Resistance of the Body to Infection-I: Leukocytes, Granulocytes, the Monocyte-Macrophage System, and Inflammation PDF

01 Resistance of the Body to Infection-I: Leukocytes, Granulocytes, the Monocyte-Macrophage System, and Inflammation Assoc. Prof. Dr. Turan Onur BAYAZIT School of Medicine Physiology & Biophysics Department : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505...

01 Resistance of the Body to Infection-I: Leukocytes, Granulocytes, the Monocyte-Macrophage System, and Inflammation Assoc. Prof. Dr. Turan Onur BAYAZIT School of Medicine Physiology & Biophysics Department : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • Our bodies are exposed continually to bacteria, viruses, fungi, and parasites, all of which occur normally and to varying degrees in the skin, mouth, respiratory passageways, intestinal tract, lining membranes of the eyes, and even the urinary tract. ‫ قارچ ها و انگل ها قرار می‬،‫ ویروس ها‬،‫• بدن ما به طور مداوم در معرض باکتری ها‬ ‫ مجاری‬،‫ دهان‬،‫گیرد که همه اینها به طور طبیعی و به درجات مختلف در پوست‬ .‫ غشای پوششی چشم ها و حتی مجاری ادراری رخ می دهند‬،‫ مجرای روده‬،‫تنفسی‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • Many of these infectious agents are capable of causing serious abnormal physiological function or even death if they invade deeper tissues. • We are also exposed intermittently to other highly infectious bacteria and viruses besides those that are normally present, and these agents can cause acute lethal diseases such as pneumonia, streptococcal infection, and typhoid fever. ‫• بسیاری از این عوامل عفونی می توانند در صورت حمله به بافت های‬ .‫ عملکرد فیزیولوژیکی غیرطبیعی جدی یا حتی مرگ ایجاد کنند‬،‫عمیق تر‬ ‫ به طور متناوب در معرض سایر‬،‫• ع"وه بر آنهایی که به طور معمول وجود دارند‬ ‫باکتری ها و ویروس های بسیار عفونی قرار می گیریم و این عوامل می توانند باعث‬ .‫ عفونت استرپتوکوک و تب حصبه شوند‬،‫بیماری های کشنده حاد مانند ذات الریه‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • Our bodies have a special system for combating the different infectious and toxic agents. .‫• بدن ما یک سیستم ویژه برای مبارزه با عوامل مختلف عفونی و سمی دارد‬ • This system is composed of blood leukocytes (white blood cells [WBCs]) and tissue cells derived from leukocytes. .‫[( و سلول های بافتی مشتق شده از لکوسیت ها تشکیل شده است‬WBCs] ‫• این سیستم از لکوسیت های خون )گلبول های سفید خون‬ • These cells work together in two ways to prevent disease: • 1) by actually destroying invading bacteria or viruses by phagocytosis; • 2) by forming antibodies and sensitized lymphocytes that may destroy or inactivate the invader. :‫• این سلول ها به دو روش برای جلوگیری از بیماری با هم کار می کنند‬ .‫( با از بین بردن باکتری ها یا ویروس های مهاجم توسط فاگوسیتوز‬1 • .‫( با تشکیل آنتی بادی ها و لنفوسیت های حساس که ممکن است مهاجم را از بین ببرد یا غیر فعال کند‬2 • : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Leukocytes (White Bood Cells=WBC) • 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. .‫ واحدهای متحرک سیستم حفاظتی بدن هستند‬،‫• لکوسیت ها که گلبول های سفید نیز نامیده می شوند‬ .‫سماسل ها( تشکیل می شوند‬O‫• تا حدی در مغز استخوان )گرانولوسیت ها و مونوسیت ها و چند لنفوسیت( و بخشی در بافت لنفاوی )لنفوسیت ها و پ‬ .‫ منتقل می شوند‬،‫ در خون به نقاط مختلف بدن که در آنجا مورد نیاز هستند‬،‫• پس از تشکیل‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Leukocytes (White Bood Cells=WBC) • The real value of WBCs 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. ‫ ها این است که بیشتر آنها به طور خاص به مناطق عفونت و التهاب‬WBC ‫• ارزش واقعی‬ .‫جدی منتقل می شوند و در نتیجه دفاعی سریع و قوی در برابر عوامل عفونی ایجاد می کنند‬ • The granulocytes and monocytes have a special ability to “seek out and destroy” a foreign invader. .‫• گرانولوسیت ها و مونوسیت ها توانایی ویژه ای در "جستجو و از بین بردن" یک مهاجم خارجی دارند‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • Six types of WBCs are normally present in the blood: neutrophils (polymorphonuclear), eosinophils (polymorphonuclear), basophils (polymorphonuclear), monocytes, lymphocytes and, occasionally, plasma cells. • In addition, there are large numbers of platelets, which are fragments of another type of cell similar to the WBCs found in the bone marrow, the megakaryocyte. .‫سما‬M‫ سلول های پ‬،‫ لنفوسیت ها و گاهی اوقات‬،‫ مونوسیت ها‬،(‫ بازوفیل ها )پلی مورفونوکلئر‬،(‫ ائوزینوفیل ها )پلی مورفونوکلئر‬،(‫ نوتروفیل ها )پلی مورفونوکلئر‬:‫ به طور معمول در خون وجود دارد‬WBC ‫• شش نوع‬ .‫ مگاکاریوسیت هستند‬،‫ های موجود در مغز استخوان‬WBC ‫کت وجود دارد که قطعاتی از نوع دیگری از سلول مشابه‬M‫ تعداد زیادی پ‬،‫وه بر این‬M‫• ع‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The first three types of cells, the polymorphonuclear cells, all have a granular appearance (7, 10, 12) and for this reason they are called granulocytes. • The granulocytes and monocytes protect the body against invading organisms by ingesting them (by phagocytosis) or by releasing antimicrobial or inflammatory substances that have multiple effects that aid in destroying the offending organism. ‫• سه نوع سلول اول یعنی سلول های پلی مورفونکلئر همگی ظاهری دانه ای دارند‬ .‫( و به همین دلیل به آنها گرانولوسیت می گویند‬12 ،10 ،7) : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The lymphocytes and plasma cells function mainly in connection with the immune system. .‫سما عمدتا ً در ارتباط با سیستم ایمنی عمل می کنند‬/‫• لنفوسیت ها و سلول های پ‬ • Finally, the function of platelets is specifically to activate the blood-clotting mechanism. .‫کت ها به طور خاص فعال کردن مکانیسم لخته شدن خون است‬/‫ عملکرد پ‬،‫• در نهایت‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 7.000 leukocyte : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Genesis of white blood cells • Aside from the cells committed to form RBCs, two major lineages of WBCs are formed, the myelocytic and the lymphocytic lineages. ‫پیدایش گلبول های سفید‬ ‫ دو دودمان اصلی‬،‫• جدای از سلول های متعهد به تشکیل گلبول های قرمز‬ .‫ دودمان میلوسیتیک و لنفوسیت‬،‫گلبول های سفید تشکیل می شود‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The myelocytic lineage, beginning with the myeloblast. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The lymphocytic lineage, beginning with the lymphoblast. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The granulocytes and monocytes are formed only in the bone marrow. .‫• گرانولوسیت ها و مونوسیت ها فقط در مغز استخوان تشکیل می شوند‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • Lymphocytes and plasma cells are produced mainly in the various lymphogenous tissues— • especially the lymph glands, spleen, thymus, tonsils, and various pockets of lymphoid tissue elsewhere in the body, such as in the bone marrow and in Peyer’s patches underneath the epithelium in the gut wall. .‫سماسل ها عمدتا ً در بافت های مختلف لنفوژن تولید می شوند‬,‫• لنفوسیت ها و پ‬ .‫ در زیر اپیتلیوم در دیواره روده‬Peyer ‫ مانند مغز استخوان و تکه های‬،‫ و پاکت های مختلف بافت لنفاوی در سایر نقاط بدن‬،‫ لوزه ها‬،‫ تیموس‬،‫ طحال‬،‫• به خصوص غدد لنفاوی‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The WBCs formed in the bone marrow are stored in the marrow until they are needed in the circulatory system. .‫ های تشکیل شده در مغز استخوان تا زمانی که در سیستم گردش خون مورد نیاز باشند در مغز استخوان ذخیره می شوند‬WBC • .‫• سپس در صورت نیاز عوامل مختلفی باعث رها شدن آنها می شود‬ • Then, when the need arises, various factors cause them to be released. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The lymphocytes are mostly stored in the various lymphoid tissues, except for a small number that are temporarily being transported in the blood. .‫ به جز تعداد کمی که به طور موقت در خون منتقل می شوند‬،‫• لنفوسیت ها بیشتر در بافت های مختلف لنفوئیدی ذخیره می شوند‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 General characteristics of leukocytes Types of White Blood Cells • The megakaryocytes (cell 3) are also formed in the bone marrow. • These megakaryocytes fragment in the bone marrow and the small fragments, known as platelets (or thrombocytes), then pass into the blood. • They are very important in the initiation of blood clotting. .‫( نیز در مغز استخوان تشکیل می شوند‬3 ‫• مگاکاریوسیت ها )سلول‬ ‫• این مگاکاریوسیت ها در مغز استخوان تکه تکه می شوند و قطعات کوچکی که به‬ .‫ سپس وارد خون می شوند‬،‫کت )یا ترومبوسیت( شناخته می شوند‬E‫عنوان پ‬ .‫• در شروع لخته شدن خون بسیار مهم هستند‬ : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Life span of white blood cells • The platelets in the blood are replaced about once every 10 days. ‫ روز یک بار تعویض‬10 • In other words, about 30,000 platelets are formed each day for each microliter of blood. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Neutrophils and macrophages defend against infections • It is mainly the neutrophils and tissue macrophages that attack and destroy invading bacteria, viruses, and other harmful agents. • The neutrophils are mature cells that can attack and destroy bacteria, even in the circulating blood. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Neutrophils and macrophages defend against infections • Conversely, the tissue macrophages begin life as blood monocytes, which are immature cells while still in the blood and have little ability to fight infectious agents at that time. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 White Blood Cells Enter the Tissue Spaces by Diapedesis • Neutrophils and monocytes can squeeze through gaps between endothelial cells of the blood capillaries and postcapillary venules by diapedesis. • Although the intercellular gaps are much smaller than a cell, a small portion of the cell slides through the gap at a time; the portion sliding through is momentarily constricted to the size of the gap. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 White Blood Cells Move Through Tissue Spaces by Ameboid Motion • Both neutrophils and macrophages can move through the tissues by ameboid motion. • Some cells move at velocities as great as 40 μm/min, a distance as great as their own length each minute. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 White Blood Cells Are Attracted to Inflamed Tissue Areas by Chemotaxis • The chemotaxic products: • 1) some of the bacterial or viral toxins; • 2) degenerative products of the inflamed tissues; • 3) several reaction products of the complement complex activated in inflamed tissues; • 4) several reaction products caused by plasma clotting in the inflamed area, as well as other substances. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 White Blood Cells Are Attracted to Inflamed Tissue Areas by Chemotaxis • The chemotaxis depends on the concentration gradient of the chemotactic substance. • The concentration is greatest near the source, which directs the unidirectional movement of the WBCs. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Phagocytosis • A major function of the neutrophils and macrophages is phagocytosis, which means cellular ingestion of the offending agent. • Phagocytes must be selective of the material that is phagocytized; otherwise, normal cells and structures of the body might be ingested. • Whether phagocytosis will occur especially depends on three selective procedures. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Phagocytosis • The C3 molecules, in turn, attach to receptors on the phagocyte membrane, thus initiating phagocytosis. • This process whereby a pathogen is selected for phagocytosis and destruction is called opsonization. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Phagocytosis by Neutrophils • A single neutrophil can usually phagocytize 3 to 20 bacteria before the neutrophil becomes inactivated and dies. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Phagocytosis by Macrophages • Macrophages are the end-stage product of monocytes that enter the tissues from the blood. • When activated by the immune system they are much more powerful phagocytes than neutrophils, often capable of phagocytizing as many as 100 bacteria. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Neutrophils and Macrophages Can Kill Bacteria • Much of the killing effect results from several powerful oxidizing agents formed by enzymes in the membrane of the phagosome or by a special organelle called the peroxisome. • These oxidizing agents include large quantities of superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl ions (OH−), which are lethal to most bacteria, even in small quantities. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Neutrophils and Macrophages Can Kill Bacteria • Also, one of the lysosomal enzymes, myeloperoxidase, catalyzes the reaction between H2O2 and chloride ions to form hypochlorite, which is exceedingly bactericidal. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Monocyte-macrophage Cell System (Reticuloendothelial System) • The macrophages mainly as mobile cells capable of wandering through the tissues. • However, after entering the tissues and becoming macrophages, another large portion of monocytes becomes attached to the tissues and remains attached for months or even years until they are called on to perform specific local protective functions. • They have the same capabilities as the mobile macrophages to phagocytize large quantities of bacteria, viruses, necrotic tissue, or other foreign particles in the tissue. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Monocyte-macrophage Cell System (Reticuloendothelial System) • In addition, when appropriately stimulated, they can break away from their attachments and, once again, become mobile macrophages that respond to chemotaxis and all the other stimuli related to the inflammatory process. • Thus, the body has a widespread monocyte-macrophage system in virtually all tissue areas. • 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. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Tissue Macrophages in Skin and Subcutaneous Tissues (Histiocytes) • The skin is mainly impregnable to infectious agents, except when it is broken. • When infection begins in a subcutaneous tissue and local inflammation ensues, local tissue macrophages can divide in situ and form still more macrophages. • Then, they perform the usual functions of attacking and destroying the infectious agents. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Macrophages in Lymph Nodes • Essentially no particulate matter that enters the tissues, such as bacteria, can be absorbed directly through the capillary membranes into the blood. • Instead, if the particles are not destroyed locally in the tissues, they enter the lymph and flow to the lymph nodes located intermittently along the course of the lymph flow. • The foreign particles are then trapped in these nodes in a meshwork of sinuses lined by tissue macrophages. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Macrophages in Lymph Nodes • Lymph entering through the lymph node capsule via afferent lymphatics, then flowing through the nodal medullary sinuses, and finally passing out the hilus into efferent lymphatics that eventually empty into the venous blood. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Alveolar Macrophages in Lungs • Another route whereby invading organisms frequently enter the body is through the lungs. • Large numbers of tissue macrophages are present as integral components of the alveolar walls. • They can phagocytize particles that become entrapped in the alveoli. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Macrophages (Kupffer Cells) in Liver Sinusoids • Another route whereby bacteria invade the body is through the gastrointestinal tract. • Large numbers of bacteria from ingested food constantly pass through the gastrointestinal mucosa into the portal blood. • Before this blood enters the general circulation, it passes through the liver sinusoids, which are lined with tissue macrophages called Kupffer cells. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Macrophages of Spleen and Bone Marrow • If an invading organism succeeds in entering the general circulation, there are other lines of defense by the tissue macrophage system, especially by macrophages of the spleen and bone marrow. • In both these tissues, macrophages become entrapped by the reticular meshwork of the two organs, and when foreign particles come into contact with these macrophages, they are phagocytized. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Inflammation: Role of neutrophils and macrophages inflammation • When tissue injury occurs, whether caused by bacteria, trauma, chemicals, heat, or any other phenomenon, multiple substances are released by the injured tissues and cause dramatic secondary changes in the surrounding uninjured tissues. • This entire complex of tissue changes is called inflammation. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Inflammation: Role of neutrophils and macrophages inflammation • Inflammation is characterized by the following: • 1) vasodilation of the local blood vessels, with consequent increased local blood flow; • 2) increased permeability of the capillaries, allowing leakage of large quantities of fluid into the interstitial spaces; • 3) often, clotting of the fluid in the interstitial spaces because of increased amounts of fibrinogen and other proteins leaking from the capillaries; • 4) migration of large numbers of granulocytes and monocytes into the tissue; • 5) swelling of the tissue cells. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Inflammation: Role of neutrophils and macrophages inflammation • Some of the many tissue products that cause these reactions are histamine, bradykinin, serotonin, prostaglandins, several diffrent reaction products of the complement system reaction products of the blood clotting system, and multiple substances called lymphokines that are released by sensitized T cells (part of the immune system). • Several of these substances strongly activate the macrophage system, and within a few hours, the macrophages begin to devour the destroyed tissues. • At times, however, the macrophages may also further injure the still-living tissue cells. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Macrophage And Neutrophil Responses During Inflammation Tissue Macrophages Provide First Line of Defense Against Infection • Within minutes after inflammation begins, the macrophages already present in the tissues, whether histiocytes in the subcutaneous tissues, alveolar macrophages in the lungs, microglia in the brain, or others, immediately begin their phagocytic actions. • When activated by the products of infection and inflammation, the fist effect is rapid enlargement of each of these cells. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Second Macrophage Invasion Into the Inflamed Tissue Is a Third Line of Defense • Along with the invasion of neutrophils, monocytes from the blood enter the inflamed tissue and enlarge to become macrophages. • However, the number of monocytes in the circulating blood is low. • Also, the storage pool of monocytes in the bone marrow is much less than that of neutrophils. • Therefore, the buildup of macrophages in the inflamed tissue area is much slower than that of neutrophils, requiring several days to become effective. • Furthermore, even after invading the inflamed tissue, monocytes are still immature cells, requiring 8 hours or more to swell to much larger sizes and develop tremendous quantities of lysosomes. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 01 Formation of Pus • When neutrophils and macrophages engulf large numbers of bacteria and necrotic tissue, essentially all the neutrophils and many, if not most, of the macrophages eventually die. • After several days, a cavity is often excavated in the inflamed tissues. • This cavity contains varying portions of necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid. • This mixture is commonly known as pus. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Eosinophils • The eosinophils normally constitute about 2% of all the blood leukocytes. • Eosinophils are weak phagocytes, and they exhibit chemotaxis, but in comparison with neutrophils, it is doubtful that eosinophils are significant in protecting against the usual types of infection. • Eosinophils, however, are often produced in large numbers in people with parasitic infections, and they migrate into tissues diseased by parasites. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Eosinophils • Eosinophils also have a special propensity to collect in tissues in which allergic reactions occur, such as in the peribronchial tissues of the lungs in people with asthma and in the skin after an allergic skin reaction. • This action is caused at least partly by the fact that many mast cells and basophils participate in allergic reactions. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Basophils • The basophils in the circulating blood are similar to the large tissue mast cells located immediately outside many of the capillaries in the body. • Both mast cells and basophils liberate heparin into the blood. • Heparin is a substance that can prevent blood coagulation. • The mast cells and basophils also release histamine, as well as smaller quantities of bradykinin and serotonin. • It is mainly the mast cells in inflamed tissues that release these substances during inflammation. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Basophils • The mast cells and basophils play an important role in some types of allergic reactions because the type of antibody that causes allergic reactions, immunoglobulin E (IgE), has a special propensity to become attached to mast cells and basophils. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Leukopenia • A clinical condition known as leukopenia, in which the bone marrow produces very few WBCs, occasionally occurs. • This condition leaves the body unprotected against many bacteria and other agents that might invade the tissues. • Normally, the human body lives in symbiosis with many bacteria because the mucous membranes of the body are constantly exposed to large numbers of bacteria. • The mouth almost always contains various spirochetal, pneumococcal, and streptococcal bacteria, and these same bacteria are present to a lesser extent in the entire respiratory tract. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Leukopenia • The distal gastrointestinal tract is especially loaded with colon bacilli. • Furthermore, one can always find bacteria on the surfaces of the eyes, urethra, • and vagina. • Any decrease in the number of WBCs immediately allows invasion of adjacent tissues by bacteria that are already present. • Within 2 days after the bone marrow stops producing WBCs, ulcers may appear in the mouth and colon, or some form of severe respiratory infection might develop. • Bacteria from the ulcers rapidly invade surrounding tissues and the blood. • Without treatment, death often ensues in less than 1 week after acute total leukopenia begins. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Leukopenia • Irradiation of the body by x-rays or gamma rays, or exposure to drugs and chemicals that contain benzene or anthracene nuclei, is likely to cause aplasia of the bone marrow. • Some common drugs such as chloramphenicol (an antibiotic), thiouracil (used to treat thyrotoxicosis), and even various barbiturate hypnotics on rare occasions cause leukopenia, thus setting of the entire infectious sequence of this disorder. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Leukemias • Uncontrolled production of WBCs can be caused by cancerous mutation of a myelogenous or lymphogenous cell. • This process causes leukemia, which is usually characterized by greatly increased numbers of abnormal WBCs in the circulating blood. • There are two general types of leukemia, lymphocytic and myelogenous. • The lymphocytic leukemias are caused by cancerous production of lymphoid cells, usually beginning in a lymph node or other lymphocytic tissue and spreading to other areas of the body. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Leukemias • The second type of leukemia, myelogenous leukemia, begins by cancerous production of young myelogenous cells in the bone marrow and then spreads throughout the body so that WBCs are produced in many extramedullary tissues—especially in the lymph nodes, spleen, and liver. • In myelogenous leukemia, the cancerous process occasionally produces partially differentiated cells, resulting in what might be called neutrophilic leukemia, eosinophilic leukemia, basophilic leukemia, or monocytic leukemia. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Effects of Leukemia on the Body • The first effect of leukemia is metastatic growth of leukemic cells in abnormal areas of the body. • Leukemic cells from the bone marrow may reproduce so much that they invade the surrounding bone, causing pain and, eventually, a tendency for bones to fracture easily. • Almost all leukemias eventually spread to the spleen, lymph nodes, liver, and other vascular regions, regardless of whether the leukemia originated in the bone marrow or lymph nodes. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist