Cytokines And Colony Stimulating Factors: Methods And Protocols

Methods in Molecular Biology TM VOLUME 215 Cytokines and Colony Stimulating Factors Methods and Protocols Edited by Dieter Körholz Wieland Kiess HUMANA PRESS Immunodeficiencies and Cytokines 3 1 Primary Immunodeficiencies Caused by Defects of Cytokines and Cytokine Receptors Volker Wahn 1. Introduction The immune system responds to antigenic stimulation with a complex array of molecular events involving antigen-presenting cells, B-cells, T-cells, and phagocytes. Cytokines and their respective receptors are intimately involved in regulating such immune responses. Their pivotal role can be illustrated in animal models for which certain cytokines or their receptors have been deleted. It is beyond the scope of this review to discuss our knowledge on growth factor or receptor deficiencies derived from animal models. I would rather like to focus on observations in children with selective molecular defects. For example, pulmonary alveolar proteinosis in some patients has been found to be associated with mutations in the genes for granulocyte macrophage–colonystimulating factor (GM-CSF) receptor `-chain, which is shared with receptors for interleukin (IL)-3 and IL-5. Certainly, in the future we should be aware of further pathogenic mutations in humans that, to date, have been demonstrated in experimental animals only. The majority of mutations in cytokine or cytokine receptor genes result in inherited immunodeficiencies. Our current knowledge on such disorders, therefore, will be summarized. 2. Interleukin-1 There is one report on defective IL-1 production associated with immunodeficiency with some evidence of famili