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

Innate Immunity

Overview of the Immune System

The immune system is a complex network of cells, tissues, and organs that protects the body from infection, cancer, and other diseases. It is divided into two main branches: innate immunity and adaptive immunity.

• Innate Immunity: Present at birth, always active, non-specific, and rapid in response.

• Adaptive Immunity: Pathogen-specific, has memory, activated upon infection, and develops throughout life.

First Line of Defense: External Innate Immunity

Skin

The skin is the most significant first line of defense against infection, providing both physical and chemical barriers to pathogens.

• Structure: Composed of two major layers:

  • Epidermis: Multiple layers of tightly packed cells. The deepest cells divide and push daughter cells toward the surface, where they flatten, die, and are shed as flakes.

  • Dermis: Contains tough fibers of collagen, providing strength and pliability. Defends nonspecifically.

• Chemical Defenses:

  • Sweat glands: Secrete perspiration containing salt, which inhibits pathogen growth.

  • Sebaceous (oil) glands: Secrete sebum, keeping skin pliable and lowering skin pH to levels inhibitory to many bacteria.

  • Lysozyme: Enzyme that destroys bacterial cell walls.

  • Antimicrobial peptides: Short, positively charged chains (20–50 amino acids) that act against microorganisms. Sweat glands secrete dermcidins, which form permeable channels in bacterial membranes.

Mucous Membranes

Mucous membranes line all body cavities open to the environment, such as the respiratory, urinary, digestive, and reproductive tracts.

• Composed of two layers:

  • Epithelium: Thin outer covering; cells are living and tightly packed to prevent pathogen entry.

  • Deeper connective tissue: Supports the epithelium.

• Respiratory System: Lined with mucous membranes. Goblet cells secrete mucus (sticky glycoproteins) that trap microorganisms. Ciliated columnar cells move mucus and trapped particles out of the lungs.

Lacrimal Apparatus (Tear Ducts)

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

• Blinking spreads tears and washes the surface of the eye.

• Tears drain into the lacrimal canal and down the pharynx to be swallowed.

• Lysozyme in tears destroys bacteria or digests them in the stomach.

Normal Microbiota

Normal microbiota (resident microbes) play a crucial role in innate immunity through microbial antagonism.

• Compete with potential pathogens for nutrients and space.

• Create environments unfavorable to other microorganisms.

• Stimulate the body’s second line of defense.

• Promote overall health by providing vitamins to the host.

Table: Comparison of Skin and Mucous Membranes

Feature	Skin	Mucous Membrane
Number of cell layers	Many	One or a few
Cells tightly packed?	Yes	Yes
Cells dead or alive?	Outer layers dead, inner alive	All alive
Dry or moist?	Dry	Moist
Presence of cilia?	No	Yes (in some locations)
Lysozyme present?	Yes	Yes
Antimicrobial peptides present?	Yes	Yes

Second Line of Defense: Internal Innate Immunity

Blood Components

The second line of defense operates when pathogens penetrate the skin or mucous membranes. It is composed of cells, antimicrobial chemicals, and associated processes found in blood.

• Plasma: Mostly water, containing electrolytes, dissolved gases, nutrients, and proteins.

• Proteins that transport iron: Transferrins bind iron, making it unavailable to microbes. Some microbes secrete siderophores to capture iron, but host cells counter with lactoferrin.

• White blood cells (leukocytes): Defend the body against invaders. Divided into granulocytes and agranulocytes.

• Platelets: Involved in blood clotting.

• Red blood cells: Carry oxygen and carbon dioxide.

Leukocytes

• Granulocytes: Contain large granules that stain different colors.

  • Basophils: Stain blue with basic dye; involved in inflammation.

  • Eosinophils: Stain red/orange with acidic dye; attack parasitic worms and are involved in allergies.

  • Neutrophils: Stain lilac with both acidic and basic dyes; phagocytize pathogens and use nonphagocytic methods to kill.

• Agranulocytes: Appear uniform under a light microscope.

  • Lymphocytes: Most involved in adaptive immunity.

  • Monocytes: Leave blood and mature into macrophages, which are named for their tissue location (e.g., microglia in CNS, alveolar macrophages in lungs).

Table: Leukocyte Types and Functions

Cell Type	Staining	Main Function
Basophil	Blue (basic dye)	Inflammation
Eosinophil	Red/orange (acidic dye)	Parasitic defense, allergy
Neutrophil	Lilac (acidic/basic dyes)	Phagocytosis, innate defense
Lymphocyte	Uniform	Adaptive immunity
Monocyte	Uniform	Phagocytosis (as macrophage)

Abnormal White Blood Cell Counts

• Increased eosinophils: Allergies or parasitic worm infection.

• Increased neutrophils: Bacterial infection.

• Increased lymphocytes: Viral infection.

Phagocytosis

Phagocytosis is the process by which certain cells engulf and destroy foreign particles or microbes.

1. Chemotaxis: Movement of phagocytes toward chemical signals from microbes.

2. Adherence: Binding of phagocyte to the microbe.

3. Ingestion: Extension of pseudopodia to engulf the microbe in a vesicle.

4. Maturation: Fusion of vesicles (phagosome and lysosome) within the phagocyte.

5. Killing: Digestive chemicals destroy the microbe.

6. Elimination: Excretion of the remainder of the microbe.

Non-Phagocytic Killing

• Eosinophils: Attack parasitic helminths by attaching to their surface and secreting toxins.

• Natural Killer (NK) Cells: Secrete toxins onto the surface of virally infected cells and tumors. Can distinguish normal from infected cells by membrane proteins.

• Neutrophils: Produce chemicals that kill invaders and generate neutrophil extracellular traps (NETs) to bind and kill bacteria.

Toll-Like Receptors (TLRs) and NOD Proteins

• TLRs: Integral membrane proteins on phagocytes that recognize pathogen-associated molecular patterns (PAMPs) and initiate defensive responses, including secretion of inflammatory mediators.

• NOD Proteins: Cytosolic proteins that bind PAMPs inside the cell and trigger immune responses.

Table: Toll-Like Receptors and Their Microbial Binding Partners

TLR/Location	PAMP (Microbial Molecule)
TLR2 (Cytoplasmic membrane)	Bacterial lipoproteins, peptidoglycan
TLR3 (Cytoplasmic membrane)	Double-stranded viral RNA
TLR4 (Cytoplasmic membrane)	Lipopolysaccharide (LPS) from Gram-negative bacteria
TLR5 (Cytoplasmic membrane)	Bacterial flagellin
TLR7/8 (Cytoplasmic membrane)	Single-stranded viral RNA

Interferons

Interferons are proteins released by host cells to nonspecifically inhibit the spread of viral infections.

• Cause symptoms such as muscle aches, chills, headache, and fever.

• Produced when viral RNA or DNA binds to TLRs.

• Types:

  • Type I (alpha and beta): Early during infection, bind to neighboring cells to induce antiviral states.

  • Type II (gamma): Later in infection, stimulates macrophages.

Complement System

The complement system is a set of serum proteins designated numerically (C1, C2, etc.) that enhance the ability of antibodies and phagocytic cells to clear microbes and damaged cells.

• Activation results in lysis of foreign cells.

• Three activation pathways:

  • Classical pathway

  • Alternative pathway

  • Lectin pathway

• Complement proteins mark microbes for immune response (opsonization) and promote inflammation.

Inflammation

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

• Involves dilation of blood vessels, migration of phagocytes, and tissue repair.

• Can be caused by heat, UV, abrasions, cuts, and pathogens.

• Types:

  • Acute: Develops quickly and resolves.

  • Chronic: Long-lasting, can result in disease (e.g., arthritis).

Fever

Fever is a body temperature over 37°C (98.6°F), resulting from pyrogens triggering the hypothalamus to increase the body’s core temperature.

• Types of pyrogens: Bacterial toxins, cytoplasmic contents of bacteria, antibody-antigen complexes.

• Physiological effects:

  • Enhances effects of some interferons.

  • Inhibits growth of some microorganisms.

  • Increases phagocytic activity.

  • If too high or prolonged, can damage cells and organs.

Additional info: The innate immune system provides immediate, non-specific defense against pathogens and is essential for the initial containment of infections before the adaptive immune system is activated.