Lymphatic System Notes PDF

LYMPHATIC SYSTEM DR FARRAH SHAFEERA @ ANN IBRAHIM annshafeera@FSK UiTM'09 1 annshafeera@FSK UiTM'09 2 annshafeera@FSK UiTM'09 3  Immunity or Resistance n Ability to ward off damage or disease through our defenses n 2 types of immunity n Innate or nonspecific immunity...

LYMPHATIC SYSTEM DR FARRAH SHAFEERA @ ANN IBRAHIM annshafeera@FSK UiTM'09 1 annshafeera@FSK UiTM'09 2 annshafeera@FSK UiTM'09 3  Immunity or Resistance n Ability to ward off damage or disease through our defenses n 2 types of immunity n Innate or nonspecific immunity – present at birth n No specific recognition of invaders, no memory component n 1st and 2nd line of defenses n Adaptive or specific immunity n Specific recognition of invaders with a memory component 4  Lymphatic system structure and function n Consists of lymph, lymphatic vessels, structures and organs containing lymphatic tissue, red bone marrow n Functions of the lymphatic system 1. Drain excess interstitial fluid 2. Transport dietary lipid 3. Carry our immune responses 5 Components of the Lymphatic System annshafeera@FSK UiTM'09 6  Lymphatic vessels and lymph circulation n Vesselsbegin as lymphatic capillaries n Closed at one end n Uniteto form large lymphatic vessels n Resemble veins in structure but thinner walls and more valves n Passes through lymph nodes n Encapsulated organs with masses and B and T cells 7  Lymphatic capillaries n Slightly large diameter than blood capillaries n Unique one-way structure n Permits interstitial fluid to flow in but not out n Anchoring filaments pull openings wider when interstitial fluid accumulates 8 Lymphatic Capillaries 9  Lymph trunks and ducts n Vessels unite to form lymph trunks n Principal trunks are the lumbar, intestinal, bronchomediastinal, subclavian and jugular n Passes from lymph trunks into 2 main channels (thoracic and right lymphatic ducts) before draining into venous blood 10 annshafeera@FSK UiTM'09 11 Routes for drainage of lymph annshafeera@FSK UiTM'09 12  Formation and flow of lymph n More fluid filters out of blood capillaries than returns to them by reabsorption n Excess filtered fluid – about 3L/day – drains into lymphatic vessels and become lymph n Important function of lymphatic vessels to return lost plasma proteins to blood stream n Contain valves n Same 2 “pumps” aiding venous return also used n Skeletal muscle pump – milking action n Respiratory pump – pressure changes during breathing 13  Relationship of the Lymphatic System to the Cardiovascular System 14  1. Lymphoid Cells n Lymphocytes are the main cells involved in the immune response n Two main varieties (protect fr antigen) n T cells n B cells 15  Lymphocytes n T cells and B cells protect the body against antigens n Antigen – anything the body perceives as foreign n Bacteria and their toxins; viruses n cancer cells 16  Lymphocytes n T cells n Manage the immune response n Attack and destroy foreign cells n B cells n Produce plasma cells, which secrete antibodies n Antibodies immobilize antigens 17  Other Lymphoid Cells n Macrophages – phagocytize foreign substances and help activate T cells n Dendritic cells – spiny-looking cells with functions similar to macrophages(capture antigen&bring them back to the lymph nodes) n Reticular cells – fibroblast–like cells that produce a stroma, or network, that supports other cell types in lymphoid organs 18  Lymphatic tissues and organs n 2 groups based on function 1. Primary lymphatic organs n Sites where stem cells divide and become immunocompetent (to produce a normal immune reponse) n Red bone marrow and thymus 2. Secondary lymphatic organs n Sites where most immune response occurs n Lymph nodes, spleen, lymphatic nodules 19 Lymphoid Organs annshafeera@FSK UiTM'09 20 Figure 20.5  1. Thymus Internal Anatomy n Thymic lobes contain an outer cortex and inner medulla n Cortex contains densely packed lymphocytes and scattered macrophages n Medulla contains fewer lymphocytes and thymic (Hassall’s) corpuscles 21 n The thymus differs from other lymphoid organs in important ways n It functions strictly in T lymphocyte maturation n It does not directly fight antigens n The stroma of the thymus consists of star-shaped epithelial cells (not reticular fibers) n These thymocytes secrete the hormones that stimulate lymphocytes to become immunocompetent 22 n Thymus n Outer cortex composed of large number of T cells n Immature T cells migrate here from red bone marrow where they proliferate and begin to mature n Dendritic cells derived from monocytes assist in T cell maturation n Specialized epithelial cells help educate T cells through positive selection – only about 25% survive n Macrophages clear out dead and dying cells n Medulla n More mature T cells migrate here from cortex n More epithelial cells, dendritic cells and macrophages n Thymus shrinks with age from 70g in infants to 3g in old age 23 24  2. Lymph nodes n Located along lymphatic vessels n Scattered throughout body n Stroma – supporting connective tissue n Capsule, trabeculae, reticular fibers and fibroblasts n Parenchyma – functional part n Outer cortex – aggregates of B cells called lymphatic nodules (follicles) – site of plasma cell and memory B cell formation n Inner cortex – mainly T cells and dendritic cells n Medulla – B cells, antibody producing plasma cells from cortex, and macrophages 25  annshafeera@FSK UiTM'09 26 Structure of a Lymph Node  Lymph n Lymph flows through a node in 1 direction only n Enters through afferent lymphatic vessels n Directs lymph inward n Lymph enters sinuses (irregular channels) n Into medulla n Medullary sinuses drain into efferent lymphatic vessels n Conveys lymph, antibodies and activated T cells out of the node n Lymph nodes function as a filter n Foreign substances trapped n Destroyed by macrophages or immune response of lymphocytes 27 n Two basic functions: a) Filtration – macrophages destroy microorganisms and debris b) Immune system activation – monitor for antigens and mount an attack against them 28  Structure of a Lymph Node n Nodes are bean shaped and surrounded by a fibrous capsule n Trabeculae extended inward from the capsule and divide the node into compartments n Nodes have two histologically distinct regions: a cortex and a medulla 29 Figure 20.4a  Structure of a Lymph Node n Cortex contains follicles with germinal centers, heavy with dividing B cells n Dendritic cells nearly encapsulate the follicles n Deep cortex houses T cells in transit n T cells circulate continuously among the blood, lymph nodes, and lymphatic stream 30  3. Spleen n Largest single mass of lymphatic tissue in the body n Stroma – capsule, trabeculae, reticular fibers, and fibroblasts n Parenchyma n White pulp – lymphatic tissue (lymphocytes and macrophages) n B cells and T cells carry out immune function n Red pulp 31 n Redpulp – blood-filled venous sinuses and splenic (Bilroth’s) cords – red blood cells, macrophages, lymphocytes, plasma cells, and granulocytes n Macrophages remove ruptured, worn out or defective blood cells n Storage of up to 1/3 of body’s platelet supply n Production of blood cells during fetal life 32 n Functions: n Site of lymphocyte proliferation n Immune surveillance and response n Cleanses the blood n Stores breakdown products of RBCs for later reuse n Spleen macrophages salvage and store iron for later use by bone marrow n Site of fetal erythrocyte production (normally ceases after birth) n Stores blood platelets 33 Structure of the Spleen annshafeera@FSK UiTM'09 34  4. Lymphatic nodules n Not surrounded by a capsule n Scattered throughout lamina propria of mucous membranes lining GI, urinary, reproductive tract n Mucosa-associated lymphatic tissue (MALT) of respiratory tract n Most small and solitary n Some larger – tonsils, Peyer’s patches, appendix 35 Lymphoid Organs annshafeera@FSK UiTM'09 36 Figure 20.5 Let’s recap https://quizlet.com/86740961/lymphatic-system- organs-functions-flash-cards/ 37 annshafeera@FSK UiTM'09 38 39 INNATE IMMUNITY 40  First line of defenses: Skin and mucous membranes n Provide both physical and chemical barriers n Physical barriers n Epidermis – closely packed, keratinized cells n Mucous membranes n Mucus traps microbes and foreign substances n Nose hairs trap and filter n Cilia of upper respiratory tract propel trapped particles up and out 41 n Fluids n Lacrimal apparatus of eye n Washing action of tears n Lysozyme breaks down bacterial cell walls – n Saliva washes mouth (by salivary gland) n Urine cleanses urinary system n Vaginal secretions, defecation and vomiting-expel the microbes n Chemicals n Sebaceous (oil) glands secrete sebum – protective film, acid n gastric juice(HCl,mucus,enzymes), vaginal secretions – all acidic-discourage bacterial growth 42  Second line of defenses: 4 Internal defenses A) Antimicrobial substances 1. Interferons nProduced by lymphocytes, macrophages, and fibroblasts infected by viruses nPrevents replication in neighboring uninfected cells 43  Second line of defenses: 4 Internal defenses A) Antimicrobial substances 2. Complement nProteins in blood plasma and plasma membranes n“complement” or enhance certain immune reactions nCauses cytolysis of microbes, promotes phagocytosis, contributes to inflammation 44 3.Iron-binding proteins nInhibit growth of bacteria by reducing available iron nTransferrin(blood and tissue fluids), lactoferin(milk,saliva,mucus), ferritin(liver spleen ,rbm), hemoglobin (rbc) 4.Antimicrobial proteins (AMPs) nShort peptides that have a broad spectrum of antimicrobial activity nCan attract dendritic cells and mast cells that participate in immune responses 45 B) Natural Killer (NK) cells n Lymphocyte but not a B or T cell n Ability to kill wide variety of infected body cells and certain tumor cells n Attack any body cell displaying abnormal or unusual plasma membrane proteins n Cause cellular detruction by releasing proteins that destroy the target cell’s membrane C) Phagocytes n Neutrophils and macrophages (from monocytes) n Migrate to infected area n 5 steps in phagocytosis 46 Phagocytosis of a microbe annshafeera@FSK UiTM'09 47  1 CHEMOTAXIS Microbe 1 CHEMOTAXIS Microbe Phagocyte Phagocyte 2 ADHERENCE 3 INGESTION 2 ADHERENCE 3 INGESTION Pseudopod Pseudopod Lysosome 4 DIGESTION Lysosome 4 DIGESTION Plasma Digested microbe membrane in phagolysosome Plasma membrane Residual body 5 KILLING (indigestible Digestive material) enzymes Digestive enzymes Phases of phagocytosis Phases of phagocytosis D) Inflammation n Nonspecific, defensive response of body to tissue damage n 4 signs and symptoms – redness, pain, heat and swelling n Attempt to dispose of microbes, prevent spread, and prepare site for tissue repair n 3 basic stages n Vasodilation and increased blood vessel permeability n Emigration n Tissue repair annshafeera@FSK UiTM'09 49 i) Vasodilation and increased permeability of blood vessels n Increased diameter of arterioles allows more blood flow through area bringing supplies and removing debris n Increased permeability means substances normally retained in the blood are permitted to pass out – antibodies and clotting factors n Histamine, kinins, prostaglandins (PGs), leukotrienes (LTs), complement 50 Inflammation annshafeera@FSK UiTM'09 51  ii) Emigration of phagocytes n Within an hour after inflammation process starts, phagocyte appear on the scene.Neutrophils start to stick to the inner surface of endotheluim of blood vessel. n The neutrophils begin to squeeze through the wall of blood vessel to reach the damaged cells (emigration) n N attempt to destroy the microbes by phagocytosis n Depends on chemotaxis n Neutrophils predominate in early stages but die off quickly n Monocytes transform into macrophages n More potent than neutrophils n Pus – pocket of dead phagocytes and damaged tissue annshafeera@FSK UiTM'09 52 annshafeera@FSK UiTM'09 53 ADAPTIVE IMMUNITY annshafeera@FSK UiTM'09 54  Adaptive immunity n Ability of the body to defend itself against specific invading agents n Antigens (Ags) – substances recognized as foreign and provoking an immune response n Distinguished from innate immunity by n Specificity n Memory annshafeera@FSK UiTM'09 55  1. Maturation of T cells and B cells n Both develop from pluripotent stem cells originating in red bone marrow n B cells complete their development in red bone marrow n T cells develop from pre-T cells that migrate from red bone marrow to the thymus n Helper T cells (CD4 T cells) and cytotoxic T cells (CD8 T cells) n Immunocompetence – ability to carry out adaptive immune response n Have antigen receptors(make protein that r inserted into their plasma membranes): to identify specific antigen 56  2. types of adaptive immunity n Cell-mediated n Cytotoxic T cells directly attack invading antigens n Particularly effective against intracellular pathogens(viruses, bacteria,fungi), some cancer cells and foreign tissue transplants(inside cell) n Involve cells attacking cells n Antibody-mediated n B cells transform into plasma cells making antibodies (Abs) or immunoglobulins n Works against extracellular pathogens in fluids outside cells n Helper T cells aid in both types n CM & AM often work together to get rid of large no. of copies of particular antigen from th body annshafeera@FSK UiTM'09 57  Cell-mediated and antibody-mediated immunity Lymph nodes,spleen ,lymp nodules annshafeera@FSK UiTM'09 58  3. Clonal selection n Process by which a lymphocyte proliferates and differentiates (highly specialized cell) in response to a specific antigen n Clone – population of identical cells all recognizing the same antigen as original cell n Occur in secondary lymphatic organ & tissue n Indicator : swollen lymph nodes+tonsils when you were sick n Lymphocyte undergoes clonal selection to produce n Effector cell (inactivation of the antigen)– active helper T cell, active cytotoxic T cell, plasma cell, die after immune response n Memory cell – do not participate in initial immune response, respond to 2nd invasion by proliferating and differentiating into more effector and memory cells, long life spans destroy the ANTG fast & vigorous b4 any sign & symptom of disease can occur 59  4. Who is Antigens???? n Antigens have 2 characteristics n Immunogenicity – ability to provoke immune response n Reactivity – ability of antigen to react specifically with antibodies it provoked n Entire microbes may act as antigen n Typically, just certain small parts of large antigen molecule triggers response (epitope or antigenic determinant) 60  Diversity of antigen receptors n Human immune system able to recognize and bind to at least a billion different epitopes n An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells n Major Histocompatibility Complex Antigens (protein self antigen: located at the plasma membrane surface of most body cells) n MHC or human leukocyte antigens (HLA) n Normal function to help T cells recognize foreign or self 61  5. Pathways of antigen processing n B cells can recognize and bind to antigens(lymph, interstitial fluid, or blood plasma) n T cells only recognize fragments of antigens that are processed and presented in a certain way n Antigen processing n Antigenic proteins are broken down into peptide fragments and associated with MHC molecules n Antigen presentation – antigen-MHC complex inserted into plasma membrane n Pathway depends on whether antigen is outside or inside body cells 62 Antigen presenting cell: -process and present the antigen -APC’s include :dendritic cells, macrophage, B cell -location: place that antigen like to penetrate (skin: langerhans cell is dendritic cell)mucous membranes of resp, gastro, urinary, reproductive tract, lymph nodes. -post action: APC’s migrate from tissue via lymphatic vessels to lymph nodes 63  Exogenous and Endogenous Antigens n Exogenous antigens – present in fluid outside body cells n Antigen-presenting cells (APCs) include dendritic cells, macrophages and B cells n Ingest antigen, process, place next to MHC-II molecule in plasma membrane, and present to T cells n Endogenous antigens – antigens inside body cells n Infected cell displays antigen next to MHC-I AFTER PROCESS AN ANTIGEN APC MIGRATE TO LYMPHATIC TISSUE TO PRESENT ANTIGEN TO T CELLS T CELL BIND WITH ANTIGEN FRAGMENT MHC COMLEX TRIGGER CELL MEDIATD / ANTIBODY MDIATED IMMUNE RESPONSE 64 Exogenous Antigens annshafeera@FSK UiTM'09 65  Key: 5 Vesicles containing antigen Antigen peptide fragments and peptide 1 Phagocytosis or MHC-II molecules fuse fragments Exogenous 6 Antigen peptide endocytosis of antigen antigen fragments bind to MHC-II MHC-II molecules self-antigen Phagosome or endosome 7 Vesicle undergoes 2 Digestion of exocytosis and antigen into antigen–MHC-II peptide fragments complexes are inserted Antigen- 4 Packaging of MHC-II presenting molecules into a vesicle into plasma membrane cell (APC) Endoplasmic reticulum 3 Synthesis of MHC-II molecules APCs present exogenous antigens in association with MHC-II molecules Endogenous Antigens annshafeera@FSK UiTM'09 67 Cell-mediated immunity 68  Cell-mediated immunity n Activation of T cells n First signal in activation n T-cell receptors (TCRs) recognize and bind to a specific foreign antigen fragments that are presented in antigen-MHC complexes n CD4 and CD8 proteins are coreceptors n Second signal required for activation n Costimulation – 20 known substances (cytokines, plasma membrane molecules)interleukin 2 n May prevent immune response from occurring accidentally n Anergy – recognition without costimulation (in both B and T cells) leads to prolonged state of inactivity 69  Activation and clonal selection of helper T cells n Most that display CD4 develop into helper T cells (CD4 T cells) n Recognize exogenous antigen fragments associated with MHC-II molecules on the surface of an APC n After activation undergoes clonal selection n Makes active helper T cells and memory helper T cells n Function:help other cells of adaptive immune response combat intruders n Active helper T cells secrete variety of cytokines n Interleukin-2 (IL-2)(costimulator) needed for virtually all immune responses(enhance activation/poliferate of restingT,B,NK cell) n Memory helper T cells are not active cells – can quickly proliferate and differentiate if the antigen appears again annshafeera@FSK UiTM'09 70 Activation and clonal selection of a helper T cell annshafeera@FSK UiTM'09 71  Activation and clonal selection of cytotoxic T cells n Most that display CD8 develop into cytotoxic T cells (CD8 T cells) n Recognize antigens combined with MHC-I n Maximal activation also requires presentation of antigen with MHC-II to cause helper T cells to produce IL-2 n Undergoes clonal selection n Active cytotoxic T cells attack body cells that have been infected n Memory cytotoxic T cells do not attack but wait for a antigen to appear again annshafeera@FSK UiTM'09 72 Activation and clonal selection of a cytoxic T cell annshafeera@FSK UiTM'09 73  Elimination of invaders n Cytotoxic T cells migrate to seek out and destroy infected target cells n Kill like natural killer cells n Major difference is T cells have specific receptor for particular microbe while NK cells destroy a wide variety of microbe-infected cells n 2 ways to kill cells n Granzymes cause apoptosis (fragmentation of cellular contents) once the infected cell is destroyed the released microbs are killed by phagocytocyte n Release 2 protein from their granule : Perforin and/ or granulysin causes cytolysis (cell bursting) n Immunological surveillance n Tumor antigens displayed on cancerous cells targeted by cytotoxic T cells, macrophages and natural killer cells 74 Activity of cytoxic T cells annshafeera@FSK UiTM'09 75 Antibody-mediated immunity 76  Antibody-mediated immunity n Activation and clonal selection of B cells n During activation, antigen binds to B cell receptor (BCRs) n Can respond to unprocessed antigen n Response much more intense when B cell processes antigen*antigen processing stage n Antigen taken into B cell, combined with MHC-II, moved to plasma membrane, helper T cell binds and delivers costimulation (interleukin-2 and other cytokines) n Once activated, B cell undergoes clonal selection.Produce: n Plasma cells secrete antibodies (4-5 days until plasma cell die) n Antibody travel in lymph and blood to the invasion site) n Memory B cells do not secrete antibodies but wait for reappearance of antigen 77 Activation and clonal selection of B cells annshafeera@FSK UiTM'09 78  Antibodies (Ab) n Can combine specifically with epitope of the antigen that triggered its production n Belong to group of glycoproteins called globulins n Ab are immunoglobulins (Igs) n 4 polypeptide chains – 2 heavy (H) chains, 2 light (L) chains n Hinge region – antibody can be T shape or Y shape n Variable (V) region at tips of each H and L chain n 2 antigen-binding sites - bivalent n Constant (C) region – remainder of H and L chain n Same in each 5 classes – determines type of reaction 79 Chemical structure of the immunoglobin (IgG) class of antibody 80  Antibody actions n Neutralizing antigen (antibody+antigen) - neutralize & prevents attachments of some virues to body cells n Immobilizing bacteria (limits bacterial spread) - To lose their motility (limits bacterial spread into nearby tissues) n Agglutinating and precipitating antigen (clumping together) - antigen antibody complex activate compleent proteinsà cytolysisàmicrobe removed n Enhancing phagocytosis (attrction) - antigen antibody bind: antibody (flag) attract phagocytes. 81  Immunological memory n Thousands of memory cells exist after initial encounter with an antigen n Next time antigen appears can proliferate and differentiate within hours n Antibody titer measure of immunological memory n Amount of Ab in serum n Primary response n Secondary response faster and stronger 82  Self-recognition and self- tolerance n Your T cells must have n Self-recognition – be able to recognize your own MHC n Self-tolerance – lack reactivity to peptide fragments from your own proteins n Pre-T cells in thymus develop self-recognition via positive selection – cells that can’t recognize your own MHC undergo apoptosis n Self-tolerance occurs through negative selection in which T and B cells that recognize self peptide fragments are eliminated n Deletion – undergo apoptosis n Anergy – remian alive but are unresponsive 83 Development of self- recognition and self-tolerance annshafeera@FSK UiTM'09 84