Chapter 14 Host defenses: Innate Immunity

Host Defense Mechanisms Overview

  • Innate, natural defenses: Present at birth, offering nonspecific resistance to infection.
  • Adaptive immunities: Specific, acquired over time.

General Features of Host Defenses (TABLE 14.1)

  • First Line of Defense
    • Innate
    • Nonspecific
    • No immunologic memory
    • Examples: Physical barriers (skin, tears, coughing, sneezing), chemical barriers (low pH, lysozyme, digestive enzymes), genetic barriers (resistance inherent in genetic makeup).
  • Second Line of Defense
    • Innate
    • Mostly nonspecific
    • No immunologic memory
    • Examples: Phagocytosis, inflammation, fever, interferon, complement.
  • Third Line of Defense
    • Acquired
    • Specific
    • Immunologic memory develops
    • Examples: T lymphocytes, B lymphocytes, antibodies.

Defense Mechanisms of the Host

  • Immune system protects against pathogens through:
    • Physical barriers
    • Immunologically active cells
    • Various chemicals
  • First Line of Defense
    • Blocks invasion at the portal of entry
    • Nonspecific
  • Second Line of Defense
    • Protective cells and fluids; inflammation and phagocytosis
    • Nonspecific
  • Third Line of Defense
    • Acquired with exposure
    • Specific; produces antibodies and memory cells
  • Lines of defense overlap and are redundant.

First Line of Defense: Barriers at the Portal of Entry

  • Inborn (innate), nonspecific defenses
  • Categories:
    • Physical/anatomical barriers
    • Chemical defenses
    • Genetic resistance to infection
  • Block entry of microbes and foreign agents (living or not).

Physical or Anatomical Barriers

  • Skin
    • Outermost layer with epithelial cells cemented together and impregnated with keratin.
    • Flushing effect of sweat.
  • Mucous membranes
    • Coating of digestive, genitourinary, and respiratory tracts.
    • Blinking and tear production.
    • Flow of saliva.
    • Flushing effect of urination, defecation, vomiting.
  • Mucous coat impedes attachment and entry of bacteria.
  • Ciliary defense of respiratory tree: nasal hair traps larger particles.

Nonspecific Chemical Defenses

  • From skin and mucous membranes
    • Sebaceous secretions
    • Antimicrobial secretions from specialized glands (meibomian glands)
  • Other defenses
    • Lysozyme: hydrolyzes bacterial cell walls
    • Defensins: lyse bacteria and fungi
    • High lactic acid and electrolyte concentration in sweat
    • Skin’s acidic pH.
  • Hydrochloric acid in stomach.
  • Digestive juices and bile of intestines.
  • Semen contains antimicrobial chemicals.
  • Vagina has acidic pH (maintained by microbiota).

Genetic Defenses

  • Some hosts are genetically immune to diseases of other hosts.
    • Example: Humans can’t acquire distemper from cats, and cats can’t get mumps from humans.
  • Genetic differences in susceptibility exist for other pathogens, sometimes within the same species.
    • Example: Humans with sickle-cell anemia are resistant to malaria.

Structure and Function of the Organs of Defense and Immunity

  • Immunology: Study of the body’s 2nd and 3rd lines of defense.
  • Primary functions:
    • Surveillance of the body.
    • Recognition and differentiation of normal versus foreign material.
    • Attack against and destruction of foreign entities.
  • White blood cells (leukocytes) recognize and differentiate foreign material.
    • Nonself: Foreign material.
    • Self: Normal cells of the body.
  • Pathogen-associated patterns (PAMPs): Molecules shared by microorganisms.
  • Pathogen recognition receptors (PRRs): Receptors on WBCs for PAMPs.

White Blood Cells (Leukocytes)

  • Innate capacity to recognize and differentiate foreign material.

Origin, Composition, and Functions of Blood

  • Whole blood: Plasma and formed elements (blood cells).
  • Serum: Liquid portion of blood after clot formation (minus clotting factors).
  • Plasma: 92% water, metabolic proteins, globulins, clotting factors, hormones, chemicals, and gases.

Survey of Blood Cells

  • Hemopoiesis (hematopoiesis): Production of blood cells.
  • Stem cells: Undifferentiated cells, precursors of new blood cells.
  • Primary cell lines:
    • Platelets (thrombocytes)
    • Red blood cells (RBCs)
    • Leukocytes or white blood cells (WBCs): Responsible for immune function.
    • Granulocytes: Lobed nucleus
    • Agranulocytes: Unlobed, rounded nucleus

Granulocytes

  • Neutrophils: 55-90%, lobed nuclei with lavender granules; phagocytes.
  • Eosinophils: 1-3%, orange granules and bilobed nucleus; destroy eukaryotic pathogens.
  • Basophils: 0.5%, constricted nuclei, dark blue granules; release potent chemical mediators.
    • Mast cells: Nonmotile elements bound to connective tissue.

Agranulocytes

  • Lymphocytes: 20-35%, specific immune response.
    • B cells (humoral immunity): Produce antibodies.
    • T cells (cell-mediated immunity): Modulate immune functions and kill foreign cells.
  • Monocytes, macrophages: 3-7%, largest of WBCs, kidney-shaped nucleus; phagocytic.
    • Macrophages: Final differentiation of monocytes.
    • Dendritic cells: Trap pathogens and participate in immune reactions.

Characteristics of Leukocytes (TABLE 14.2)

  • Neutrophils
    • Prevalence: 55% to 90%
    • Primary Function: General phagocytosis
    • Features: Life span of 2 days, multilobed nuclei, small purple granules containing digestive enzymes.
  • Eosinophils
    • Prevalence: 1% to 3%
    • Primary Function: Destruction of parasitic worms; mediators of allergy
    • Features: Bilobed nucleus with large orange granules containing toxic proteins, inflammatory mediators, and digestive enzymes.
  • Basophils
    • Prevalence: 0.5%
    • Primary Function: Active in allergy, inflammation, parasitic infections
    • Features: Cytoplasmic granules contain histamines, prostaglandins.
  • Monocytes
    • Prevalence: 3% to 7%
    • Primary Function: Phagocytosis, differentiation into macrophages and dendritic cells; secrete chemicals that moderate immune functions.
    • Features: Largest WBC; nuclei large, ovoid, and often indented.
  • Lymphocytes
    • Prevalence: 20% to 35%
    • Primary Function: Specific (acquired) immunity
    • Features: T cells (cell-mediated immunity), B cells (humoral immunity); small spherical cells with uniformly staining dark, round nuclei.

Erythrocytes and Platelet Lines

  • Erythrocytes: Develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobin.
  • Platelets: Formed elements in circulating blood, not whole cells.

Lymphatic System

  • Provides an auxiliary route for return of extracellular fluid to the circulatory system.
  • Acts as a drain-off system for inflammation.
  • Surveillance, recognition, and protection against foreign material.

Lymphatic Fluid

  • Plasma-like liquid carried by lymphatic circulation.
  • Formed when blood components move out of blood vessels into extracellular spaces.
  • Made up of water, dissolved salts, 2-5% proteins.
  • Transports white blood cells, fats, cellular debris, and infectious agents.

Lymphatic Vessels

  • Lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus.
  • Thin walls easily permeated by extracellular fluid.
  • Functions to return lymph to circulation; flow is one-direction toward the heart.

Classification of Lymphoid Organs and Tissues

  • Primary organs
    • Sites of lymphocytic origin and maturation
    • Thymus gland
    • Bone marrow
  • Secondary organs and tissues
    • Circulatory-based locations
    • Lymph nodes
    • Spleen
  • Collections of cells distributed throughout skin and mucous membranes
    • MALT: Mucosal-associated lymphoid tissue
    • SALT: Skin-associated lymphoid tissue
    • GALT: Gut-associated lymphoid tissue (Peyer’s patches).

Lymphoid Organs

  • Thymus
    • High growth and activity until puberty, then begins to shrink.
    • Site of T-cell maturation.
  • Lymph nodes
    • Small, encapsulated, bean-shaped organs along lymphatic channels and large blood vessels.
  • Spleen
    • Below the diaphragm and left of the stomach.
    • Filters circulating blood to remove worn out RBCs and pathogens.

Second-Line Defenses: Inflammation

  • Mechanisms: Recognition, inflammation, phagocytosis, interferon, complement.
  • Nonspecific effects; support and interact with specific immune responses.

Inflammatory Response

  • Reaction to any traumatic event in the tissues to restore homeostasis.
  • Clears away invading microbes and cellular debris.
  • Signs and symptoms:
    • Redness: Increased circulation and vasodilation.
    • Warmth: Heat given off by increased blood flow.
    • Swelling: Increased fluid in the tissue (edema); WBCs, microbes, debris, and fluid collect to form pus.
    • Pain: Stimulation of nerve endings.

Major Inflammatory Events

  • Injury/Immediate Reactions: Blood vessels narrow (vasoconstriction); blood clots; mast cells release chemokines and cytokines.
  • Vascular Reactions: Nearby blood vessels dilate; increased blood flow; increased vascular permeability; leakage of fluid forms exudate.
  • Edema and Pus Formation: Collection of fluid; edema/swelling; infiltration by neutrophils formation of pus.
  • Resolution/Scar Formation: Macrophages, lymphocytes, and fibroblasts migrate in; initiate immune response and repair of injury; scar formation.

Chemical Mediators of Inflammatory Response

  • Formation of a blood clot: fibrinogen converted to fibrin.

Unique Characteristics of Leukocytes

  • Diapedesis: Migration of cells out of blood vessels into the tissues.
  • Chemotaxis: Migration in response to specific chemicals at the site of injury or infection.

Fever: An Adjunct to Inflammation

  • Initiated by circulating pyrogens that reset the hypothalamus.
    • Exogenous pyrogens: Products of infectious agents; endotoxin.
    • Endogenous pyrogens: Liberated by monocytes, neutrophils, and macrophages; interleukin-1 (IL-1) and tumor necrosis factor (TNF).
  • Benefits of fever:
    • Inhibits multiplication of temperature-sensitive microorganisms.
    • Impedes nutrition of bacteria by reducing available iron.
    • Increases metabolism and stimulates immune reactions.

Second-Line of Defenses: Phagocytosis

  • General activities of phagocytes:
    • Survey tissue compartments.
    • Ingest and eliminate materials.
    • Extract immunogenic information from foreign matter.
  • Major categories of phagocytes:
    • Neutrophils: General-purpose, react early.
    • Eosinophils: Attracted to parasitic infections and antigen-antibody reactions.
    • Macrophages: Derived from monocytes; scavenge and process foreign substances.

Development of Monocytes and Macrophages

  • After leaving the bloodstream, monocytes transform into macrophages or dendritic cells.
  • Macrophages and dendritic cells can remain nomadic or reside in a specific organ.

Phagocytic Recognition

  • Toll-like receptors (TLRs) within cell membrane of macrophages detect foreign molecules.

Mechanisms of Phagocytosis

  • Chemotaxis, binding, and ingestion:
    • Phagocytes migrate to inflammation.
    • Bind pathogen-associated molecular patterns (PAMPs) using TLRs.
  • Phagolysosome formation:
    • Phagocyte extends pseudopods to enclose pathogen in a phagosome.
    • Lysosomes fuse with the phagosome to form a phagolysosome and digest the pathogen.
  • Destruction and elimination:
    • Oxygen-dependent system (respiratory burst).
    • Liberation of lactic acid, lysozyme, and nitric oxide.
    • Undigestible debris released by exocytosis.

Interferon

  • Small protein produced by WBCs and tissue cells.
  • Types:
    • Interferon alpha: Product of lymphocytes and macrophages.
    • Interferon beta: Product of fibroblasts and epithelial cells.
    • Interferon gamma: Product of T cells.
  • Produced in response to viruses, RNA, immune products, and antigens.
  • Binds to cell surfaces; induces expression of antiviral proteins and inhibits expression of cancer genes.
  • IFNs alpha and beta stimulate phagocytes; IFN gamma is an immune regulator.

Complement

  • Consists of 26 blood proteins that work to destroy bacteria and viruses.
  • Activated by cleavage (cascade reaction).
  • Pathways:
    • Classical: Activated by antibodies bound to microorganism.
    • Lectin pathway: Nonspecific reaction of a host serum protein that binds mannan.
    • Alternative: Begins when complement proteins bind to cell wall and surface components of microorganisms.

Overview of the Major Host Defenses

  • Innate, Nonspecific (First Line)
    • Physical barriers
    • Chemical barriers
    • Genetic barriers
    • Surface protection that keeps microbes from penetrating sterile body compartments.
  • Innate, Nonspecific (Second Line)
    • Inflammatory response
    • Interferons
    • Phagocytosis
    • Complement
    • Cellular and chemical system that comes into play if infectious agents pass surface defenses.
  • Acquired, Specific (Third Line)
    • B and T lymphocytes, antibodies, cytotoxicity
    • Specific host defenses developed for each microbe through specialized white blood cells; marked by activity toward specific pathogens and development of memory.