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Hematolymphatic System/Anatomy BLOOD: INTRODUCTION • The blood is formed of cells and fluid called plasma. • Cells: RBCs (erythrocytes), WBCs (leucocytes) and Platelets (thrombocytes). • The plasma contain many substances such as nutrition, proteins hormones, minerals (Na, K, Ca and others). • When we remove coagulation factors removes from the plasma it became serum. So, serum is plasma without clotting factors such as fibrinogen Plasma Proteins and their functions • Albumin: maintains osmotic pressure + • Globulin: transport vitamins, lipids, iron + • Clotting proteins: examples; prothrombin and fibrinogen • Complement proteins: kill microbes and initiate inflammation • Other proteins Cells:All cells are formed within the bone marrow WBCs are biconcave Discs WBCs: Granulated (neutrophiles, eosinophiles and basophil) and non-granulated (monocytes and lymphocytes. Platelets: the smallest blood cells What you should know about cells • • • • • • Shape Size Structure Number (ratio) Function Features and identification RBCs: About 43% of the blood volume • Shape: Biconcave disks • Diameter: about 7.5 um with thickness 2um at peripheral and < 1 um in the center. • Number: 5 millions/cubic mm in male and 4.5 cubic millions in female • Structure: In human; RBCs have no nuclei or organelles. They are filled with Hemoglobin. Also, they contain enzymes such as carbonic anhydrase • Function: main function is to carry O2. • RBCs: life about 120 days and old cells destroyed by spleen RBCs: Scanning EM RBCs: Light Microscope (LM) WBCs • About 1% of the blood volume and form then layer between the RBCs and the blood plasma on centrifugation called Buffy coat • Classified based on whether they contain specific granules or not into: • Granuloctes (neutrophiles, eosinophiles and basophil) and • Non-granulocytes (monocytes and lymphocytes). WBCs Features Neutrophils Eosinophils Basophils Lymphocytes Monocytes Numb/ Ratio 3500-7000 60-70% 150-400 2-4% 50-100 <1% 1500-2500 20-25% 200-800 3-8% Diameter/ 8-9 um 9-11 7-8 7-8 10-12 Nucleus 3-5 lobules 2 lobules S-shape round Kidney shape Specific granules + Fine - - Life span <1 week <2 weeks 1-2 years Months to Years Days in blood Months in CT Function Kill bacteris Kill parasites Histamine Heparin +.. Immune response Give Macrophage + Medium + Large LM/ Neutrophils: Barr body (sex chromosome): drumstick structure attached to the neutrophils nuclei and contains X chromosome in females LM/ Neutrophils LM/ Neutrophils LM/ Eosinophils LM/ Basophil • LM/ Monocyte LM/ Monocyte Lymphocytes: B and T lymphocytes LM/ Plasma cells Platelets or thrombocytes • The plateletes are small (2-4 um) non-nucleated fragments of large cells in the bone marrow called megakaryocytes • Number:250000-400000/cubic mm and live less that 14 days • It is formed of peripheral clear (light) zone called hyalomere and central darker region called granulomere. • Hyalomere contains: 1-10-15 parallel microtubules and actin and myocin that can form contractile apparatus and 2-two tubular systems (surface and dense tubular systems). The lumen of the surface coiled tubular system one outside and therefore increase the syrface area of the platellets 7-8 times. • Granulomere: contains three types of granules (alpha, delta and lambda (the lambda are lysosomes), some mitochondria, peroxisomes, glycogen and enzymes. • Function: the platelets limit hemorrhage (bleeding). Platelets:LM & TEM LM/Identify these cells LM/ Identify these cells LM/Identify these cells SEM:RBC, WBC and platellet Identify/TEM Hempoisies: formation of blood cells • About 100 bilion BCs produced daily with our BM to replace the BCs that die or leave the circulation • Pahses: 1-mesoblastic in the YS in the 3rd weeks of the prenatal life…..>nucleated erythrocytes. 2-Hepaticby 6th week of the prenatal life …..>nucleated erythrocytes. 3-Splenic begins during the second trimester …..>nucleated erythrocytes,4-myeloid start in the 5th month to the end of life of the prenatal life …..>non-nucleated erythrocytes Sites of Hemopoiesis Hemopoiesis:Growth Factors Hemopoiesis:Stem cell...>Progenitor cells....>Precursor cells...>BCs ERYTHROPOIESIS ERYTHROPOIESIS • The precursor cells called Proerythroblast….> • Basophilic erythroblast….> Polychromatophilic erythroblast….>Orthochromatophilic erythroblast….>Reticulocytes….>Erythrocytes • Size decrease from 14-19um to 7-8um • Nucleus decrease in size then leave the Orthochromatophilic erythroblasts (normoblast) and become reticulocytes that leave bone marrow to become mature in the circulation (erythrocytes). • Cytoplasm:blue…>yellow-pink in blue background in Polychromatophilic erythroblast….>pink in blue background……>pink in reticulocytes and erythrocytes. Bone Marrow • The only site of hemopoiesis after birth • Structure: The BM background is reticular CT with reticular fibers and reticular cells. Within this tissue, there are large blood capillaries (sinusoids) between arterioles and venules. Between these sinusoids, there are islands of hemopoiesis cells which include stem cells, progenitor cells, precursor cells and different types of blood cells in different stages of development. Also, there are macrophages (nurse cells) in the BM which remove nuclei of erythroblasts, bring hem (iron) for the developing RBCs, remove deformed cells and help development and maturation of some types of blood cells • Types: Red BM (more active) and Yellow BM. In Babies, all of the BM is Red. At age 20 years, the BM of diaphysis of long bones become yellow MB because the reticulocytes store fat. Bone Marrow: Structure RBM and YBM: at age 20, BM in diaphysis become yellow BM LYMPHATIC (IMMUNE) SYSTEM: INTRODUCTION • Lymph • Lymphatics • Lymphatic tissue Lymph:extra amount of intercellular fluid that enter lymphatic capillaries Lymphatic vessels:left lymphatic duct (thoracic duct) and right lymphatic duct Body parts drained by left lymphatic duct (thoracic duct) and right lymphatic duct Lymph capillaries similar to blood capillaries but thinner while the lymph vessels are similar to the veins with valves but thinner Lymphoid Tissue • Diffuse lymphatic tissue : lymphocytes: free or organized in lymph follicles (nodules). • Aggregated lymphatic tissue : 1.Capsulated ( surrounded by dense irregular CT capsule that send trabeculae C.T capsule ) : , lymph nodes , spleen and thymus . The background of these organs are formed of reticular CT. 2. Partially capsulated : tonsils 3.Non-capsulated : peyer’s patches . Lines of body defence • A-Physical barriers exs: skin and MM • B-Immune system which is classified into two systems: • 1-Innate immune system and • 2-Adaptive immune system The Innate Immune System • Features: 1-natural, 2-rapid and with no immunological memory and 3-non-specific. • Components: • A- Cells: 1-Neutrophiles, 2-Macrophages and 3-Natural killer cells (NKCs). • B-Chemicals:1-complements,2-antimicrobial peptides and cytokines of different types. Cells of the Innate Immune System • -Neutrophiles: Kill bacteria • -Macrophages: They act as antigen presenting cells, have receptors for antibodies and release colony-stimulating factors (CSF): G-CSF and GM-CSF that stimulate the formation and releasing of neutrophiles. • NKCs: Kill tumor cells, virally infected cells, bacteria and parasites. They have receptors for antibodies that mediate their cytotoxicity (antibody-dependent cellular cytotoxicity), also they have both killer-activating receptors and killer-inhibitory receptors. The killerinhibitory receptors recognize MHC I (major histocompatibility complex type I) that are located in the plasma membrane of healthy cells, So, the NKCs recognize the healthy cells and do not kill them Notes on cells of the Innate Immune System • 1- The NKCs recognize MHC I (major histocompatibility complex type I) of healthy cells, So, they do not kill them. But these MHC I are necessary for another killer cells (T Killer or T cytotoxic lymphocytes). This make these T lymphocytes unable to recognize and kill tumor and virally infected cells which suppress (inhibit) the production of MHC I. However, this maneuver by the tumor and virally infected cells make then targets to the NKCs. • 2-The cells of the innate immune system depend on ToLL-like receptors to initiate their inflammatory and immune responses. The ToLL-lke receptors are of different types and locations (both intracellular and parts of the plasma membrane (see page 275). Chemicals of the innate immune system • 1-complements: blood proteins that can kill microbes by damaging their plasma membrane • 2-antimicrobial peptides: ex: defensins that produces by epithelial cells and can kill gramnegative bacteria • 3-cytokines: there are different cytokines released by various cells of both innate and adaptive immune systems. Exs:1-interleukins released by lymphocytes, 2-interferons have antiviral activity, 3-colonystimulating factors (CSF) that stimulate production of blood cells (hemopoeisis) and 4-chemokines that attract WBCs to sites of inflammation. Adaptive immune system • A-features: acquired, have immune memory, specific and have self/nonself recognition • Components: 1-B lymphocytes, 2-T lymphocytes and 3-antigen presenting cells (macrophages) B and T lymphcytes • B lymphcytes: activated by antigen (microbes) and start mitosis and differentiate into: 1-B memory cells and 2-plasma cells.....>antibodies (humorally mediated immune response). Immunogloblins types:IgM, IgA, IgG, IgD and IgE. • T lymphocytes enter thymus as immature cells, then leave the thymus after programmed as immunologically competent cells called naive cells which when activated by tumor or microbes (bacteria, virus) they divide by mitosis and differentiate into: 1-memory cells and 2-effector cells (T-helper cells, Cytotoxic T-lymphocytes/T killer cells......>cellularly mediated immune response and T-regulatory cells) Capsulated lymphatic tissue :Lymph Nodes Lymph drainage from different parts of the body Lymph Nodes • Ovale or kidney shape organs with convex and concave surfaces with hilum with diameter normally less than 3 cm. • Distribution:widespread especially in the neck, axilla, groin and along the large blood vessels. • It is surrounded by CT capsule that send trabeculae with subcabsular sinus and paratrabecular sinuses. • It is formed of 1-cortex with lymphoid follicles (nodules)/B lymphocytes and plasma cells,2-paracortex/T-lymphocytes and medulla with medullary cords (B-lymphocytes, plasma cells and macrophages) and medullary sinuses (filled with lymph). • Lymph circulation: lymph enter through affarrent lymphatics…….> subcabsular sinus………>paratrabecular sinuses…….>efferent lymphatics. The lymph nodes filtrate lymph and become large and hard in cases of infection or tumor. Lymph Nodes: Main parts Lymph Nodes:Cross section It’s coverd by capsule (capsulated) wihch invades the tissue but without separating it into lobes. - In the lymph node you have two areas, cortex which is darker in color, and the medulla. - The lymph nodules are all found in the cortex. - The medulla is composed of: medullary cord and sinuses. Lymph Nodes: Cortex and Medulla Lymph Nodes: Lymphoid Follicles Zones of the Germinal Centers: • Central dark zone formed of centroblasts……> basal light zone formed of centrocytes with switch immunoglobulins (sIgs)…….>light apical zone to become either B memory lymphocytes or plasma cells Capsulated lymphatic tissue : Spleen The spleen • Remember this rule about the spleen:1x3x5 (dimentions in inchesx7 (weight in oz, in grams=150-200)x9x11(related left ribs). • Surfaces, borders and relations: 1-diaphragmatic (smooth and convex and directed upward, backward and laterally) the spleen is related to the diahphragm which separate it from the left 9-11 ribs and left lung and plura 2-visceral with gastric (directed forward upward and to the right and located behined the stomach) and renal (posteriorly) parts.concave with hilum. Also, this surface related to the tail of pancrease and colon. The spleen has anterior and posterior borders. • Supplied mainley by the splenic artery/branch of the celiac trunck and drained by splenic vein (part of the portal venus system) • Functions: 1-remove old RBCs (Red Bulbs), 2-part of our immune system (White Bulbs), 3-other functions such as RBCs production in embryo and production of lymphocytes. • It has only efferent (with no afferents) lymphatics • The spleen developed from mesoderm (from and within the dorsal mesentery). Spleen: cross section shows White Pulps and Red Pulps - It’s covered by connective tissue capsule that send trabeculae. - The spleen is formed of red pulps and white pulps. -The red pulps and white pulps are scattered everywhere in the organ. --The white pulps are formed of nodules (Malpighian nodules)/B-lymphocytes and periarteriolar lymphatic sheath (PALS)/T-lymphocytes while the red pulps are formed of splenic sinuses (filled with blood)and splenic cords (lymphocytes, macrophages) Spleen Spleen: closed and open circulation Spleen: White Pulp Spleen: White pulb Capsulated lymphatic tissue : Thymus Thymus:location, development,blood supply and hormones • It is located in the superior mediastinum just behind the manubrium. It may exten upward to reach the thyroid gland and downward to the anterior medistinum. It is large in children then start to decrease with age so, in old people it is replaced by almost fat tissue. • It is arise from the third pharyngeal pouch high in the neck then descends down to its normal position in the superior mediastinum. Tissue of the thymus gland may be found along its descending path or even embedded in the thyroid gland. • It is supplied by the internal thoracic a. and drained into the brachiocephalic vein and the internal thoracic vein. • It release hormones like thymopoietin, thymoycin and thymonolin to control development and maturation of T-lymphcytes • Like the spleen, the thymus has efferents but not afferents lymphatics. Thymus: cross section The thymus is also capsulated organ. - There is no lymphatic nodules in the thymus. - it’s divided by the connective tissue into completely separated lobes. - You can identify the cortex (dark zone) and the medulla (light zone) in the thymus in each lobe. Thymus: Cross section * Each lobule has an outer, darker staining cortex and an inner, paler staining medulla. Cortex of thymus: Cell Types • A-T-Lymphcytes (Thymocytes) • B-Epithelial reticular cells: three types: Types I separate the cortex from the CT capsule and trabculae and from BV with tight junctions between them, Type II located in the midcortex with long, wide sheath-like processes with desmosomes between them to divide cortex into compartents, Type III located in the center with long, wide sheath-like processes to form compartments and also located close to the medulla with tight junvtions to isolate cortex from the medulla Medulla of the thymus: Cell Types • A-T-Lymphcytes (Thymocytes) • B-Epithelial reticular cells: three types: Types IV located close to the cortex, Type V located in the middle of the medulla, Type VI large pale stained cell that………….>Hassale’s corpuscles that increase with age • NOTE:the cortex is formed of more Tlymphocytes and less Epithelial reticular cells, So it has dense (blue) stain while the medulla is formed of more Epithelial reticular cells and less T-lymphocytes, So it has light stain Thymus: Hassall’s corpuscles Thymic corpuscle Thymus: Development and Location Partially capsulated (Tonsils) : • They belong to Mucosal Associated Lymphoid Tisse (MALT) but considered organs because they are partially encapsulated. • Tonsils are covered by epithelium. • They include: - Palatine tonsils - Pharyngeal tonsils - Lingual tonsils. Palatine Tonsil it’s partially capsulated tissue and partially covered by epithelium ⇒ Tonsil. -The noncapsulated surface is covered by stratified sqaumous epithelium. - The most important identification mark is the crypts .. If you have multiple crypts which are very deep ⇒ Palatine tonsil. Lingual Tonsil Tonsil which covered by stratified squamous epithelium without deep crypts ⇒ Lingual tonsil. Pharyngeal Tonsil Tonsil that has nodules and covered by psedostratified squamous epithelium (respiratory epithelium) ⇒ Pharyngeal tonsil Mucosa-associated lymphoid tissue (MALT) : Diffuse or non-capsulated aggregated -Within the lamina propria of the mucosa of: the respiratory, gastrointestinal, urinary and reproductive tracts. - It is formed of diffuse lymphocytes or lymphocytes organized in follicles or both -At some location it is formed of many follicles in this case we can give them names: example; the Peyer’s patches of the ilium. Lymphoid follicles or nodules: Primary and secondary. The secondary GC stained light because its cells are large with large cytoplasm and small nuclei while the peripheral part stained dark and called mantle or corona. The can be present in all types of lymphoid tissue (diffuse and aggregated, except the thymus)