chemicals with antimicrobial properties (e.g., saliva, stomach acid, bile, urine, vaginal secretions).

Secretions and Activities Contributing to the First Line of Defense

System	Secretion/Activity	Function
Digestive	Saliva	Washes microbes, contains lysozyme
Digestive	Stomach acid	Digests/inhibits microorganisms
Digestive	Bile	Inhibitory to most microorganisms
Urinary	Urine	Acidity inhibits microbes, washes ureters/urethra
Reproductive	Vaginal secretions	Acidity inhibits microbes, sequesters iron
Cardiovascular	Blood flow	Removes microbes from wounds

The Body’s Second Line of Defense

Defense Components of Blood

• Plasma: Contains water, electrolytes, proteins (including complement and antibodies), and iron-binding compounds.

• Formed elements:

  • Erythrocytes: Transport oxygen and carbon dioxide.

  • Platelets: Involved in clotting and inflammation.

  • Leukocytes: Defend against invaders; divided into granulocytes and agranulocytes.

Leukocytes: Granulocytes and Agranulocytes

• Granulocytes:

  • Basophils: Release inflammatory chemicals.

  • Eosinophils: Phagocytize pathogens, attack helminths, involved in allergies.

  • Neutrophils: Phagocytize pathogens, can kill without phagocytosis.

• Agranulocytes:

  • Lymphocytes: Most involved in adaptive immunity; natural killer (NK) cells kill infected/tumor cells.

  • Monocytes: Mature into macrophages, which are phagocytic.

Lab Analysis of Leukocytes

• Differential white blood cell counts can indicate disease:

  • Increased eosinophils: Allergies or parasitic infection

  • Increased neutrophils: Bacterial infection

  • Increased lymphocytes: Viral infection

Phagocytosis

Phagocytosis is the process by which certain cells (phagocytes) ingest and destroy pathogens. It occurs in six stages:

1. Chemotaxis

2. Adhesion

3. Ingestion

4. Maturation

5. Killing

6. Elimination

Nonphagocytic Killing

• Eosinophils: Secrete toxins to kill helminths; release mitochondrial DNA/proteins to kill bacteria.

• Natural Killer (NK) cells: Secrete toxins onto virally infected or tumor cells.

• Neutrophils: Release chemicals and form neutrophil extracellular traps (NETs) to kill microbes.

Nonspecific Chemical Defenses

• Toll-like receptors (TLRs): Recognize pathogen-associated molecular patterns (PAMPs) and trigger immune responses (e.g., inflammation, apoptosis).

• NOD proteins: Cytosolic proteins that bind PAMPs and trigger innate responses.

• Interferons: Proteins released by host cells to inhibit viral spread; include Type I (alpha, beta) and Type II (gamma) interferons.

Table: Characteristics of Human Interferons

Type	Principal Source	Inducing Agent	Action
Alpha (IFN-α)	Epithelium, leukocytes	Viruses	Stimulates production of antiviral proteins
Beta (IFN-β)	Fibroblasts	Viruses	Stimulates production of antiviral proteins
Gamma (IFN-γ)	Activated T and NK lymphocytes	Adaptive immune responses	Stimulates phagocytic activity

Complement System

• A set of serum proteins that, when activated, result in lysis of foreign cells, inflammation, and opsonization.

• Activation pathways: Classical, alternative, and lectin.

Inflammation

• A nonspecific response to tissue damage, characterized by redness, heat, swelling, and pain.

• Types:

  • Acute: Rapid, short-lived, beneficial for defense and repair.

  • Chronic: Long-lasting, can cause tissue damage.

• Key events:

  • Vasodilation and increased vascular permeability (mediated by histamine, prostaglandins, etc.)

  • Migration of phagocytes to the site of infection

  • Tissue repair

Fever

• Defined as a body temperature above 37°C, triggered by pyrogens acting on the hypothalamus.

• Pyrogens include bacterial toxins, cytoplasmic contents of bacteria, antibody-antigen complexes, and pyrogens released by phagocytes.

• Fever enhances interferon effects, inhibits some microbes, and may enhance phagocyte and tissue repair activities.

Summary Table: Nonspecific Components of Innate Immunity

First Line	Second Line
Barriers (skin, mucous membranes, chemicals)	Phagocytes (macrophages, neutrophils, eosinophils)
Antimicrobial peptides	Extracellular killing (eosinophils, NK cells, neutrophils)
Secretions (sweat, acid, lysozyme, mucus)	Complement, interferons, inflammation, fever

Key Terms

• Innate immunity: Nonspecific defense mechanisms present from birth.

• Phagocytosis: Cellular process of engulfing and destroying pathogens.

• Complement system: Group of proteins that enhance immune responses.

• Inflammation: Localized response to injury or infection.

• Fever: Systemic increase in body temperature as a defense mechanism.