Lymphatic System PDF

Lymphatic System harry potter symbol - Bing images defense against the dark arts - Bing images Randal Gregg, PhD Learning Objectives 1) Identify the site of hematopoiesis and cell differentiation occurring to generate all of the white blood cells. 2) Distinguish between the cells and functions o...

Lymphatic System harry potter symbol - Bing images defense against the dark arts - Bing images Randal Gregg, PhD Learning Objectives 1) Identify the site of hematopoiesis and cell differentiation occurring to generate all of the white blood cells. 2) Distinguish between the cells and functions of the red and white pulp of the spleen as well as the follicle, medulla, and paracortex of the lymph nodes. 3) Recall the functions of the lymphatic system and define how osteopathic manipulative medicine can affect the lymphatics and immunity. 4) Identify the site of lymphatic drainage into the blood. 5) Distinguish between afferent and efferent lymphatic vessels and the role of high endothelial venules in immune cell trafficking. 6) Recognize the structural features and associated immune cells of the secondary lymphoid tissues (liver, MALT, GALT, and BALT). 2 ORGANS OF THE IMMUNE SYSTEM PRIMARY LYMPHOID ORGANS Site of immune cell birth and development (or maturation) 3 Bone marrow (BM) RED MARROW • Spongy (cancellous) portion of the bone • Flat bones (hip, breast, skull, ribs, vertebrae, scapula) • Epiphysis of long bones (femur, humerus) YELLOW MARROW • Storage of fat cells for energy reserve • All marrow is red at birth – 50% red and 50% yellow in adults (about 6 lbs) 4 Bone marrow stroma • Bone marrow is the niche devoted to protected cell proliferation • Hematopoiesis = process of generating blood cells • Bone marrow stromal cells are tissues not directly involved in the primary function of hematopoiesis o Provides the microenvironment that facilitates hematopoiesis by the parenchymal cells o Generate colony stimulating factors to impact development and differentiation of cells • Blood enters the bone, enters the stroma, collected in sinuses • Newly produced cells extravasate into the sinuses to enter the circulation 5 Hematopoietic stem cells differentiate into lymphoid and myeloid precursors Common Lymphoid Progenitor Common Myeloid Progenitor 6 CLP differentiate into lymphocytes Common Lymphoid Progenitor (CLP) 7 CMP differentiate into granulocytes, monocytes, red blood cells and platelets Common Myeloid Progenitor (CMP) Mast cell 8 Central macrophages surrounded by erythroblasts • Up to 30 erythroblasts bound to each central macrophage • Macrophage transfers iron directly to the erythroid progenitors • Young reticulocytes expel nuclei which are taken up by the macrophage • Reticulocytes detach and enter the sinuses 9 Destinations for cells leaving the BM Blood Tissue Bone Marrow Spleen Thymus Lymph Nodes 10 ORGANS OF THE IMMUNE SYSTEM SECONDARY LYMPHOID ORGANS Site of immune cell storage, activation and response to infection Organized to optimize interactions of antigens, antigen-presenting cells and lymphocytes for a productive adaptive immune response 11 Newly formed (NF) B cells can exit the BM and enter spleen Naïve B cells acquire a receptor in the BM 12 Red pulp contains dendritic cells and macrophages that filter blood for antigens Red Pulp • Filters blood, removes old red blood cells and pathogens • Vascular sinusoids separated by connective tissue called splenic cords (contain high numbers of plasma cells, dendritic cells, macrophages and red blood cells) • Reserve store of blood (in case of hemorrhage) • Site of hematopoiesis if bone marrow fails 13 B and T cells are localized to the white pulp White Pulp • Periarteriolar lymphoid sheath (PALS) containing dendritic cells and T cells • B cells in lymphoid follicles Marginal Zone • Area between red and white pulp • Site where Ag in blood is captured • Residence for marginal zone B (MZB) cells (rapid IgM response) 14 SPLEEN NF B cells localize to the T cell zone Newly Formed (NF) B cell 15 NF B cells produce transition B cells and then follicular (FO) and marginal zone (MZ) B cells FO B cells NF B cells Transition B cells In T cell zone MZ B cells 16 FO B cells move to the follicles NF B cell FO B cell MZ B cell 17 MZ B cells migrate to the marginal zone NF B cell FO B cell MZ B cell 18 T cells from the thymus localize to the T cell zone NF B cell FO B cell MZ B cell T cell 19 Microbes or antigens in the BLOOD can now be detected and a response generated 20 LYMPHATIC SYSTEM 21 Lymph and lymphatic vessels • Lymph is a collection of fluid derived from cellular secretions and the clear liquid pushed out of capillaries – the fluid that surrounds and bathes tissues • The lymph is collected from tissue into lymphatic capillaries and directed to lymph nodes which filter (sample) the lymph prior to returning the fluid to venous circulation 22 Organization of the lymph nodes (LN) Afferent lymphatic vessel FO B cell T cell Efferent lymphatic vessel LN Compartmentalization • Naïve B cells and Follicular DC (FDC) are localized in follicles and activated B cells/plasma cells are concentrated within the germinal centers • T cells and DC in paracortex • Macrophages and Plasma cells (PC) in medulla 23 Function of the lymphatics 1 Maintain fluid balance in the internal environment • Plasma filters into interstitial space from blood flowing through the capillaries • If fluid remains → tissue damage would result • Interstitial fluid is: o Absorbed by tissue cells o Reabsorbed into blood o Taken up by lymphatic vessels which returns it to circulation 24 Function of the lymphatics 2 Aid with absorption of digested fat • Transport of dietary lipids into circulation is different from what occurs with sugars and amino acids • Monoglycerides and fatty acids from the diet enter by simple diffusion across enterocyte membranes or via transporter proteins • In the enterocyte – monoglycerides and fatty acids converted to triglycerides • Triglycerides are packaged w/ cholesterol, lipoproteins, other lipids into chylomicrons • Chylomicrons are released from enterocytes and taken up by lymphatic vessels • Chylomicron-rich lymph drains into lymphatics eventually emptying into the venous blood 25 Absorption of digested fat • When large numbers of chylomicrons are being absorbed, the lymph draining from the small intestine appears milky and the lymphatics are easy to visualize • In the image of abdominal contents from a coyote, the fine white lines (arrows) are intestinal lymphatics packed with chylomicrons • The lymph passes through mesenteric lymph nodes (LN) and then into larger lymphatics 26 Function of the lymphatics 3 Generate immune response against pathogens (antigens) • 600-700 lymph nodes in the average human • Lymph nodes (LN) filter lymph before returning it to the circulation • Immune cells activated in LN • Damaged or destroyed LN do not regenerate • Pressure from interstitial fluid forces the single cell endothelial cells of lymphatic capillaries to open briefly • Lymph enters and surrounding tissue movement drives lymph through the vessels LN 27 Valves in the lymphatics aid lymph flow 28 Mechanisms for lymph movement • Lymphatics designed so lymph only flows upward traveling from extremities toward the neck • Lymph moves through the thoracic duct at 125 ml/hr and enters the subclavian veins to become plasma in the bloodstream • Mechanisms promoting movement of lymph: o Breathing o Skeletal muscle contractions o Segmental contractions o Posture changes o Message or osteopathic manipulative medicine (OMM)   Lymph flow increases 10- to 15-fold during exercise Smooth muscle of lymphatic vessels contract to move lymph slowly 29 Improving lymph flow • • Damage disturbs the flow of lymph o When lymphatic tissue or nodes are damaged, destroyed or removed, lymph cannot drain normally from the affected areas o Excess lymph accumulates and results in swelling (edema) (1926) Lymphatic pump o • C. E. Miller Method of manipulation used by osteopathic physicians to increase the rate of lymph flow and reduce edema to fight infections by “exaggerating respiratory movement” Lymphatic Pump Techniques (LPT): o Thoracic LPT o Pedal Pump o Abdominal LPT 30 Abdominal pump Abdominal lymphatic pump treatment increases lymphatic flow 31 Lymphatic drainage Left Lymphatic Drainage Right Lymphatic Drainage • • • Right side of head & neck Right arm Upper right quadrant Empties into Right Lymphatic Duct • • • • * * Left side of head and neck Left arm Upper left quadrant Lower trunk & both legs Cisterna Chyli (transient storage of lymph from abdomen and legs) Thoracic Duct (transports lymph upward to empty into Left Lymphatic Duct) Duct empties into Right Subclavian Vein* Duct empties into Left Subclavian Vein* 32 33 Major lymph nodes • Cervical • Axillary • Thoracic Cavity • Supratrochlear • Abdominal • Pelvic Cavity • Inguinal – – – – – – – Drains head and neck Drains upper arm and upper thoracic area (+ breast) Drains organs of thorax (heart, lungs) Drains above bend of elbow (lower arm) Drains areas of the GI tract and trunk Drains pelvic area including internal genitals Drains legs and external genitals 34 Immune cells enter LN from TISSUES by afferent lymphatic vessels 35 Immune cells enter LN from BLOOD CIRCULATION by high endothelial venules Entry into LN by HEV requires expression of CCR7 by the cells CCR7 binds CCL19/CCL21 on HEV surface 36 ORGANS OF THE IMMUNE SYSTEM SECONDARY LYMPHOID ORGANS Other sites of immune reactivity Often these sites are the first to contact an infectious agent 37 Bloodborne pathogen detection in the liver • Largest glandular organ in the body • Divided into four unequal lobes • Functions: o Breaks down fats, converts glucose to glycogen o Makes proteins (including acute phase proteins) o Stores vitamins and minerals (A, D, K, B12) o Contains Kupffer cells (liver macrophages)   Capture antigens (pathogens) from blood Remove antigens (pathogens) bound by antibodies 38 Organization of the liver Hepatic lobule 39 Hepatic lobules 40 Sinusoids are sites of immune reactivity Antigen-rich blood from the GI tract is directed through a network of sinusoids and scanned by antigen-presenting cells and lymphocytes (NK, B and T cells) Antigen is presented by LSEC (liver sinusoid endothelial cells), KC (Kupffer cells) and resident DC (dendritic cells) 41 Mucosal associated lymphoid tissue (MALT) are sites of immune reactivity in the mucosa “Tonsils” • Lymphoid tissue found on both sides of the throat targeting pathogens of the upper respiratory & GI tracts • Three sets of tonsils: • Largest at puberty then regress in adulthood • Surveys oro-pharynx for inhaled/ingested pathogens • Tonsillar crypts catch food particles and sample for pathogens (site of pus collection) − − − Palatine (back of the throat) Pharyngeal (adenoids) Lingual (base of tongue) 42 General organization of the MALT 43 Gut associated lymphoid tissue (GALT) “Peyer’s Patches” – Tonsils of the Intestines Aggregations of lymphoid tissue in lamina propria (mucosa) of intestines 44 Microfold (M) cells are key to GALT responses “Peyer’s Patches” • Antigen presenting cells near surface to sample gut contents • M cells are phagocytic and direct gut materials to follicles and lymph nodes • Macrophages, T cells and dendritic cells operate to promote IgA production by B cells • IgA limits mucosal colonization by pathogens • Bronchial associated lymphoid tissue in the lungs similar in architecture and function to the GALT 45 Other GALT “Appendix” • Blind-ended pouch protruding off of the colon • Site of cellulose digestion (horses, cows) • Harbors commensal intestinal flora • Contains lymphoid tissue similar to Peyer’s Patches 46 Vast immune components in the skin 47 Questions? hogwarts dining hall wallpaper - Bing images 48 Next… Antigens and Immunogens Hogwarts Express Wallpaper (65+ images) (getwallpapers.com) 49