Innate Immunity: Nonspecific Defenses of the Host (Chapter 16 Study Notes)

Innate Immunity: Nonspecific Defenses of the Host

Introduction to Immunity

Immunity is the body's ability to defend itself against infectious disease. The absence of immunity is termed susceptibility. The immune system is divided into innate (nonspecific) and adaptive (specific) defenses.

• Immunity: The ability to ward off disease through body defenses.

• Susceptibility: The lack of immunity to a disease.

The Concept of Immunity

• Innate Immunity: All body defenses that protect against any kind of pathogen, regardless of its identity.

• Adaptive Immunity: Defenses (such as antibodies) that target specific microorganisms.

• Toll-like Receptors (TLRs): Proteins on macrophages and dendritic cells that recognize and bind to components of invading microbes, triggering immune responses.

First Line of Defense: Skin and Mucous Membranes

Physical Factors

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

• Skin: The intact skin and its waterproof protein, keratin, provide a strong barrier to microbial invasion.

• Lacrimal Apparatus: Produces tears that wash away irritants and microorganisms from the eyes.

• Saliva: Washes microbes from teeth and gums, reducing colonization.

• Mucus: Traps microorganisms in the respiratory and digestive tracts; the ciliary escalator moves mucus (and trapped microbes) out of the lower respiratory tract.

• Urine Flow: Flushes microorganisms out of the urinary tract.

• Vaginal Secretions: Help remove microbes from the vagina.

Chemical Factors

• Sebum and Earwax: Contain fatty acids that inhibit the growth of pathogenic bacteria.

• Perspiration: Washes microbes off the skin.

• Lysozyme: An enzyme present in tears, saliva, nasal secretions, and sweat that breaks down bacterial cell walls.

• Gastric Juice: Highly acidic (pH 1.2–3.0), preventing microbial growth in the stomach.

Normal Microbiota and Innate Immunity

• Normal Microbiota: The community of microorganisms that live on and in the human body. They compete with pathogens for nutrients and alter the environment, often preventing pathogen colonization (a process called microbial antagonism).

Second Line of Defense

If pathogens breach the first line of defense, the body activates internal mechanisms including phagocytes, inflammation, fever, and antimicrobial substances.

Formed Elements in Blood

• Blood: Composed of plasma (fluid) and formed elements (cells and platelets).

• Leukocytes (White Blood Cells): Key immune cells, divided into:

  • Granulocytes: Neutrophils, basophils, eosinophils.

  • Agranulocytes: Lymphocytes and monocytes.

The Lymphoid System

• Lymphoid System: Includes lymph vessels, lymph nodes, and lymphoid tissues (e.g., tonsils, spleen, Peyer's patches).

• Interstitial Fluid: Fluid between cells, returned to blood plasma via lymphatic vessels.

Phagocytes and Phagocytosis

• Phagocytosis: The process by which certain cells (phagocytes) ingest and destroy microorganisms or particles.

• Phagocytes: Include neutrophils, monocytes (which become macrophages), and dendritic cells.

• Macrophages: Can be wandering (move through tissues) or fixed (reside in specific tissues as part of the mononuclear phagocytic system).

• Granulocytes (especially neutrophils): Predominate early in infection; macrophages predominate later.

The Mechanism of Phagocytosis

1. Chemotaxis: Phagocytes are attracted to sites of infection by chemical signals.

2. Adherence: Phagocyte TLRs bind to microbial cells; opsonization (coating with serum proteins) enhances adherence.

3. Ingestion: Pseudopods engulf the microbe, forming a phagosome.

4. Digestion: Lysosomal enzymes and oxidizing agents kill and digest the microbe.

Inflammation

Inflammation is a localized response to tissue injury, characterized by pain, redness, immobility, swelling, and heat (PRISH).

• Acute-Phase Proteins: Produced in response to TNF-α, these proteins enhance the inflammatory response.

• Vasodilation and Increased Permeability: Mediated by histamine, kinins, and prostaglandins, allowing immune cells to access the site of infection.

• Blood Clots: May form around abscesses to contain infection.

• Phagocyte Migration: Phagocytes stick to blood vessel walls (margination) and squeeze through (diapedesis) to reach infected tissue.

• Pus: Accumulation of dead cells, microbes, and phagocytes.

• Tissue Repair: Involves regeneration of stroma (supporting tissue) or parenchyma (functioning tissue); fibroblasts may produce scar tissue.

Fever

• Fever: An abnormally high body temperature, often in response to infection.

• Inducers: Bacterial endotoxins, interleukin-1 (IL-1), and TNF-α can trigger fever.

• Chill: Indicates rising body temperature; crisis (sweating) signals temperature is falling.

Antimicrobial Substances

The Complement System

The complement system is a group of serum proteins that work together to destroy invading microbes.

• Activation: Complement proteins are activated in a cascade, amplifying the response.

• Outcomes of C3 Activation: Cell lysis, inflammation, and opsonization.

• Pathways: Classical, alternative, and lectin pathways.

• Deficiencies: Complement deficiencies increase susceptibility to infections.

• Evasion: Some bacteria evade complement by capsules, surface lipid–carbohydrate complexes, or destroying C5a.

Interferons (IFNs)

• IFN-α and IFN-β: Induce uninfected cells to produce antiviral proteins (AVPs) that inhibit viral replication.

• IFN-γ: Activates neutrophils and macrophages to kill bacteria.

Iron-Binding Proteins

• Function: Transport and store iron, making it less available to pathogens that require iron for growth.

Antimicrobial Peptides (AMPs)

• Mechanisms: Inhibit cell wall synthesis, form pores in microbial membranes (causing lysis), and destroy DNA/RNA.

• Production: Produced by nearly all plants and animals; bacterial resistance to AMPs is rare.

Other Factors Affecting Resistance

• Genetic Resistance: Some individuals are genetically less susceptible to certain infections.

• Age: Very young and elderly individuals may have weaker immune responses.

• Healthy Protocols: Good hygiene and health practices enhance resistance to infection.

Summary Table: Major Components of Innate Immunity

Component	Main Function	Example
Physical Barriers	Prevent entry of pathogens	Skin, mucous membranes
Chemical Barriers	Destroy or inhibit microbes	Lysozyme, gastric acid, sebum
Cellular Defenses	Engulf and destroy pathogens	Phagocytes (neutrophils, macrophages)
Inflammation	Localize infection, recruit cells	Redness, swelling, heat, pain
Fever	Inhibit pathogen growth, enhance immune response	Elevated body temperature
Antimicrobial Substances	Directly attack or inhibit microbes	Complement, interferons, AMPs

Key Equations and Terms

• pH of Gastric Juice: $1.2 \leq \text{pH} \leq 3.0$

• PRISH (Inflammation): Pain, Redness, Immobility, Swelling, Heat

Example: When a bacterium enters through a cut in the skin, the innate immune system responds first with physical barriers (skin), then with phagocytes and inflammation if the barrier is breached. Complement proteins may be activated to lyse the bacterium, and fever may develop to inhibit its growth.

Additional info: The complement system is sometimes discussed with adaptive immunity due to its role in antigen–antibody reactions, but its activation is a key part of innate defenses as well.