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

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Innate Immunity

Overview of the Body’s Defenses

The human body is constantly exposed to pathogens, but it possesses multiple defense mechanisms to prevent infection. These defenses are organized into three main lines:

First Line of Defense: Nonspecific, external barriers such as skin and mucous membranes.
Second Line of Defense: Nonspecific, internal mechanisms including protective cells, chemicals, and physiological processes.
Third Line of Defense: Adaptive immunity, involving lymphocytes that target specific pathogens (covered in Chapter 16).

The Body’s First Line of Defense

The Role of Skin in Innate Immunity

The skin acts as a physical and chemical barrier to pathogens.

Epidermis: Multiple layers of tightly packed cells prevent entry of most microbes. Dendritic cells in the epidermis phagocytize invaders.
Dermis: Contains collagen fibers for strength and flexibility, blood vessels, and glands. Sweat glands secrete perspiration containing salt, antimicrobial peptides (defensins, dermacidins), and lysozyme (an enzyme that destroys bacterial cell walls). Sebaceous glands secrete sebum, which keeps skin pliable and lowers pH, inhibiting microbial growth.

The Role of Mucous Membranes in Innate Immunity

Mucous membranes line body tracts exposed to the environment and provide both physical and chemical protection.

Epithelium: Thin, tightly packed layer of cells that are continually shed and replaced. Dendritic cells below the epithelium phagocytize invaders.
Goblet cells: Secrete mucus to trap pathogens.
Ciliated cells: Move mucus and trapped microbes out of the body (e.g., via coughing).
Chemical defenses: Production of defensins and lysozyme.

The Role of the Lacrimal Apparatus in Innate Immunity

The lacrimal apparatus protects the eyes by producing and draining tears.

Tears: Wash away pathogens and contain lysozyme to destroy bacteria.

The Role of the Microbiome in Innate Immunity

The normal microbiota (microbiome) of the skin and mucous membranes provides protection through competitive inhibition (microbial antagonism).

Competes with pathogens for nutrients and attachment sites.
Alters pH to create unfavorable environments for pathogens.
Stimulates the body’s second line of defense.
Produces antimicrobial compounds and important vitamins.
Probiotics: Administration of live bacteria to restore or enhance the microbiome.

Other First-Line Defenses

Antimicrobial peptides: Found on skin and mucous membranes; damage pathogens by disrupting membranes, interfering with enzymes, or acting as chemotactic factors.
Other secretions: Stomach acid (destroys microbes), saliva (contains lysozyme and washes away microbes).

The Body’s Second Line of Defense

Defense Components of Blood

The second line of defense includes cells and chemicals found in blood, but not physical barriers.

Plasma: Fluid component containing water, electrolytes, nutrients, gases, and proteins (clotting factors, complement, antibodies).
Serum: Plasma without clotting factors.
Iron-binding proteins: Transferrin and ferritin sequester iron, limiting microbial growth. Some microbes counter this with siderophores or hemolysin.

Defensive Blood Cells: Leukocytes

Formed elements: Erythrocytes (RBCs), leukocytes (WBCs), and platelets.
Leukocytes: Divided into granulocytes and agranulocytes.

Type	Appearance	Function
Neutrophils (PMNs)	Granulocyte, lilac stain	Phagocytosis, nonphagocytic killing
Eosinophils	Granulocyte, red-orange stain	Phagocytosis, attack helminths, nonphagocytic killing
Basophils	Granulocyte, blue stain	Release inflammatory chemicals
Lymphocytes	Agranulocyte, large nucleus	Adaptive immunity (B, T cells), NK cells (innate defense)
Monocytes	Agranulocyte, lobed nucleus	Mature into macrophages (phagocytic)

Macrophages: Can be wandering (move through tissues) or fixed (e.g., alveolar macrophages in lungs, microglia in CNS).
Dendritic cells: Phagocytic, found in skin and mucous membranes (not WBCs).
Natural killer (NK) cells: Lymphocytes that kill infected or abnormal cells.
Differential white blood cell count: Used in diagnosis; abnormal proportions indicate disease.

Phagocytosis

Phagocytosis is the process by which certain cells ingest and destroy pathogens. It occurs in five steps:

Chemotaxis: Movement toward chemical signals (chemokines, defensins, complement peptides).
Adhesion: Phagocyte attaches to pathogen via complementary molecules. Opsonization (coating with opsonins like antibodies or complement) enhances attachment.
Ingestion: Pseudopods surround and internalize the microbe, forming a phagosome.
Phagosome Maturation and Microbial Killing: Fusion with lysosomes forms a phagolysosome (acidic, contains digestive enzymes). Most pathogens are killed within 30 minutes.
Elimination: Waste is expelled by exocytosis.

Nonphagocytic Killing

Eosinophils: Attack helminths by secreting toxins; can release mitochondrial DNA and proteins to kill bacteria.
Natural killer (NK) cells: Secrete toxins onto virally infected or tumor cells; spare normal cells by recognizing self-proteins.
Neutrophils: Produce toxic chemicals (e.g., , , hypochlorite) and neutrophil extracellular traps (NETs) to trap and kill bacteria. Also produce nitric oxide (inflammatory mediator).

Nonspecific Chemical Defenses Against Pathogens

Lysozyme: Enzyme that breaks down bacterial cell walls.
Toll-like receptors (TLRs): Membrane proteins on phagocytes that recognize pathogen-associated molecular patterns (PAMPs), triggering immune responses (apoptosis, inflammation, interferon production).
NOD proteins: Cytosolic proteins that recognize PAMPs and trigger apoptosis and inflammation.
Interferons (IFNs): Proteins released by host cells to inhibit viral replication.

Type	Source	Function
Type I (alpha, beta)	Monocytes, macrophages, lymphocytes, fibroblasts	Trigger antiviral protein production in uninfected cells
Type II (gamma)	T cells, NK cells	Activate macrophages, enhance phagocytosis

Complement system: Series of proteins that enhance phagocytosis (opsonization), attract immune cells (chemotaxis), trigger inflammation and fever, and form membrane attack complexes (MACs) that lyse pathogens.

Complement can be activated by:

Classical pathway: Triggered by antibodies.
Alternative pathway: Triggered by direct binding to pathogen surfaces.
Lectin pathway: Triggered by lectin binding to mannose on pathogens.

Inflammation

Inflammation is a nonspecific response to tissue damage, characterized by redness, heat, swelling, and pain.

Acute inflammation: Rapid, short-lived, usually beneficial (destroys pathogens, initiates repair).
Chronic inflammation: Long-lasting, can cause tissue damage and disease.
Key mediators: Bradykinin, prostaglandins, leukotrienes, histamine (from basophils, platelets, mast cells).
Process: Vasodilation and increased vascular permeability allow immune cells and proteins to reach the site of infection. Blood clots may form, trapping pathogens and forming pus. Tissue repair follows, but may result in scar tissue if fibroblasts are involved.
Clinical management: Antihistamines and antiprostaglandins can reduce inflammation.

Fever

Fever is an elevated body temperature (>37°C) triggered by pyrogens (e.g., bacterial toxins, antigen-antibody complexes) that reset the hypothalamic thermostat.

Mechanisms: Shivering, reduced sweating, and vasoconstriction raise body temperature.
Benefits: Enhances interferon effects, inhibits microbial growth, boosts phagocyte and immune cell activity, and promotes tissue repair.
Risks: High fever can denature proteins, inhibit nerve impulses, and cause hallucinations, coma, or death.

Summary Table: First and Second Lines of Defense

Line of Defense	Main Components	Mechanisms
First	Skin, mucous membranes, microbiome, secretions	Physical barrier, chemical defenses, microbial antagonism
Second	Phagocytes, NK cells, complement, interferons, inflammation, fever	Phagocytosis, nonphagocytic killing, chemical signaling, pathogen lysis, tissue repair