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

Innate Immunity

Overview of Host Defenses

Innate immunity represents the body’s nonspecific defense mechanisms, always present and ready to respond to pathogens. It is distinct from acquired (adaptive) immunity, which is specific and develops after exposure to antigens.

• First Line of Defense: Physical, chemical, and genetic barriers that prevent pathogen entry.

• Second Line of Defense: Cellular and chemical responses that act when pathogens breach the first line.

First Line of Defense

Physical and Chemical Barriers

The first line of defense includes structures and secretions that block pathogen entry. These barriers are constitutive, meaning they do not improve with repeated exposure.

• Physical Defenses: Skin, mucous membranes, and associated structures.

• Chemical Defenses: Antimicrobial peptides, lysozyme, sebum, and acidic pH.

• Phagocytic Defenses: Epidermal dendritic cells and other phagocytes in tissues.

• Inflammatory Defenses: Initial response to tissue damage.

The Skin as a Barrier

The skin is composed of two major layers: the epidermis and dermis. The epidermis consists of tightly packed cells, making it difficult for pathogens to penetrate. Shedding of dead skin cells removes microorganisms, and dendritic cells phagocytize pathogens. The dermis contains collagen fibers that resist abrasions.

Chemical Defenses of the Skin

• Perspiration: Contains salt, antimicrobial peptides, and lysozyme, which inhibit microbial growth and destroy bacterial cell walls.

• Sebum: Secreted by sebaceous glands, keeps skin pliable and lowers pH, inhibiting many bacteria.

Mucous Membranes

Mucous membranes line all body cavities open to the environment. They consist of tightly packed cells and continually shed cells to remove microorganisms. Dendritic cells phagocytize pathogens, and goblet and ciliated columnar cells help remove invaders.

Comparison of Skin and Mucous Membranes

Skin and mucous membranes differ in structure and function, but both serve as effective barriers against pathogens.

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

Lacrimal Apparatus

The lacrimal apparatus produces and drains tears, which wash the surface of the eye. Lysozyme in tears destroys bacteria.

Secretions and Activities Contributing to Defense

Various organs secrete chemicals with antimicrobial properties, contributing to the first line of defense.

Secretion/Activity	Function
Digestive System	Saliva, stomach acid, intestinal enzymes, defecation remove or destroy microbes
Urinary System	Urine washes microbes from urethra
Reproductive System	Acidity and mucus inhibit microbes
Cardiovascular System	Blood removes pathogens from wounds

Second Line of Defense

Blood Components

When pathogens penetrate the first line, the second line of defense is activated. Blood contains plasma (water, electrolytes, proteins), cells, and platelets. Plasma contains iron-binding compounds, complement proteins, and antibodies.

Hematopoiesis: Production of Blood Cells

Blood cell production begins in the yolk sac during embryonic development, then shifts to the liver and lymphatic organs, and finally to the bone marrow.

Types of Blood Cells

• Erythrocytes (RBCs): Transport oxygen and carbon dioxide; do not have immune function.

• Platelets: Cell fragments involved in blood clotting and inflammation.

• Leukocytes (White Blood Cells): Key players in immune defense.

Classification of White Blood Cells

• Granulocytes: Neutrophils, eosinophils, basophils; contain granules and have lobed nuclei.

• Agranulocytes: Monocytes, lymphocytes; have unlobed, rounded nuclei.

Functions of White Blood Cells

• Neutrophils: Phagocytosis and production of toxic chemicals.

• Eosinophils: Attack large eukaryotic pathogens (e.g., worms).

• Basophils: Involved in inflammatory responses and histamine production.

• Monocytes/Macrophages: Phagocytic cells, fixed or wandering in tissues.

• Lymphocytes: Major component of specific immunity (T cells and B cells).

Phagocytosis

Phagocytosis is the process by which phagocytes ingest and destroy pathogens. It involves chemotaxis, binding, ingestion, lysosomal fusion, killing, and waste elimination.

Mechanisms of Killing by Phagocytes

• Enzymatic Hydrolysis: Lysozyme, lipases, proteases, nucleases break down pathogens.

• Oxidative Burst: Production of strong oxidizers such as superoxide anion, hydrogen peroxide, and hypochlorite.

Microbial Evasion of Phagocytosis

Some pathogens possess mechanisms to evade or survive phagocytosis, such as capsules or resistance to lysosomal enzymes.

Nonphagocytic Killing Mechanisms

• Eosinophils: Secrete toxins to kill helminths; eosinophilia indicates infestation or allergies.

• Neutrophils: Produce chemicals and NETs to kill microbes.

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

Toll-like Receptors (TLRs)

TLRs are membrane proteins produced by phagocytic cells that bind pathogen-associated molecular patterns (PAMPs) and initiate defensive responses.

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

Interferons

Interferons are protein molecules released by host cells to inhibit the spread of viral infections. INF Alpha and Beta stimulate phagocytosis, while INF Gamma regulates T and B cell actions.

Complement System

The complement system consists of over 30 blood serum proteins that act in a cascade reaction to stimulate inflammation, attract phagocytes, and form membrane attack complexes.

Inflammation

Inflammation is a nonspecific response to tissue damage. The classic signs are rubor (redness), calor (heat), tumor (swelling), and dolor (pain). Vasodilation and increased permeability of blood vessels deliver clotting proteins and facilitate tissue repair.

Events of Inflammation

Following a cut and infection, inflammation involves migration of phagocytes, tissue repair, and clearing of debris. Acute inflammation is beneficial and short-lived, while chronic inflammation can cause tissue damage.

Migration of Phagocytes and Tissue Repair

Phagocytes are recruited to the site of infection by chemotactic factors, attach to blood vessel receptors (marginalization), and squeeze between cells (diapedesis). Delivery of nutrients and oxygen facilitates repair.

Fever

Fever is a body temperature over 37°C, triggered by pyrogens that stimulate the hypothalamus. Fever enhances interferon effects, inhibits microbial growth, and may enhance phagocyte activity and tissue repair.

Summary Table: Nonspecific Components of Innate Immunity

First Line	Phagocytosis	Extracellular Killing	Complement	Interferons	Antimicrobial Peptides	Inflammation	Fever
Skin and mucous membranes	Phagocytes ingest pathogens	Eosinophils and NK cells kill pathogens	Components stimulate inflammation and attack pathogens	Increase resistance to viral infections	Interfere with microbial growth	Redness, swelling, pain, heat	Modifies internal environment, inhibits pathogens