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

Innate Immunity

Overview of Human Defenses

Humans possess species resistance to certain pathogens and utilize three overlapping lines of defense against infection. The first two lines constitute innate immunity, which is nonspecific and protects against a wide variety of pathogens. The third line is adaptive immunity, which is specific to individual antigens.

• Innate immunity: Nonspecific, immediate defense mechanisms.

• Adaptive immunity: Specific, acquired responses to particular antigens.

The Body's First Line of Defense

Physical and Chemical Barriers

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

• Skin: Composed of an outer epidermis and deeper dermis. Dendritic cells in the epidermis phagocytize pathogens.

• Sweat glands: Produce salty sweat containing lysozyme (an enzyme that breaks down bacterial cell walls) and antimicrobial peptides (defensins).

• Sebum: Oily substance that lowers skin pH, inhibiting microbial growth.

• Mucous membranes: Tightly packed cells, frequently replaced by stem cell division, coated with mucus from goblet cells.

• Tears and saliva: Contain lysozyme and flush microbes from eyes and mouth.

• Stomach acid: Low pH inhibits most swallowed microbes.

• Microbiome: Normal flora compete with pathogens (competitive inhibition).

• Probiotics: Beneficial microbes administered to improve health or prevent disease.

Antimicrobial peptides (defensins) are found on skin, mucous membranes, and in neutrophils, acting broadly against pathogens.

The Body's Second Line of Defense

Cellular and Chemical Components

The second line of defense is activated when pathogens breach the first line. It includes specialized cells, antimicrobial chemicals, and physiological processes.

• Cells: Mainly phagocytes (macrophages, neutrophils, dendritic cells).

• Antimicrobial chemicals: Toll-like receptors (TLRs), NOD proteins, interferons, complement, lysozyme, antimicrobial peptides.

• Processes: Phagocytosis, inflammation, fever.

Blood Components

Blood consists of formed elements (cells and cell fragments) suspended in plasma. Serum is plasma without clotting factors.

• Erythrocytes: Red blood cells.

• Leukocytes: White blood cells.

• Platelets: Cell fragments involved in clotting.

Leukocyte Classification

Leukocytes are classified based on staining characteristics:

• Granulocytes: Basophils, eosinophils, neutrophils.

• Agranulocytes: Lymphocytes, monocytes (which become macrophages upon leaving blood).

Basophils release histamine during inflammation. Eosinophils and neutrophils phagocytize pathogens. All three exit capillaries via diapedesis.

Phagocytic Cells

Macrophages, neutrophils, and dendritic cells are key phagocytes. Macrophages are often named for their location (e.g., alveolar macrophages in lungs, microglia in nervous system).

Differential White Blood Cell Count

This laboratory technique measures the relative numbers of leukocyte types and aids in disease diagnosis.

Phagocytosis Process

• Chemotactic factors (e.g., chemokines) attract phagocytes to infection sites.

• Adhesion: Phagocytes attach to pathogens.

• Opsonization: Pathogens are coated with opsonins (e.g., complement proteins, antibodies) to enhance phagocytosis.

• Phagosome formation: Pseudopods surround the microbe, forming a phagosome.

• Phagolysosome: Phagosome fuses with lysosome; pathogen is killed.

Recognition of Foreign Cells

Leukocytes distinguish normal from foreign cells via receptor molecules for foreign components or opsonization by complement/antibodies.

Nonphagocytic Killing

• Eosinophils and natural killer (NK) cells attack pathogens nonphagocytically, especially helminths and cancer cells.

• Eosinophilia: High eosinophil count, often indicating helminth infection.

• Neutrophils: Can kill nonphagocytically by producing toxic oxygen forms and neutrophil extracellular traps (NETs).

Pathogen Recognition and Signaling

• Pathogen-associated molecular patterns (PAMPs): Microbial molecules recognized by host.

• Toll-like receptors (TLRs): Membrane proteins that bind PAMPs, triggering immune responses.

• NOD proteins: Intracellular sensors for PAMPs.

Interferons

Interferons (IFNs) are proteins that inhibit viral spread.

• Alpha (IFN-α) and Beta (IFN-β) Interferons: Released within hours of infection; induce antiviral proteins (AVPs) in neighboring cells.

• Gamma (IFN-γ) Interferon: Produced days after infection; activates macrophages and neutrophils.

Complement System

The complement system is a group of proteins that enhance immune responses.

• Acts as chemotactic attractants, triggers inflammation and fever.

• Destroys foreign cells via membrane attack complexes (MACs) that create fatal holes in membranes.

• Activated by three pathways:

  • Classical pathway: Involves antibodies.

  • Alternative pathway: Triggered by bacterial chemicals.

  • Lectin pathway: Triggered by mannose on microbial surfaces.

Inflammation and Fever

Inflammation

Acute inflammation develops quickly and eliminates pathogens; chronic inflammation develops slowly and may cause tissue damage.

• Signs: Redness, heat, swelling, pain.

• Blood clotting triggers bradykinin, a potent mediator of inflammation.

• Macrophages with TLRs or NOD proteins release prostaglandins and leukotrienes, increasing blood vessel permeability.

• Mast cells, basophils, platelets release histamine in response to complement peptides.

• Blood clots may isolate infection, forming an abscess (e.g., pimple, boil).

• Margination: Leukocytes stick to blood vessel walls at infection sites.

• Diapedesis: Leukocytes exit vessels to reach damaged tissue.

• Increased blood flow brings nutrients and oxygen for repair.

Fever

Fever is a systemic response to infection, resulting from pyrogens (substances released by bacteria and phagocytes) affecting the hypothalamus and raising body temperature. The exact mechanisms are not fully understood.

Table: Leukocyte Types and Functions

Leukocyte Type	Classification	Main Function
Basophil	Granulocyte	Releases histamine during inflammation
Eosinophil	Granulocyte	Phagocytizes pathogens; attacks helminths nonphagocytically
Neutrophil	Granulocyte	Phagocytizes pathogens; produces toxic oxygen and NETs
Lymphocyte	Agranulocyte	Adaptive immunity (B and T cells); NK cells attack infected/cancerous cells
Monocyte	Agranulocyte	Becomes macrophage; phagocytizes pathogens

Example: Complement Activation Pathways

• Classical pathway: Antibody binds to pathogen, activating complement.

• Alternative pathway: Complement proteins bind directly to pathogen surfaces.

• Lectin pathway: Mannose-binding lectin binds to microbial carbohydrates, activating complement.

Key Terms and Definitions

• Species resistance: Inherent immunity to certain pathogens based on species-specific factors.

• Innate immunity: Nonspecific defense mechanisms present at birth.

• Adaptive immunity: Specific, acquired immune responses.

• Phagocytosis: Cellular process of engulfing and digesting pathogens.

• Opsonization: Enhancement of phagocytosis by coating pathogens with opsonins.

• Diapedesis: Movement of leukocytes out of capillaries into tissues.

• Pyrogens: Substances that induce fever by acting on the hypothalamus.

Additional info: The notes expand on the original content by providing definitions, examples, and a summary table for leukocyte types and functions. The complement activation pathways are described for clarity. All key terms are defined for self-contained study.