The Lymphatic System and Immunity

Lecture Presentation by Betsy C. Brantley - Valencia College

Module 20.1: Lymphatic System Overview

Lymphatic System Definition
  • Functions:
    • Immunity: The ability to defend the body against infection, illness, and disease.
    • Returning Interstitial Fluid: Excess interstitial fluid is returned to the bloodstream.
Components of the Lymphatic System
Lymphocytes
  • Definition: Primary cells of the lymphatic system.
  • Response to:
    • Invading Pathogens: Such as bacteria and viruses.
    • Abnormal Body Cells: Such as virus-infected or cancerous cells.
    • Foreign Proteins: Such as bacterial toxins.
  • Characteristics:
    • Surrounded by lymph, which is interstitial fluid that has entered a lymphatic vessel.
Lymphatic Vessels
  • Also known as lymphatics.
  • Begin in peripheral tissues and end at connections with veins.
Lymphoid Tissues and Organs
  • Distribution: Scattered throughout the body.
  • Primary Lymphoid Tissues and Organs:
    • Sites where lymphocytes are formed or matured, including:
    • Red bone marrow
    • Thymus gland
  • Secondary Lymphoid Tissues and Organs:
    • Sites where lymphocytes are activated and cloned (duplicated), including:
    • Lymph nodes
    • Tonsils
    • Mucosa-associated lymphoid tissue (MALT)
    • Appendix
    • Spleen
Lymphatic System Diagram
  • Illustration: Depicts various components including organs, ducts, and nodes (Figure 20.1).
    • Lymph Nodes: Cervical, axillary, and inguinal.
    • Ducts: Thoracic duct and right lymphatic duct.
    • Other Components: Thymus, spleen, and MALT in various tracts.

Module 20.2: Lymphatic Vessels

Definition and Function
  • Purpose: Carry lymph from peripheral tissues to the venous system.
  • Association: Found closely tied to blood vessels.
  • Network starts with: Lymphatic capillaries, which are:
    • The smallest lymphatic vessels, present in almost every tissue and organ.
    • Collect interstitial fluid (which becomes lymph) and transport it to larger lymphatic vessels.
Characteristics of Lymphatic Capillaries
  • Differences from Blood Capillaries:
    • Originate as pockets instead of continuous tubes.
    • Have larger diameters and thinner walls.
    • Basement membrane may be incomplete or missing.
    • Typically appear flattened or irregular in cross-section.
  • Structural Features:
    • Overlapping endothelial cells creating one-way valves:
    • Allow entry of fluid, solutes (including proteins), viruses, bacteria, and cell debris.
    • Prevent backflow into intercellular spaces.
Structure of Larger Lymphatic Vessels
  • Similar to veins, larger lymphatics possess valves that are close together.
  • Appearance: Bulges at each valve give them a bead-like look.
  • Functionality: Low pressure in lymphatic vessels necessitates valve function to prevent backflow.
  • Aids in Flow: Contraction of surrounding skeletal muscles assists lymph flow.
Distribution of Lymphatic Vessels
  • Prominent Locations:
    • In the small intestine: Lacteals transport absorbed lipids from the digestive tract.
    • Absent Areas:
    • Regions lacking blood supply, like the cornea of the eye, bone marrow, and central nervous system.

Module 20.3: Lymphatic Flow

Overview of Lymphatic Vessel Locations
  1. Superficial Lymphatics:
    • Found in subcutaneous layers, mucous membranes of various tracts, and serous membranes (pleural, pericardial, peritoneal).
  2. Deep Lymphatics:
    • Accompanying deep arteries and veins that supply skeletal muscles and various organs.
  • Both sets of lymphatic vessels converge to form lymphatic trunks.
Collecting Ducts
  • Key Structures:
    • Thoracic Duct:
    • Collects lymph from body regions below the diaphragm and the left side above it.
    • Drains into the left subclavian vein.
    • Right Lymphatic Duct:
    • Collects lymph from the right side above the diaphragm.
    • Drains into the right subclavian vein.
Cisterna Chyli
  • Expanded, saclike chamber at the base of the thoracic duct.
  • Receives lymph from:
    • The inferior part of the abdomen,
    • The pelvis,
    • The lower limbs through lumbar trunks and intestinal trunks.
Lymphedema
  • Definition: Swelling due to blocked lymphatic drainage resulting in the accumulation of interstitial fluids.
  • Clinical Implications:
    • Affected areas become swollen and distended, often permanent.
    • Connective tissue loses elasticity; stagnant fluids can accumulate pathogens and toxins.
    • Local immune responses may become overwhelmed.

Module 20.4: Lymphocytes

Types of Lymphocytes
  • General Information: Account for 20-40% of circulating leukocytes; predominantly located within lymphatic tissues.
  1. T Cells (~80%):
    • Associated with cell-mediated immunity.
  2. B Cells (10-15%):
    • Responsible for antibody-mediated immunity.
  3. Natural Killer (NK) Cells (5-10%):
    • Involved in immune surveillance.
Antigens and Lymphocyte Function
  • Definition: Antigens are primarily proteins (but can be lipids, polysaccharides, or nucleic acids) that trigger specific immune responses leading to the destruction of pathogens or other foreign compounds.
Classifications of T Cells
  • Types with Functions:
    • Cytotoxic T Cells: Attack foreign and infected body cells, primarily through direct contact.
    • Helper T Cells: Stimulate activity and function of both T and B cells, also known as regulatory T cells.
    • Suppressor T Cells: Inhibit the activation and function of T and B cells to control immune response sensitivity.
B Cells
  • Upon stimulation, they differentiate into plasma cells that secrete antibodies, responsible for humoral immunity.
NK Cells
  • Target foreign cells, virus-infected cells, and cancer cells, continuously monitoring peripheral tissues.
Lymphocyte Production (Lymphopoiesis)
  • Processes Involved:
    • Occurs in red bone marrow and thymus, also involving peripheral lymphoid tissues.
    • Hematopoietic stem cells in red bone marrow produce lymphoid stem cells.
Development of T Cells and B Cells
  • T cells migrate to the thymus and undergo selection to ensure non-reactivity with normal body cells, while B cells remain in the red bone marrow before entering circulation and lymphoid tissues.

Module 20.5: Lymphoid Tissues and Organs

Lymphoid Tissues Overview
  • Connective tissues that are primarily populated by lymphocytes.
  • Lymphoid Nodules: Densely packed areas within areolar tissue without fibrous capsules.
  • Major Locations:
    • Aggregated Lymphoid Nodules (Peyer’s Patches): Located deep to the intestinal epithelium, including germinal centers where lymphocytes divide.
    • MALT: Protects epithelia from pathogens in various bodily tracts.
Tonsils
  • Large lymphoid nodules located in the pharynx:
    • Pharyngeal Tonsil (Adenoid) at the nasopharynx's posterior wall.
    • Palatine Tonsils: Located in the oral cavity's posterior margin.
    • Lingual Tonsils: Deep to the epithelium at the tongue's base.
Lymph Nodes
  • Small lymphoid structures encased in fibrous connective tissue, filtering pathogens from lymph (99% removal efficiency).
  • Path of Lymph through a Node: Afferent lymphatics bring lymph into the node, flowing through various sinuses containing T and B cells before exiting through efferent lymphatics.
Clinical Disorders of Lymphoid Tissues
  • MALT infections can cause disorders such as tonsillitis and appendicitis due to inflammation.

Module 20.6: The Thymus

Size and Function
  • The thymus produces hormones (thymosins) crucial for T cell development.
  • Size declines with age, leading to increased disease susceptibility (e.g., reduces from 40 g before puberty to <12 g by age 50).
Anatomy of the Thymus
  • Description: Pink, grainy organ located in the mediastinum, covered by a fibrous capsule that divides it into distinct lobes and lobules.
Thymus Histology
  • Each lobule consists of:
    • An outer cortex rich in dividing lymphocytes and thymic epithelial cells creating a blood-thymus barrier.
    • A central medulla without this barrier, where T cells can enter circulation or lymphatics.

Module 20.7: The Spleen

Spleen's Role in the Body
  • Contains the largest mass of lymphoid tissue, filtering blood similar to lymph nodes.
    • Functions:
    • Removes abnormal red blood cells through phagocytosis.
    • Stores iron recycled from hemoglobin.
    • Initiates immune responses by B and T cells.
Gross Anatomy of the Spleen
  • Location: Lies against the lateral border of the stomach, attached by the gastrosplenic ligament. About 12 cm long (~160 g).
    • Two indentations on the visceral surface correspond to the gastric and renal areas.
    • The hilum serves as a point for blood and lymphatic vessel entry.
Internal Anatomy
  • Outer collagen and elastic fiber capsule with trabeculae that support blood vessels.
  • Contains two pulps:
    • Red Pulp: Rich in red blood cells and macrophages.
    • White Pulp: Resembles lymphoid nodules, contains various lymphocytes.

Module 20.8: Innate Immunity

Definition
  • The body's first line of defense against pathogens, present from birth, non-specific in nature, providing resistance without distinguishing between types of threats.
Mechanisms of Innate Immunity
  • Includes physical barriers (e.g., skin), immune surveillance, inflammation, fever, and cellular defenses like phagocytes and complement systems.

Module 20.9: Physical Barriers and Phagocytes

Physical Barriers Overview
  • The integumentary system serves as a major physical barrier via skin, mucus membranes, and various secretions that can wash away or destroy pathogens.
Phagocytes
  • Types include neutrophils, eosinophils, and macrophages, forming the first line of cellular defense against pathogens and cellular debris.
Functional Characteristics
  • Phagocytes can migrate through capillaries via diapedesis and are attracted to sites of infection via chemotaxis.
  • The process of phagocytosis involves attachment to targets, engulfing, and destruction.

Module 20.10: Immune Surveillance

Definition
  • Immune surveillance involves constant monitoring by NK cells, identifying abnormal or infected cells and destroying them.
Mechanism of Action
  • NK cells recognize and bind to stressed cells, releasing perforins to create pores, leading to target cell destruction.

Module 20.11: Interferons and the Complement System

Interferons (IFNs)
  • Small proteins secreted by activated lymphocytes and infected tissues to trigger defensive mechanisms in nearby cells.
Types of Interferons
  1. Alpha IFNs: Attract and stimulate NK cells.
  2. Beta IFNs: Slow inflammation.
  3. Gamma IFNs: Stimulate macrophage activity.
Complement System
  • Composed of over 30 proteins that enhance immune defenses by forming complexes leading to pathogen lysis, phagocyte attraction, and inflammation.
  • Pathways: Classical (initiated by antibody binding) and Alternative (activated by pathogen exposure).

Module 20.12: Inflammation and Fever

Inflammation Description
  • A localized response to injury characterized by redness, swelling, heat, pain, and possible loss of function.
Fever
  • Body temperature exceeding 37.2°C (99°F), often beneficial in fighting infection by inhibiting pathogens, increasing metabolic activity, and mobilizing immune defenses.

Module 20.13: Adaptive Immunity

Definition
  • Specific immunity acquired through exposure to antigens and mediated by lymphocytes, involving active and passive immunity.
Mechanisms of Active Immunity
  • Natural and artificial means by which immunity can be acquired, often requiring prior exposure for development.
Mechanisms of Passive Immunity
  • Transfer of antibodies, either naturally (from mother) or artificially (injection).

Module 20.14: Triggering Adaptive Immunity

Overview of Immune Response
  • Begins with antigen presentation by phagocytes, activating T cells or B cells, leading to an immune response.
Classes of MHC Proteins
  • Class I (on nucleated cells) and Class II (on antigen-presenting cells), crucial for T cell activation.

Module 20.15: Activation of T Cells by Infected Cells

CD Markers
  • Classification based on immune response, including CD8 and CD4 markers.
  • Activation of CD8 T Cells: Necessary for cytotoxic response, leading to division and differentiation into effector and memory cells.

Module 20.16: CD4 T Cell and B Cell Activation

Activation Processes
  • CD4 T cells and B cells require antigen recognition, followed by costimulation for full activation, leading to differentiated effector cells that produce cytokines and antibodies, respectively.

Module 20.17: Antibodies

Structure and Types of Antibodies
  • Composed of heavy and light chains with variable segments for diversity across antibody types (IgG, IgA, IgM, IgD, IgE).
Antibody Mechanisms
  • Methods by which antibodies neutralize pathogens, stimulate inflammation, opsonization, and agglutination.

Module 20.19: Clinical Module - Allergies and Anaphylaxis

Definitions
  • Allergies are inappropriate immune responses causing rapid and severe reactions upon exposure to allergens, sometimes leading to systemic issues like anaphylaxis.

Module 20.21: Clinical Module - Immune Disorders

Types of Immune Disorders
  • Autoimmune disorders, where the immune system attacks self-antigens, and immunodeficiency diseases, like AIDS, resulting in insufficient immune function as described.
    • Effects include an increased risk of infections and cancer, particularly as adaptive immunity wanes over time due to aging.