Microbiology Chapter 15: Host Defenses I

The Three Lines of Host Defense

• First-Line Defenses: This level of defense consists of innate, physical, and chemical barriers that impede the entry of microbes into the body. Notable examples include the skin, mucous membranes, hair, and stomach acid.
• Second-Line Defenses: If the first line is breached, the second line of defense involves non-specific internal processes and cellular activities. Four examples of these defenses are phagocytes, fever, inflammation, and antimicrobial proteins.
• Third-Line Defenses: This is the adaptive or acquired immunity level, characterized by specificity and memory. Its primary components are $B \text{ cells}$ and $T \text{ cells}$.

Physical and Chemical Barriers of the First Line

• Skin as an Innate Barrier: The skin serves as a highly effective physical barrier against microbial invasion due to several specific factors:
  • $pH$: The acidity of the skin inhibits the growth of many pathogenic microorganisms.
  • Electrolytes: The presence of salts and electrolytes creates a harsh environment for many microbes.
  • Keratin: This tough, fibrous protein provides structural integrity and resistance to enzymatic digestion by microbes.
• Skin vs. Mucous Membranes: A fundamental difference exists between these two barriers. Skin epithelial cells are impregnated with keratin (keratinized), whereas mucosal epithelial cells provide barrier protection without a keratinized layer.
• Anatomical Structures:
  • Cilia: These hair-like projections are responsible for the movement of mucus out of body tracts (e.g., the respiratory tract).
  • Microvilli: These are cellular extensions designed to increase the surface area for absorption or secretion rather than for moving material.
• Chemical Defenses:
  • Lysozyme: An enzyme found in tears, saliva, semen, and breast milk. Its primary function is to hydrolyze peptidoglycan, a component found in the cell walls of bacteria.
  • Microbial Antagonism: This occurs when established cultures of resident microorganisms prevent the intrusion of foreign strains of microbes.
  • Nonspecific Chemical Defenses: These include sebaceous secretions, lysozyme, lactic acid, electrolytes, oils, and waxes.

The Immune System: Surveillance and Recognition

• Primary Responsibilities of a Healthy Immune System:
  1. Surveillance: Constantly monitoring the body for foreign material.
  2. Recognition: Distinguishing between self cells and non-self (foreign) invaders.
  3. Destruction: Eliminating the detected pathogens.
• Markers:
  • Definition: Molecules located on the surfaces of cells.
  • Composition: They are composed of proteins and/or sugars (glycoproteins or glycolipids).
  • Function: They are evaluated by cells of the immune system to determine if the cell is native to the host or a foreign entity.

Body Compartments Participating in Immune Function

• The immune system operates through four major body compartments:
  1. Mononuclear Phagocyte System (MPS): A support network of connective tissue fibers (reticular system) originating in the basal lamina. It interconnects tissues and organs and meshes with the massive connective tissue network surrounding all organs.
  2. Extracellular Fluid (ECF): The spaces surrounding tissue cells that contain fluid.
  3. Bloodstream: Involved in the transport of immune cells and chemicals throughout the body.
  4. Lymphatic System: A network of vessels and organs that transport lymph.
• Lymphoid Tissue Acronyms:
  • GALT: Gut Associated Lymphoid Tissue.
  • MALT: Mucus Associated Lymphoid Tissue.
  • SALT: Skin Associated Lymphoid Tissue.
  • BALT: Bronchial Associated Lymphoid Tissue.

The Lymphatic System and Organs

• Lymphatic Fluid:
  • A plasma-like liquid carried by the lymphatic circulation.
  • Composition: Primarily water, dissolved salts, and between $2\%$ to $5\%$ protein.
  • Function: Transports white blood cells, fats, cellular debris, and infectious agents that have entered tissue spaces.
• Differences from the Circulatory System:
  • Direction of Flow: Lymph moves in one direction only, from the extremities toward the heart.
  • Transport Mechanism: Lymph is transported only through the contraction of skeletal muscles, unlike blood which is pumped by the heart.
• The Thymus: A triangular organ located in the pharyngeal region. It serves as the site for $T \text{ cell}$ maturation. The size of the thymus decreases (atrophies) with age.
• The Spleen:
  • Primary Function: To remove worn-out red blood cells from circulation.
  • Immunologic Function: To filter pathogens from the blood for phagocytosis by macrophages.
• Lymph Nodes:
  • Definition: Small, encapsulated, bean-shaped organs stationed in clusters along lymphatic channels and large blood vessels.
  • Major Aggregations: These are found in the loose connective tissue of the armpit (axillary), groin (inguinal), and neck (cervical).

Blood Composition and Hematopoiesis

• Serum vs. Plasma:
  • Serum: This is the liquid portion of the blood after a clot has formed; it contains no clotting factors. Serum is the component used in immune therapy.
  • Plasma: This is the liquid portion of un-clotted blood and contains all clotting factors.
• Fibrinogen: A specific protein found in blood that is involved in the process of blood coagulation.
• Buffy Coat: The thin, whitish layer in a tube of un-clotted blood containing the white blood cells (WBCs).
• Cell Production (Hematopoiesis):
  • Definition: The process of blood cell production.
  • Site: In adulthood, this primarily occurs in the red bone marrow.
  • Stem Cells: Immature or unspecialized cells capable of developing into specialized, mature cells.
• Cell Types:
  • Erythrocyte: Red blood cell (RBC).
  • Leukocyte: White blood cell (WBC).
  • Thrombocyte: Platelets.
  • Megakaryocyte: The specific cell type responsible for producing platelets.

Detailed Classification of Leukocytes

• Granulocytes vs. Agranulocytes:
  • Granulocytes: Characterized by a lobed nucleus and prominent cytoplasmic granules that stain with eosin or methylene blue. These granules function in numerous physiological events.
  • Agranulocytes: Characterized by an unlobed, rounded nucleus and the absence of visible granules.
• Important Granulocytes:
  1. Neutrophils: Comprise $55\%$ to $90\%$ of circulating leukocytes. They are responsible for phagocytosis and the production of toxic chemicals.
  2. Eosinophils: Their granules contain peroxidase, lysozyme, digestive enzymes, toxic proteins, and inflammatory chemicals. They are specialized to attack and destroy large eukaryotic pathogens.
  3. Basophils: Make up less than $0.5\%$ of circulating WBCs. They share morphological and functional characteristics with mast cells.
  4. Mast Cells: Responsible for triggering local inflammatory reactions and many allergic reactions.
• Agranulocyte Differentiation:
  • Monocytes: These can differentiate into two main cell types: Macrophages and Dendritic cells.
• Immunity Roles:
  • Humoral Immunity: Carried out by $B \text{ cells}$.
  • Cell-Mediated Immunity: Carried out by $T \text{ cells}$.

Mechanisms of Phagocytosis

• Phagocytosis Definition: A process with three main missions:
  1. Surveying tissue compartments to discover microbes, particulate matter, and injured/dead cells.
  2. Recognizing immunogenic information (antigens) in foreign matter.
  3. Ingesting and eliminating these materials.
• Process Stages:
  • Phagosome: A vacuole formed by the ingestion of extracellular material.
  • Phagolysosome: Forms when lysosomes migrate to and fuse with the phagosome. Within this structure, granules containing antimicrobial chemicals are released to destroy the ingested material.
  • Outcome: Phagolysosomal activity typically causes the death of bacteria within $30$ minutes.
• Killing Agents:
  • Enzymes: Lysozyme, DNase, protease, and RNase.
  • Reactive Oxygen Products: An oxygen-dependent system involving myeloperoxidase which forms halogen ions (such as hypochlorite, $OCl^{-}$). Other products include superoxide anion, singlet oxygen, and the hydroxyl free radical.
• Pathogen-Associated Molecular Patterns (PAMPs): Examples include Peptidoglycan, Lipopolysaccharide, and double-stranded RNA (found in viruses).

Inflammation and Fever

• Signs of Inflammation:
  1. Rubor (Redness)
  2. Tumor (Swelling)
  3. Dolor (Pain)
  4. Calor (Heat)
  5. Loss of Function
• First Responder: The neutrophil is the phagocytic granulocyte considered the "first responder" during an injury.
• Signaling Molecules:
  • Cytokine: General cell signaling molecules.
  • Chemokine: Specific chemotactic factors that recruit cells to a site.
• Pyrogens (Fever Induction):
  • Exogenous Pyrogens: Originate outside the body (e.g., products of infectious agents like viruses, bacteria, protozoans, fungi, endotoxin, vaccines, or injectable solutions).
  • Endogenous Pyrogens: Originate inside the body. They are released by monocytes, neutrophils, and macrophages during phagocytosis.
  • Main Endogenous Pyrogens: Interleukin-1 ($IL-1$) and Tumor Necrosis Factor ($TNF$).

Antimicrobial Proteins: Interferon and Complement

• Interferon: A cytokine that inhibits virus replication and is used intravenously to treat certain viral infections.
• Complement Pathways: There are three pathways to activate the complement system:
  1. Classical
  2. Lectin
  3. Alternative
• The End Goal: All three complement pathways result in the formation of the Membrane Attack Complex (MAC), which destroys the target cell membrane.