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

Innate Immunity

Overview of Innate Immunity

Innate immunity is the body’s immediate, nonspecific defense mechanism against invading pathogens. It consists of physical barriers, chemical defenses, and cellular responses that act rapidly to prevent infection and disease.

The Body’s First Line of Defense

Physical and Chemical Barriers

The first line of defense includes structures, chemicals, and processes that prevent pathogens from entering the body. These barriers are primarily the skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems.

The Role of Skin in Innate Immunity

• Structure: The skin is composed of two major layers:

  • Epidermis: Multiple layers of tightly packed cells that few pathogens can penetrate. Shedding of dead skin cells removes microorganisms. Epidermal dendritic cells phagocytize pathogens.

  • Dermis: Contains collagen fibers that help the skin resist abrasions, reducing the risk of pathogen entry.

• Chemical Defenses:

  • Perspiration: Secreted by sweat glands; salt inhibits pathogen growth, antimicrobial peptides act against microorganisms, and lysozyme destroys bacterial cell walls.

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

The Role of Mucous Membranes in Innate Immunity

• Structure: Mucous membranes line all body cavities open to the environment and consist of two layers:

  • Epithelium: Thin, living outer covering; tightly packed cells prevent pathogen entry. Continual shedding removes microorganisms. Dendritic cells below the epithelium phagocytize pathogens. Goblet and ciliated columnar cells help remove invaders.

  • Deeper Connective Layer: Supports the epithelium and produces chemicals that defend against pathogens.

The Role of the Lacrimal Apparatus in Innate Immunity

• Lacrimal Apparatus: Produces and drains tears. Blinking spreads tears and washes the surface of the eye. Lysozyme in tears destroys bacteria.

The Role of the Microbiome in Innate Immunity

• Microbial Antagonism: The microbiome competes with potential pathogens by consuming nutrients, creating unfavorable environments, preventing pathogen attachment, stimulating the second line of defense, generating antimicrobial compounds, and providing vitamins to the host.

Other First-Line Defenses

• Antimicrobial Peptides: Present in skin, mucous membranes, and neutrophils; act against a variety of microbes through multiple mechanisms.

• Other Chemicals: Many organs secrete chemicals with antimicrobial properties.

The Body’s Second Line of Defense

General Features

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

Defense Components of Blood

• Plasma: Mostly water with electrolytes, dissolved gases, nutrients, and proteins. Contains iron-binding compounds, complement proteins, and antibodies.

• Serum: Plasma without clotting factors.

• Formed Elements: Cells and cell fragments in plasma, including erythrocytes (carry oxygen and carbon dioxide), platelets (involved in clotting), and leukocytes (defend against invaders).

Leukocytes

• Granulocytes: Contain large granules that stain different colors.

  • Basophils: Stain blue with basic dye; release inflammatory chemicals.

  • Eosinophils: Stain red/orange with acidic dye; phagocytize pathogens and are involved in defense against parasitic worms.

  • Neutrophils: Stain lilac; phagocytize pathogens and are capable of diapedesis.

• Agranulocytes: Cytoplasm appears uniform under a light microscope.

  • Lymphocytes: Most involved in adaptive immunity; includes natural killer cells.

  • Monocytes: Leave the blood and mature into macrophages, which are phagocytic cells that devour foreign objects.

Lab Analysis of Leukocytes

• Differential white blood cell count can signal disease.

• Increased eosinophils indicate allergies or parasitic worm infection.

• Bacterial diseases often show increased leukocytes and neutrophils.

• Viral infections show increased lymphocytes.

Phagocytosis

Phagocytosis is the process by which certain cells (phagocytes) ingest and destroy pathogens. It can be divided into six stages: chemotaxis, adhesion, ingestion, maturation, killing, and elimination.

Nonphagocytic Killing

• Eosinophils: Attack parasitic helminths by adhering to their surface and secreting toxins. Eosinophilia is indicative of helminth infestation or allergies. Eosinophil mitochondrial DNA and proteins can kill some bacteria.

• Natural Killer (NK) Lymphocytes: Secrete toxins onto the surface of virally infected cells and tumors, distinguishing normal body cells by their membrane proteins.

• Neutrophils: Can destroy microbes without phagocytosis by producing chemicals and generating extracellular fibers called neutrophil extracellular traps (NETs) that bind and kill bacteria.

Nonspecific Chemical Defenses Against Pathogens

• Toll-like Receptors (TLRs): Integral membrane proteins produced by phagocytic cells that bind pathogen-associated molecular patterns (PAMPs) and initiate defensive responses, including secretion of inflammatory mediators, stimulation of adaptive immunity, and apoptosis.

• NOD Proteins: Cytosolic proteins that bind PAMPs and trigger inflammation, apoptosis, and other innate responses.

• Interferons: Protein molecules released by host cells to nonspecifically inhibit the spread of viral infections. Two types: Type I (alpha and beta) and Type II (gamma). Interferons cause many symptoms associated with viral infections.

Complement System

The complement system is a set of serum proteins that, when activated, result in the lysis of foreign cells and trigger inflammation and fever. Complement can be activated by three pathways: classical, alternative, and lectin.

Inflammation

Overview of Inflammation

Inflammation is a nonspecific response to tissue damage from various causes, characterized by redness, heat, swelling, and pain. There are two types: acute (short-lived and typically beneficial) and chronic (long-lasting and potentially damaging).

Acute Inflammation

• Develops quickly and is short-lived.

• Important in the second line of defense: involves dilation and increased permeability of blood vessels, migration of phagocytes, and tissue repair.

Chronic Inflammation

• Long-lasting; can cause tissue damage and disease.

Dilation and Increased Permeability of Blood Vessels

• Vasodilation produces redness and localized heat.

• Chemicals such as bradykinins, prostaglandins, leukotrienes, and histamine trigger and promote dilation.

• Delivers blood clotting proteins to the site of injury.

Migration of Phagocytes and Tissue Repair

• Neutrophils and monocytes are delivered to the site of infection, recruited by chemotactic factors.

• Phagocytes attach to receptors on blood vessels, squeeze between cells (diapedesis), and enter the site of infection.

• Delivery of nutrients and oxygen facilitates tissue repair, though some tissues cannot be repaired.

Fever

Mechanism and Outcomes of Fever

Fever is a body temperature over 37°C, resulting when pyrogens trigger the hypothalamus to increase the body’s core temperature. Pyrogens include bacterial toxins, cytoplasmic contents of bacteria released by lysis, antibody-antigen complexes, and pyrogens released by phagocytes. The exact mechanism is not fully understood.

• Fever continues as long as pyrogens are present.

• Outcomes of fever include enhanced effects of interferons, inhibition of some microbial growth, and enhanced activities of phagocytes, cells of specific immunity, and tissue repair.

Additional info: This summary covers the main concepts of innate immunity, including the first and second lines of defense, the roles of physical and chemical barriers, cellular responses, inflammation, and fever. It is suitable for exam preparation in a college-level microbiology course.