CHAPTER 21: LECTURE A

Immune System Overview

• The immune system provides resistance to disease.

• Comprised of two intrinsic systems:

  • Innate Defense System (Nonspecific):

  • Constitutes the first and second lines of defense:

    • First Line of Defense: External body membranes (skin and mucosae)

    • Second Line of Defense: Antimicrobial proteins, phagocytes, and other cells. It inhibits the spread of invaders with inflammation being the most important mechanism.

  • Adaptive Defense System (Specific):

  • Third Line of Defense: Targets particular foreign substances; it takes longer to react compared to innate defenses.

Functional Aspects of the Immune System

• The immune system functions as a functional system rather than a strict organ system.

• Innate and adaptive defenses are interrelated:

  • Both systems release and recognize numerous defensive molecules.

  • Innate defenses contain specific pathways for certain substances.

  • Innate responses release proteins that alert the adaptive system to foreign molecules.

Innate Defenses (Part 1)

• The innate system employs the first and/or second lines of defense to thwart pathogens (disease-causing microorganisms).

1. First Line of Defense: Surface Barriers

• Surface barriers include skin and mucous membranes along with their secretions:

  • Physical Barriers:

  • Skin acts as a barrier to most microorganisms.

  • Keratin in skin resists weak acids, bases, bacterial enzymes, and toxins.

  • Mucosae provide similar mechanical barriers.

Protective Chemicals of Surface Barriers

• Skin and mucous membranes produce protective chemicals inhibiting or destroying microorganisms:

  • Acid: The acidity of skin and some mucous secretions inhibits growth (acid mantle).

  • Enzymes: Lysozyme in saliva, respiratory mucus, and lacrimal fluid kills many microorganisms; the stomach contains enzymes that destroy pathogens.

  • Mucin: Sticky mucus in the digestive/respiratory tract traps microorganisms.

  • Defensins: Antimicrobial peptides that inhibit microbial growth.

  • Other Chemicals: Lipids in sebum and dermicidin in sweat are toxic to some bacteria.

Respiratory System Modifications

• The respiratory system has features to stop pathogens:

  • Mucus-coated hairs trap inhaled particles.

  • Cilia in the upper respiratory tract sweep dust- and bacteria-laden mucus toward the mouth.

• If surface barriers are compromised (e.g., cuts or nicks), the second line of defense activates to protect deeper tissues.

2. Second Line of Defense: Cells and Chemicals

• The second line of defense becomes essential when microorganisms invade deeper tissues. It includes:

  • Phagocytes

  • Natural Killer (NK) Cells

  • Inflammatory Response: Involves macrophages, mast cells, WBCs, and inflammatory chemicals.

  • Antimicrobial Proteins: Includes interferons and complement proteins.

  • Fever

Phagocytes

• Definition: Phagocytes are white blood cells that ingest and digest foreign invaders.

  • Neutrophils: The most abundant type of phagocyte that die fighting pathogens and become active upon exposure to infection.

  • Macrophages: Develop from monocytes and serve as the chief phagocytic cells; they are more robust than neutrophils:

  • Free Macrophages: Wander through tissue spaces (e.g., alveolar macrophages).

  • Fixed Macrophages: Permanent residents of certain organs (e.g., stellate macrophages in the liver, microglia in the brain).

Phagocytosis Process

• The process starts when a phagocyte recognizes and adheres to a pathogen's carbohydrate signature:

  • Some microorganisms possess external capsules that conceal surface carbohydrates, helping them evade phagocytosis.

  • Opsonization: Antibodies or complement proteins coat pathogens, acting as "handles" for phagocytes. This enhances phagocytosis.

• The process continues with:

  1. Adhesion: Phagocyte adheres to pathogens or debris.

  2. Engulfment: Cytoplasmic extensions (pseudopods) bind to and engulf particles forming a vesicle called a phagosome.

  3. Formation of Phagolysosome: The phagosome fuses with a lysosome.

  4. Digestion: The phagolysosome is acidified, and lysosomal enzymes digest the particles.

  5. Exocytosis: Indigestible material is expelled from the phagocyte.

Natural Killer (NK) Cells

• Nonphagocytic, large granular lymphocytes that monitor blood and lymph:

  • Can kill cancer and virus-infected cells before the adaptive immune system activates.

  • Targets cells that lack self cell-surface receptors, inducing apoptosis in cancer and virus-infected cells.

  • Secretes potent chemicals that enhance the inflammatory response.

Inflammation: Tissue Response to Injury

• Triggered by bodily tissue injuries, which can occur from:

  • Trauma, heat, irritating chemicals, or infections.

• Benefits of inflammation include:

  • Preventing the spread of damaging agents.

  • Disposing of cell debris and pathogens.

  • Alerting the adaptive immune system.

  • Setting the stage for repair.

Cardinal Signs of Acute Inflammation

1. Redness

2. Heat

3. Swelling

4. Pain

5. Impaired function (sometimes observed if movement is hampered).

Stages of Inflammation

1. Inflammatory Chemical Release

   • Chemicals are released into the extracellular fluid by injured tissues, immune cells, or blood proteins.

   • Example: Histamine, released by mast cells, is key in triggering inflammation.

   • Macrophages and epithelial cells bear Toll-like receptors (TLRs). TLRs recognize microbes, leading to chemical release promoting inflammation.

2. Vasodilation and Increased Vascular Permeability

   • Vasodilation causes hyperemia (congestion with blood), resulting in redness and heat.

   • Increased permeability leads to exudate (fluid containing clotting factors and antibodies) leaking into tissues, causing swelling (edema) which also results in pain due to pressure on nerve endings.

3. Phagocyte Mobilization

   • Neutrophils flood the area, followed by macrophages if inflammation is due to pathogens; this activates complement and brings in elements of adaptive immunity.

Phagocyte Mobilization Steps

• Leukocytosis: Neutrophils are released from bone marrow in response to inflammatory factors from injured cells.

• Margination: Endothelial cells in inflamed areas express cell adhesion molecules (CAMs) to slow down and capture neutrophils.

• Diapedesis: Neutrophils flatten and squeeze between endothelial cells into interstitial spaces.

• Chemotaxis: Inflammatory chemicals act as chemotactic agents promoting neutrophil movement toward injury.

• Subsequent arrival of monocytes occurs after 12 hours, transforming into macrophages for cleanup before repair.

Antimicrobial Proteins

• Antimicrobial proteins enhance innate defenses by:

  • Attacking microorganisms directly or hindering their reproduction.

  • Interferons (IFNs):

  • Family of immune-modulating proteins.

  • Virus-infected cells secrete IFNs to warn neighboring cells, stimulating the production of proteins that block viral reproduction and degrade viral RNA, such as IFN-a and IFN-b.

  • Complement System:

  • Comprises ~20 blood proteins circulating in inactive form (C1–C9, factors B, D, P).

  • Provides a major mechanism for destroying foreign substances.

  • Activation enhances inflammation and directly destroys bacteria by forming the membrane attack complex (MAC) that causes cell lysis.

Benefits of Moderate Fever

• Fever is an abnormally high body temperature as a systemic response to invading microorganisms.

• Caused by pyrogens secreted by leukocytes and macrophages when exposed to foreign substances.

• Raise body temperature via hypothalamic action.

• Benefits include:

  • Sequestering iron and zinc (needed by microorganisms) by the liver and spleen.

  • Increasing metabolic rates to enhance repair processes.

Tables

Table 21.1: First Line of Defense - Surface Membrane Barriers

Table 21.2: Inflammatory Chemicals

Table 21.3: The Second Line of Defense: Innate Cellular and Chemical Defenses