Blood Physiology Professor A.M.A Abdel Gader MD, PhD, FRCP (Lond., Edin), FRSH (London) Professor of Physiology, College of Medicine & King Khalid University Hospital Riyadh Lecture # 4 & 5 Leucocytes White Blood Cells (WBCs) Granulocytes, The Monocyte-Macrophage System Leucocytes (WBCs) • • • • General Characteristics & types of WBCs Genesis (Production) of WBCs Life Span of WBCs Defense properties of neutrophils & macrophages – – – – Chemotaxis Diapedesis Amaeboid Motion Phagocytosis Blood Film Hematopoiesis Leucocytes (WBCs) – cont. General Characteristics & types of WBCs • Types of WBC 1. Granular (polymorphnuclear): • Neutrophil 62%. – 10-16um, nucleus 2-5 lobes, purple cytoplasmic granules • Eosinophil 2.3%. – 12-18um, 2 lobes nucleus, coarse red granules • Basophil .4%. – 10-14um, rarely segmented nucleus, nucleus hidden by large round bluish granules Leucocytes (WBCs) – cont. General Characteristics & types of WBCs • Types of WBC 2. Agranular WBC – Monocytes 5.3% • 15-20um, kidney shape nucleus – Lymphocyte 30% • round nucleus – small (5-8um) – large (9-15um) Formed Elements of Blood • Red blood cells ( erythrocytes ) • White blood cells ( leukocytes ) – granular leukocytes • neutrophils • eosinophils • basophils – agranular leukocytes • lymphocytes = T cells, B cells, and natural killer cells • monocytes • Platelets Leucocytes (WBCs) – cont. Genesis (Production) of WBCs Pluripotential stem cell Committed Stem cell RBCs Mylocytic Linage WBCs Platelets Lymphocytic Linage Hematopoiesis Leucocytes (WBCs) – cont. Genesis (Production) of WBCs- leucopoiesis) Sites of WBC formation • Granulocytes (neutrophil, basophil, eosinophil): – bone marrow • Agranulocytes – lymphocytes- bone marrow, thymus, lymphoid tissues – monocytes- bone marrow Life Span of WBCs Granulocytes: • 4 to 8 hrs (transit time ) in blood circulation • 4 to 5 hrs in tissues – In infections life span a few hours Monocytes : – 10 to 20 hrs in blood circulation – Leave capillaries to tissues, increase in size to become tissue macrphages which live for months Life Span of WBCs-cont. Lymphocytes: • A few hrs in blood circulation >> tissues >> lymph >>> Blood (Recirculation) ?Life span: weeks to months Leucocytes (WBCs) • • • • General Characteristics & types of WBCs Genesis (Production) of WBCs Life Span of WBCs Defense properties of neutrophils & macrophages – – – – Chemotaxis Diapedesis Amaeboid Motion Phagocytosis Defense properties of neutrophils & macrophages • Attack and destroy bacteria, viruses • Sequence of events: – – – – Chemotaxis Diapedesis Amaeboid Motion Phagocytosis Netrophils function-cont. Defense properties of neutrophils & macrophages-cont Phyagocytosis: Engulfing and killing of bacteria or any invading organism Steps: Chemotaxis: – – Bacterial & viral toxins • Products of damaged tissues : attract neutrophil to accumulate at infected site. Opsonization: plasma substances (IgG) attached to the bacteria to make them easy to phagocyte Diapedesis Diapedesis http://www.whfreeman.com/immunology/CH01/diapedesis.htm Defense properties of neutrophils & macrophages • Attack and destroy bacteria, viruses • Sequence of events: – – – – Chemotaxis Diapedesis Amaeboid Motion Phagocytosis Defense properties of neutrophils & macrophages • Attack and destroy bacteria, viruses • Sequence of events: – – – – Chemotaxis Diapedesis Amaeboid Motion Phagocytosis Phagocytosis- cont. Phagocytosis is selective: Distinguish self from non-self…... How? – Normal tissues have smooth surface – Normal tissues have protective protein surface – Antibodies coating bacteria (Opsonization) Phagocytosis Phagocytosis by neutrophils- cont. Neutrophils attach to bacteria & encircled it with pseudopodia and take it into a vacuole (phagosome). • One Neutrophil can engulf 3 to 20 bacteria • One Macrophage can engulf up to 100 bacteria Microbial killing: fusion of neutrophil granules with vacuole, – – Discharge of lysozyme, myeloperoxidase enzymes into the vacuole, killing and digesting the engulfed bacteria. Release of Free radicals by oxidizing agents: superoxide, hydrogen peroxide to kill the bacteria Leucocytes (WBCs) – cont. • Types of WBC 1. Granular (polymorphnuclear): • Neutrophil 62%. – 10-16um, nucleus 2-5 lobes, purple cytoplasmic granules • Eosinophil 2.3%. – 12-18um, 2 lobes nucleus, coarse red granules • Basophil .4%. – 10-14um, rarely segmented nucleus, nucleus hidden by large round bluish granules Blood Film Eosinophils Function: • Phagocytosis: Phagocytosis is same as neutrophil, but less efficient • Chemotaxis: eosinophil attracted towards chronic inflammation/allergic tissue (allergic disease of skin & lungs) By eosinophil chemotactic factor Phagocytose (& detoxify) antigen/antibody complexes Eosinophils cont, • High eosinophil count: – Parasitic (hook worm, ascaris, bilharzia) – Allergic (asthma, rhinitis, drug reaction) – Allergic skin diseases Leucocytes (WBCs) – cont. • Types of WBC 1. Granular (polymorphnuclear): • Neutrophil 62%. – 10-16um, nucleus 2-5 lobes, purple cytoplasmic granules • Eosinophil 2.3%. – 12-18um, 2 lobes nucleus, coarse red granules • Basophil .4%. – 10-14um, rarely segmented nucleus, nucleus hidden by large round bluish granules Leucocytes (WBCs) – cont. • Types of WBC 1. Granular (polymorphnuclear): • Neutrophil 62%. – 10-16um, nucleus 2-5 lobes, purple cytoplasmic granules • Eosinophil 2.3%. – 12-18um, 2 lobes nucleus, coarse red granules • Basophil .4%. – 10-14um, rarely segmented nucleus, nucleus hidden by large round bluish granules Blood Film Basophils • • • • Similar to tissue mast cells Non-phagocytic cells Granules: dark blue color. Granules contain: – Heparin – Histamine – Serotonin (5HT). Released during allergic reactions Hematopoiesis Blood Film Defensive Functions of the Monocytes • Directly: – phygocytosis of bacteria, dead cells etc • Indirectly: – Cooperates with lymphocytes by: • Recognizing the foreign body • Ingesting the foreign body • Processing the foreign body • Presenting it to lymphocytes Monocyte-macrophage system Reticulo-endothelial System Reticuloendothelial System-RES Blood Monocyte Tissue macrophage Attached (fixed) Mobile Function is phagocytosis of: • • • • Bacteria Viruses Dead tissues Foriegn particles Immune function Reticuloendothelial System-RES • RES is widespread in the body Cells of the RES: – Monocytes (blood macrophages) – Mobile and fixed tissue Macrophages – Specialiazed endothelial cells in bone marrow, lymph nodes and spleen – Reticular cells of lymph nodes spleen & bone marrow. Reticuloendothelial System-RES Cells of the RES - Distribution: • Tissue Macrophages in skin SC tissues • Tisssue Macrophages of lymph nodes • Tissue macrophages in lungs • Macrphages (kupffer cells) in the liver • Macrphages in the spleen and bone marrow Reticuloendothelial System-RES Blood Monocyte Tissue macrophage Attached (fixed) Mobile Function is phagocytosis of: • • • • Bacteria Viruses Dead tissues Foriegn particles Immune function