Leucocytes or white blood cells are nucleated cells that can be found in the peripheral blood and are dedicated, in various ways, to defending the body against potential pathogens. There are five different subpopulations of leucocytes in the blood, each with different morphological features and functions: neutrophil, eosinophil and basophil granulocytes, lymphocytes and monocytes.
Like the other blood cells (red blood cells and platelets), leucocytes originate in the bone marrow (Fig. 1) starting from totipotent progenitor cells which first differentiate into the lymphoid lineage, which gives rise to the lymphocytes that will then mature in lymphoid organs, and the myeloid lineage, which will give rise, through intermediate precursors, to the cells of the erythroid and myelomonocytic lineages and to megakaryocytes, precursors of platelets. The precursors of the myelomonocytic lineage then divide into precursors of monocytes, which through successive stages become monocytes and precursors of the three granulocytic lineages. The granulocytic lineage precursors then differentiate into precursors of neutrophil, eosinophil and basophil granulocytes (also known as neutrophils, eosinophils and basophils, respectively), which will reach full maturation in the bone marrow through intermediate stages of maturation.
NEUTROPHIL GRANULOCYTES
Neutrophils originate in the bone marrow starting from the same progenitor cells as those of the other granulocyte lines and the monocyte line; in their turn these progenitor cells have been derived from precursors in common with those of other myeloid elements (erythrocytes and platelets). In normal conditions neutrophils complete their maturation in the bone marrow where there is always a proportion of mature neutrophils which form the bone marrow reserve pool. Once they enter the circulation, neutrophils form two pools of cells in dynamic equilibrium with each other: the marginal pool, attached to the endothelium, which can rapidly enter the circulation if needed, and the true circulating pool, formed of the cells actually present in the blood stream.
Neutrophils are cells of about 15 µm in diameter characterized by an abundant cytoplasm containing granules that do not stain with the routinely used haematological stains and by a multilobulated nucleus (Fig. 2). The number of lobes is proportional to the age of the cell: young cells do not have lobes (non-segmented neutrophils or bands, Fig. 3), while the old ones have numerous lobes. In the case of neutrophil activation, particularly when stimulated by bacteria, toxic neutrophils can be found in the circulation: these neutrophils are characterized by cytoplasmic anomalies such as Döhle bodies (activated lysosomes), vacuolation and cytoplasmic basophilia (Fig. 4). Toxic neutrophils appear frequently in cats while they are usually associated with particularly severe bacterial infections in dogs. Neutrophils are cells dedicated to phagocytosis and the main activators of the neutrophil response are, therefore, mediators of inflammation and glucocorticoids.
EOSINOPHIL GRANULOCYTES
Eosinophils have a diameter of about 12-15 µm, a lobulated nucleus whose number of lobes, as for neutrophils, increases with age, and pinkish-orange granules in the cytoplasm (Fig. 5). These cells are produced in the bone marrow from a precursor cell, common to all the granulocytic lineage, under stimulation from specific haematopoietic cytokines such as interleukin (IL)-3 and IL-5. The main function of eosinophils is to intervene in allergic and antiparasitic processes. In particular, they are attracted to sites of infestation or development of allergy by cytokines, released from inflammatory cells and/or mast cells, which have specific chemotactic actions for eosinophils (eotaxins). The eosinophils act by releasing the substances contained in their granules, the most important of which are some basic proteins that have lytic effects on parasite cuticles, and histaminase, which inactivates the histamine released by mast cells in the site of inflammation.
BASOPHIL GRANULOCYTES
Basophils are morphologically similar to eosinophils and neutrophils, but with the difference that the granules within their cytoplasm appear blue-violet in the dog and greyer in the cat (Fig. 6). The main function of these cells is participation in allergic and antiparasitic processes: in animals previously sensitised to an allergen, IgE specific for the allergen is fixed to the membrane of basophils. In the case of subsequent contact with the allergen, the allergen binds to the IgE on the basophil membrane causing degranulation and release of histamine.
LYMPHOCYTES
Lymphocytes are roundish cells of about 8-12 µm in diameter which have a round, central or eccentric nucleus surrounded by a thin rim of cytoplasm (Fig. 7), which is more abundant in younger cells and in those responding to inflammatory/immunological stimuli (activated lymphocytes, Fig. 8). Lymphocytes can be divided into at least two, large, functionally different, but often morphologically indistinguishable subpopulations: T helper (Th) lymphocytes and T suppressor/cytotoxic lymphocytes. These latter, like the natural killer lymphocytes, may contain granules in their cytoplasm and, therefore, appear as granular lymphocytes (Fig. 9); the contents of the granules are substances with cytolytic effects. Lymphocytes are involved in specific immune responses. Antigens are phagocytosed and processed by macrophages or other “antigen-presenting cells”, which display the different epitopes on their cell membrane in association with antigens of the major histocompatibility complex, thus presenting them to the Th lymphocytes. These lymphocytes can activate cell-mediated immune responses (Th1) producing some cytokines such as IL-12 or interferon-γ, which activate cytotoxic lymphocytes, natural killer cells and macrophages, or they can activate humoral responses (Th2) producing cytokines such as IL-4 and IL-10, which stimulate B lymphocytes to differentiate into plasma cells and to produce antibodies.
MONOCYTES
Monocytes are roundish cells with an irregular outline and a diameter of about 15 µm. They are characterized by an irregularly shaped nucleus and abundant, weakly basophilic and often vacuolated cytoplasm (Fig. 10). They are produced in the bone marrow starting from a precursor cell common to the granulocytic lineage and their main role is to migrate into tissues and transform into macrophages which, as the “resident” macrophages in tissues (e.g., Küppfer cells, glial cells), phagocytose and process antigens to present to lymphocytes in order to activate specific immune responses. In the case of inflammatory stimuli, monocytes in the blood may appear more basophilic and contain larger vacuoles or cytoplasmic granules (activated macrophages).
Suggested readings
- Feldman B.F., Zinkl J.G., Jain N.C.: Schalm’s Veterinary Hematology, 5a edizione. Philadelphia: Lippincott Williams & Wilkins, 2000.
- Stockham S.L., Scott M.A.: Fundamentals of Veterinary Clinical Pathology, 2a edizione. Blackwell Publishing, 2008.
- Paltrinieri S., Bertazzolo W., Giordano A. Patologia Clinica del Cane e del gatto. Approccio pratico alla diagnostica di laboratorio. ISBN: 978-88-2143-159-3. Elsevier Masson, 2010.