Innate Immunity

Overview of Immune Responses

Immunity is the body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells. The immune system is divided into two main branches: innate (nonspecific) immunity and adaptive (specific) immunity. Innate immunity provides immediate, general defense against pathogens, while adaptive immunity targets specific threats and develops memory for future responses.

The Body’s First Line of Defense

Surface Barriers

The first line of defense consists of physical and chemical barriers that prevent pathogens from entering the body. These include the skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems.

• Skin: Multiple layers of tightly packed cells, shedding of dead cells, and presence of immune cells (leukocytes, mast cells) provide a formidable barrier.

• Mucous membranes: Line all body cavities open to the environment, with tightly packed living cells, mucus production, and immune cells beneath the epithelium.

Chemical Defenses of the Skin

• Perspiration: Contains salt (inhibits microbial growth), antimicrobial peptides (dermcidin, defensins), 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

Mucous membranes consist of an epithelium and a deeper connective tissue layer. The epithelium is tightly packed and continually sheds, removing microorganisms. Goblet and ciliated cells help trap and remove invaders, while dendritic cells phagocytize pathogens.

Comparison of Skin and Mucous Membranes

Lacrimal Apparatus

The lacrimal apparatus produces and drains tears, which contain lysozyme to destroy bacteria and help wash the surface of the eye.

The Role of the Microbiome

The normal microbiome competes with potential pathogens through microbial antagonism. It consumes nutrients, creates unfavorable environments for pathogens, prevents pathogen attachment, stimulates the second line of defense, and produces vitamins and antimicrobial compounds.

Other First-Line Defenses

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

• Other secretions: Saliva, stomach acid, bile, urine, and vaginal secretions contain chemicals or enzymes that inhibit or eliminate microorganisms.

The Body’s Second Line of Defense

Defense Components of Blood

When pathogens penetrate the first line of defense, the second line is activated. This includes cells, antimicrobial chemicals, and processes, many of which are found in the blood.

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

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

Leukocytes (White Blood Cells)

• Granulocytes: Neutrophils (main phagocytes, bacteria slayers), eosinophils (attack parasites, modulate immunity), basophils (release histamine, inflammation).

• Agranulocytes: Lymphocytes (B & T cells for adaptive immunity, NK cells for innate immunity), monocytes (mature into macrophages, phagocytic, antigen-presenting).

Leukopoiesis

Leukopoiesis is the production of white blood cells, stimulated by interleukins and colony-stimulating factors. All leukocytes originate from hemocytoblasts in the bone marrow. Granulocytes and monocytes share a myeloid lineage, while lymphocytes derive from lymphoid stem cells.

Phagocytosis

Phagocytosis is the process by which cells (mainly neutrophils and macrophages) ingest and destroy pathogens. The process involves six stages: chemotaxis, adhesion, ingestion, maturation, killing, and elimination.

Extracellular Killing

• Eosinophils: Attack large parasites by secreting toxins.

• Natural Killer (NK) cells: Induce apoptosis in virus-infected and cancer cells by releasing perforins and granzymes.

• Neutrophils: Can kill microbes by releasing chemicals and forming neutrophil extracellular traps (NETs).

Nonspecific Chemical Defenses

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

• NOD proteins: Cytosolic proteins that detect PAMPs and trigger innate responses.

• Interferons: Proteins released by host cells to inhibit viral spread. Type I (α, β) stimulate antiviral proteins; Type II (γ) activates macrophages and NK cells.

Complement System

The complement system consists of about 50 proteins that circulate in inactive form and are activated by pathogens. Activation leads to inflammation, cell lysis (via the membrane attack complex), and opsonization (enhanced phagocytosis). There are three activation pathways: classical (antibody-mediated), lectin (carbohydrate-binding proteins), and alternative (spontaneous activation on pathogen surfaces).

Inflammation

Inflammation is a nonspecific response to tissue damage, characterized by redness, heat, swelling, and pain. Acute inflammation is beneficial and involves vasodilation, increased permeability, migration of phagocytes, and tissue repair. Chronic inflammation can cause tissue damage and disease.

Fever

Fever is an elevated body temperature triggered by pyrogens. It enhances the effects of interferons, inhibits microbial growth, and may enhance phagocyte activity and tissue repair.

Summary Table: Nonspecific Components of Innate Immunity

Key Terms

• Innate immunity: Nonspecific, immediate defense mechanisms present at birth.

• Phagocytosis: Cellular process of engulfing and destroying pathogens.

• Complement system: Group of plasma proteins that enhance immune responses.

• Interferons: Proteins that interfere with viral replication.

• Inflammation: Localized response to injury or infection.

• Fever: Systemic increase in body temperature in response to infection.