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

The Body’s Defenses Against Infection

Overview of Host Defenses

The human body is equipped with multiple defense mechanisms to resist infection by pathogens. These defenses are categorized into innate (non-specific) and adaptive (specific) immunity. Innate immunity provides immediate, general protection, while adaptive immunity develops more slowly and targets specific pathogens.

• Species resistance: Many pathogens cannot infect humans due to incompatible physiological processes or the absence of necessary receptors.

• Innate immunity: Includes first-line (barriers) and second-line (cellular and chemical) defenses.

• Adaptive immunity: Involves highly specific responses, such as antibody production.

The Body’s First Line of Defense

Physical and Chemical Barriers

The first line of defense consists of structures, chemicals, and processes that prevent pathogens from entering the body. The primary barriers are the skin and mucous membranes.

• Skin: Composed of the epidermis (multiple layers of tightly packed cells) and dermis (collagen fibers for strength).

• Shedding of skin cells: Removes attached microorganisms.

• Epidermal dendritic cells: Phagocytize pathogens.

• Chemical defenses: Perspiration (contains salt, antimicrobial peptides, lysozyme) and sebum (lowers pH, keeps skin pliable).

Mucous Membranes and the Lacrimal Apparatus

Mucous membranes line all body cavities open to the environment, such as the respiratory, digestive, urinary, and reproductive tracts. They consist of a thin epithelium and a deeper connective tissue layer.

• Tightly packed epithelial cells: Prevent pathogen entry.

• Continual shedding: Removes microorganisms.

• Lacrimal apparatus: Produces and drains tears, washing the eye surface; tears contain lysozyme, which destroys bacteria.

Role of Normal Microbiota

Normal microbiota (resident microbes) protect the host through microbial antagonism, making it difficult for pathogens to colonize the body.

• Competition for nutrients and production of inhibitory substances.

• Stimulation of the immune system and provision of vitamins.

Other First-Line Defenses

• Antimicrobial peptides: Present in skin, mucous membranes, and neutrophils; act against a variety of microbes.

• Other chemicals: Many organs secrete antimicrobial substances.

The Body’s Second Line of Defense

Defense Components of Blood

When pathogens breach the first line of defense, the second line is activated. This includes cellular and chemical components, many of which are found in the blood.

• Plasma: Contains water, electrolytes, nutrients, proteins (including complement proteins and antibodies).

• Formed elements: Erythrocytes (oxygen transport), platelets (clotting), and leukocytes (defense).

• Leukocytes: Divided into granulocytes (basophils, eosinophils, neutrophils) and agranulocytes (lymphocytes, monocytes).

Phagocytosis

Phagocytosis is a process by which certain cells (phagocytes) ingest and destroy pathogens. It occurs in six stages:

1. Chemotaxis: Movement toward chemical signals from pathogens or damaged tissue.

2. Adherence: Attachment of phagocyte to microbe, often enhanced by opsonins.

3. Ingestion: Engulfment of the microbe into a phagosome.

4. Maturation: Fusion of phagosome with lysosome to form a phagolysosome.

5. Killing: Destruction of the microbe by enzymes and toxic substances.

6. Elimination: Expulsion of debris by exocytosis.

Nonphagocytic Killing

Some leukocytes kill pathogens without phagocytosis:

• Eosinophils: Attack parasitic worms by secreting toxins; can also kill some bacteria with mitochondrial DNA and proteins.

• Natural killer (NK) lymphocytes: Secrete toxins onto virally infected cells and tumors.

• Neutrophils: Release chemicals and form neutrophil extracellular traps (NETs) to bind and kill bacteria.

Nonspecific Chemical Defenses

• Toll-like receptors (TLRs): Recognize pathogen-associated molecular patterns (PAMPs) and trigger defensive responses (e.g., apoptosis, inflammation).

• NOD proteins: Cytosolic proteins that bind PAMPs inside the cell.

• Interferons: Proteins released by host cells to inhibit viral spread; two types: Type I (alpha, beta) and Type II (gamma).

Complement System

The complement system is a group of serum proteins that, when activated, lead to the lysis of foreign cells. Activation can occur via three pathways:

• Classical pathway: Triggered by antibodies bound to antigens.

• Alternative pathway: Triggered by microbial surfaces.

• Lectin pathway: Triggered by mannose-binding lectin binding to pathogen surfaces.

Activation results in a cascade of reactions, leading to opsonization, inflammation, and formation of the membrane attack complex (MAC), which lyses cells.

Inflammation

Inflammation is a nonspecific response to tissue damage, characterized by redness, heat, swelling, and pain. It can be acute (short-lived, beneficial) or chronic (long-lasting, potentially harmful).

• Acute inflammation: Involves vasodilation, increased vascular permeability, migration of phagocytes, and tissue repair.

Fever

Fever is an elevated body temperature (above 37°C) that results when pyrogens (e.g., bacterial toxins, cytoplasmic contents, antibody-antigen complexes) trigger the hypothalamus to increase the body’s temperature set point. Fever enhances the effects of interferons, inhibits some microbial growth, and may enhance tissue repair.

Additional info: These notes cover the main concepts of innate immunity, including the first and second lines of defense, as outlined in Chapter 15 - Innate Immunity. The explanations have been expanded for clarity and completeness, and only directly relevant images have been included to reinforce key concepts.