Leukocyte Chemotaxins Types of chemotaxins C5a attracts neutrophils and monocytes Made by bacteria Peptide clipped off N-terminus(beginning with N formylmethionine during peptide maturation after protein synthesis Made by bacteria and nucleated blood cells Leucotrienes--lipid products of cell membrane metabolism BIOL 533 Lecture 6
BIOL 533 2 Lecture 6 Leukocyte Chemotaxins • Types of chemotaxins – C5a attracts neutrophils and monocytes – Made by bacteria • Peptide clipped off N-terminus (beginning with Nformylmethionine) during peptide maturation after protein synthesis – Made by bacteria and nucleated blood cells • Leucotrienes—lipid products of cell membrane metabolism
Leukocyte Chemotaxins Function of chemotaxins Enhance and direct motility of phagocytic cells To a limited extent oxidative metabolism of phagocytic cells BIOL 533 Lecture 6
BIOL 533 3 Lecture 6 Leukocyte Chemotaxins • Function of chemotaxins – Enhance and direct motility of phagocytic cells – To a limited extent, oxidative metabolism of phagocytic cells
3 Opsonization and Opsonins y General aspects Substances that enhance ability of phagocytes to ingest microbes Defend against presence of capsules and other microbial mechanisms that interfere with phagocytosis BIOL 533 Lecture 6
BIOL 533 4 Lecture 6 Opsonization and Opsonins • General aspects – Substances that enhance ability of phagocytes to ingest microbes • Defend against presence of capsules and other microbial mechanisms that interfere with phagocytosis
3 Opsonization and Opsonins y Types of opsonins Antibodies C3b component of complement Binds covalently to bacterial surface and is recognized by receptors on neutrophils, monocytes and macrophage Bacteria become bound to surface of phagocyte facilitating their uptake BIOL 533 Lecture 6
BIOL 533 5 Lecture 6 Opsonization and Opsonins • Types of opsonins – Antibodies – C3b component of complement • Binds covalently to bacterial surface and is recognized by receptors on neutrophils, monocytes, and macrophage – Bacteria become bound to surface of phagocyte facilitating their uptake
3 Opsonization and Opsonins y Types of opsonins, continued Mechanism White blood cell receptors for C3b At least 3--CR1, CR2, CR3(complement receptor) Children deficient in CR3 very vulnerable to bacterial infections BIOL 533 Lecture 6
BIOL 533 6 Lecture 6 Opsonization and Opsonins • Types of opsonins, continued – Mechanism • White blood cell receptors for C3b • At least 3—CR1, CR2, CR3 (complement receptor) • Children deficient in CR3 very vulnerable to bacterial infections
Phagocytes-Types of Cells Neutrophils--cell origin Actively motile cells produced in bone marrow Differentiate from stem cells over about a two-Week period Production of granules during this time Azurophil Produce specific granules later BIOL 533 7 Lecture 6
BIOL 533 7 Lecture 6 Phagocytes—Types of Cells • Neutrophils—cell origin – Actively motile cells produced in bone marrow – Differentiate from stem cells over about a two-week period • Production of granules during this time – Azurophil – Produce specific granules later
Phagocytes-Types of Cells Neutrophils--cell origin, continued Upon maturation(in numbers of 1010 per day, they move into peripheral blood and circulate for about 6.5 hours Next move into capillary bed and marginate BIOL 533 Lecture 6
BIOL 533 8 Lecture 6 Phagocytes—Types of Cells • Neutrophils—cell origin, continued – Upon maturation (in numbers of 1010 per day), they move into peripheral blood and circulate for about 6.5 hours – Next move into capillary bed and marginate
Phagocytes-Types of Cells Neutrophils--cell origin, continued Margination caused by stickiness due to interleukin-1 Summoned by chemotaxis, they move through endothelial cell junctions(diapdesis) into extravascular tissue spaces BIOL 533 Lecture 6
BIOL 533 9 Lecture 6 Phagocytes—Types of Cells • Neutrophils—cell origin, continued – Margination caused by stickiness due to interleukin-1 – Summoned by chemotaxis, they move through endothelial cell junctions (diapdesis) into extravascular tissue spaces
Phagocytes-Types of Cells Neutrophils are most active in gut Gut has enormous microbial population lying just one cell layer away from aseptic tissue Flora generates large amounts of chemotaxins that recruit most of body s available leukocytes BIOL 533 Lecture 6
BIOL 533 10 Lecture 6 Phagocytes—Types of Cells • Neutrophils are most active in gut – Gut has enormous microbial population lying just one cell layer away from aseptic tissue • Flora generates large amounts of chemotaxins that recruit most of body’s available leukocytes
Phagocytes-Types of Cells As a result submucosa of gut is in a constant state of inflammation Keep microbial flora down Synthesis of neutrophils inhibited by chemicals or radiation Infections in gut region BIOL 533 11 Lecture 6
BIOL 533 11 Lecture 6 Phagocytes—Types of Cells – As a result, submucosa of gut is in a constant state of inflammation • Keep microbial flora down – Synthesis of neutrophils inhibited by chemicals or radiation • Infections in gut region