WBC

• White Blood Cells


  Agents that combat infection and toxic agents in the body
• Our bodies are exposed continually to bacteria, viruses, fungi, and parasites in various parts of the body
• Deeper tissue invasion by pathogens can cause more serious infections
• How our bodies fight infection


  • Blood leukocytes (white blood cells)
  • Tissue cells derived from leukocytes
• How white blood cells destroy invading bacteria/viruses


  • Phagocytosis
  • Forming antibodies and sensitizing lymphocytes
• Types of White Blood Cells


  • Granulocytes (Polymorphonuclear Neutrophils, Polymorphonuclear Eosiniphils, Polymorphonuclear Basophils)
  • Monocytes
  • Lymphocytes
  • Plasma cells

  
• Genesis of White Blood Cells (Leukopoesis)

  1. Formation of the different blood cells from the stem cell

  2. Two major lineages: Myelocytic and lymphocytic
• Where white blood cells are formed


  • Partially in the bone marrow (granulocytes and monocytes)
  • Partially in the lymph tissue (lymphocytes and plasma cells)
• Life Span of White Blood Cells


  • Granulocytes: 4-8 hrs circulating, 4-5 days in tissues
  • Monocytes: 10-20 hrs in blood, live for months as macrophages
  • Lymphocytes: Enter circulatory system continually, pass out of blood after a few hrs, lifespan of weeks to months
• How white blood cells move


  1. Enter tissue by diapedesis

  2. Move through tissue by ameboid motion

  3. Attracted to inflamed tissue by chemotaxis
• Diapedesis


  Process where the cell squeezes through the pores of the blood capillaries by a small portion sliding through at a time
• Chemotaxis


  Concentration gradient of inflammatory products that directs movement of white blood cells from capillaries to inflamed area
• Phagocytosis by Neutrophils and Macrophages


  1. Attach to particle

  2. Project pseudopodia around particle

  3. Fuse pseudopodia to form chamber with particle inside

  4. Invaginate chamber to form free-floating phagocyte

  5. Lysosomes and granules dump digestive enzymes and bactericidal agents into vesicle to digest particle
• Neutrophils


  • Already mature cells
  • Can phagocytize 3-20 bacteria before dying
  • Most abundant white blood cell (62% of average adult count)
• Neutrophil count


  • Normal: 1500-8000 cells/microliter
  • Neutrophilia (>8000): Likely have an infection
  • Neutropenia (<1500): Underlying disease causing low production
• Monocytes/Macrophages


  • Monocytes increase in size and develop lysosomes when entering tissues to become macrophages
  • Can phagocytize up to 100 bacteria (more than neutrophils)
  • Can engulf larger particles than neutrophils
  • After digestion, can continue to function for months
• Where macrophages are found

  • Skin (Histiocytes)
  • Lymph nodes
  • Lungs (Alveolar macrophages)
  • Liver (Kupffer cells)
  • Spleen and bone marrow
  • CNS (Microglia)
• Reticuloendothelial system (monocyte-macrophage system)


  Combination of monocytes, mobile macrophages, fixed tissue macrophages, and specialized endothelial cells
• Inflammation: Role of Neutrophils and Macrophages

  1. Vasodilation of local blood vessels

  2. Increased capillary permeability

  3. Fluid clotting

  4. Migration of granulocytes and monocytes into tissue

  5. Swelling of tissue cells
• Inflammation: 1st line of defense


  Rapid enlargement of macrophages at site of infection, attached macrophages become mobile
• Inflammation: 2nd line of defense

  Large number of neutrophils invade inflamed area, stick to capillary walls, pass into tissue spaces, migrate towards injured tissue, increased neutrophil production in bone marrow
• Inflammation: 3rd line of defense


  Monocytes from blood enter inflamed tissue and enlarge to macrophages, increased monocyte production in bone marrow
• Inflammation: 4th line of defense

  Increased production (20-50X) of granulocytes and monocytes by bone marrow via progenitor pathway, can continue for months-years
• Basophils


  • Found in circulating blood, similar to tissue mast cells
  • Release heparin, histamine, bradykinin, serotonin
  • Role in allergic reactions
• Inflammation


  1. Large number of neutrophils invade the inflamed area

  2. Stick to the capillary walls (margination)

  3. Pass from the blood into the tissue spaces (diapedesis)

  4. Migrate towards the injured tissue (chemotaxis)

  5. Stored neutrophils in the bone marrow are mobilized into the circulating blood, cause 4-5X increase in numbers of neutrophils (neutrophilia)
• Inflammation (continued)


  1. Monocytes from the blood enter the inflamed tissue and enlarge to macrophages (8hrs)

  2. Bone marrow increases production of new monocytes

  3. Increased production (20-50X) of granulocytes and monocytes by bone marrow via progenitor pathway, can continue for months - years
• Basophils


  • Found in the circulating blood, similar to tissue mast cells found immediately outside of the capillaries
  • Release heparin into the blood (prevents clotting), also histamine, bradykinin, seratonin (mainly mast cells)
  • Role in allergic reactions because immunoglobulin E (IgE) attaches to mast cells and basophils
  • When antigen (Ag) attaches to IgE antibody (Ab), cells rupture, releasing large amounts histamine, bradykinin, seratonin, heparin, slow reacting substance of anaphylaxis (induces prolonged, slow contraction of smooth muscle and has a major bronchoconstriction role in asthma) - allergic manifestation
• Eosinophils


  • Under normal conditions found in the spleen, lymph nodes and gastrointestinal tract where they survive for several days, circulate for 8-12 hours
  • Usually produced in large numbers in people with parasitic infections, weak phagocytes, instead attach to the parasites by special surface molecules and release hydrolytic enzymes from their granules, highly reactive forms of oxygen (peroxidases), highly larvicidal polypeptide = major basic protein
  • Also collect in tissues in which allergic reactions occur (lungs, skin), partly due to release of eosinophil chemotactic factor by mast cells and basophils
  • Detoxify inflammation-inducing substances released by mast cells and basophils, phagocytose and destroy allergen-antibody complexes
• Lymphocytes


  • Large nucleus, little cytoplasm, smallest of WBCs but size increases when activated by foreign antigen
  • Play the central role in all immunological defence mechanisms, provide specific immune response (acquired)
  • Produced in bone marrow but may undergo further development and division elsewhere (e.g. thymus - T cells; liver - B cells (from bursa of Fabricius)
  • They migrate to lymphoid tissue (mostly lymph nodes, spleen, tonsils, lymphoid follicles in gastrointestinal tract) to encounter foreign antigen
• Lymphocyte clones


  1. Occurs when specific antigens come into contact with the lymphocytes

  2. Lymphocytes are activated

  3. B lymphocytes produce antibodies when activated

  4. T lymphocytes produce activate T cells (can destroy infected cells)

  5. Activated lymphocytes react highly specifically against the antigens that initiated their development

  6. Produces tremendous amounts of duplicate lymphocytes = clones
• Leukopenia


  When bone marrow produces very few WBCs, allows invasion of bacteria normally present (symbiotic bacteria) into adjacent tissues, ulcers appear in mouth and colon, respiratory infection, bacteria invade surrounding tissue and blood, without treatment (transfusion; antibiotics) death in <2weeks, some stem cells, myeloblasts and hemocytoblasts are capable of regenerating the bone marrow - may take weeks to months - therefore need treatment
• Leukemias


  • Caused by cancerous mutation of myelogenous or lymphogenous cell, results in increased numbers of abnormal WBCs
  • Lymphocytic - cancerous production of lymphoid cells, usually begins in lymph node and spreads to other areas of the body
  • Myelogenous - cancerous production of young myelogenous cells in the bone marrow, spreads throughout the body so that WBCs produced in extra-medullary tissue (outside of the bone marrow) - especially lymph nodes, spleen, liver, occasionally produces partially differentiated cells (neutrophillic, eosinophillic etc) - chronic, sometimes developing slowly over 10-20 years, mostly undifferentiated - the more undifferentiated, the more acute - can lead to death within a few months
• Effects of Leukemia on the body


  • Metastatic growth of leukemic cells in abnormal areas, eg leukemic cells from the bone marrow may invade surrounding bone, causing pain and eventually a tendency for bones to fracture easily
  • Almost all spread to the spleen, lymph nodes, liver and other vascular organs
  • Development of infection, severe anemia, bleeding caused by thrombocytopenia (lack of platelets)
  • Excessive use of metabolic substrates by the cancerous cells (eg foodstuffs, amino acids, vitamins)
  • Causes lack of energy, deterioration of normal protein tissues (amino acids)
  • After metabolic starvation has continued long enough, this alone is sufficient to cause death
• Platelets (thrombocytes)


  Minute disc 1-4um in diameter, formed in the bone marrow from megakaryocytes (extremely large cells), fragment into minute platelets in the bone marrow or soon after entering the blood, megakaryocytes and platelets bind thrombopoietin, when platelet count is low there is increased free thrombopoietin which can stimulate megakaryocytes, when the platelet count is high, there is decreased free thrombopoietin and decreased stimulation of megakaryocytes, 300000 platelets per microliter blood, replaced once every 10 days, eliminated from the circulation by the macrophages, especially in the spleen
• Platelet Characteristics


  No nuclei, cytoplasm has actin and myosin molecules and thrombosthenin which are contractile proteins, residuals of ER and Golgi apparatus - store large quantities calcium ions, mitochondria and enzyme systems capable of forming ATP and ADP, enzyme systems that synthesize prostaglandins (local hormones) - cause vascular and other tissue reactions, fibrin-stabilizing factor - coagulation, growth factor - help repair damaged vascular walls, cell membrane has coat of glycoproteins - selectively adheres to injured endothelium, phospholipids - activate multiple stages in the blood-clotting process