Chapter 9 Blood, Lymph, and Immunity 231 WHITE BLOOD CELLS All white blood cells develop in the bone marrow except Any nucleated cell normally found in blood is a white blood for some lymphocytes (they start out in bone marrow but cell. White blood cells are also known as WBCs or leukocytes. develop elsewhere). At the beginning of leukopoiesis all the When white blood cells accumulate in one place, they grossly immature white blood cells look alike even though they're appear white or cream-colored. For example, pus is an accu- already committed to a specific cell line. It's not until the mulation of white blood cells. Mature white blood cells are cells start developing some of their unique characteristics larger than mature red blood cells. that we can tell them apart. There are five types of white blood cells. They are neu- Function trophils, eosinophils, basophils, monocytes and lymphocytes (Table 9-2). The function of all white blood cells is to provide a defense White blood cells can be classified in three different ways: for the body against foreign invaders. Each type of white 1. Type of defense function blood cell has its own unique role in this defense. If all the • Phagocytosis: neutrophils, eosinophils, basophils, mono- white blood cells are functioning properly, an animal has a cytes good chance of remaining healthy. Individual white blood • Antibody production and cellular immunity: lympho- cell functions will be discussed with each cell type (see cytes Table 9-2). 2. Shape of nucleus In providing defense against foreign invaders, the white • Polymorphonuclear (multilobed, segmented nucleus): blood cells do their jobs primarily out in the tissues. The neutrophils, eosinophils, basophils (Figure 9-4) white blood cells use the peripheral blood to travel from • Mononuclear (single, rounded nucleus): lymphocytes their site of production (bone marrow) to their site of activ- • Pleomorphic (varying shapes, nonsegmented nucleus): ity (tissue). There is a constant flow of white blood cells out monocytes of marrow and into tissues in an attempt to control the mil- 3. Presence or absence of specific staining cytoplasmic lions of foreign invaders that attack a body every day. It's granules happening in us too. And as long as they do their job, we Granulocytes (presence of granules): neutrophils, don't even realize what's going on and we remain healthy. eosinophils, basophils • Agranuloctyes (absence of granules): lymphocytes, monocytes Formation The general term for the formation of white blood cells is ~ TEST YOURSELF . leukopoiesis. All white blood cell production starts out in the red bone marrow from the same pluripotent stem cell 1. List the five white blood cells and indicate if each one is (PPSC) population that produced red blood cells and mega- a granulocyte or an agranulocyte. karyocytes. It is the stimuli that act upon the PPSCs that 2. What is the common function of all white blood cells? determine which cell type will be produced. Each type of 3. Which cell is the only white blood cell not capable of phagocytosis? white blood cell has its own stimulus for production. TABLE 9-2 White Blood Cells Name Cytoplasmic Granules Nuclear Shape Function Site of Action Neutrophil Don't stain (usually Polymorphonuclear Phagocytosis Body tissues invisible) Eosinophil Stain red Polymorphonuclear Allergic reactions, anaphylaxis, Body tissues phagocytosis Basophil Stain blue Polymorphonuclear Initiation of immune and allergic Body tissues reactions Monocyte None Pleomorphic Phagocytosis and process antigens Body tissues or blood (macrophage) B cell None Mononuclear Antibody production and Lymphoid tissue (lymphocyte) humoral immunity T cell None Mononuclear Cytokine production and Lymphoid tissue and (lymphocyte) cell-mediated immunity other body tissues 232 Chapter 9 Blood, Lymph, and Immunity Nucleus :•~"':'r:;;-;':' • •...' ::::.::::..~ • • ..'..:::~~.~. ~' •••..~.. ~:o.::::' ~. -, ~:'::..":'~ :::". ;"::'@-:':':'. ;..··tI:: ~.:.. ;..... ' "1': .:"• :" Vi l?o0.,'. • • ::.~".: • : •• ' .'.:' • : " :. .: " ,,\\. " " .' . .:W ." . '...., ~ " ~" .. ", : .. .. .... : 0.. : " .. ",," ..: 0:: .. .... : 0,,":" :"" Figure 9-4 Normal neutrophils showing polymorphonuclear characteristics. he total white blood cell count and differential count are differential count, commonly referred to as "the diff." Because Tused to evaluate a patient for the diagnosis or prognosis you're counting 100 cells,the number of each celltype you see of an abnormal condition. For example,. if an infection is' can be expressed as a percentage. For example, if you count present in the body, there will be an increased need for neu- 100 cells and find that 20 of the cells are neutrophils and 80 trophils to killthe invading microorganisms. The bone marrow of the cells are lymphocytes, you would report you saw 20% responds to this need by releasing more neutrophils into the neutrophils and 80% lymphocytes. bloodstream that willtravel to the infected tissue. There are automated hematology analyzers that will The increased number of neutrophils in the blood will provide these numbers, but they won't pick up all cellular increase the total white blood cell count. The total white blood abnormalities. For this reason, you should always look at a cell count is equal to the sum of each of the individual white stained blood smear even if you're using an automated ana- blood cell counts. If one cell type increases or decreases, the lyzer. You don't have to complete a differential count; just total white blood cell count will increase or decrease accord- look for physical abnormalities. ingly. Sounds simple, doesn't it? Unfortunately, it's not always For every species of common domestic animal, there is a that simple. If one cell type increases and another cell type value range that represents a normal white blood cell count. decreases, the net effect could be a normal total white blood There is also a normal range for individual white blood cell cell count. That's the tricky part, so the total white blood cell types. For example, a dog willnormally have between 6 billion count is only one of a series of tests performed to evaluate and 17 billion white blood cells per liter of blood, and 60% the white blood cells. to 70% of these cells should be neutrophils. Cattle will have To find out which white blood cells are affecting the total between 4 billion and 12 billion white blood cells per liter and white blood cell count, we have to look at a stained smear of only 15% to 45% of the cells should be neutrophils. the blood. The usual method for evaluating the blood smear Taken together, the total white blood cell count and the is to count the first 100 white blood cells and keep track of the differential count can provide a lot of information about an number of each white blood cell type you see. This is called a animal's state of health. Granulocytes II CLINICAL APPLICATION The granulocytes are the neutrophils, eosinophils, and baso- phils. They are named for the color of the granules in their :/.ld.r~~h!J!i!~~ti~2·;Z~'.!~;~.~i&z1~;i"~l0C~~;t~,.::.;;]cytoplasm when viewed on a stained blood smear (see an earlier discussion of stains in this chapter). Eosinophil gran- he word leukemia means "white blood." It is caused by ules pick up the acidic stain and appear red, basophil gran- Tan abnormal proliferation of one of the white blood cell ules pick up the basic stain and appear blue, and neutrophils types. In response to some unknown stimulus, the stem cells don't pick up either stain very well, so for the most part, the in the bone marrow start producing abnormal cells in one neutrophil granules appear colorless or faintly violet on a cell line at an increased rate. These abnormal cells show up stained blood smear. in peripheral blood in large numbers, many times before they are mature, and cause the total white blood cellnumbers Formation. The production of all granulocytes is called to increase dramatically aeukocytosis}. Leukemias are con- granulopoiesis. In the bone marrow, early granulocytes are sidered a form of malignancy or cancer and can be acute impossible to distinguish from one another. They are all or chronic. They are classified by the type of cell involved (e.g., lymphocytic leukemia, monocytic leukemia, eosino- large cells with lots of cytoplasm and large round nuclei. philic leukemia). Initially there are no cytoplasmic granules. As the granulo- cytes mature, a first set of granules is formed. Chapter 9 Blood, Lymph, and Immunity 233 These granules are the same in all three granulocytes and are called nonspecific granules. Gradually, the nonspecific granules are replaced by a new set of granules that is unique to each granulocyte type. These are called specific granules. The Golgi apparatus produces both nonspecific and specific granules. f a neutrophil nucleus in peripheral blood has more than The substances found in its granules determine the func- Ifive segments, it is called a hypersegmented nucleus (see tion of a granuloctye. For example, neutrophil granules figure). This indicates that the neutrophil has stayed in periph- contain chemicals called lysosomal enzymes, which aid in eral blood longer than normal, because hypersegmenting killing microorganisms that have been engulfed by the neu- usually takes place in tissue as part of the normal aging trophil. Neutrophils have therefore become a major factor process. The presence of hypersegmented neutrophils on a stained blood smear can be indicative of a pathological in preventing invading microorganisms from causing disease. condition that prevented neutrophils from leaving circulation, An early granulocyte has blue cytoplasm indicating that or it can mean the smear was made from old blood. Remem- it is a metabolically active cell. As it matures, the cytoplasm ber, blood is still living when it is removed from the animal, becomes less active and therefore doesn't stain as blue. and it will continue the aging process as long as it can. So Mature granulocytes in circulation contain almost colorless hypersegmented neutrophils may be just aging normally in cytoplasm containing the specific granules.