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

Infection, Infectious Diseases, and Epidemiology

Occurrence of Disease: Endemic, Epidemic, Pandemic, and Sporadic

The occurrence of infectious diseases can be classified based on their frequency and geographic distribution. Understanding these terms is essential for epidemiology and public health.

• Endemic Disease: A disease that is constantly present at a stable frequency within a particular geographic area.

• Sporadic Disease: A disease that occurs infrequently and irregularly.

• Epidemic Disease: A disease that occurs at a greater frequency than usual in a given area or population.

• Pandemic Disease: An epidemic that occurs simultaneously on more than one continent.

• Key Point: The number of cases alone does not determine whether a disease is an epidemic or pandemic; the expected baseline and geographic spread are critical factors.

Innate Immunity

Overview of the Body’s Defenses

Innate immunity refers to the nonspecific defense mechanisms that come into play immediately or within hours of an antigen's appearance in the body. These defenses are present at birth and provide the first and second lines of defense against pathogens.

• Species Resistance: Many pathogens are unable to infect humans due to physiological incompatibilities, such as the absence of necessary receptors or unsuitable environmental conditions.

• First Line of Defense: External physical barriers (skin and mucous membranes) and associated chemicals/processes.

• Second Line of Defense: Internal defenses including protective cells, bloodborne chemicals, and processes that inactivate or kill invaders.

The Body’s First Line of Defense

The first line of defense consists of physical and chemical barriers that prevent pathogen entry.

The Role of Skin in Innate Immunity

• Epidermis: Multiple layers of tightly packed cells; shedding removes microorganisms; dendritic cells phagocytize pathogens.

• Dermis: Collagen fibers provide strength and resistance to abrasions.

• Chemical Defenses: Perspiration (contains salt, antimicrobial peptides, lysozyme), sebum (keeps skin pliable, lowers pH).

The Role of Mucous Membranes in Innate Immunity

• Epithelium: Thin, living, tightly packed cells; continual shedding removes microbes; dendritic cells below epithelium phagocytize pathogens.

• Goblet and Ciliated Columnar Cells: Produce mucus and move trapped pathogens out of the body.

• Deeper Connective Layer: Supports the epithelium and produces defensive chemicals.

Comparison of Skin and Mucous Membranes

The following table compares the main features of skin and mucous membranes as barriers to infection:

	Skin	Mucous Membrane
Number of Cell Layers	Many	One to a few
Cells Tightly Packed?	Yes	Yes
Cells Dead or Alive?	Outer layers: dead; inner layers: alive	Alive
Mucus Present?	No	Yes
Relative Water Content	Dry	Moist
Defensins Present?	Yes	With some
Lysozyme Present?	Yes	With some
Sebum Present?	Yes	No
Cilia Present?	No	Trachea, uterine tubes
Constant Shedding and Replacement of Cells?	Yes	Yes

The Role of the Lacrimal Apparatus in Innate Immunity

• Lacrimal Apparatus: Produces and drains tears; blinking spreads tears and washes the eye surface.

• Lysozyme in Tears: Destroys bacterial cell walls.

The Role of the Microbiome in Innate Immunity

• Microbial Antagonism (Competitive Inhibition): The microbiome competes with potential pathogens for nutrients and attachment sites.

• Additional Benefits: Microbiome members create unfavorable environments for pathogens, stimulate the second line of defense, generate antimicrobial compounds, and provide vitamins to the host.

Other First-Line Defenses

• Antimicrobial Peptides: Present in skin, mucous membranes, and neutrophils; act against a variety of microbes by disrupting membranes or interfering with metabolism.

• Other Secretions and Activities: Many organs secrete chemicals with antimicrobial properties.

Secretions and Activities That Contribute to the First Line of Defense

Various body systems contribute to innate immunity through secretions and activities that inhibit or eliminate pathogens:

Secretion/Activity	Function
Saliva	Washes microbes from teeth, gums, and palate; contains lysozyme
Stomach acid	Digests and/or inhibits microorganisms
Gastroferritin	Sequesters iron, making it unavailable for microbial use
Bile	Inhibitory to most microorganisms
Intestinal secretions	Digest and/or inhibit microorganisms
Peristalsis	Moves GI contents, eliminating pathogens
Defecation/Vomiting	Eliminates microorganisms
Urine	Contains lysozyme; acidity inhibits microorganisms
Vaginal secretions	Acidity inhibits microorganisms; contains iron-binding proteins
Menstrual flow	Cleanses uterus and vagina
Prostate secretion	Contains iron-binding proteins
Blood flow	Removes microorganisms from wounds
Coagulation	Prevents entrance of many pathogens

The Body’s Second Line of Defense

The second line of defense is activated when pathogens penetrate the skin or mucous membranes. It includes cellular and chemical components found in the blood and tissues.

Defense Components of Blood

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

• Formed Elements: Erythrocytes (transport gases), platelets (clotting), and leukocytes (defense against invaders).

• Leukocytes: Divided into granulocytes (basophils, eosinophils, neutrophils) and agranulocytes (lymphocytes, monocytes).

Lab Analysis of Leukocytes

• Differential White Blood Cell Count: Used to diagnose infections and diseases.

• Increased Eosinophils: Indicate allergies or parasitic worm infection.

• Bacterial Infections: Often show increased leukocytes and neutrophils.

• Viral Infections: Often show increased lymphocytes.

Phagocytosis

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

1. Chemotaxis

2. Adhesion

3. Ingestion

4. Maturation

5. Killing

6. Elimination

Nonphagocytic Killing

• Eosinophils: Attack parasitic helminths by secreting toxins.

• Natural Killer (NK) Cells: Secrete toxins onto the surface of virally infected cells and tumors.

• Neutrophils: Produce chemicals and extracellular traps (NETs) to kill bacteria.

Nonspecific Chemical Defenses Against Pathogens

• Toll-like Receptors (TLRs): Integral membrane proteins on phagocytes that recognize pathogen-associated molecular patterns (PAMPs) and initiate defensive responses such as inflammation, apoptosis, and stimulation of adaptive immunity.

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

• Interferons: Proteins released by host cells to inhibit the spread of viral infections. Two types: Type I (alpha and beta) and Type II (gamma).

TLR	PAMP (Microbial Molecule)
TLR1	Bacterial lipopeptides and certain proteins in multicellular parasites
TLR2	Peptidoglycan, lipoteichoic acid (Gram-positive cell wall), and cell wall of yeast
TLR4	Lipid A in LPS (Gram-negative bacteria)
TLR5	Flagellin (bacterial flagella)
TLR6	Bacterial lipopeptides, lipoteichoic acid, and cell wall of yeast
TLR10	Unknown component of influenzaviruses
TLR3	Double-stranded RNA (viruses)
TLR7	Single-stranded viral RNA
TLR8	Single-stranded viral RNA
TLR9	Unmethylated cytosine-guanine pairs of viral and bacterial DNA

Inflammation

Inflammation is a nonspecific response to tissue damage, characterized by redness, heat, swelling, and pain. It can be acute (short-lived and beneficial) or chronic (long-lasting and potentially damaging).

• Acute Inflammation: Involves vasodilation, increased permeability of blood vessels, migration of phagocytes, and tissue repair.

• Chronic Inflammation: Can result in tissue damage and disease.

Fever

Fever is a systemic response to infection, defined as a body temperature above 37°C. It is triggered by pyrogens, which reset the hypothalamic thermostat. Fever enhances the effects of interferons, inhibits the growth of some microbes, and may enhance the activities of phagocytes and tissue repair.

• Pyrogens: Include bacterial toxins, cytoplasmic contents of bacteria, antibody-antigen complexes, and substances released by phagocytes.

• Mechanism: Not fully understood, but involves the hypothalamus and various immune mediators.