Lymphatic System and Innate Immunity Practice Flashcards

Overview and Functions of the Lymphatic System

• Definition and Scope: The lymphatic system consists of a network of lymphatic vessels (often termed "lymphatics"), lymphatic fluid (lymph), and variety of lymphoid tissues and organs.

• Primary Functions:

  • Immunity: Providing defense against pathogens and abnormal body cells.

  • Fluid Homeostasis: Returning interstitial fluid from the periphery back to the bloodstream to maintain blood volume.

• Lymph Composition: Lymph is defined as interstitial fluid that has entered the lymphatic vessels. It contains various components including lymphocytes and solutes from the interstitial space.

Anatomy of the Lymphatic Network and Drainage

• Lymphatic Capillaries: These are the site of origin for lymph drainage.

  • Differences from Blood Capillaries:

    • Originate as pockets or blind-ended tubes rather than continuous loops.

    • Possess larger diameters.

    • Feature thinner walls.

    • Appear flattened or irregular in cross-section.

  • Structure:

    • Lined by endothelial cells that overlap to act as one-way valves. This structural arrangement allows debris, viruses, bacteria, fluids, and solutes to enter the vessel but prevents them from leaving.

    • The basement membrane is either incomplete or entirely missing.

  • Distribution: Lymphatic capillaries are found everywhere blood flows, with specific exceptions such as the cornea of the eye.

• Lymphatic Vessels and Valves:

  • Vessels lead from the capillaries to the venous system.

  • Valves: Lymphatic vessels contain valves that prevent backflow and cause characteristic bulges along the vessel path.

  • Categories:

    • Superficial Lymphatics: Located in the subcutaneous areolar tissues.

    • Deep Lymphatics: Accompany deep arteries and veins.

• Major Lymphatic Ducts:

  • Thoracic Duct: The larger of the two ducts. It collects lymph from the entire body inferior to the diaphragm and the left side of the body superior to the diaphragm. It originates at the Cisterna chyli and enters the venous system at the left subclavian vein.

  • Right Lymphatic Duct: Collects lymph from the right side of the body superior to the diaphragm. It enters the venous system at the right subclavian vein.

• Flow Hierarchy: The progression of lymph follows the path: Lymphatic capillaries —> Superficial/Deep lymphatics —> Lymphatic trunks —> Thoracic duct or Right lymphatic duct.

• Lymphedema: A condition resulting from the blockage of lymphatic drainage. If left untreated, it can become permanent and lead to the accumulation of toxins and pathogens in the affected area.

Lymphocytes and Lymphopoiesis

• General Characteristics: Lymphocytes make up $20-30\%$ of circulating white blood cells, totaling approximately $10^{12}$ cells in the body (weighing about $2.2\,lb$). All lymphocytes are sensitive to antigens, which include proteins, lipids, polysaccharides, and nucleic acids.

• Classes of Lymphocytes:

  • T Cells (Thymus-dependent): Account for approximately $80\%$ of circulating lymphocytes. They provide cell-mediated immunity.

    • Cytotoxic T Cells: Direct attack on foreign cells.

    • Helper T Cells: Coordinate immune response.

    • Suppressor T Cells: Inhibit immune response to control its scale.

  • B Cells (Bone marrow-derived): Account for $10-15\%$ of circulating lymphocytes. They differentiate into Plasma Cells, which produce antibodies for antibody-mediated immunity.

  • NK Cells (Natural Killer cells): Account for $5-10\%$ of circulating lymphocytes. They provide immune surveillance by destroying abnormal cells.

• Lymphopoiesis (Production and Differentiation):

  • Hematopoietic Stem Cells: Located in the Red Bone Marrow, these produce lymphoid stem cells.

  • Differentiation Pathways:

    • One group of lymphoid stem cells remains in the red bone marrow to differentiate into B cells and NK cells.

    • Another group migrates to the Thymus. In the thymus, protected by the blood-thymus barrier, these cells undergo production and differentiation into various T cells. Approximately $98\%$ of these cells undergo apoptosis (programmed cell death) during the selection process.

  • Peripheral Tissues: Once mature, these cells enter the peripheral tissues to execute their respective immune functions. All lymphocytes retain the ability to divide (clonally).

Lymphoid Tissues and Organs

• Lymphoid Tissues (Non-encapsulated):

  • Lymphoid Nodules: Densely packed lymphocytes in areolar tissue with indistinct boundaries (no capsule).

  • MALT (Mucosa-Associated Lymphoid Tissue): Lymphoid nodules that protect the epithelia of the digestive, respiratory, urinary, and reproductive tracts.

  • Peyer’s Patches: Aggregated lymphoid nodules specifically located in the mucosa of the small intestine.

  • Tonsils: Large lymphoid nodules in the walls of the pharynx. There are five tonsils:

    • Pharyngeal tonsil (adenoid): Located in the nasopharynx.

    • Palatine tonsils (2): Located at the posterior margin of the oral cavity; prone to tonsillitis.

    • Lingual tonsils (2): Located at the base of the tongue.

• Lymphoid Organs (Encapsulated): Separated from surrounding tissues by a dense fibrous capsule.

  • Lymph Nodes:

    • Small organs (maximum size approximately $1\,in$) distributed along lymphatic vessels (e.g., cervical, axillary, lumbar, pelvic, inguinal nodes).

    • Function: Detect pathogens before they reach vital organs, remove $99\%$ of pathogens from lymph, and stimulate immune responses.

    • Structure: Consists of a capsule, trabeculae (internal partitions), cortex (containing germinal centers and lymphoid follicles), medulla (containing medullary cords and sinuses), and a hilum (exit point for efferent vessels).

    • Vessels: Afferent lymphatic vessels bring lymph into the node; Efferent lymphatic vessels carry lymph out at the hilum.

  • Thymus:

    • Located in the mediastinum, posterior to the sternum. It is the site for T cell development.

    • Involution: The thymus shrinks with age, from about $40\,g$ in infants to $12\,g$ in elder adults, contributing to increased disease susceptibility.

    • Histology: Divided into two lobes and many lobules by septa. Each lobule contains a cortex (densely packed lymphocytes) and a medulla.

    • Thymic Epithelial Cells: Regulate T cell development and form the blood-thymus barrier in the cortex.

    • Thymic Corpuscles: Structures in the medulla where mature T cells (after $3$ weeks of development) can enter the bloodstream.

  • Spleen:

    • The largest lymphoid organ, located on the left side between the stomach and the diaphragm.

    • Anatomy: Features a gastrosplenic ligament, gastric area, renal area, and a hilum (where the splenic artery, vein, and lymphatic vessels connect).

    • Functions:

      1. Removal of abnormal or damaged blood cells via phagocytosis.

      2. Storage of iron recycled from red blood cells.

      3. Initiation of immune responses by B and T cells.

    • Histology:

      • Red Pulp: Contains many red blood cells, collagen, elastic fibers, and fixed/free macrophages.

      • White Pulp: Resembles lymphoid nodules; dominated by lymphocytes.

    • Blood Flow: Splenic artery —→ Trabecular arteries —→ Central arteries (surrounded by white pulp) —→ Capillaries tissue of red pulp —→Sinusoids —→ Trabecular veins ——> Splenic vein at the hilum.

    • Clinical Note: A splenectomy increases the risk of bacterial infection.

Innate (Nonspecific) Immunity

• Definition: General defenses that do not distinguish between specific threats; these are present at birth.

• Physical Barriers:

  • Integumentary System: Includes the epithelium, hair, and secretions (sweat/sebum) that flush surfaces and contain antimicrobial chemicals like lysozymes.

  • Epithelial Linings: Tight junctions and mucous membranes in various tracts trap particles and prevent penetration.

• Phagocytes: The first line of cellular defense. They respond to foreign substances and clean up debris.

  • Types:

    • Neutrophils and Eosinophils: Circulate in the blood and enter tissues during injury.

    • Monocytes/Macrophages: Monocytes in blood become macrophages in tissues. Can be fixed (permanent residents) or free (mobile).

  • Functional Characteristics:

    • Diapedesis (Emigration): Squeezing between endothelial cells of capillaries.

    • Chemotaxis: Attraction to or repulsion by chemicals (chemoattractants/chemorepellents) in the environment.

    • Adhesion: Binding of receptors to the target's surface.

  • Phagocytosis Steps:

    1. Adhesion to target.

    2. Formation of pseudopods to engulf the particle, creating a phagosome.

    3. Fusion with a lysosome to form a phagolysosome.

    4. Destruction of the pathogen via toxic compounds and lysosomal enzymes.

    5. Exocytosis of residual material.

Immunological Surveillance and the NK Cell Response

• NK Cell Function: Monitor peripheral tissues for abnormal cells, including cancer cells presenting tumor-specific antigens.

• Mechanism of Destruction:

  1. NK cell recognizes an abnormal antigen and adheres to the target cell.

  2. The Golgi apparatus moves to align with the target; secretory vesicles containing perforins form.

  3. Perforins are released via exocytosis.

  4. Perforins create pores in the target cell membrane, leading to lysis.

• Immunological Escape: Cancer cells may grow too quickly for NK cells to manage, or daughter cells may fail to display antigens, allowing them to "escape" detection and form secondary tumors.

Interferons and the Complement System

• Interferons: Small proteins (cytokines) released by activated lymphocytes, macrophages, and virus-infected cells.

  • Mechanism: They bind to receptors on neighboring cells, triggering the production of antiviral proteins that block viral reproduction.

  • Types:

    • Interferon Alpha: Produced by virus-infected cells; stimulates NK cells and nearby cells.

    • Interferon Beta : Secreted by fibroblasts; slows inflammation.

    • Interferon Gamma: Secreted by T cells and NK cells; stimulates macrophage activity.

• Complement System: A system of over $30$ specialized proteins that "complement" the action of antibodies.

  • Pathways:

    1. Classical Pathway: Activated by antibodies coating the target cell.

    2. Lectin Pathway: Activated by lectins binding to specific sugars on the microorganism.

    3. Alternative Pathway: Activated spontaneously due to a lack of inhibitors on the pathogen surface.

  • Effects:

    • Opsonization: Coating pathogens to enhance phagocytosis (C3b).

    • Inflammation: Enhancing the inflammatory response (C3a, C5a) and stimulating histamine release.

    • Membrane Attack Complex (MAC): Proteins (C5b–C9) form a pore in the target cell membrane to cause lysis.

  • Clinical Disorders: Examples include SLE (lupus), HA (hereditary angioedema), and TCPD (meningococcal risk).

Inflammation and Fever

• Inflammation: A localized tissue response to injury (impact, abrasion, chemicals, or pathogens).

  • Cardinal Signs: Redness (Rubor), Swelling (Tumor), Heat (Calor), and Pain (Dolor).

  • Process:

    1. Tissue injury triggers the release of inflammatory chemicals (histamine, kinins, prostaglandins).

    2. Arterioles dilate (hyperemia), causing redness and heat.

    3. Capillary permeability increases, leading to exudate formation and swelling (edema).

    4. Leukocytosis occurs; neutrophils and then macrophages migrate to the area via margination, diapedesis, and chemotaxis.

    5. A fibrin patch forms to wall off the area.

• Fever: A body temperature greater than $99^{\circ}F$.

  • Pyrogens: Fever-inducing proteins that reset the hypothalamus "thermostat."

    • Endogenous: Cytokines like Interleukin-1 (IL-1) produced by the body’s own macrophages.

    • Exogenous: Bacterial endotoxins (LPS).

  • Mechanism: IL-1 induces the hypothalamus to produce prostaglandins, which raise the set point. This causes shivering and vasoconstriction until the new temperature is reached.

  • Benefit: Inhibits some pathogens and increases metabolic rate by approximately $10\%$ per degree Celsius, speeding up repair and defense.

Questions & Discussion

• Review Prompt: What type of innate immune defense might protect you from…

  • Viruses: Interferons and NK cells.

  • A mosquito bite: Inflammation and physical barriers skin.

  • A cancerous cell: NK cells (Immunological surveillance).

  • Bacteria: Phagocytes (Neutrophils/Macrophages) and the Complement system.

  • Spread of an infection: Inflammation (walling off the area) and Fever.