Innate Immunity: Nonspecific Defenses of the Host

Big Picture: Immunity Part 1

Overview of Immunity

Immunity refers to the body's ability to ward off disease caused by pathogens such as viruses, bacteria, and fungi. The immune system is divided into two main branches: innate immunity (nonspecific, present at birth, rapid response) and adaptive immunity (specific, slower response, memory component). Susceptibility is the lack of resistance to disease.

• Innate immunity: Defenses against any pathogen; includes barriers and cellular responses.

• Adaptive immunity: Immunity or resistance to a specific pathogen; involves lymphocytes and memory.

First Line of Defense: Skin and Mucous Membranes

Physical Barriers

The first line of defense consists of physical and chemical barriers that prevent pathogen entry. The skin and mucous membranes are the primary physical barriers.

• Skin: Composed of the dermis (connective tissue) and epidermis (tightly packed epithelial cells with keratin). Shedding and dryness inhibit microbial growth.

• Mucous membranes: Line the gastrointestinal, respiratory, and genitourinary tracts. Mucus traps microbes and prevents drying.

• Lacrimal apparatus: Drains tears and washes the eye.

• Ciliary escalator: Moves mucus and trapped microbes away from the lungs.

• Other mechanisms: Earwax, urine flow, vaginal secretions, peristalsis, defecation, vomiting, and diarrhea help expel microbes.

Chemical Barriers

Chemical factors enhance the effectiveness of physical barriers by creating hostile environments for pathogens.

• Sebum: Forms a protective film and lowers skin pH (3–5).

• Lysozyme: Enzyme in perspiration, tears, saliva, and urine that destroys bacterial cell walls.

• Gastric juice: Low pH (1.2–3.0) destroys most bacteria and toxins.

• Vaginal secretions: Low pH (3–5) inhibits microbes.

Second Line of Defense

Leukocytes and Blood Components

When pathogens bypass the first line of defense, the body relies on cellular and molecular responses. White blood cells (leukocytes) play a central role in innate immunity.

• Formed elements in blood: Erythrocytes (RBCs), leukocytes (WBCs), and platelets, all produced in red bone marrow via hematopoiesis.

• Granulocytes: Neutrophils (phagocytic, early infection), basophils (release histamine, allergy), eosinophils (phagocytic, toxic to parasites/helminths).

• Agranulocytes: Monocytes (mature into macrophages), dendritic cells (phagocytic, in skin/mucosa/thymus), lymphocytes (T cells, B cells, NK cells; adaptive immunity).

The Lymphatic System

The lymphatic system is a network that transports lymph, containing lymphocytes and phagocytic cells, and filters pathogens through lymph nodes.

• Lymph: Fluid that carries microbes to lymph nodes for destruction by lymphocytes and macrophages.

• Difference from blood circulatory system: Lymphatic system is unidirectional and lacks red blood cells.

Phagocytes

Definition and Types

Phagocytes are cells that ingest and destroy microbes and cellular debris. The process is called phagocytosis.

• Fixed macrophages: Reside in specific tissues and organs.

• Free (wandering) macrophages: Move through tissues and gather at infection sites.

Mechanism of Phagocytosis

Phagocytosis involves several steps:

• Chemotaxis: Chemical signals attract phagocytes to microorganisms.

• Adherence: Attachment of phagocyte to microbe surface.

• Ingestion: Microbe is engulfed; opsonization (coating with serum proteins) enhances ingestion.

• Digestion: Microbe is destroyed inside a phagolysosome.

Inflammation

Stages and Mediators

Inflammation is a local response to infection or injury, characterized by pain, redness, immobility, swelling, and heat. It aims to destroy or limit the injurious agent and repair tissue.

• Stages: Vasodilation and increased permeability, phagocyte migration, and tissue repair.

• Mediators: Histamine, kinins, prostaglandins, leukotrienes, and cytokines are released by damaged cells and immune cells.

Vasoactive Mediator	Source	Effect
Histamine	Mast cells, basophils, platelets	Vasodilation and increased permeability of blood vessels
Kinins	Blood plasma	Chemotaxis by attracting neutrophils
Prostaglandins	Damaged cells	Intensify effects of histamine and kinins; help phagocytes move through capillary walls
Leukotrienes	Mast cells, basophils	Increased permeability of blood vessels; help attach phagocytes to pathogens
Complement	Blood plasma	Stimulates release of histamine, attracts phagocytes, promotes phagocytosis
Cytokines	Fixed macrophages	Vasodilation and increased permeability of blood vessels

Process of Inflammation

The process involves the release of chemical mediators, formation of a blood clot, migration of phagocytes, and phagocytosis of invading bacteria.

• Margination: Phagocytes stick to blood vessel endothelium.

• Diapedesis: Phagocytes squeeze between endothelial cells to reach the site of infection.

• Phagocytosis: Destruction of pathogens by neutrophils and macrophages.

Fever

Mechanism and Role

Fever is an abnormally high body temperature, usually in response to infection. Cytokines stimulate the hypothalamus to raise the body's temperature set point, which helps inhibit pathogen growth and enhances immune responses. When cytokines are removed, the body cools down via vasodilation and sweating.

Antimicrobial Substances

The Complement System

The complement system consists of serum proteins produced by the liver that enhance immune responses. Complement activation occurs in a cascade and leads to:

• Cytolysis: Formation of a membrane attack complex (MAC) that lyses microbes.

• Opsonization: Coating of microbes to enhance phagocytosis.

• Inflammation: Activation of mast cells and release of histamine.

Interferons

Interferons are cytokines with antiviral activity. They are species-specific and inhibit viral replication, as well as activate neutrophils and macrophages to kill bacteria.

Other Antimicrobial Substances

• Iron-binding proteins: Sequester iron, limiting microbial growth.

• Antimicrobial peptides (AMPs): Inhibit cell wall synthesis and disrupt microbial membranes.

Other Factors Affecting Immunity

• Genetic resistance: Certain genetic traits (e.g., sickle cell trait) confer resistance to specific pathogens (e.g., Plasmodium falciparum).

• Age: The very young and elderly are more susceptible to disease.

• Hygiene: Observing healthy protocols, such as handwashing, reduces disease risk.

Summary Table: Nonspecific Host Defenses

The following table summarizes the main components and functions of nonspecific (innate) host defenses.