Leukocytes (White Blood Cells) Types of leukocytes Production (Leukopoiesis ) Functional characteristics of the different leukocytes The leukocytes, also called white blood cells, are the mobile units of the body’s protective system. They are formed partially in the bone marrow (granulocytes and monocytes and a few lymphocytes) and partially in the lymph tissue (lymphocytes and plasma cells). After formation, they are transported in the blood to different parts of the body where they are needed. The real value of the white blood cells is that most of them are specifically transported to areas of serious infection and inflammation, thereby providing a rapid and potent defense against infectious agents. As we see later, the granulocytes and monocytes have a special ability to “seek out and destroy” a foreign invader.

Five types of white blood cells are normally present in the blood Types of White Blood Cells WBCs. Five types of white blood cells are normally present in the blood Leukocytosis Leukopenia On average, there are 4000-10000 WBC/l of blood. Average no.=7000 l of blood Remember they account for about 1% of total blood cells. Compare them to RBCs. Storage pool ***megakaryocyte similar to WBCs, will give platlets

Types of White Blood Cells WBCs. ***Conspicuous nucleus **granulocytes and monocytes protect body by ingestion (phogocytosis) of invading organisms( for example bacteria). They are formed in bone marrow. ** lymphocytes protects body through immune system. They are formed in lymphogenous tissues (lymph glands, spleen, tonsils, thymus, Peyer’s patches in intestinal wall.

Genesis of the White Blood Cells Leukopoiesis Genesis of white blood cells. The different cells of the myelocyte series are 1, myeloblast; 2, promyelocyte; 3,megakaryocyte; 4, neutrophil myelocyte; 5, young neutrophil metamyelocyte; 6, “band” neutrophil metamyelocyte; 7, polymorphonuclear neutrophil; 8, eosinophil myelocyte; 9,eosinophil metamyelocyte; 10,polymorphonuclear eosinophil; 11,basophil myelocyte; 12,polymorphonuclear basophil; 13-16,stages of monocyte formation.

Life Span of the White Blood Cells Granulocytes stay in blood for 4-8 hours and in the tissues 5 days. When there is serious infection their whole life span is shortened to few hours Monocytes stay in the blood for 10-20 hours and then they leave to different tissues where they form tissue macrophages. Tissue macrophages can live for months. If there is infection these macrophages may die earlier. Lymphocytes circulate between blood and lymphoid tissues through lymph and they survive for weeks and months

Neutrophils: first responders/ bacteria Eosinophils: parasites Leukocytes functions Neutrophils: first responders/ bacteria Eosinophils: parasites Basophils: allergies Lymphocytes: viruses, cancer (bad cells) antigens foreign antigens Monocytes: phagocytes during inflammation

Role of neutrophils Appearance: Contain fine granules Multilobulated nucleus 3-5 lobes Mature cells The first responder mainly attack bacteria and destroy them by phagocytosis Neutrophilia; after the onset of acute, sever inflammation, neutrophils number increases in the blood 4-5 folds above normal 62% of WBCs in blood 4000-5000 cells/ul

Neutrophils recruitment to the area of inflammation Tissue injury occurs, whether caused by bacteria, trauma, chemicals, heat, or any other phenomenon. Injured tissues release chemical substances e.g. some of the bacterial or viral toxins degenerative products of the inflamed tissues themselves several reaction products of the “complement complex” activated in inflamed tissues several reaction products caused by plasma clotting in the inflamed area, as well as other substances. 3. These chemical substances will induce the release of neutrophils from bone marrow into blood stream. 4. These chemical substances especially histamine from tissue mast cells will increase the permeability of tissue capillaries allowing neutrophils to migrate to the damaged tissues. 5. The same chemical substances release from the damaged area will attract neutrophils. (this process is called Chemotaxis. 6. Neutrophils will destroy the bacteria: Phagocytosis Releasing bactericidal agents that kill most bacteria ( most of them are oxidizing agents). e.g. of these bactericidals are superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl ions (OH− and hypochlorite (ClO-) myeloperoxidase How do neutrophils get recruited to the inflammation site and how do they perform their function? Melioperoxidase.

Diapedesis Chemical substances ( chemokines) e.g. TNf and IL-1 from inflamed tissues are released. these chemokines will induce expression adhesion molecules selectins and intracellular adhesion molecule- 1 (ICAM-1) on endothelia cells of capillaries. These adhesion molecules attach to their complemntray integrin molecules on neutrophils 4. chemokines also increase the permeability of capillaries ( histamine) allowing neutrophils to pass into interstitial flowed by diapedesis 5. Filially, the concentration gradient of chemokines cause Movement of neutrophils to the injured area by a process Called chemotaxis

Movement of WBCs by Chemotaxis towards an area of tissue damage Chemical substances (chemotactic substance, chemotaxins) found and produced in the tissues or released by other leukocytes that attract WBCs toward these chemicals. Chemotaxins include 1. Bacterial or viral toxins Degenerative products of inflamed tissues Reaction products of ‘complement complex’ Reaction products of plasma clotting Chemotactic signals effective till 100m

Amoeboid motion of Leukocytes neutrophils can phagocytize 3-20 bacteria and macrophages can phagocytize up to 100 bacteria http://harunyahya.com/en/Books/3752/the-miracle-in-the-cell/chapter/4966

Factors determining if phagocytosis will take place or not 1. Selective – Natural structures is protected from phagocytosis by smooth surface and protective proteins. While foreign bodies have rough surfaces and no protective proteins so they are liable to be phagocytized. 2. Antibodies adhere to surface of bacteria and make them susceptible for phagocytosis (opsonization).

Eosinophils 2.3% of WBCs Very large rosy granules Bilobed nucleus Responsible for protection against parasitic infection Their granules contain: 1.Hydrolytic enzymes, which are modified lysosomes 2. highly reactive forms of oxygen that are especially lethal to parasites; and 3. highly larvacidal polypeptide called major basic protein. Eosinophils are attracted by chemotactic factor released by basophils and mast cells toward allergic tissues. They detoxify the substances that released during allergic reaction. Also they engulf antibodies-antigens complexes so they help in reducing spread of allergic reaction

Basophils Large histamine-containing granules Affinity for basic dyes so they stain purplish black (baso = basic). Similar in function to mast cells. Mast cells are found in the tissues. Both mast cells and basophils liberate histamin and heparin, small quantities of bradykinins and serotonin. 1% of WBCs

Basophils Basophils and mast cells play important role in allergic reactions. IgE attached to surface of basophils and when antigen bind with IgE on the surface, degranulation follows this binding and release of histamine, bradykinin, serotonin, Slow Reactive Substance of Anaphylaxis, heparin and other lysosomal enzymes antigen 15

Lymphocytes Agranulocyte: does not contain visible granules in the cytoplasm. Second most common WBCs 30% Large round nucleus that fills most of the cytoplasm Responsible for the specific immunity (Acquired immunity) bad cells/ antigens/foreign antigen T cells come from PHSC and maturate in the thymus. B cells originate from bone marrow PHSC and maturate in the liver and bone marrow. T lymphocytes called the cell-mediated immunity B lymphocytes are known as humoral immunity because they produce anti bodies from plasma cells.

Monocyte Agranulocyte with pale-blue cytoplasm Horse-shoe shaped nucleus or kidney shape Immature in the blood stream, undergoes chemotaxis during inflammation So it migrates from blood in to tissue spaces and enlarges their to become macrophage Macrophage is a strong phagocyte, can phagocytize whole RBC, malarial parasites and dead neutrophils has a very important function in the initiation of the specific immune system

Role of macrophages in activation of lymphocytes When macrophage phagocytize invading microorganisms and digest them, the antigenic products liberated into macrophage cytoplasm. Macrophages pass these antigens directly to lymphocytes leading to activation of specific lymphocytes that can make proper immune reaction against invading microorganism. Also macrophages produce substance (interleukin-1) that stimulates growth and reproduction of specific lymphocytes. bacteria macrophage lymphocyte

Monocyte-Macrophage Cell System (Reticuloendothelial System) Mobile macrophages migrate from blood stream into tissue space and attack foreign invaders. Another large portion become attached to the tissues and remains their for months or even years until they are called to action These attached tissue macrophages have the same capabilities as mobile one, under stimulation they can detach and again become mobile , phagocytizing many particles. The total combination of monocytes, mobile macrophages, fixed tissue macrophages, and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes is called the reticuloendothelial system or monocyte-macrophage system

Tissue Macrophages in the Skin and Subcutaneous Tissues (Histiocytes). Macrophages in the Lymph Nodes Alveolar Macrophages in the Lungs. Macrophages (Kupffer Cells) in the Liver Sinusoids. Macrophages of the Spleen and Bone Marrow. Macrophages in the brain are called micrglia