Fundamentals of Anatomy & Physiology PDF

PRAYER BEFORE CLASS Holy Spirit, Divine Creator, true source of light and fountain of wisdom! Pour forth your brilliance upon my dense intellect, dissipate the darkness which covers me, that of sin and of ignorance. Grant me a penetrating mind to understand, a retentive memory, method and ease of le...

PRAYER BEFORE CLASS Holy Spirit, Divine Creator, true source of light and fountain of wisdom! Pour forth your brilliance upon my dense intellect, dissipate the darkness which covers me, that of sin and of ignorance. Grant me a penetrating mind to understand, a retentive memory, method and ease of learning, the lucidity to comprehend, and abundant grace in expressing myself. Guide the beginning of my work, direct its progress and bring it to successful completion. This I ask through Jesus Christ, true God and true man, living and reigning with You and the Father, forever and ever. Amen. Fundamentals of Anatomy & Physiology Twelfth Edition, Global Edition Chapter 22 The Lymphatic System and Immunity Lecture Presentation by Dr. Virginia Irintcheva, Truckee Meadows Community College © 2024 Pearson Education Ltd. All Rights Reserved. Introduction Lymphatic system (lymphoid system) – cells tissues and organs responsible for defending the body from environmental hazards and internal threats Immune system – all body cells and tissues involved in immunity, including parts of the lymphatic, integumentary, skeletal, cardiovascular, respiratory and digestive systems. Immunity – the ability to resist infection and disease Pathogens – organisms that cause disease, such as viruses, bacteria, fungi and parasites Components of the Lymphatic System Components of the lymphatic system Lymph – fluid similar to plasma but without plasma proteins Lymphatic vessels – carry lymph from the peripheral tissues to veins Lymphoid cells – lymphocytes, phagocytes, and other cells Lymphoid tissues – connective tissues dominated by lymphocytes Lymphoid organs – organs where lymphocytes may form, mature or become activated The Components of the Lymphatic System The Components of the Lymphatic System  Primary lymphoid tissues and organs- sites where lymphocytes are formed and mature Red bone marrow and thymus Secondary lymphoid tissues and organs- sites where lymphocytes are activated Tonsils, mucosa associated lymphatic tissue (M A L T), lymph nodes, and spleen  Functions of the lymphatic system Produce, maintain, and distribute lymphocytes and other lymphoid cells Return excess fluid from tissues to the bloodstream to maintain normal blood volume Regulates the composition of interstitial fluid by transporting hormones, nutrients, and wastes from their tissues of origin to the general circulation  Lymphatic vessels (lymphatics) – carry lymph from peripheral tissues to the venous system Lymph – interstitial fluid that has entered the lymphatic vessels Meningeal lymphatics – network of vessels found in the dura mater that drains C S F to cervical lymph nodes, remove wastes and transport immune cells Lymphatic capillaries – smallest lymphatic vessels, present at almost every tissue of the body Lymphatic lacteals – lymphatic capillaries in the small intestine that transport lipids absorbed by the digestive tract  Lymphatic capillaries Compared to blood capillaries, lymphatic capillaries: Are closed at one end and begin in tissues Have larger luminal diameters Have thinner walls Have a flattened or irregular outline in sectional view Lined by endothelial cells loosely bound together Overlap of endothelial cells acts as a one-way valve Allows fluids, solutes, viruses, and bacteria to enter and prevents them from returning to the intercellular spaces Lymphatic Capillaries The interwoven network formed by blood capillaries and lymphatic capillaries. Arrows indicate the movement of fluid out of blood capillaries and the net flow of interstitial fluid and lymph. Lymphatic Capillaries A sectional view indicating the movement of fluid from the plasma, through the tissues as interstitial fluid, and into the lymphatic system as lymph.  Lymph flows from lymphatic capillaries to larger lymphatic vessels Small to medium lymphatic vessels contain Three layers in the vessel wall similar to veins Valves to prevent lymph backflow Often share the same path with blood vessels Lymphedema – obstruction of lymphatic vessels that prevents lymph drainage Causes severe swelling, which can become permanent Interferes with immune system function Lymphatic Vessels and Valves A diagrammatic view of areolar connective tissue containing blood vessels and a lymphatic vessel. The cross-sectional view at right emphasizes their structural differences. Lymphatic Vessels and Valves Photo credit: Frederic H. Martini Like valves in veins, each lymphatic valve consists of a pair of flaps that permit movement of fluid in only one direction.  Major lymph-collecting vessels Superficial lymphatics – vessels in the subcutaneous layer, areolar layer of mucous membranes and serous membranes Deep lymphatics – larger vessels that accompany arteries and veins Superficial and deep lymphatics converge to form large lymphatic trunks that empty into two major collecting vessels: Thoracic duct Right lymphatic duct  Thoracic duct – collects lymph from all body regions inferior to the diaphragm and from the left side of the body superior to the diaphragm Cisterna chyli – expanded chamber at the base of the thoracic duct, which receives lymph from the inferior parts of the abdomen, the pelvis and the lower limbs The thoracic duct empties into the left subclavian vein Right lymphatic duct – collects lymph from the right side of the body superior to the diaphragm Empties into the right subclavian vein The Relationship between the Lymphatic Ducts and the Venous System The thoracic duct carries lymph from tissues inferior to the diaphragm and from the left side of the upper body. The smaller right lymphatic duct carries lymph from the rest of the body. The Relationship between the Lymphatic Ducts and the Venous System The thoracic duct empties into the left subclavian vein. The right lymphatic duct empties into the right subclavian vein.  Lymphoid cells – immune system cells and support cells in lymphoid tissues Phagocytic immune system cells: macrophages, microphages, and other phagocytes Lymphocytes – immune system cells that respond to specific invading pathogens T (thymus-dependent) cells B (bone marrow–derived) cells N K (natural killer) cells  Lymphoid tissues Lymphoid nodules (lymphatic nodules) – areolar tissue densely packed with lymphocytes Lymphoid nodules in the deep to the respiratory mucosa= tonsils Present along the digestive, urinary, and reproductive tracts Distributed in lymphatic organs such as the lymph nodes and spleen Germinal center – central zone of the nodule which contains dividing lymphocytes Lymphoid Nodules Aggregated lymphoid nodules in the intestine. Lymphoid Nodules Photo credit: Robert B. Tallitsch Aggregated lymphoid nodules in the intestine.  Lymphoid tissues Tonsils – large lymphoid nodules in the wall of the pharynx Pharyngeal tonsil (adenoid) – in the posterior wall of the nasopharynx Left and right palatine tonsils – at the posterior inferior margin of the oral cavity Two lingual tonsils – deep to the epithelium covering the base of the tongue Tonsillitis – inflammation of the tonsils, especially palatine tonsils Lymphoid Nodules The locations of the tonsils. Lymphoid Nodules Photo credit: Biophoto Associates/Science Source The locations of the tonsils.  Lymphoid tissues Mucosa-associated lymphoid tissue (M A L T) – lymphoid tissues associated with the mucosa of the digestive, respiratory, urinary and reproductive systems Aggregated lymphoid nodules (Peyer's patches) – clusters of lymphoid nodules deep to intestinal epithelial lining Appendix (vermiform appendix) – tube-shaped sac between the small and the large intestine Contains a mass of fused lymphoid nodules  Lymphoid organs Separated from the surrounding tissues by a connective tissue capsule Include Lymph nodes Thymus Spleen  Lymph nodes – small lymphoid organs found along lymphatic vessels Structure Surrounded by a capsule Trabeculae – bundles of collagen fibers that extend from capsule into the interior of the lymph node Hilum – shallow indentation where blood vessels and nerves reach the lymph node Afferent lymphatics – carry lymph from peripheral tissues to the lymph node Efferent lymphatics – carry lymph away from the lymph node The Structure of a Lymph Node The Structure of a Lymph Node  Lymph flow through lymph nodes From the afferent lymphatics through the subcapsular space – meshwork of reticular fibers, macrophages and dendritic cells Through the cortex (outer region) – contains B cells within germinal centers Through the paracortex – contains mostly T cells Through the medulla (inner region) – organized into medullary cords Medullary cords – elongated masses of dense lymphoid tissue that contain B cells and macrophages Finally, the lymph enters the efferent lymphatics at the hilum  Lymph node functions Filters lymph before it returns to the venous circulation Removes 99 percent of antigens (foreign microorganisms and substances) Phagocytes engulf debris and pathogens in the lymph node or arrive at the lymph node from peripheral tissues Antigens are then presented to lymphocytes Lymphoid tissues and lymph nodes monitor peripheral infections and activate the immune response before they reach vital organs  Lymph nodes Lymph nodes of the gut, trachea, lungs and the thoracic duct protect against pathogens in the digestive and respiratory systems The largest lymph nodes are in the groin, axillae, and at the base of the base of neck Activated lymph nodes enlarge, because of cell division of lymphocytes and phagocytes Lymphadenitis – inflammation of the lymph nodes Lymphadenopathy – refers to disease of the lymph nodes; observed as chronic or excessive enlargement of the lymph nodes  Thymus – pink, grainy lymphoid organ located in the mediastinum above the heart Atrophies after puberty and becomes inactive Structure: Divided into two thymic lobes Septa – fibrous partitions that originate at the capsule and divide the lobes into smaller lobules Each lobule has Outer cortex – contains densely packed lymphocytes surrounded by epithelial reticular cells Inner medulla – contains epithelial reticular cells in concentric layers called thymic (Hassall's) corpuscles The Thymus The appearance and position of the thymus in relation to other organs in the chest. The Thymus Anatomical landmarks on the thymus. The Thymus Photo credit: Robert B. Tallitsch (c) Fibrous septa divide the tissue of the thymus into lobules resembling interconnected lymphoid nodules. (d) Higher magnification reveals the unusual structure of thymic corpuscles. The small cells are lymphocytes in various stages of development.  Functions of the thymus Regulates T cell lymphocyte development and maturation T cells divide in the cortex Maturing T cells migrate into the medulla Mature T cells leave thymus by medullary blood vessels Epithelial reticular cells maintain the blood thymus barrier in cortex to separate developing T cells from the general circulation Hormone production Thymosin—an extract from thymus containing several hormones that promotes the development and maturation of T cells  Spleen – large lymphoid organ lateral to the stomach Functions: Filters blood to remove abnormal blood cells and other blood components by phagocytosis Storage of iron recycled from red blood cells Immune responses to antigens in blood by macrophages, B cells, T cells  Spleen Attached to the stomach by the gastrosplenic ligament Contacts the diaphragm and the left kidney Splenic veins, arteries, and lymphatic vessels enter the spleen at the hilum Histology of the spleen Cellular components within the capsule make up the pulp Red pulp contains many red blood cells White pulp resembles lymphoid nodules The Spleen A transverse section through the trunk, showing the typical position of the spleen projection into the peritoneal cavity. The shape of the spleen conforms to the shapes of adjacent organs. The Spleen A posterior view of the surface of an inface spleen, showing major anatomical landmarks. The Spleen Photo credit: Robert B. Tallitsch White pulp is dominated by lymphocytes; it appears purple because the nuclei of lymphocytes stain very darkly. Red pulp contains large number of red blood cells.  Spleen Trabecular arteries branch extensively Finer branches surrounded by the white pulp Capillaries discharge blood into the red pulp The red pulp contains all the elements of circulating blood plus fixed and free macrophages Reticular fibers of the red pulp filter blood and then it enters large sinusoids, which empty into veins and ultimately the trabecular veins  Spleen Rupture of the spleen The spleen tears easily when there is trauma to the left side of the abdomen Rupture can lead to serious internal bleeding Splenectomy – removal of a severely ruptured spleen Removal of the spleen results in increased risk of bacterial infections Innate and Adaptive Immunity Immunity – the ability to resist and defend against infectious organisms and other damaging substances Immune response – body’s reaction to infectious agents and other abnormal substances Resistance – ability of the body to maintain immunity  Types of immunity Innate (nonspecific) immunity Physical barriers and internal defenses that prevent the entry of pathogens or attack them when they enter Present at birth Does not distinguish one threat from another Always works the same way against any type of threat Adaptive (specific) immunity Protects against specific antigens Depends on activities of B and T lymphocytes Develops when there is exposure to an antigen Protects against future attacks by the same pathogen  Lymphocytes – B cells, T cells, and N K cells Lymphocyte distribution Tissues maintain different T cell and B cell populations Lymphocytes move through tissues and enter blood vessels or lymphatics for transport Have a long life-span and can survive for many years Lymphocytopoiesis – lymphocyte production Involves the red bone marrow, thymus and peripheral lymphoid tissues Hemocytoblasts in the bone marrow divide lymphoid stem cells which produce all lymphocytes  Lymphoid stem cells One population remains in the bone marrow and develops with the help of stromal cells Produces B cells and N K cells B cells differentiate with exposure to interleukin-7 As they mature, B cells and N K cells enter the circulation and migrate to peripheral tissues Second population migrates to the thymus Develop and mature in an environment isolated from blood T cells differentiate and are selected with exposure to hormones When they mature they enter the circulation and travel to peripheral tissues The Origin and Distribution of Lymphocytes The Origin and Distribution of Lymphocytes Innate Defenses Innate (nonspecific) defenses – first line of defense Physical barriers Phagocytes Immune surveillance Interferons Complement Inflammation Fever Innate Defenses Innate (nonspecific) defenses deny pathogens access to the body or destroy them without distinguishing among specific types of pathogens. Innate Defenses Innate (nonspecific) defenses deny pathogens access to the body or destroy them without distinguishing among specific types of pathogens.  Physical barriers – precent pathogens from entering the body Skin Hair Mucous membranes of internal passageways Mucus Secretions that flush away materials Sweat and urine Secretions that kill or inhibit microorganisms Containing enzymes, antibodies, or stomach acid  Phagocytes Cells that attack and engulf microorganisms and debris Microphages Neutrophils and eosinophils Enter peripheral tissues to fight infections by phagocytosis Macrophages Large phagocytic cells derived from monocytes Make up the monocyte–macrophage system (reticuloendothelial system)  Phagocytes Macrophages Activated macrophages respond to pathogens by: Engulfing the pathogen and destroying it with lysosomal enzymes Binding to the pathogen to remove it from the interstitial fluid so other cells can destroy it Destroying the pathogen by releasing toxic chemicals such as tumor necrosis factor, nitric oxide or hydrogen peroxide  Phagocytes Macrophages Types of macrophages Fixed macrophages (histiocytes) – reside in specific tissues and organs (e.g., dermis and bone marrow) Microglia found in the central nervous system Stellate macrophages (Kupffer cells) found in liver sinusoids Free macrophages (wandering macrophages) – travel throughout the body Migrate to tissues traveling in blood Alveolar macrophages (dust cells) found in the lungs  Free macrophages and microphages Move through capillary walls (emigration) Are attracted or repelled by chemicals in surrounding fluids (chemotaxis) Phagocytosis begins when the phagocyte attaches to the target (adhesion) and forms a vesicle to internalize it. The vesicle then fuses with a lysosome or peroxisome to digest the target.  Immune surveillance Natural killer cells look for abnormal cells in peripheral tissues, such as cancer cells or cells infected by viruses Steps in N K cell activation 1. Recognition and adhesion – identifies abnormal membrane components and adheres to abnormal cells 2. Realignment of the Golgi apparatus – the Golgi apparatus moves to face the abnormal cell and produces vesicles containing perforins 3. Secretion of perforins by exocytosis 4. Lysis of the abnormal cell because perforins form pores in its plasma membrane How Natural Killer Cells Kill Cellular Targets How Natural Killer Cells Kill Cellular Targets How Natural Killer Cells Kill Cellular Targets How Natural Killer Cells Kill Cellular Targets  Immune surveillance Cancer cells have tumor-specific antigens on their plasma membranes that are recognized by N K cells Some cancer cells avoid detection or destroy N K cells (immunological escape) Cells infected with viruses present viral proteins on their plasma membranes Allows N K cells to identify and destroy them  Interferons (I F N s)- small proteins released by activated lymphocytes and macrophages, and by tissue cells infected with viruses Interferons are cytokines – chemical messengers released by tissue cells, important to the immune response Trigger the production of antiviral proteins in healthy cells Types of interferons Interferon alpha − produced by cells infected with viruses; interferes with viral replication and stimulates N K cells Interferon beta – secreted by fibroblasts and slows inflammation Interferon gamma – secreted by T cells and N K cells and stimulates macrophage activity Interferons  Complement system More than 30 special complement proteins in plasma Assists antibodies in the destruction of pathogens Complement proteins work together in cascades Three routes of activation of complement Classical pathway Lectin pathway Alternative pathway  Complement system Classical pathway Most rapid and effective mode of activation Begins with binding of complement protein C1 to two antibodies attached to an antigen The protein acts as an enzyme and catalyzes a chain reaction resulting in the production of C3b Pathways of Complement Activation  Complement system Lectin pathway Mannose-binding lectin (M B L) binds to carbohydrates on pathogen surfaces Bound M B L acts as an enzyme that produces C3b Alternative pathway Begins when Properdin (factor P), Factor B and Factor D interact in plasma and produce C3b Pathways of Complement Activation Pathways of Complement Activation  Complement system All three complement system pathways involve conversion of the inactive C3 protein to activated C3a and C3b proteins C3a proteins activate the inflammatory response by stimulating histamine release from mast cells and basophils C3b proteins attach to the antigen and enhance phagocytosis (opsonization) facilitates the formation of a membrane attack complex (M A C) that destroys the membrane of the antigen Pathways of Complement Activation  Inflammation Localized tissue response to injury triggered by any stimulus that kills cells or injures tissue Cardinal signs and symptoms of inflammation Redness (due to increased blood flow) Swelling (due to increase capillary permeability) Heat (due to increased blood flow) Pain (due chemicals released by injured cells and detected by pain receptors)  Inflammation Effects of inflammation Temporarily repairs injury so no additional pathogens enter Slows the spread of pathogens away from the injury Mobilizes local, regional, and systemic defenses to overcome the pathogens and facilitate permanent repairs (regeneration)  Inflammation Steps of inflammation Mast cells activated by chemical changes in tissue due to injury Mast cells release histamine, heparin and other chemicals Capillaries become more permeable and blood flow in the area increases (histamine) Sensory nerves detect pain Clot forms around injured area for temporary repair Complement proteins leave blood and attack pathogens Inflammation and the Steps in Tissue Repair  Inflammation Steps of inflammation More phagocytes arrive at the sire of inflammation due to increased blood flow and positive chemotaxis Neutrophil activation stick to the vessel wall and emigrate out into tissue their metabolic rate increases and they produce reactive compounds to destroy engulfed pathogens and debris Secrete cytokines to attract other neutrophils and macrophages More macrophages arrive and help with phagocytosis and stimulate fibroblasts to repair damaged tissue Inflammation and the Steps in Tissue Repair  Inflammation Some unwanted effects of inflammation Necrosis – local tissue destruction and death in the area of injury Pus – mixture of debris, fluid, dead and dying tissue cells, dead neutrophils and necrotic tissue Abscess – accumulation of pus in an enclosed space  Fever Body temperature greater than Pyrogens – fever-inducing agents that cause the hypothalamus to raise body temperature Can be produced by bacteria, molds, viruses, and yeasts Endogenous pyrogens include Interleukin-1, interferons, and tumor necrosis factor Functions of fever: Increases metabolic rate May inhibits some viruses and bacteria Adaptive Defenses Adaptive (specific) defenses Result from the coordinated activities of lymphocytes known as T cells and B cells B cells – differentiate into plasma cells and produce antibodies  Types of T cells Cytotoxic T cells – attack antigens physically and chemically Helper T cells – stimulate responses of T cells and B cells Regulatory T cells – moderate the immune response Memory T cells – respond to previously encountered antigens Inflammatory T cells – stimulate regional inflammation Suppressor-inducer T cells – suppress B cell activity Classes of Lymphocytes  Cell-mediated immunity (cellular immunity) Mediated by cytotoxic T cells Defends against abnormal cells and pathogens inside cells Antibody-mediated immunity (humoral immunity) Mediated by B cells Defends against antigens and pathogens in body fluids An Overview of Adaptive Immunity  Antigens – chemical targets that stimulate an immune response Can be pathogens, parts of pathogens, products of pathogens or other foreign substances Lymphocyte activation A lymphocyte becomes activated when it comes in contacts with an appropriate antigen Clonal selection The activated lymphocyte divides to produce a clone (all the identical cells that are sensitive to the same antigen)  Forms of adaptive immunity Active immunity – develops after the immune system encounters an antigen and mounts an immune response Naturally acquired active immunity – through environmental exposure to pathogens Artificially acquired active immunity – through vaccines (preparations designed to induce an immune response) Passive immunity – produced by transferring antibodies from another source Naturally acquired passive immunity – antibodies acquired from the mother across the placenta or from milk Artificially acquired passive immunity – by an injection of antibodies Forms of Immunity SmartArt Video: The Immune Response Use the link below to view ADA complaint video: SmartArt Video: The Immune Response https://mediaplayer.pearsoncmg.com/assets/secs-aandp-smartart- immune-response  Types of vaccines Inactivated vaccines – contained killed pathogen Live-attenuated vaccines – use live weakened forms of the pathogen Messenger RNA (mRNA) vaccines – stimulate synthesis of viral proteins that trigger an immune response Subunit, recombinant, polysaccharide and conjugate vaccines – use pieces of the pathogen Toxoid vaccines – use altered or weakened forms of bacterial toxins Viral vector vaccines – use modified versions of a different virus to deliver protection  Properties of adaptive immunity Specificity – each T or B cell responds only to a specific antigen and ignores all others Versatility – can recognize a large number of antigens due to lymphocytes and antibodies with varied antigen sensitivity Memory – some inactive lymphocytes (memory cells) stay in the circulation after an infection and provide immunity against new exposure Tolerance – the immune system ignores self-antigens T Cells and Immunity Antigen presentation T cells recognize antigens that are "presented" by antigen- presenting cells M H C proteins – membrane glycoproteins that serve as "signature" to identify the cell as "self" Genetically coded by the major histocompatibility complex (M H C) in chromosome 6 Also called human leukocyte antigens (HLA) Antigen presentation occurs when an antigen-M H C protein combination appear in the membrane and is recognized by a T cell  Antigen presentation Classes of M H C proteins Class M H C proteins Found in the membranes of all nucleated cells Pick up small peptides from the cytoplasm of the cell and present them on the cell surface T cells ignore peptides from a normal healthy cell Abnormal peptides or viral proteins activate T cells Antigens and M H C Proteins Infected body cell. Antigens and M H C Proteins Photo credit: Steve Gschmeissner/Science Source Two cells exposed to fluorescent-tagged antibodies. The green cell is an A P C and the red cell is a lymphocyte.  Antigen presentation Classes of M H C proteins Class M H C proteins Found in the membranes of lymphocytes and antigen-presenting cells (A P C s) such as dendritic cells and macrophages Antigen processing – A P C s engulf and break down the pathogen and antigenic fragments bind to class MHC and are presented on the plasma membrane T cells recognize the M H C-antigen complex and get activated Antigens and M H C Proteins Antigen-presenting cell (A P C).  Antigen recognition T cells have receptors that bind to or M H C proteins The receptors also have binding sites for a specific antigen Binding (antigen recognition) occurs when the antigen matches the receptor on T cell C D (cluster of differentiation) markers Proteins in T cell membranes that provide the molecular mechanism for antigen recognition  Important C D markers C D 3 receptor complex – found on all T cells C D 8 markers – found on cytotoxic T cells and regulatory T cells Respond to antigens on M H C proteins C D 4 markers – found on helper T cells Respond to antigens on M H C proteins C D 8 and C D 4 markers are bound to the C D 3 receptor complex Costimulation – T cells binds to stimulating cell at second site, which confirms the first signal and only then activation will occur  C D 8 T cells Activated by exposure to antigens on M H C proteins Cytotoxic T cells responds quickly and produce memory cells Regulatory T cells respond slowly Once a cytotoxic T cells is activated and undergoes cell division, the produced clones go out to tissues and release perforins to destroy target cell’s plasma membrane release cytokines and activate genes in target cell to trigger apoptosis Secrete poisonous lymphotoxin to kill target cell Antigen Recognition and Activation of Cytotoxic T Cells  Memory cells Produced by the same cell division that produces cytotoxic T cells Stay in circulation and immediately form cytotoxic T cells if same antigen appears again Regulatory T cells Secrete inhibitory cytokines called suppression factors Inhibit the responses of T and B cells Act after initial immune response to limit immune reaction to a single stimulus  C D 4 T cells Activated by exposure to antigens on M H C proteins Once a helper T cells ( cell) is activated and undergoes cell division and the produced clones secrete a variety of cytokines Functions of cytokines secreted by helper T cells Stimulate T cell divisions that produce memory T cells and accelerate cytotoxic T cell maturation Attract and stimulate macrophages Attract and stimulate the activity of cytotoxic T cells Promote the activation of B cells Memory cells are also produced and remain in the circulation Antigen Recognition and Activation of Helper T Cells Inactive C D 4 T cells) must be exposed to appropriate antigens Mcells H C proteins. bound cells toundergo activation, dividing to then The and cells produce active cells memory.  Cytokines – chemicals released by cells involved in the immune response Groups of cytokines Interleukins Interferons Tumor necrosis factors Phagocyte-activating chemicals Colony-stimulating factors Miscellaneous cytokines Leukotrienes, lymphotoxins, perforin and suppression factors  Interleukins Produced by lymphocytes and macrophages, endothelial cells, fibroblasts and astrocytes Functions: 1. Increasing T cell sensitivity to antigens exposed on macrophage membranes 2. Stimulating B cell activity, plasma cell formation, and antibody production 3. Enhancing innate immunity by stimulating inflammation, mast cell formation, A C T H secretion, scar tissue formation, elevation of body temperature 4. Moderating and shortening the immune function  Interleukins IL-1 and IL-2, are important in stimulating and maintaining the immune response When released by activated macrophages and lymphocytes, these cytokines stimulate activities of other immune cells and of the secreting cell Result is a positive feedback loop that helps to recruit additional immune cells  Interferons Produced by cells infected with a virus, fibroblasts and N K cells Functions: Make the cells that produce them and the neighboring cells resistant to vital infection Attract and stimulate N K cells Slow the progress of inflammation associated with viral infection Stimulate macrophages  Tumor necrosis factors (T N F s) Produced by activated macrophages and cytotoxic T cells Functions Slow the growth of tumors and kill sensitive tumor cells Stimulate granular leukocyte production, promote eosinophil activity, cause fever, and increase T cell sensitivity to interleukins  Phagocyte-activating chemicals Several cytokines coordinate immune defenses by adjusting activities of phagocytic cells Some attract free macrophages and microphages and prevent their premature departure from the site of injury Colony-stimulating factors (C S F s) Produced by active T cells, cells of the monocyte – macrophage system, endothelial cells, and fibroblasts Stimulate production of blood cells in the red bone marrow and lymphocytes in the lymphoid tissues and organs  Cytokines are often classified according to their origin Lymphokines are produced by lymphocytes Monokines are secreted by active monocytes, macrophages, and other antigen-presenting cells Lymphocytes and macrophages may secrete the same cytokines Cells involved in adaptive immunity and tissue repair can also secrete cytokines A Summary of the Pathways of T Cell Activation Activation MHC by proteins A Summary of the Pathways of T Cell Activation Activation MHC by proteins B Cells and Immunity B cell sensitization B cells have specific surface antibodies (B cell receptors) If an antigen in interstitial fluids binds to a corresponding B cell receptors, the antigen is Taken into the B cell by endocytosis Processed Reappears on the surface, bound to a M H C protein The Sensitization and Activation of B Cells A B cell is sensitized by exposure to antigens. Once antigens are bound to antibodies in the B cell plasma membrane, the B cell displays those antigens on MHC proteins in its plasma membrane. Activated helper T cells encountering the antigens release cytokines that costimulate the sensitized B cell and trigger its activation. The activated B cell then divides, producing memory B cells and plasma cells that secrete antibodies.  B cell activation Sensitized B cell present the antigen to a helper T cell via the MHC The helper T cell secretes cytokines that promote B cell activation The activated B cell undergoes cell division Some of the daughter cells differentiate into plasma cells and synthesize and secrete antibodies into the interstitial fluid Memory B cells remain in reserve in the circulation to respond to the next infection The Sensitization and Activation of B Cells A B cell is sensitized by exposure to antigens. Once antigens are bound to antibodies in the B cell plasma membrane, the B cell displays those antigens on MHC proteins in its plasma membrane. Activated helper T cells encountering the antigens release cytokines that costimulate the sensitized B cell and trigger its activation. The activated B cell then divides, producing memory B cells and plasma cells that secrete antibodies.  Antibodies Soluble proteins Structure Two pairs of polypeptide chains One pair of heavy chains One pair of light chains Each chain contains constant and variable segments The variable segments of light and heavy chains form the antigen-binding sites of antibody molecule, which bind to antigenic determinant sites (epitopes) of antigen molecules Antibody Structure and Function A diagrammatic view of the structure of an antibody. Antibody Structure and Function Photo credit: Petarg/123RF A computer-generated image of a typical antibody.  Classes of antibodies, or immunoglobulins (I g s) IgG IgE IgD IgM IgA  IgG Largest and most diverse class of antibodies 80 percent of all antibodies Responsible for resistance against many viruses, bacteria, and bacterial toxins Can cross the placenta Maternal I g G provides passive immunity to the fetus Anti-R h antibodies produced by R h-negative mothers that produce hemolytic disease of newborn are I g G  IgE Attaches to the exposed surfaces of basophils and mast cells When an antigen is bound by an I g E molecules, these cells are stimulated to release histamine and other chemicals that accelerate inflammation Also important in the allergic response  IgD Antibodies on the surface of B cells, where it can bind antigens in extracellular fluid Binding plays a role in the sensitization of the B cell involved IgM First class of antibody secreted Concentration declines as production accelerates Plasma cells secrete individual I g M molecules. Which then polymerize and circulate as five-antibody units Anti-A and anti-B antibodies responsible for agglutination of incompatible blood types are I g M May also attack bacteria that are insensitive to I g G  IgA Found primarily in glandular secretions such as mucus, tears, saliva, and semen Attack pathogens before they gain access to internal tissues Circulate in blood individually or in pairs Epithelial cells absorb them from blood and attach a secretory piece, before secreting I g A molecules onto the epithelial surface  Antigen–antibody complex – an antibody bound to an antigen A complete antigen has at least two antigenic determinant sites Binds to both antigen-binding sites of the variable segments of an antibody Exposure to a complete antigen leads to B cell sensitization and immune response Hapten (partial antigen) – must attach to a carrier molecule to act as a complete antigen Antibodies will attack both the hapten and the carrier molecule If carrier is normal, the antibody attacks normal cells Example: penicillin allergy Antibody Structure and Function Antibodies bind to portions of an antigen called antigenic determinant sites, or epitopes. Antibody Structure and Function Antibody molecules can bind a hapten (partial antigen) once it has become a complete antigen by combining with a carrier molecule.  Actions of antibodies Neutralization – prevent pathogens or toxins from binding and entering or injuring cells Precipitation and agglutination − formation of immune complexes which with precipitate out of solution Activation of the complement system − the complement proteins destroy the antigen Attraction of phagocytes − phagocytize and destroy the antigen- antibody complexes Opsonization (coating) − increases phagocyte efficiency Stimulation of inflammation − stimulate mast cells and basophils Prevention of bacterial and viral adhesion − prevent entry into the body  Immune responses to antigen exposure Primary response − after initial exposure to an antigen Takes time to develop Antibody titer (level of antibodies in plasma) rises slowly Peak response can take two weeks to develop and declines rapidly I g M antibodies produced first, the I g G Secondary response − subsequent exposure to the same antigen More extensive and prolonged Memory cells already primed The Primary and Secondary Responses in Antibody-Mediated Immunity The primary response takes about 2 weeks to develop peak antibody levels (titers). l g M and l g G antibody levels do not remain elevated.  Immune responses to antigen exposure Secondary response − subsequent exposure to the same antigen Activates memory B cells at lower antigen concentrations Antibodies are secreted in massive quantities and immediately I g G antibodies rise very high and very quickly and can remain elevated for extended time I g M production is also quicker The Primary and Secondary Responses in Antibody-Mediated Immunity The secondary response has a very rapid increase in l g G antibody concentration and rises to levels much higher than those of the primary response. Antibody levels remain elevated for an extended period after the second exposure to the antigen Immunocompetence Immunocompetence − ability to produce an immune response after exposure to an antigen Development of immunocompetence Cell-mediated immunity begins as early as 3rd month of fetal development, antibody mediated immunity by the 4th month A P C s take residence in different tissues Fetus receives I g G antibodies from mother across the placenta and after birth the infant receives I g A antibodies form milk  Immunocompetence Development of immunocompetence During childhood, the immune system encounters and responds to numerous antigens and the concentration of circulating antibodies and memory B and T cells increase. Cells that Participate in Tissue Defenses Cell Functions Neutrophils Phagocytosis; stimulation of inflammation Eosinophils Phagocytosis of antigen–antibody complexes; suppression of inflammation; participation in allergic response Mast cells and basophils Stimulation and coordination of inflammation by release of histamine, heparin, leukotrienes, prostaglandins Blank ANTIGEN-PRESENTING CELLS Macrophages (free and fixed Phagocytosis; antigen processing; antigen presentation with class II macrophages, MHC proteins; secretion of cytokines, especially interleukins and stellate macrophages, and microglia) interferons Dendritic cells Pinocytosis; antigen processing; antigen presentation bound to class II MHC proteins Blank LYMPHOCYTES NK cells Destruction of plasma membranes containing abnormal antigens Cytotoxic T cells (CD8 marker) Lysis of plasma membranes containing antigens bound to class I MHC proteins; secretion of perforins, defensins, lymphotoxins, and other cytokines Cells that Participate in Tissue Defenses Cell Functions Helper T cells (CD4 marker) Secretion of cytokines that stimulate cell-mediated and antibody- mediated immunity; activation of sensitized B cells B cells Differentiation into plasma cells, which secrete antibodies and provide antibody mediated immunity Regulatory T cells (CD8 marker) Secretion of suppression factors that inhibit the immune response Memory cells (T cells, B cells) Produced during the activation of T cells and B cells; remain in tissues awaiting antigen reappearance  Immune response to bacterial infection In the early stages of infection, neutrophils and N K cells migrate to area and destroy bacteria Cytokines draw more phagocytes to the area Cytotoxic T cells are activated by antigen presentation and destroy the bacteria B cells are activated and antibody concentration rises Antibodies bind to bacteria and their toxins and target them for destruction by lysis or phagocytosis The Course of the Body’s Response to a Bacterial Infection The basic sequence of events begins with the appearance of bacteria in peripheral tissues at time 0.  Immune response to viral infection Infected tissue cells release interferons to limit viral spread Infected cells also present the virus on their plasma membrane to activate N K and cytotoxic T cells to destroy the infected cells A P C s also present the virus and activate helper T cells B cells become activated and produce antibodies that target the virus for destruction and prevent it from entering cells An Integrated Summary of the Immune Response Defenses against Bacterial and Viral Pathogens (a) Defenses against bacteria involve phagocytosis and antigen presentation by APCs. (b) Defenses against viruses involve direct contact with virus-infected cells and antigen presentation by APCs.  Stress and the immune response Inteleukin-1 stimulates the release of A C T H which stimulates the adrenal cortex to produce Glucocorticoids Secreted to limit the immune response Long-term secretion (chronic stress) – inhibits the immune response and lowers resistance to disease Functions of glucocorticoids Depression of inflammation Reduction in the abundance and activity of phagocytes in peripheral tissues Inhibition of interleukin secretion depresses the response of lymphocytes  Immune disorders Hypersensitivities (allergies) – excessive immune responses to antigens Allergens – antigens that trigger allergic reactions Categories of hypersensitivities Immediate hypersensitivity Cytotoxic reactions Immune complex disorders Delayed hypersensitivity  Immediate hypersensitivity – rapid and especially severe response to an antigen Example: environmental allergies Sensitization to an allergen leads to the production of large amounts of I g E antibodies Subsequent encounter causes the antibodies to bind to basophils and mast cells and the cells release histamine, heparin, cytokines and prostaglandins which cause sudden massive inflammation Severity of the reaction depends on individual sensitivity and locations involved Allergens in the bloodstream may cause anaphylaxis  Immediate hypersensitivity Anaphylaxis – systemic allergic reaction Can be fatal Changes capillary permeability Produces swelling and hives on skin Smooth muscles of respiratory system contract making breathing extremely difficult Widespread peripheral vasodilation can cause circulatory collapse (anaphylactic shock) The Mechanism of Anaphylaxis The Mechanism of Anaphylaxis  Antihistamines – drugs that block the action of histamine Can relieve mild symptoms of immediate hypersensitivity Example: Benadryl  Immune disorders Autoimmune disorders – the immune system malfunctions to attack "self" antigens Sometimes the self antigens are similar to foreign antigens and the immune system is confused Activated B cells make autoantibodies against body cells Examples Thyroiditis Rheumatoid arthritis Type 1 diabetes Multiple sclerosis  Immune disorders Immunodeficiency diseases – result from problems with embryonic development of lymphoid organs and tissues, viral infections or immunosuppressive drugs and radiation treatments Severe combined immunodeficiency disease (S C I D)- genetic disease that leads to absence of cell-mediated or antibody-mediated immunity Infection with the human immunodeficiency virus (H I V) destroys helper T cells and can result in A I D S (acquired immunodeficiency syndrome) Effects of Aging on Immune Response The immune response diminishes with age, increasing the vulnerability to infections and cancer Effects of aging Thymic hormone production is greatly reduced T cells become less responsive to antigens Fewer helper T cells reduces responsiveness of B cells Immune surveillance against tumor cells declines Immune System Integration The nervous and endocrine systems can influence the immune response Integration of the LYMPHATIC system with the other body systems presented so far Copyright This work is protected by United Kingdom copyright laws and is provided solely for the use of instructors in teaching their courses and assessing student learning. Dissemination or sale of any part of this work (including on the World Wide Web) will destroy the integrity of the work and is not permitted. The work and materials from it should never be made available to students except by instructors using the accompanying text in their classes. All recipients of this work are expected to abide by these restrictions and to honor the intended pedagogical purposes and the needs of other instructors who rely on these materials. PRAYER AFTER CLASS Grant me, O Lord my God, a mind to know you, a heart to seek you, wisdom to find you, conduct pleasing to you, faithful perseverance in waiting for you, and a hope of finally embracing you. Amen.