9.1 from notes - Leukocytes: Types and Concentrations

• The body defends against infectious agents via phagocytosis (direct destruction) and antibodies/sensitized lymphocytes (inactivation).
• Leukocytes, or white blood cells (WBCs), and leukocyte-derived tissue cells form this defense system.

Types of Leukocytes

• Neutrophils, eosinophils, and basophils are granulocytes.
• Monocytes, lymphocytes, and plasma cells are also leukocytes.
• Platelets are megakaryocyte fragments that aid in blood clotting.
• Granulocytes and monocytes protect against invaders through phagocytosis or releasing antimicrobial substances.
• Lymphocytes and plasma cells are part of the immune system.
• Platelets activate blood clotting.

WBC Concentrations in Blood

• Adults average 7,000 WBCs per microliter of blood, compared to 5 million RBCs.
• Differential counts: Neutrophils constitute 62.0%, eosinophils 2.3%, basophils 0.4%, monocytes 5.3%, and lymphocytes 30.0%.
• Platelets typically range from 150,000 to 450,000 per microliter, averaging 300,000.

Genesis and Storage of WBCs

• WBCs originate in bone marrow (granulocytes, monocytes, some lymphocytes) and lymph tissue (lymphocytes, plasma cells) then are transported by blood.
• Myelocytic lineage creates granulocytes and monocytes.
• Lymphocytic lineage forms lymphocytes.
• Bone marrow stores granulocytes and monocytes, with roughly a 6-day supply in reserve; lymphocytes reside mainly in lymphoid tissues.
• Bone marrow megakaryocytes fragment to produce platelets.

Life Spans of WBCs

• Granulocytes last 4 to 8 hours in circulation and 4 to 5 days in tissues but shorten to hours during infections.
• Monocytes spend 10 to 20 hours in the blood before becoming tissue macrophages, surviving months unless phagocytized.
• Lymphocytes circulate through blood and tissues, living weeks or months based on need.
• Platelets are replaced every 10 days.

Defense Mechanisms

• Neutrophils and macrophages target bacteria, viruses, and harmful agents.
• Neutrophils are mature cells that attack bacteria directly in the blood.
• Monocytes mature into macrophages in tissues, increasing in size (up to fivefold) and fighting disease.

Movement to Inflamed Areas

• Diapedesis allows neutrophils/monocytes to squeeze through blood capillary walls.
• Ameboid motion enables movement through tissue.
• Chemotaxis attracts WBCs to inflamed areas through chemical signals from bacterial toxins, tissue breakdown, complement complexes, and clotting reactions, effective up to 100 micrometers.

Phagocytosis

• Phagocytosis involves cellular ingestion, influenced by a particle's surface, protein coatings, and opsonization.
• Rough surfaces are more easily phagocytized.
• Protective protein coats repel phagocytes; dead tissues lack these.
• Opsonization uses antibodies and complement C3 to enhance phagocytosis.
• Neutrophils phagocytize 3-20 bacteria then die.
• Macrophages phagocytize up to 100 bacteria or larger particles, survive longer, and extrude residual products.

Digestion

• Phagosomes merge with lysosomes, releasing digestive enzymes.
• Neutrophils/macrophages use proteolytic enzymes to digest bacteria.
• Macrophages use lipases to digest lipid membranes.
• Oxidizing agents (superoxide, hydrogen peroxide) kill bacteria with myeloperoxidase forming bactericidal hypochlorite.
• Some bacteria resist digestion.

Monocyte-Macrophage System

• Macrophages attach in tissues providing local protection
• Includes monocytes, mobile/fixed macrophages, and specialized endothelial cells; synonymous with reticuloendothelial system.
• Tissue macrophages (histiocytes) divide in skin during inflammation.
• Lymph node macrophages trap particles entering lymph; alveolar macrophages in lungs phagocytize particles.
• Liver Kupffer cells filter bacteria from portal blood, spleen, and bone marrow macrophages trap particles in general circulation.

Inflammation

• Inflammation includes vasodilation, increased capillary permeability, clotting, granulocyte/monocyte migration, and swelling, caused by histamine, bradykinin, and other substances.
• Inflammation helps to wall off injury with fibrinogen clots, proportional to injury; staphylococci cause rapid walling-off.
• Macrophages act within minutes as the first line of defense, followed by neutrophil invasion (second line), triggered by cytokines and adhesion molecules.
• Extravasation/diapedesis is WBC movement from blood to tissues.
• Neutrophilia occurs in acute inflammation, increasing blood neutrophils to 15,000-25,000/µl.
• Monocytes enter as macrophages (third line) within 8+ hours, becoming dominant after days/weeks.
• Bone marrow increases granulocyte/monocyte production in 3-4 days, potentially multiplying 20-50 times normal (fourth line).
• Macrophage response is controlled by TNF, IL-1, GM-CSF, G-CSF, and M-CSF.

Pus Formation

• Pus contains dead tissue, neutrophils, macrophages, and fluid; it undergoes autolysis and absorption after infection control.

Eosinophils

• Eosinophils weakly phagocytize and are chemotactic.
• They increase in parasitic infections, releasing enzymes/toxins to kill parasites and collect during allergic reactions, detoxifying inflammatory substances.

Basophils

• Basophils release heparin and histamine, similar to mast cells, and contribute to allergic reactions through IgE antibodies.

Leukopenia

• Leukopenia is low WBC production, leading to bacterial invasion and potential death.
• Causes include radiation/chemicals and can be treated with transfusions/antibiotics.

Leukemias

• Leukemia involves cancerous myelogenous or lymphogenous cell mutation, causing uncontrolled WBC production.
• Lymphocytic leukemias originate in lymphoid tissues.
• Myelogenous leukemias start in bone marrow.
• Cell differentiation varies; undifferentiated cells indicate acute leukemia, while differentiated cells lead to chronic leukemia.
• Effects include metastatic growth, anemia, bleeding, and metabolic depletion.

Body Defense: Leukocytes, Granulocytes, and Immunity

• Granulocytes and monocytes are stored in bone marrow and circulate/reside in tissues, moving via chemotaxis.
• Monocytes transform into macrophages in tissues, lasting months.
• Eosinophils protect against parasites and basophils liberate heparin, histamine, and serotonin.

Defense Mechanisms

• Phagocytosis depends on surface texture, protective coats, and antibodies.
• Particles are engulfed, fuse with lysosomes, and are broken down by enzymes/bactericidal agents.
• Diapedesis and ameboid motion enable cell movement through capillary walls.

Reticuloendothelial System

• The reticuloendothelial system is a network of monocytes, macrophages, and endothelial cells involved in killing cells.

Defense at Entry Points

• Local tissue macrophages attack bacteria entering through the skin.
• Bacteria entering the lymph travel to lymph nodes with macrophages.
• Invading organisms in the lungs are met by alveolar macrophages.
• Kupffer cells in liver sinusoids remove bacteria from portal blood.
• Spleen/bone marrow macrophages trap foreign particles.

Inflammation

• Inflammation causes vasodilation, permeability, clotting, and cell aggregation.
• Tissue products like histamine contribute.
• Walling off limits spread and tissue macrophages act immediately; neutrophils invade within an hour, leading to neutrophilia.
• Monocytes enlarge into macrophages but respond slower; bone marrow stores fewer.

Leukemia

• Leukemia involves uncontrolled WBC production (lymphocytic or myelogenous).
• Acuteness depends on cell differentiation, with undifferentiated cells leading to acute leukemia.
• Decreases in WBCs lead to bacterial invasion and ulcers.