Chapter 12: Host Defenses – Overview and Innate Defenses

Host Defenses: Overview and Innate Defenses

Introduction to Host Defenses

The human body is protected by a multilevel network of defenses that include both innate (nonspecific) and adaptive (specific) mechanisms. These defenses are organized into three lines, each with distinct roles in preventing and combating infection.

• First Line of Defense: Physical and chemical barriers that block invasion at the portal of entry. These are general, inborn, and nonspecific.

• Second Line of Defense: Internalized system of protective cells and fluids, including inflammation and phagocytosis. Acts rapidly at both local and systemic levels.

• Third Line of Defense: Acquired on an individual basis as each foreign substance is encountered by lymphocytes. Produces unique protective substances and provides long-term immunity.

Mandate of the Immune System

A healthy immune system is responsible for:

• Surveillance of the body

• Recognition of foreign material

• Destruction of entities deemed to be foreign

Immune Function

Self vs. Nonself Recognition

White blood cells (WBCs) constantly patrol the body, distinguishing between self (body's own cells) and nonself (foreign material). The ability to evaluate macromolecules as self or nonself is central to immune function. Autoimmune disorders arise when this system fails, leading to attacks on the body's own tissues.

Markers and Antigens

The immune system evaluates cells by examining surface molecules called antigens or markers (proteins and/or sugars). These markers allow immune cells to identify threats and mark them for destruction, most commonly via phagocytosis.

PAMPs and PRRs

• Pathogen-Associated Molecular Patterns (PAMPs): Shared molecular structures found on many microbes but not on mammalian cells. Examples: peptidoglycan, lipopolysaccharide (bacteria), double-stranded RNA (viruses).

• Pattern Recognition Receptors (PRRs): Host cell receptors (on phagocytes, dendritic cells, etc.) that recognize and bind PAMPs, triggering innate immune responses.

The Immune System as a Network

The immune system is a diffuse network of cells and fluids permeating every organ and tissue, promoting surveillance and recognition of harmful substances.

Tissues, Organs, and Cells in Immunity

• Mononuclear Phagocyte System (MPS): A network of connective tissue fibers (reticulum) supporting phagocytic cells in direct contact with tissue cells and extracellular fluid. Blood and lymphatic capillaries penetrate these tissues, allowing immune cells and chemicals to diffuse throughout the body.

• Locations: Thymus, lymph nodes, tonsils, spleen, and mucosal lymphoid tissue (gut, respiratory tract).

Lymphatic System

Structure and Function

The lymphatic system is a compartmentalized network of vessels, cells, and organs that transports lymph through a system of vessels and nodes, eventually draining into the circulatory system.

• Lymphatic Fluid: Plasma-like liquid formed from blood components that have moved into extracellular space and lymphatic capillaries. Transports WBCs, fats, debris, and infectious agents.

• Functions: Returns extracellular fluid to circulation, drains inflammatory exudate, and provides surveillance and protection via lymphocytes, phagocytes, and antibodies.

• Lymphatic Vessels: Thin-walled, accompany blood capillaries, permeable to extracellular fluid, found throughout the body except in CNS, bone, placenta, and thymus. Lymph flow is driven by skeletal muscle contraction.

Lymphatic Organs

• Primary: Red bone marrow (site of blood cell production and B cell maturation), thymus (T cell maturation).

• Secondary: Lymph nodes, spleen, and associated lymphoid tissues (sites of immune cell activation and function).

Associated Lymphoid Tissues

• Skin-associated lymphoid tissue (SALT)

• Mucosa-associated lymphoid tissue (MALT)

• Gut-associated lymphoid tissue (GALT): Includes appendix, lacteals, and Peyer's patches.

• Tonsils: Active lymphocyte source in the pharynx.

The Blood and Hematopoiesis

Blood Components

• Blood cells: Formed elements suspended in plasma.

• Plasma: Clear, yellowish fluid.

• Serum: Plasma without clotting factors; used in immune testing and therapy.

Hematopoiesis is the production of blood cells from stem cells in the bone marrow, which differentiate into red blood cells, platelets, and white blood cells (leukocytes).

White Blood Cells (Leukocytes)

• Granulocytes and agranulocytes are classified by their staining patterns.

• These cells are essential for both nonspecific (innate) and specific (adaptive) immunity.

Cytokines: Cell Communication

Cytokines are small, active molecules secreted to regulate, stimulate, suppress, or control many aspects of cell development, inflammation, and immunity. They are produced by a variety of cells, including monocytes, macrophages, lymphocytes, fibroblasts, mast cells, platelets, and endothelial cells.

Type	Examples	Source	Target
Pro-inflammatory cytokines	Interleukin-1 (IL-1), TNF-β	Macrophages, T cells	B cells, T cells, phagocytes, tumor cells
Anti-inflammatory cytokines	Interleukin-10 (IL-10)	T cells	B cells, macrophages
Vasodilators/vasoconstrictors	Serotonin, histamine	Platelets, mast cells	Blood vessels, sensory neurons
Growth factors	Interleukin-7 (IL-7), erythropoietin	Bone marrow cells, endothelial cells	Stem cells

First Line of Defense: Physical and Chemical Barriers

Skin

• Stratum corneum: Tough, waterproof outer layer.

• Constant shedding removes microbes.

• Hair and sweat provide additional removal mechanisms.

Mucous Membranes

• Mucous coat impedes entry and attachment of bacteria.

• Blinking, tears, and saliva flush surfaces.

• Vomiting and defecation remove harmful substances.

• Respiratory tract: Nasal hair, mucus, cilia, sneezing, and coughing expel irritants.

• Genitourinary tract: Urine flow and vaginal secretions cleanse the tract.

Normal Microbiota

• Blocks pathogen access to epithelial surfaces.

• Competes for nutrients and alters local pH, creating an unfavorable environment for pathogens.

Chemical Defenses

• Sebaceous secretions, sweat (acidic pH, electrolytes), and specialized glands produce antimicrobial substances.

• Lysozyme in tears and saliva hydrolyzes bacterial cell walls.

• Stomach acid, digestive juices, bile, and vaginal pH inhibit microbial growth.

Second Line of Defense: Internalized Nonspecific Defenses

Major Categories

• Phagocytosis

• Inflammation

• Fever

• Antimicrobial proteins

Phagocytosis

Phagocytes survey tissues, ingest and eliminate microbes, and process antigens. Main types include neutrophils, monocytes, and macrophages. Steps:

1. Chemotaxis

2. Ingestion

3. Phagolysosome formation

4. Destruction

5. Excretion

Inflammation

Characterized by redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function. Functions to mobilize immune components, repair tissue, and destroy microbes. Stages include vascular changes, edema, pus formation, and resolution/scar formation.

Fever

Elevated body temperature, often due to infection. Pyrogens (exogenous or endogenous) reset the hypothalamic thermostat. Benefits include inhibiting pathogen growth, reducing iron availability, and enhancing immune responses.

Antimicrobial Products

• Interferons: Small proteins produced by WBCs and tissue cells; regulate immune responses and inhibit viral replication by degrading viral RNA and preventing protein synthesis.

• Complement System: Over 30 blood proteins that act in a cascade to destroy bacteria, viruses, and infected cells. The classical pathway is antibody-dependent; the alternative pathway is antibody-independent.

• Antimicrobial Peptides: Short proteins (e.g., defensins) that insert into microbial membranes, forming pores and causing cell lysis.

Summary Table: Major Components of Host Defenses

Line of Defense	Components	Examples
First	Physical, chemical, and microbiological barriers	Skin, mucous membranes, normal microbiota, secretions
Second	Cellular and chemical defenses	Phagocytes, inflammation, fever, complement, interferons
Third	Adaptive immunity	B cells, T cells, antibodies

Key Terms and Definitions

• Antigen/Marker: Molecule on cell surfaces recognized by the immune system.

• PAMP: Pathogen-associated molecular pattern, a common microbial signature.

• PRR: Pattern recognition receptor, a host cell receptor for PAMPs.

• Cytokine: Signaling molecule for immune cell communication.

• Phagocytosis: Cellular process of engulfing and destroying particles.

• Complement: System of proteins that enhances immune responses.

• Interferon: Protein that interferes with viral replication and modulates immunity.