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

Innate Immunity

Overview of Host 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 include physical barriers, cellular responses, and chemical mediators that prevent infection and eliminate pathogens.

The Body’s First Line of Defense

Physical and Chemical Barriers

The first line of defense consists of structures, chemicals, and processes that prevent pathogens from entering the body. The primary components are the skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems.

• Skin: Composed of the epidermis (multiple layers of tightly packed cells, with outer layers dead and continually shed) and the dermis (contains collagen fibers for resistance to abrasions).

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

• Mucous Membranes: Line all body cavities open to the environment. Consist of a thin epithelium (living, tightly packed cells, continually shed) and a deeper connective tissue layer. Goblet and ciliated columnar cells help remove invaders.

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

Lacrimal Apparatus

The lacrimal apparatus produces and drains tears, which contain lysozyme that destroys bacteria. Blinking spreads tears and washes the surface of the eye.

The Role of the Microbiome

The normal microbiome provides microbial antagonism, competing with potential pathogens by consuming nutrients, creating unfavorable environments, preventing attachment, stimulating the second line of defense, generating antimicrobial compounds, and providing vitamins.

Other First-Line Defenses

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

• Secretions and Activities: Various organs secrete chemicals with antimicrobial properties (e.g., saliva, stomach acid, bile, urine, vaginal secretions, blood flow, coagulation).

The Body’s Second Line of Defense

Defense Components of Blood

When pathogens penetrate the first line of defense, the second line operates, involving cells, antimicrobial chemicals, and processes, many of which are found in the blood.

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

• Formed Elements: Erythrocytes (oxygen and CO2 transport), platelets (clotting), and leukocytes (defense).

Leukocytes

• Granulocytes: Basophils (inflammation), eosinophils (phagocytosis, helminth defense), neutrophils (phagocytosis, diapedesis).

• Agranulocytes: Lymphocytes (adaptive immunity, NK cells), monocytes (mature into macrophages, phagocytic).

• Lab Analysis: Differential white blood cell counts can indicate disease (e.g., increased eosinophils in allergies or parasitic infection, increased neutrophils in bacterial infection, increased lymphocytes in viral infection).

Phagocytosis

Phagocytosis is the process by which phagocytes ingest and destroy pathogens. It involves six stages: chemotaxis, adhesion, ingestion, maturation, killing, and elimination.

Nonphagocytic Killing

• Eosinophils: Attack helminths by secreting toxins; can also kill some bacteria with mitochondrial DNA and proteins.

• Natural Killer (NK) Cells: Secrete toxins onto virally infected cells and tumors, sparing normal cells.

• Neutrophils: Produce chemicals and extracellular traps (NETs) to kill microbes without phagocytosis.

Nonspecific Chemical Defenses

• Toll-like Receptors (TLRs): Integral membrane proteins on phagocytes that bind pathogen-associated molecular patterns (PAMPs) and initiate defensive responses (e.g., inflammation, apoptosis).

• NOD Proteins: Cytosolic proteins that bind PAMPs and trigger inflammation and apoptosis.

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

Complement System

The complement system is a set of serum proteins that, when activated, result in lysis of foreign cells, inflammation, and opsonization. Activation occurs via the classical, alternative, or lectin pathways.

Inflammation

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

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

• Chronic Inflammation: Can cause tissue damage and disease.

Fever

Fever is a body temperature above 37°C, triggered by pyrogens that act on the hypothalamus. It enhances interferon effects, inhibits some microbes, and may enhance phagocyte activity and tissue repair.

Summary Table: Nonspecific Components of Innate Immunity

First Line	Second Line
Barriers and chemicals (skin, mucous membranes, sweat, acid, lysozyme, mucus)	Phagocytes (macrophages, neutrophils, eosinophils)
Extracellular killing (eosinophils, NK cells, neutrophils)	Complement (attracts phagocytes, stimulates inflammation, attacks membranes)
	Interferons (increase resistance to viral infection)
	Antimicrobial peptides (disrupt membranes, signaling, metabolism)
	Inflammation (increases blood flow, capillary permeability, leukocyte migration)
	Fever (mobilizes defenses, accelerates repair, inhibits pathogens)

Key Terms

• Innate Immunity: Nonspecific defense mechanisms present from birth.

• Phagocytosis: Cellular process of engulfing and destroying pathogens.

• Complement System: Group of serum proteins that enhance immune responses.

• Inflammation: Localized response to injury or infection.

• Fever: Elevated body temperature as a systemic response to infection.