Lymphatic System: Function, Vessels and Immunity

Lymphatic System Overview

• Includes cells, tissues, and organs responsible for immunity, returning interstitial fluid to the bloodstream, and absorbing dietary fat.
• Immune and lymphatic systems function together, and work to defend the body.
• Does not contain any organs or tissues, but includes leukocytes/WBCs and immune proteins in plasma.
• Lymphocytes are the primary immune cells of the lymphatic system.
• Lymphocytes respond to invading pathogens, abnormal body cells, and foreign proteins, while surrounded by lymph

Lymphatic Vessels

• Called lymphatics, and begin in peripheral tissues, ending at connections to veins.
• Carry lymph from peripheral tissues to the venous system, and the network begins with lymphatic capillaries and is found in almost every tissue and organ.
• Closely associated with blood capillaries and collects interstitial fluid (now called lymph), and transports it to larger lymphatic vessels.
• Overlapping endothelial cells in lymphatic capillaries act as a one-way valve, permitting the entry of fluid/solutes, viruses, bacteria, and cell debris.
• This prevents return of these materials to the intercellular space.

Lymphatic Flow

• Two large vessels receive lymph from the lymphatic trunks: thoracic duct and right lymphatic duct.
• The thoracic duct collects lymph from body parts inferior to the diaphragm, and the left side of the body superior to the diaphragm, and drains into the left subclavian vein.
• The right lymphatic duct collects lymph from the right side of the body superior to the diaphragm, and drains into the right subclavian vein.
• Lymphedema is caused by blocked lymphatic drainage, and is characterized by interstitial fluid accumulation, swelling/distention of the affected area, and is most often seen in the limbs, but can affect other areas.
• The swelling may become permanent, connective tissue loses elasticity, stagnant interstitial fluids may accumulate toxins and pathogens, and local immune defenses can become overwhelmed.

Lymphocytes and Immunity

• Accounts for 20–40% of circulating leukocytes, and most lymphocytes are in lymphatic tissues.
• Three classes circulate in the blood: T cells, B cells, and NK cells
• T cells (~80% of circulating lymphocytes) facilitate cell-mediated immunity.
• B cells (10-15% of circulating lymphocytes) facilitate antibody-mediated immunity.
• NK cells (5-10% of circulating lymphocytes) are used for immune surveillance.
• All classes are sensitive to specific chemicals (antigens) that stimulate an immune response (ID as non-self) and leads to destruction of the target compound/organism.
• T cells have 3 categories: cytotoxic T cells, helper T cells, and suppressor T cells.

T Cells

• Cytotoxic T cells attack foreign cells or body cells infected by viruses, commonly via direct contact, primary cells involved in production of cell-mediated immunity (cellular immunity).
• Helper T cells stimulate the activation and function of T and B cells, and are also known as regulatory T cells, which work with suppressor T cells to control the sensitivity of immune response.
• Suppressor T cells inhibit the activation and function of T and B cells, and prevent autoimmune conditions.

B Cells and NK Cells

• B cells become plasma cells that produce and secrete antibodies when stimulated.
• B cells are responsible for antibody-mediated immunity (humoral immunity), with antibodies circulate in body fluids to attack targets throughout the body.
• T and B cells migrate from their sites of origin, retain their ability to divide, and produce daughter cells of the same type in lymphopoiesis.
• Natural killer (NK) cells attack foreign cells, virus-infected body cells, and cancer cells, while providing continuous monitoring of peripheral tissues.

Lymphoid Tissues and Organs

• Structures of the lymphatic system include lymphoid tissues, connective tissues dominated by lymphocytes, and lymphoid nodules, which are densely packed lymphocytes in an area of areolar tissue.
• Nodules may cluster together and form larger masses without a fibrous capsule.
• Lymphoid nodule locations include aggregated lymphoid nodules (Peyer's patches), which are clusters of lymphoid nodules deep to the epithelial lining of the small intestines.
• Each nodule often has a central zone (germinal center) containing dividing lymphocytes and mucosa-associated lymphoid tissue (MALT) help protect epithelia of digestive, respiratory, urinary, and reproductive tracts from pathogens and toxins.
• Tonsils are large lymphoid nodules in the walls of the pharynx, and include the pharyngeal tonsil (or the adenoid), the palatine tonsils (left and right), and the lingual tonsils.

Lymph Nodes and The Spleen

• Small lymphoid organs surrounded by a fibrous connective tissue capsule, ranging from 1–25 mm that function as filters, removing 99% of pathogens from lymph before fluid returns to the bloodstream.
• The spleen lies along the curving lateral border of the stomach on the left side, and is attached to the lateral border of the stomach by the gastrosplenic ligament.
• The spleen has a diaphragmatic surface, and is smooth and convex conforming to the shape of the diaphragm and the body wall.
• The spleen contains red pulp (with large quantities of RBCs and macrophages) and white pulp (resembles lymphoid nodules with lymphocytes)

Immunity

• Innate (nonspecific) immunity provides nonspecific resistance, does not distinguish one type of threat from another, and the response is the same regardless of the type of invading agent, present at birth, prevents the approach, denies entry, limits the spread of microbes or other environmental hazards.
• Adaptive (specific) immunity utilizes adaptive defenses, protects against particular threats, depends on the activities of specific lymphocytes , produces a state of protection known as specific resistance.
• Physical barriers, such as the integumentary system and glands secrete substances, act as the first line of defense
• Secretions from sebaceous and sweat glands wash away microorganisms and chemical agents and also contain bactericidal chemicals, destructive enzymes (lysozymes), and antibodies.
• Hair provides protection from mechanical abrasion and prevents hazardous materials/insects from contacting skin and provides nonspecific defense.

Physical Barriers

• Epithelial covering provides multiple layers of epithelial cells with keratin that are connected with desmosomes.
• Other epithelial linings are found along digestive, respiratory, urinary, and reproductive tracts, provide a physical barrier, and secretions (mucus, enzymes, stomach acid) often ensnare, destroy, or wash away pathogenic material.
• MALT provides nonspecific defense and provides nonspecific defense.
• Phagocytes engulf and destroy foreign substances, pathogens, and cellular debris. and act as front line of cellular defense against pathogenic invasion.
• It can attack and remove microorganisms even before lymphocytes detect their presence.

Phagocytes

• Three different types of phagocytes target different pathogen threats, and all function in the same basic way.
• Neutrophils (in bloodstream and tissues) are abundant, mobile, fast-acting and phagocytize cellular debris or bacteria.
• Eosinophils, less abundant than neutrophils, phagocytize foreign compounds and antibody-coated pathogens.
• The Monocyte-macrophage system (reticuloendothelial system) contains macrophages (derived from monocytes) that are either fixed (scattered among connective tissues/immobile) or free (travel throughout body).

Immune Surveillance

• Constant monitoring of normal tissues by natural killer (NK) cells occur and normal cells are generally ignored by immune system.
• Cancer cells often contain tumor-specific antigens, and NK cells recognize as abnormal and destroy bacteria, foreign cells, virus-infected cells, and cancer cells.

Interferons and The Complement System

• Interferons are molecules released from virus-infected cells, and cause surrounding cells to become more resistant to viral replication and also attract NK cells and macrophages to kill infected cells before the virus replicates.
• The complement system name refers to the fact that the system complements the action of antibodies and is formed by over 30 special proteins.
• Two possible pathways that proteins can interact with one another in chain reactions or cascades in the complement system: the classical pathway and the alternative pathway.

Complement System Pathways

• The classical pathway of the complement system is the most rapid and effective complement activation method and complement proteins attach to antibody molecules already bound to a pathogen.
• The attached protein activates and initiates a cascade to activate and attach other complement proteins.
• The alternative pathway is important defense against bacteria, some parasites, and virus-infected cells.
• Several complement proteins (notably properdin) interact in the plasma and the interaction triggered by exposure to foreign substances.
• The end result of these complement systems is enhancement of phagocytosis, attraction of phagocytes (making targets easier to engulf), histamine release (by mast cells and basophils), and increasing inflammation/blood flow to the region.

Inflammation and Fever

• Inflammation is a localized tissue response to injury, and produces signs and symptoms of redness, swelling, heat, pain, and sometimes lost function
• Various stimuli that kill cells, damage connective tissue fibers, or injure tissue, can cause change in chemical composition of the interstitial fluid, damaged cells release prostaglandins, proteins, and potassium ions. Foreign proteins or pathogens may be introduced, and the changes trigger complex inflammation response.
• Fever is classified as a body temperature >37.2°C (99°F), and is is caused by pyrogens (pyro-, fever or heat, + -gen, substance).
• Circulating fever-inducing proteins rest the temperature thermostat in the hypothalamus and raise the body temperature. It can be beneficial within limits, may inhibit some viruses and bacteria, and increases metabolic rate to accelerate tissue defenses/repair process.

Innate Immunity

• Includes physical barriers that prevent approach and deny access to pathogens.
• Phagocytes remove debris and pathogens and immune surveillance, and destroys abnormal cells.
• Interferons increase resistance of cells to viral infections and slow the spread of disease.
• The complement system attacks and breaks down surfaces of cells, bacteria, and viruses, attracts phagocytes, and stimulates inflammation.
• Fever mobilizes defenses, accelerates repairs, and inhibits pathogens.

Adaptive Immunity

• Coordinated and produced by T cells and B cells is not present at birth, but acquired by exposure to an antigen , and active immunity.
• Adaptive immunity include active (naturally acquired/ develops after natural exposure to antigens) and passive forms.
• An example includes contracting the measles gives immunity against future infection by that specific pathogen/transfer of maternal antibodies across placenta or breast milk
• Artificially included: vaccination (immunization) after administration of an antigen, and administration of antibodies to a patient.

Properties of Adaptive Immunity

• Specificity: T cells and B cells have receptors for only one specific antigen, and responses of activated T cell or B cell are also specific.
• Versatility: Millions of lymphocytes, each sensitive to a different antigen, and when activated, a lymphocyte divides and produces more lymphocytes with same specificity.
• Immunologic memory: Activated lymphocytes produce two groups of cells, with one group attacking invaders immediately, and another that remains inactive unless exposed to the same antigen later.
• Tolerance: Immune response ignores “self” but targets abnormal and foreign "non-self” cells and toxins, and can develop over time in response to chronic exposure to an antigen.

Triggering Adaptive Immunity

• The acquired immune system uses a molecular system (antigens) to identify objects (bacteria, viruses, virus infected cells, mutated cells, etc.)
• Antigens are “processed” by phagocytes and displayed on the plasma membrane of the phagocyte, this triggers an immune response.
• Presentation of specific antigens stimulates cell-mediated defenses (T cells) and antibody-mediated defenses (B cells).
• The immune system completes this through major histocompatibility complex (MHC) proteins: genetically determined antigens capable of activating T cells.
• Triggered by viral or bacterial infection of a body cell when the pathogen is already inside the cell.

Respiratory System

• Respiration is the primary function of the system, and it provides body cells with oxygen and removes waste product carbon dioxide, and includes 4 processes: pulmonary ventilation, pulmonary gas exchange, gas transport, and tissue gas exchange.
• Other functions of it are mechanism for speech and sound production, neurons for sense of smell, expel contents from abdominopelvic cavity to assist with contents, urination, and childbirth by increasing pressure in the thoracic cavity.
• Pressure changes in thoracic cavity assist with flow of venous blood and lymph, an isCritical in maintaining acid-base balance in extracellular fluid.
• Synthesizes an enzyme involved in the production of angiotensin-II, critical to the maintenance of blood pressure and fluid homeostasis
• Organs of this system are found in head, neck, and thoracic cavity include blood vessels of pulmonary circuit, rib cage, respiratory muscles, both lungs, and respiratory tract.
• Lower respiratory system passage ways from trachea to respiratory tracts terminal structure.

Respiratory System Breakdown

• Consists of tubes that collectively exchange gases.
• Includes upper (passageways from nasal cavity to larynx) and lower respiratory systems.
• The upper respiratory system filters, warms, and humidifies incoming air, protects more sensitive lower tract, and reabsorbs heat and water in outgoing air.
• Lower respiratory system includes passageways from trachea to respiratory tract's terminal structures (alveoli), moves air to gas exchange surfaces and exchanges gases with capillaries.
• Respiratory System is classified functionally into conducting (1) and respiratory (2) zones.
• Conducting zone is designed to conduct air while respiratory zone function as an area for gas exchange.

Respiratory Defense System

• Protects from inhaled debris or pathogens, and includes cells/structures of the respiratory mucosa has pseudostratified ciliated columnar epithelium and numerous mucous cells to produce sticky mucus.
• Beating of cilia sweeps mucus/trapped debris toward pharynx, and is either swallowed (and exposed to acids in stomach) or coughed out.
• This flow of mucus is called the mucus escalator, and the layer of mucus traps particles larger than ~5 µm.
• Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians of Northern European descent (1 in 2500 births).
• Cystic fibrosis results in production of abnormally thick and sticky mucus in conducting division of respiratory tract that restricts airflow and possibly blocks smaller passageways.

Upper Respiratory System Anatomy

• The external anatomy of the nose is covered with skin and supported by muscle, bone, and cartilage, and includes the root and bridge (between eyebrows and eyes), and the dorsum nasi (anterior margin of nose; apex – tip of nose).
• Alae, lateral to apex, surround the nostrils/anterior nares which are paired openings into nasal cavity.
• Structures associated with the upper respiratory system
• pharynx divides into regions
• Is the nasopharynx: superior region.
• Is the oropharynx: between soft palate and tongue
• Is the laryngopharynx: between hyoid bone and larynx

Structures of the Upper Respiratory System

• Hard palate (bony floor of the nasal cavity) separates nasal cavity from oral cavity and the soft palate is the fleshy portion extending posterior to the hard palate.
• Glottis is the opening to larynx and larynx (surrounds and protects glottis) and the trachea (conducts air toward lungs).
• The larynx is sometimes called the "voice box" and is made of cartilage structures including epiglottis (projects superior to the glottis and folds back during swallowing to prevent solids/liquids from entering respiratory tract).
• Thyroid cartilage which forms most of anterior and lateral walls of the larynx: the prominent anterior surface is called the laryngeal prominence or Adam's apple (attaches to the hyoid bone, epiglottis, and smaller laryngeal cartilages).
• Cricoid cartilage (ring shaped) is a complete ring of cartilage, and together with thyroid cartilage, protects glottis and larynx and provides attachment sites for laryngeal muscles and ligaments.

Larynx

• Air enters and leaves the larynx through the glottis, made up of the vocal folds and the openings between the vocal folds and contain the vocal ligaments, and are involved in the production of sound.
• Requires two processes: sound production from larynx (vibration of the vocal cords produces sound waves with pitch pending on the diameter, length, and tension in the vocal cords (controlled by voluntary muscles) and the modification of sounds by tongue, teeth, and lips.
• Amplification and resonance occur in pharynx, oral and nasal cavities, and paranasal sinuses.

Trachea and Branchial Branches

• Trachea branches into right and left primary bronchi (each bronchus leads to a lung).
• Most foreign objects entering the trachea end up in the right primary bronchus rather than the left because the right primary bronchus is larger in diameter than the left and it descends at a steeper angle.
• Once inhaled air reaches the carina, it can enter either left or right primary bronchus.
• Once inside lung, each bronchus branches into bronchial tree with two primary bronchi and lead to the lungs.
• Undergo a series of division and at each branch the diameter decreases.

Bronchioles

• Respiratory and Trachea consists of two types: Terminal bronchioles (from tertiary bronchi/lead to pulmonary lobules) and respiratory bronchioles (after terminal bronchioles)
• In the airways: trachea --> primary bronchi --> secondary bronchi --> tertiary bronchi --> bronchioles --> terminal bronchioles --> respiratory bronchioles --> alveoli.
• At each new branch the diameter decreases.

Respiratory Physiology

• Respiration consists of two integrated processes: external and internal respiration.
• External respiration facilitates exchange of gasses between interstitial fluids and external environment (only in lungs), and involves pulmonary ventilation (breathing).
• Internal respiration is between RBC and tissue and facilitates absorption of oxygen from blood and the release of carbon dioxide by tissue cells.
• Gas diffusion occurs across the respiratory membrane between alveoli and capillaries and also across capillary walls between blood and other tissues and gas transport is also critical to respiratory function.

Respiratory Issues

• Abnormalities affecting external respiration can ultimately affect cellular activities by way of - Low tissue oxygen levels place severe limits on metabolic activities and can't be in this state for a long time.
• Anoxia (a-, without ox-, oxygen) is no oxygen supply, and much of damage caused by heart attacks and strokes is the result of localized anoxia.
• You can't pump blood with no oxygen, and it will shut down after a few minutes.
• During inhalation: the thoracic cavity wall enlarges and increases in volume which decreases pressure (Poutside > Pinside) and air moves in from an area of high pressure to low pressure.
• During exhalation: the thoracic cavity decreases in volume increases pressure (Poutside < Pinside) and air is forced out from an area of high pressure to low pressure.

Respiration

• Respiratory muscles include primary and accessory inspiratory muscles and involve those that are quiet breathing.
• Accessory inspiratory muscles increase the speed and amount of rib movement, allowing deeper breathing and greater oxygen intake
• Hemoglobin performs this function of moving oxygen. Red blood cells are really just cell membranes with huge amounts of hemoglobin inside.
• Hemoglobin is a protein made from 4 subunits. Each subunit has a heme unit with an iron ion in the center: Each iron ion can carry one molecule of oxygen meaning it can carry four molecules of O2.

Oxygen

• Since hemoglobin carries most of the oxygen in the blood, how much oxygen it is carrying is the most critical measure of the oxygen available to the tissues of the body.
• Oxygen saturation measures how many of all of the oxygen binding sites on all of the hemoglobin molecules are carrying oxygen measured with a pulse oximeter using changes in light transmission (bound= redder).
• Aerobic metabolism in peripheral tissues generates carbon dioxide and it is transported in three ways: Dissolved in plasma (~7 percent), Bound to the protein portion of hemoglobin molecules within RBCs (~23 percent), and converted to a molecule of carbonic acid (~70 percent)
• The pCO2 of the blood is what determines the moment to moment minute ventilation (amount of air moving in and out of the lungs).
• pO2 changes have very little effect on respiration until it gets very low (less than 60 mmHg).
• The concentration gradient between blood and alveoli is much smaller for CO2 and much larger for O2, meaning that CO2 is the rate limiting diffusion step.
• It is better for our blood to carry O2 than it is for it to rid of CO2.