kidney

White Blood Cells Leukocytes

White Blood Cells Leukocytes Protect against disease

Granulocytes Agranulocytes Monocytes Neutrophils Eosinophils Basophils Lymphocytes

Types of Leucocytes

Development of Neutrophils

Stages of Leucopoiesis (Eosinophils) Pluripotential hemopoietic stem cell Committed stem cell (CFU-GM) Myeloblast Promyelocyte Early Eosinophilic Myelocyte Late Eosinophilic Myelocyte Eosinophilic Metamyelocyte Eosinophil

Stages of Leucopoiesis (Basophils) Pluripotential hemopoietic stem cell Committed stem cell (CFU-GM) Myeloblast Promyelocyte Early Basophilic Myelocyte Late Basophilic Myelocyte Mature Basophil

GENERAL CHARACTERISTICS: Leukocytes are the least numerous of the cellular elements. 1 WBC for every 700 RBCs.(they are merely in transit while in blood).

General Characteristics of WBC

Neutrophils

Neutrophils 54% - 62% of leukocyte Fine abundant Purple granules in acid- base stain Lobed nucleus. The granules contain enzymes Proteases Myeloperoxidases Elastases

Neutrophils Also contain antibiotic like substances Defensins Membrane contains NADPH oxidase All these are helpful in destroying the bacteria and toxic substances Each can kill 3-20 bacteria. Elevated in bacterial infections . 14-13

Eosinophils

Eosinophils 1% - 4% of leukocytes Deep red coarse granules in acid stain Bilobed nucleus (usually) Elevated in worm (Parasitic infestations) and allergic reaction. 14-15

Basophils

Basophils Less than 1% of leukocytes Deep blue Coarse granules in basic stain 2-3 lobed nucleus Release histamine, bradykinin and serotonin Release heparin Have receptors for IgE Involved in allergic and hypersensitivity reactions 14-14

Monocyte

Monocytes 3% - 9% of leukocytes Largest blood cell Kidney-shaped or oval nuclei Secrete Interleukin-I Platelet activating factor Colony stimulating factor Leave bloodstream to become macrophages Elevated in typhoid fever, malaria, tuberculosis 14-16

Lymphocytes

Lymphocytes About the size of RBC Large spherical nuclei Thin rims of cytoplasm T cells B cells Important in immunity Produce antibodies 25% - 33% of leukocytes Decreased T Cells in AIDS 14-17

LEUCOCYTES (DLC) Polymorphonuclear Granulocytes Neutrophils 45-65 % Eosinophils 1-4 % Basophils 0-1 % Mononuclear Agranulocytes Lymphocytes 25-35 % Monocytes 3-8 %

Normally 2/3 of circulating leukocytes are granulocytes (mostly neutrophils). 1/3 are agranulocytes (mostly lymphocytes). Number and % change according to the defense needs of the body.

LIFE SPAN of WBCs Granulocytes- 4 to 8 hrs after being released from the bone marrow in the blood 4 to 5 days in tissues. Monocytes- 10 to 20 hrs in blood Tissue macrophages live for months. Lymphocytes- weeks or months. Platelets –replaced once every 10 days, 30,000 platelets formed each day /microliter of blood.

Clinical Significance Leucocytosis Acute inflammations/infection→↑ Neutrophils Chronic inflammation →↑ Lymphocytes Allergy, worm infestation →↑ Eosinophils Leucopenia Bone marrow depression X rays Atomic radiation specially gamma rays Chemicals Some infections e.g. typhoid fever

Properties of Leucocytes Margination Diapedesis Amoeboid movement Chemotaxis Phagocytosis Opsonization

Properties of Neutrophils Phagocytosis Chemotaxis Diapedesis Margination

Diapadesis Leukocytes squeeze through capillary walls to enter tissue space outside the blood vessel 14-18

Chemotaxis Downloaded from: StudentConsult (on 15 January 2007 05:55 AM) © 2005 Elsevier

Chemotaxis Inflamed area produce chemicals Which attract neutrophils and Macrophages Chemotactic substances are Bacterial or viral toxins Degenerative products of inflamed tissue Complement complexes Plasma clotting in the inflamed tissue

Phagocytosis Recognition Attachment and binding Pseudopodia around Ingestion (Neutrophils 5-20 bacteria Macrophage upto100 bacteria) Phagocytic vesicle or phagosome Lysosomal digestion Leukocytes consume and destroy foreign invaders and dead cells Ejected as Pus

Opsonins Most microorganisms will NOT be phagocytosed without opsonins Primary Opsonins IgG Complement factor C3 Pseudopods extend to cover particle (but only the part that is opsonized) Changes the organism’s surface attractive “tasty” to phagocytes

(Opsonization & Phagocytosis)

Reticuloendothelial system (Monocyte-macrophage system)

Reticuloendothelial system (Monocyte-macrophage system) The total combination of Monocytes Mobile Macrophages Fixed Tissue Macrophages Specialized Endothelial cells

Histiocytes Tissue macrophages in the skin and subcutaneous tissue. Attack and destroy the invading agent.

Macrophages in Lymph nodes

MACROPHAGES IN THE LYMPH NODE If the particles are not destroyed locally in the tissues they enter lymph and flow to the lymph nodes. The foreign particles are trapped in these nodes in a meshwork of sinuses lined by tissue macrophages. Macrophages phagocytize them and prevent their spread throughout the body.

Alveolar Macrophages Macrophages present in the lungs

ALVEOLAR MACROPHAGES IN THE LUNGS Many invading organisms enter the body through the lungs. Large number of tissue macrophages are present in the alveolar walls which can phagocytize particles that become entrapped in the alveoli. If particles are digestible, macrophages can digest them and release the digestive products into the lymph. If not digestible, macrophages form a giant cell capsule around the particle until slowly dissolves e.g T.B bacilli, silica dust and carbon particles.

Kupffer Cells Macrophages present in the liver sinusoids

KUPFFER CELLS IN THE LIVER SINUSOIDS Many bacteria invade via GIT. Bacteria pass through the GIT mucosa and enter the portal blood. Before this blood enter the general circulation it passes through the sinusoids of the liver. These sinusoids are lined by the tissue macrophages called KUPFFER CELLS. These form an effective particulate filtration system. Almost none of the bacteria pass from the portal blood to the general circulation.

MACROPHAGES OF THE SPLEEN AND BONE MARROW Invading organism enters the general circulation Bone marrow Spleen Trabeculae of the red pulp Venous sinuses

Inflammation & Role of Leucocytes

Inflammation The changes occurring at and around the area of tissue injury caused by bacteria, trauma, chemicals, heat etc are collectively called Inflammation. This is basically local response of the body to the injury.

Tissue Macrophages – 1st line of defense Neutrophils ---- 2nd line of defense Second macrophage invasion--- 3rd line of defence . Stimulation of CFU-GM system --- 4th line of defense

Inflammation Macrophages –1st line of defense Local tissue macrophages Swelling and enlargement of local macrophages Histiocytes, alveolar macrophages, microglia, Kupffer cells etc Macrophages are more powerful phagocytes than neutrophils. Cause destruction of invading antigen or bacteria Tissue macrophages may become wandering again

Inflammation 2nd line of defense - Neutrophils Margination Diapedesis Chemotaxis Phagocytosis

Third line of defense is the second macrophage invasion. Along with the invasion of neutrophils monocytes from the blood enter the inflammed tissue and enlarge to become macrophages. Storage pool of monocytes in the bone marrow is smaller than neutrophils Monocytes require 8 hours to swell and develop tremendous quantities of lysosomes. After several weeks macrophages predominate because of production by the bone marrow.

4th line of defense - stimulation of CFU-GM system Both granulocytes and monocytes Takes 3 or 4 days before newly formed cells leave the bone marrow.

CONTROL OF MACROPHAGE RESPONSE TO INFLAMMATION GM-CSF G-CSF M-CSF TNF IL-1

Clinical Significance Leukemia Myeloid Leukemia Bone marrow produces too many immature granulocytes Leukemic cells crowd out other blood cells Lymphoid Leukemia Lymphocytes are cancerous Symptoms similar to myeloid leukemia

Common effects of Leukemia Anemia Bleeding Susceptible to infections Pain , Bone fracture Metabolic starvation Treatments Blood transfusions Marrow transplants Anti-cancer drugs Stem cell transplants

Thank-you Questions ??