title: The genetic basis of primary, predominantly specific immunodeficiencies.
abstract: The presented review lists primary immunodeficiencies which essentially involve a mutation in genes coding for functionally important molecules, membrane antigens (e.g., MHC), chains of lymphokine receptors, protein kinases of the signal cascade, transcription factors, and some important regulators of cellular metabolism. Mutations are expressed as early as during embryogenesis (lymphopoiesis-I) as well as during induction of the immune response by antigen ligand binding to cell receptors, TCR, BCR (immunopoiesis-II). Immunodeficiencies are classified by the stage of development (I) or immune response induction (II) in which they occur most markedly, even in clinical terms. It has been pointed out that the same autoactivation stimuli and mechanisms, allowing differentiation-maturation of cells during embryogenesis (action of stem cell factor (SFC), IL-3, IL-7, and activation cascade), serve even later as a functional prerequisite for an adaptive immune response to antigen. As a result, this attempt to classify primary immunodeficiencies by differentiation periods (when they become evident most markedly in terms of their function) has an inherent logical limitation. Some early mutations turn immediately lethal, some express themselves by blocking embryonic lymphopoiesis while other mutations do not become demonstrable until after cell stimulation by antigens. This explains why the developmental differentiation scheme is bound to turn, in the future, into an immunodeficiency classification by localization of gene mutations and their incidence in time, e.g., increased mutation incidence during proliferation following cell stimulation by antigen stimuli.
authors.affiliation: Department of Clinical Immunoendocrinology, Institute of Endocrinology, Prague, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Sterzl
authors.forename: J
authors.initials: J
authors.lastname: Sterzl
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D005314:Embryonic and Fetal Development; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008024:Ligands; D011946:Receptors, Antigen / Q000276:immunology
chemical_list: D000941:Antigens; D008024:Ligands; D011946:Receptors, Antigen