Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- 1 Histiocytic disorders of children and adults: introduction to the problem, overview, historical perspective and epidemiology
- 2 The diagnostic histopathology of Langerhans cell histiocytosis
- 3 Histiocyte function and development in the normal immune system
- 4 The immunological basis of Langerhans cell histiocytosis
- 5 The genetics of Langerhans cell histiocytosis
- 6 Langerhans cell histiocytosis: a clinical update
- 7 Histiocytosis of the skin in children and adults
- 8 Langerhans cell histiocytosis of bone
- 9 Special aspects of Langerhans cell histiocytosis in the adult
- 10 Adult lung histiocytosis
- 11 Central nervous system disease in Langerhans cell histiocytosis
- 12 The treatment of Langerhans cell histiocytosis
- 13 Treatment of relapsed and/or refractory Langerhans cell histiocytosis
- 14 Late effects of Langerhans cell histiocytosis and its association with malignancy
- 15 Uncommon histiocytic disorder: the non-Langerhans cell histiocytoses
- 16 The histopathology of hemophagocytic lymphohistiocytosis
- 17 Genetics and pathogenesis of hemophagocytic lymphohistiocytosis
- 18 Clinical aspects and therapy of hemophagocytic lymphohistiocytosis
- 19 Secondary haemophagocytic syndromes associated with rheumatic diseases
- 20 Malignancies of the monocyte/macrophage system
- 21 Psychosocial aspects of the histiocytic disorders: staying on course under challenging clinical circumstances
- Index
- Plate section
17 - Genetics and pathogenesis of hemophagocytic lymphohistiocytosis
Published online by Cambridge University Press: 27 August 2009
- Frontmatter
- Contents
- List of contributors
- Preface
- 1 Histiocytic disorders of children and adults: introduction to the problem, overview, historical perspective and epidemiology
- 2 The diagnostic histopathology of Langerhans cell histiocytosis
- 3 Histiocyte function and development in the normal immune system
- 4 The immunological basis of Langerhans cell histiocytosis
- 5 The genetics of Langerhans cell histiocytosis
- 6 Langerhans cell histiocytosis: a clinical update
- 7 Histiocytosis of the skin in children and adults
- 8 Langerhans cell histiocytosis of bone
- 9 Special aspects of Langerhans cell histiocytosis in the adult
- 10 Adult lung histiocytosis
- 11 Central nervous system disease in Langerhans cell histiocytosis
- 12 The treatment of Langerhans cell histiocytosis
- 13 Treatment of relapsed and/or refractory Langerhans cell histiocytosis
- 14 Late effects of Langerhans cell histiocytosis and its association with malignancy
- 15 Uncommon histiocytic disorder: the non-Langerhans cell histiocytoses
- 16 The histopathology of hemophagocytic lymphohistiocytosis
- 17 Genetics and pathogenesis of hemophagocytic lymphohistiocytosis
- 18 Clinical aspects and therapy of hemophagocytic lymphohistiocytosis
- 19 Secondary haemophagocytic syndromes associated with rheumatic diseases
- 20 Malignancies of the monocyte/macrophage system
- 21 Psychosocial aspects of the histiocytic disorders: staying on course under challenging clinical circumstances
- Index
- Plate section
Summary
Introduction
Farquhar and Claireaux published a report in 1952 of a disease characterized by progressive erythropaenia, neutropaenia and thrombocytopaenia, despite a reactive bone marrow, and named it familial hemophagocytic reticulosis (Farquhar and Claireaux, 1952). In the 50 years since their seminal report, the knowledge and understanding of this condition, now termed hemophagocytic lymphohistiocytosis (HLH), has increased rapidly. It is now well established that familial HLH (FHL) is a primary immunodeficiency, characterized by hypercytokinemia (elevated serum levels of inflammatory cytokines) and a concomitant defect in natural killer (NK) cell cytotoxicity (Perez et al., 1984; Arico et al., 1988; Eife et al., 1989; Henter et al., 1998; Sullivan et al., 1998; Kogawa et al., 2002). Recent genetic studies have revealed underlying molecular defects in FHL patients, greatly improving our understanding of the basic pathogenesis of this disease. Deciphering the underlying molecular mechanism of immunodeficiency in FHL patients may also teach us more about the role of cellular cytotoxicity in immune homoeostasis under normal conditions.
Pathogenesis of HLH
Cytotoxic T lymphocytes- and NK cell-mediated apoptosis
Lymphocyte-mediated cytotoxicity is the main pathway for tumour surveillance and for eradicating virus-infected cells and intracellular pathogens. The effector lymphocytes are the cytotoxic T lymphocytes (CTLs) and NK cells, which act by killing their cellular targets through induction of apoptosis. CTLs and NK cells utilize either of two mechanisms for killing, both of which require direct contact between effector and target cells.
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- Histiocytic Disorders of Children and AdultsBasic Science, Clinical Features and Therapy, pp. 337 - 352Publisher: Cambridge University PressPrint publication year: 2005
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