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Leucocytes in health and disease 

Leucocytes in health and disease

Chapter:
Leucocytes in health and disease
Author(s):

Joseph Sinning

and Nancy Berliner

DOI:
10.1093/med/9780199204854.003.220401_update_001

February 27, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

Update:

Chapter reviewed December 2012—minor changes only. References updated.

Updated on 30 May 2013. The previous version of this content can be found here.
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date: 29 April 2017

White cells (leucocytes) mediate inflammatory and immune responses and are key to the defence of the host against microbial pathogens. Subpopulations of leucocytes include (1) granulocytes—neutrophils, eosinophils (see Chapter 22.4.6) and basophils, (2) monocytes, and (3) lymphocytes (see Section 5 and Chapter 22.4.2).

Neutrophils and their disorders

Neutrophils comprise half the peripheral circulating leucocytes and are characterized by (1) heterogeneous primary and secondary granules—with contents including a variety of degradative enzymes, and (2) a segmented nucleus. Maturation from the haematopoietic stem cell occurs in the bone marrow and takes 10 to 14 days, after which neutrophils circulate in the intravascular space for 4 to 12 h before migrating through the vascular endothelium into the extravascular space, where they survive for 1 to 3 days.

Neutrophilia—defined as an increase in the circulating neutrophil count to >7.5 × 106/µl, usually occurs as an acquired reactive response to underlying disease. Causes include (1) infection, particularly bacterial—the commonest cause of an elevated leucocyte count; (2) drugs—e.g. steroids; (3) malignancies—including myeloproliferative disorders and nonhaematological cancers; and (much less commonly) (4) hereditary conditions—including hereditary neutrophilia, leucocyte adhesion deficiency, chronic idiopathic neutrophilia.

Neutropenia—defined as a reduction in the absolute neutrophil count to <1.5 × 106/µl, is of particular importance because, when severe (<0.5 × 106/µl), it markedly increases the risk of life-threatening infection. Causes include (1) drugs and toxins. Mechanisms of drug-induced neutropenia include (a) direct marrow suppression, (b) immune destruction with antibody- or complement-mediated damage of myeloid precursors, and (c) peripheral destruction of neutrophils; common offending drugs that cause dose-dependent neutropenia include cancer chemotherapeutic agents, phenothiazines, anticonvulsants and ganciclovir; (2) postinfectious—particularly after viral infections; (3) nutritional deficiencies—e.g. vitamins B12, folic acid; (4) autoimmune—usually attributable in adults to disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis; (5) large granular lymphcytosis; (6) congenital—including severe congenital neutropenia, cyclic neutropenia.

Disorders of neutrophil function include (1) chronic granulomatous disease—a heterogeneous group of rare disorders (most X-linked) characterized by defective production of superoxide by neutrophils, monocytes and eosinophils; patients usually present in childhood with severe infections, often with catalase-negative pathogens; (2) leucocyte adhesion deficiency, (3) myeloperoxidase deficiency, and (4) Chediak–Higashi syndrome.

Monocytes and their disorders

Monocytes share a common myeloid precursor with granulocytes, present antigens to T cells, produce several important cytokines with immunomodulatory and inflammatory functions, and are the precursors to resident tissue macrophages. They are especially important in defence against intracellular pathogens.

Causes of monocytosis (>0.9 × 106/µl) include (1) chronic infection—e.g. tuberculosis, endocarditis; (2) autoimmune diseases—e.g. SLE; (3) malignancy—e.g. primary malignancies of the marrow or marrow infiltration with solid tumours.

Basophils and their disorders

Basophils are nonphagocytic granulocytes that function in immediate-type hypersensitivity. Basophilia (> 0.2 × 106/µl) is seen in myeloproliferative disorders, hypersensitivity reactions, and with some viral infections.

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