Granulocytes Monocytes, and reticuloendothelial system Fundamental Functions of white blood cells • Defense against invading micro-organisms. • Recognition and destruction of neoplastic cells. • Clearing of senescent (old) and apoptotic cells by phagocytosis. • Production of various cytokines White blood cells (WBC’s) • Divided into 2 main groups: • 1) PHAGOCYTES: include neutrophils, eosinophils, basophils, and • monocytes. • 2) Immunocytes: include lymphocytes and plasma cells. • - Neutrophils, eosinophils, basophils are called granulocytes because they contain granules in their cytoplasm. - Production of WBC occurs in BM. - Only mature phagocytes and lymphocytes are found in blood. Neutrophil • Granulopoiesis is the production of granulocytes in BM. • Many growth factors are involved in granulopoiesis including IL1, IL3, IL5, GMCSF, • AND G-CSF. • Neutrophils are released from BM to blood and spend only 6-10 h in the circulation before they move into body tissues. Neutrophil • - The earliest recognizable granulocyte precursors in the marrow are promyelocytes. - In the tissues, they function as phagocytic cells. - Neutophil live in tissues about 4-5 days. - Eosinophils and basophils are produced in the marrow in a similar process. Neutrophil • Structure: - This cell has a large nucleus consisting of 2-5 lobes and a pale cytoplasm. - The cytoplasm contains many pink-blue or grey granules. - Granules can be primary or secondary granules. - Granules contain lysosomal enzymes which are important for phagocytosis (ingestion and killing) of bacteria or old cells. • Primacy granules contains myeloperoxidase and acid phosphatase • Secondary granules contain collagenase, lactoferrin and lysozymes • Count: Neutrophils are the most numerous leucocytes comprising 65% of circulating phagocytes • Function: Killing of bacteria and fungi. Eosinophils • Structure: Similar to neutrophil structure except: 1- granules in the cytoplasm are courser. 2- granules are bright orange to deep red. 3- maximum number of nuclear lobes is 3. • Count: (5-10 % of WBC). • Function: 1- Involved in allergic reactions. 2- Defense against parasites. • Cytokines control: IL-5 is the most lineage-specific factor involved in eosinophil production. Basophils • Structure: • - Basophils have a bilobed nucleus. • - Have many dark granules which cover the nucleus. - Granules contain heparin and histamine. • They express on their surface the FC receptor that binds to the Fc portion of IgE antibody. - When they move from blood to tissue they become mast cells. Basophils • - Count: occasional in peripheral blood (less than 0.5 % in blood WBC). • - Functions: • 1-have significant roles in a number of allergic and inflammatory disorders. • 2- host defense mechanisms against parasites. • - Cytokines: The major growth and differentiation factor for basophils is IL-3. Monocytes • Monocytes production occurs in the bone marrow and is controlled by growth factors. • Structure: -Larger than other WBC. -Have large central oval nucleus with clumped chromatin. -Blue cytoplasm that contain fine vacuoles. - May have cytoplasmic granules. • Production and maturation: - Once produced in BM, they live in blood for 20-40 h, before they enter the tissues. - In the tissue they mature become macrophages and live for months-years. - Cytokines: GM-CSF and M-CSF are involved in production and activation. Phagocytosis • Phagocytes ingest and destroy pathogens and cell debris. • Phagocytes are attracted to bacteria at the site of inflammation by chemotactic substances released from damaged tissues or by complement components. Phagocytosis • Opsonization is the coating of cells or foreign particles by immunoglobulin or complement; this aids phagocytosis (engulfment) because phagocytes have Fc and C3b receptors. • Killing involves reduction of pH within the phagocytic vacuole, the release of granule contents and the production of antimicrobial oxidants and superoxides.