Immunology Second Line of Host Defense

Immunology (Second Line of Host Defense)

• Second Line of Host Defense Components:
  • Fever
  • Inflammation
  • Phagocytosis
  • Natural killer cells
  • Antimicrobial Substances:
    • Complement
    • Interferons
    • Lysozymes
    • Acute phase proteins

Fever

• Definition: A systemic non-specific response to infection.
• Pyrogen Sources:
  • Exogenous: LPS, pathogens, foreign cells, vaccines.
  • Endogenous: Interleukin-1 (IL-1 and 6) and Tumor necrosis factor (TNF-α).
• Mechanism: Monocytes, neutrophils, and macrophages reset the hypothalamus (in the brain) thermostat to a higher setting.
• Significance: Low-grade fever (38-38.5°C) is an effective defense against disease.

Inflammation

• Mechanism of Action: When pathogens cross skin/mucous membranes into the body, injury to tissues and histamine release initiates this response.
• Key Players: Mast cells (primarily), and then basophils, are the major histamine producers.

Pro-Inflammatory Cytokines

• List: Tumor necrosis factor (TNF-α), Interleukin-1, Interleukin-6, Interleukin-8, Chemokines, Interferons.

Phagocytosis

• Definition: "Eat and cell," a process by white blood cells (monocytes/macrophages, neutrophils, and occasionally eosinophils and dendritic cells).
• Neutrophils: Predominate early in infections.
• Macrophages (Histiocytes): Fixed locations in tissues such as liver, nervous system, lungs, lymph nodes.
• Phagotic Cells (details):
  • Macrophage: Monocytes that reside in tissues and organs. They can phagocytose, or secrete toxic substances for killing pathogens. They are also antigen-presenting cells (APCs).
  • Monocyte: Functions in blood similar to macrophages in tissues, transforming into macrophages. Phagocytosis in tissues and organs, also APCs.
  • Neutrophil: Phagocytosis and secretion of substances involved in inflammation.
  • Dendritic Cell: Phagocytosis in tissues and organs, while being antigen-presenting cells (APCs). They link innate and adaptive immune responses.

Origin of Phagocytic Cells (Macrophages, Neutrophils, and Eosinophils)

• Origin: Myeloid and Lymphoid stem cells.

Cellular Elements of Blood

• Cell Type | # Cells/mm³ | Function
• Erythrocytes (RBC) | 4.8-5.4 million | Carry O2 and CO2
• Leukocytes (WBC) | 5000-9000 | Various (including phagocytosis, antibody production)
• Granulocytes | |
• Neutrophils (Microphage) | 70% WBC | Phagocytosis
• Basophils | 1% | Produce histamine
• Eosinophils | 4% | Toxins against parasites, some phagocytosis
• Agranulocytes | |
• Monocytes (Macrophages) | 5% | Phagocytosis
• Lymphocytes | 20% | Antibody production and cell-mediated immunity
• Platelets | 300,000 | Blood clotting

Stages of Phagocytosis

• Chemotaxis: Phagocytes attracted to infection site by chemical factors from microbes, damaged tissues and inflammatory cells.
• Adherence: Phagocyte plasma membrane adheres to pathogen/foreign material. Bacterial capsules can inhibit adherence. Opsonization (coating) with opsonins enhances adherence (antibodies and complement proteins).
• Ingestion (Endocytosis): Phagocyte extensions (pseudopods) engulf the microbe, enclosing it in a phagosome.
• Digestion: Phagosome fuses with a lysosome forming a phagolysosome. Lysosomal enzymes kill microbes (e.g., lysozymes, lipases, proteases, RNAses, DNAses) within minutes.
• Exocytosis: Undigested material is discharged

Natural Killer (NK) Cells

• Description: Large granular lymphocytes (LGL).
• Function: Kill virus-infected and tumor cells. They secrete cytokines such as IFNγ and TNFα.
• Activation: Activated by IL-2 and IFN-γ to become Lymphokine Activated Killer (LAK) cells.

5.a. Complement

• Definition: A large group of serum proteins (around 30 types).
• Functions: Lysis of foreign cells, inflammation, and phagocytosis.
• Inactivation: Lytic activity is destroyed upon heating at 56°C for 30 minutes.
• Origin: Produced mainly by hepatocytes, monocytes, and epithelial cells (GI & Genitourinary tracts)
• Complement Components (Nomenclature):
  • Many are proenzymes (zymogens) until activated.
  • Named with capital letters (C1, C2...), with cleaved fragments having small letters (C3a, C3b).

Complement Pathways

• Classical Pathway: Antibody-dependent, most specific, using C1.
• Lectin Pathway: Some specificity, using mannose-binding protein to bind C4.
• Alternative Pathway: Non-specific, auto-activation of C3.

Mannose-binding Lectin (MBL) Pathway

• MBL Function: Binds to carbohydrates (D-mannose and L-fucose) on pathogen surfaces (e.g., bacteria, yeasts, viruses, parasites).

Consequences of Complement Activation

• Cytolysis: Formation of the Membrane Attack Complex (MAC) creates lesions in microbial membranes.
• Inflammation: Complement components (C3a) trigger histamine release, increasing vascular permeability.
• Opsonization: Complement components (C3b) bind microbial surfaces enhancing phagocytosis.
• Inactivation of Complement: Regulatory proteins prevent damage to host cells.

5.b. Interferons

• Description: Antiviral proteins.
• Functions: Interfere with viral replication, important in acute/short-term infections.
• Specificity: Host-specific but not virus-specific.
• Types:
  • Type I (α, β): Produced by lymphocytes and macrophages (α), fibroblasts and epithelial cells (β).
  • Type II (γ): Produced by T cells and NK cells.

5.c. Lysozyme

• Description: An antimicrobial enzyme in the innate immune system.
• Function: A glycoside hydrolase that catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan, a major component of Gram-positive bacterial cell walls causing bacterial lysis.
• Location: Abundant in secretions like tears, saliva, human milk, and mucus; also in macrophage and neutrophil cytoplasmic granules.

5.d. Acute-Phase Proteins

• Description: Proteins whose plasma levels change in response to inflammation.
• Functions: Fever, acceleration of peripheral neutrophil circulation, and repair from tissue damage.
• Mechanism: Local inflammatory cells (neutrophils and macrophages) release cytokines (IL-1, IL-6, IL-8, and TNF-α) into the bloodstream, stimulating the liver to produce various acute-phase proteins (ex: C-reactive protein).

Innate Immunity vs. Adaptive Immunity

• Innate: Present from birth. Non-specific; rapid response; limited/lower potency; no immunological memory; includes physical and chemical barriers, phagocytes, leukocytes, dendritic cells, and NK cells.
• Adaptive: Developed in response to foreign exposure. Specific response to pathogens/antigens; slower response; high potency; immunological memory; involves B and T cells (cell-mediated and humoral).

Test your knowledge on the second line of host defense in immunology, including the roles of fever, inflammation, and phagocytosis. This quiz covers various components such as natural killer cells and antimicrobial substances like complement and interferons. Dive into how these mechanisms work together to protect the body against infections.