Ch. 21 Lymphatics and Immunity PDF

Chapter 21 Lymphatics/Immunity Lymphatic System: Overview Consists of two semi-independent parts: – A network of lymphatic vessels – Lymphoid tissues and organs scattered throughout the body Returns interstitial fluid and leaked plasma proteins back to the blood Lymph – interstitial fluid once it ha...

Chapter 21 Lymphatics/Immunity Lymphatic System: Overview Consists of two semi-independent parts: – A network of lymphatic vessels – Lymphoid tissues and organs scattered throughout the body Returns interstitial fluid and leaked plasma proteins back to the blood Lymph – interstitial fluid once it has entered lymphatic vessels Lymphatic System: Overview Lymphatic System Lymphatic system has lymphoid organs and tissues that provides the structural basis of the immune system Consists of three parts 1. Lymph 2. A network of lymphatic vessels (lymphatics) 3. Lymph nodes Lymph Lymph consists of interstitial fluid and all that is in it: – – – – – – – Plasma proteins Cell debris White blood cells Pathogens Cancer cells Wastes etc. Lymph returns all these items back into the blood Lymphatic Vessels One-way system, lymph flows toward the heart Lymph vessels (lymphatics) include: – Lymphatic capillaries – Lymphatic collecting vessels – Lymphatic trunks and ducts Lymphatic Capillaries Similar to blood capillaries – Very permeable (take up cell debris, pathogens, and cancer cells) – Have minivalves for one-way entry anchored by collagen filaments that prevents collapse of capillaries Lymphatic Capillaries Lymphatic capillaries are absent from: – Bones – Teeth – Bone marrow – CNS Lacteals: specialized lymph capillaries present in intestinal lining – Absorb digested fat and deliver fatty lymph to the blood Lymphatic Capillaries Lymphatic Collecting Vessels Collecting vessels in the skin travel with superficial veins Deep vessels travel with arteries Nutrients are supplied from branching vasa vasorum Distribution varies from person to person Lymphatic Ducts Lymphatic Ducts Lymph is delivered into one of two large ducts – Right lymphatic duct drains the right upper arm and the right side of the head and thorax – Thoracic duct arises from the cisterna chyli and drains the rest of the body Each empties lymph into venous circulation at the junction of the internal jugular and subclavian veins on its own side of the body Lymph Transport Lymph is propelled by – Pulsations of nearby arteries – Contractions of smooth muscle in the walls of the lymphatics – Muscular pump – Respiratory pump Lymphoid Cells Lymphocytes are the main warriors of the immune system Two main varieties – T cells (T lymphocytes) – B cells (B lymphocytes) T cells and B cells protect against antigens – Anything the body perceives as foreign Bacteria and their toxins; viruses Mismatched RBCs or cancer cells Lymphocytes T cells – Manage the immune response – Attack and destroy foreign cells B cells – Produce plasma cells, which secrete antibodies Other Lymphoid Cells Macrophages phagocytize foreign substances and help activate T cells Dendritic cells are a type of macrophage that capture antigens and deliver them to lymph nodes Reticular cells produce stroma that supports other cells in lymphoid organs Lymphoid Tissue Houses and provides a proliferation site for lymphocytes Furnishes a surveillance vantage point Two main types – Diffuse lymphatic tissue – Lymphatic follicles Lymphoid Tissue Diffuse lymphatic tissue comprises scattered reticular tissue elements in every body organ Lymphatic follicles (nodules) are solid, spherical bodies of tightly packed reticular elements and cells – Germinal center composed of dendritic cells and B cells – Form part of larger lymphoid organs Lymph Nodes Principal lymphoid organs of the body Embedded in connective tissue, in clusters along lymphatic vessels Clusters are in the inguinal, axillary, and cervical regions of the body Functions 1. Filter lymph—macrophages destroy microorganisms and debris 2. Immune system—lymphocytes are activated and mount an attack against antigens Lymph Nodes Circulation in the Lymph Nodes Lymph – Enters via afferent lymphatic vessels – Travels through large subcapsular sinus and smaller sinuses – Exits the node at the hilus via efferent vessels Fewer efferent vessels, causing flow of lymph to stagnate, allowing lymphocytes and macrophages time to carry out functions Spleen Largest lymphoid organ Functions – Site of lymphocyte proliferation and immune surveillance and response – Cleanses the blood of aged cells and platelets and debris – Stores breakdown products of RBCs (e.g., iron) for later reuse – Stores blood platelets – Contains lymphocytes, macrophages, and huge numbers of erythrocytes Structure of the Spleen Two distinct areas – White pulp around central arteries – Red pulp in venous sinuses and splenic cords Rich in macrophages for disposal of worn-out RBCs and bloodborne pathogens Structure of the Spleen Thymus Size with age – In infants, it is found in the inferior neck and extends into the mediastinum, where it partially overlies the heart – Increases in size and is most active during childhood – Stops growing during adolescence and then gradually atrophies Thymus Only organ not directly involved in immunity Differs from other lymphoid organs in important ways – It functions strictly in T lymphocyte maturation – It does not directly fight antigens Provides the environment in which T lymphocytes become immunocompetent Thymus Tonsils Simplest lymphoid organs Have tonsillar crypts that trap and destroy bacteria and particulate matter Form a ring of lymphatic tissue around the pharynx – Palatine tonsils—at posterior end of the oral cavity – Lingual tonsils—grouped at the base of the tongue – Pharyngeal tonsil—in posterior wall of the nasopharynx Tonsils Aggregates of Lymphoid Follicles Peyer’s patches – In the wall of the small intestine – Contain clusters of lymphoid follicles Appendix – Located on the first portion of the large intestines – Contain clusters of lymphoid follicles Peyer’s patches and the appendix – Destroy bacteria, preventing them from breaching the intestinal wall – Generate “memory” lymphocytes MALT Mucosa-associated lymphatic tissue (MALT), including – Peyer’s patches, tonsils, and the appendix (digestive tract) – Lymphoid nodules in the walls of the bronchi (respiratory tract) Protects the digestive and respiratory systems from foreign matter MALT Immunity Immunity is the resistance to disease Immune system has two intrinsic systems – Innate (nonspecific) defense system – Adaptive (specific) defense system Pathogen: harmful or disease causing microorganisms Overview of Innate and Adaptive Defenses Surface Barriers - Skin - Mucous membranes Innate Defenses Adaptive Defenses Internal defenses - Antimicrobial proteins - Fever - Inflammation - NK Cells - Phagocytes Humoral Immunity - B cells Cellular Immunity - T cells Cooperation Between the Two Defenses Immunity 1. Innate defense system has two lines of defense – First line of defense is external body membranes (skin and mucosa) – Second line of defense is antimicrobial proteins, phagocytes, and other cells Inhibit spread of invaders Inflammation is its most important mechanism Immunity 2. Adaptive defense system –Third line of defense attacks particular foreign substances Takes longer to react than the innate system Innate and adaptive defenses are deeply intertwined 1st Line Defenses - Mechanical Intact Skin: is acidic and contains keratin and acts as a physical barrier to microorganisms. Keratin is resistant to most weak acids, bases, bacterial enzymes and toxins. Mucous Membranes: form mechanical barriers that prevents entry of pathogens Lacrimal apparatus: produces a fluid that contains lysozyme, an enzyme that kills microorganisms 1st Line Defenses - Mechanical Saliva: cleanses the oral cavity and teeth. Contains lysozymes and defensins Ciliary escalator: cilia of upper respiratory tract sweep dust and bacteria-laden mucus from lower respiratory passages Urine Flow: normally acid pH inhibits bacterial growth which cleanses lower urinary tract Vaginal Secretions: are very acidic and inhibits bacteria and fungi 1st Line Defenses - Chemical Sebum: oil from sebaceous glands with lipids and bactericidal action Perspiration: contains dermcidin and is toxic to bacteria Gastric Juices: contains concentrated hydrochloric acid and protein-digesting enzymes to destroy pathogens in the stomach 2nd Line Defenses  The body uses nonspecific cellular and chemical devices to protect itself ◦ Phagocytes and natural killer (NK) cells ◦ Antimicrobial proteins in blood and tissue fluid ◦ Inflammatory response enlists macrophages, mast cells, WBCs, and chemicals  Harmful substances are identified by surface carbohydrates unique to infectious organisms 2nd Line Defenses Phagocytes - Macrophages: from monocytes – Fixed macrophages: permanent residents in particular organs Kupffer cells (liver) Microglia (brain) – Free macrophages: wonder through tissue spaces in search for cellular debris or foreign invaders Alveolar macrophages in the lungs 2nd Line Defenses Phagocytes (cont.) – Neutrophils: Become phagocytic on encountering infectious material in tissues – Eosinophils: phagocytic to parasitic worms Mast cells: release histamine which is a potent inflammatory chemical Phagocyte mobilization 1. Leukocytosis: increase in WBCs (neutrophils which are phagocytes) 2. Margination: the clinging of neutrophils to the inner walls of the capillaries 3. Diapedesis: the neutrophils flatten and squeeze through the capillary walls 4. Chemotaxis: neutrophils following the chemical trail to the injury site 2nd Line Defenses Natural Killer (NK) Cells – “Police” the blood and lymph, can lyse and kill cancer cells and virus-infected body cells before the adaptive immune system is activated – Nonspecific – Not phagocytic – Lysis – involves the release of perforins: insert into the target cell membrane allowing enzymes into the target cell that lead to killing the cell 2nd Line Defenses Inflammatory Response Triggered whenever body tissues are injured or infected Benefits: 1. Prevents the spread of damaging agents 2. Disposes of cell debris and pathogens 3. Sets the stage for repair The four cardinal signs of acute inflammation are redness, heat, swelling, and pain Inflammatory Response Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs) TLRs recognize specific classes of infecting microbes Activated TLRs trigger the release of cytokines that promote inflammation Inflammatory Response Inflammatory mediators – Histamine (from mast cells) – Blood proteins – Kinins, prostaglandins (PGs), leukotrienes, and complement Released by injured tissue, phagocytes, lymphocytes, basophils, and mast cells Vasodilation and Increased Vascular Permeability Inflammatory chemicals cause – Dilation of arterioles, resulting in hyperemia – Increased permeability of local capillaries and edema. Fluid is called exudate. Functions of the surge of exudate – Moves debris and pathogens into lymphatic vessels – Delivers clotting proteins to form a scaffold for repair and to isolate the area Exudate contains – Proteins – clotting factors – antibodies Interferons Interferons (IFNs) – Viral-infected cells are activated to secrete IFNs – IFNs enter neighboring cells – Neighboring cells produce antiviral proteins that block viral reproduction – Hinder microorganisms’ ability to reproduce Interferons Functions – Anti-viral – Reduce inflammation – Activate macrophages and mobilize NK cells Genetically engineered IFNs for – Antiviral agents against hepatitis and genital warts virus – Multiple sclerosis treatment Complement ~20 blood proteins that circulate in an inactive form Include C1–C9, factors B, D, and P, and regulatory proteins Major mechanism for destroying foreign substances Amplifies all aspects of the inflammatory response Kills bacteria and certain other cell types by cell lysis Enhances both nonspecific and specific defenses Complement Activation Two pathways 1. Classical pathway Antibodies bind to invading organisms C1 binds to the antigen-antibody complexes (complement fixation) 2. Alternative pathway Triggered when activated C3, B, D, and P interact on the surface of microorganisms Complement Activation Activated complement – Enhances inflammation – Promotes phagocytosis – Causes cell lysis C3b initiates formation of a membrane attack complex (MAC) MAC causes cell lysis by inducing a massive influx of water C3b also causes opsonization, and C3a causes inflammation Complement Activation Fever Fever: systemic response to invading microorganisms Utilizes pyrogens: secreted by leukocytes and macrophages exposed to foreign substances Pyrogen: substance produced by bacterium that causes fever Benefits: 1. Causes the liver and spleen to sequester iron and zinc (needed by microorganisms) 2. Increases metabolic rate, which speeds up repair Adaptive Defenses The adaptive immune (specific defense) system – Protects against infectious agents and abnormal body cells – Amplifies the inflammatory response – Activates complement Adaptive Defenses Adaptive immune response – Is specific – Is systemic – Has memory Two separate overlapping arms 1. Humoral (antibody-mediated) immunity 2. Cellular (cell-mediated) immunity Antigens Antigens: – Substances that can mobilize the adaptive defenses and provoke an immune response – Most are large, complex molecules not normally found in the body (nonself) Antigenic determinate: – There are many different determinants on the surface of an antigen – Immune components bind to the determinants Antigenic Determinants Antigen Processing and Presentation Cells of the Adaptive Immunity All are formed in red bone marrow Immunocompetent: each lymphocyte must become able to recognize its one specific antigen by binding to it – B cells (lymphocytes): mature in the red bone marrow – T cells (lymphocytes): mature in the thymus Cells of the Adaptive Immunity Antigen-presenting cells (APCs): – Major types: Dendritic cells in connective tissues and epidermis Macrophages in connective tissues and lymphoid organs – They engulf Ag, digest, and display a piece on their surface Cells of the Adaptive Immunity Structure of Antibodies Five Classes of Antibodies/Immunoglobulins Classes of Antibodies IgM – First antibody released – Potent agglutinating agent IgA – In saliva, sweat, intestinal juices, and milk – Stops pathogens from attaching to epithelial surfaces IgD – Attached on B cells surface – Functions as a B cell receptor IgG – 75-85% on antibodies in plasma – Protects against bacteria, viruses, and toxins – Passed from pregnant mother to fetus IgE – Active in some allergies and parasitic infections – Causes mast cells and basophils to release histamine Antibody Formation Antibody Response Active versus Passive Immunity