THE GENETIC-BASIS OF PRIMARY, PREDOMINANTLY SPECIFIC IMMUNODEFICIENCIES

The presented review lists primary immunodeficiencies which essentiall y involve a mutation in genes coding for functionally important molecu les, membrane antigens (e.g., MHC), chains of lymphokine receptors, pr otein kinases of the signal cascade, transcription factors, and some i mportant regulators of cellular metabolism. Mutations are expressed as early as during embryogenesis (lymphopoiesis - I) as well as during i nduction of the immune response by antigen ligand binding to cell rece ptors, TCR, BCR (immunopoiesis - II). Immunodeficiencies are classifie d by the stage of development (I) or immune response induction (II) in which they occur most markedly, even in clinical terms. It has been p ointed out that the same autoactivation stimuli and mechanisms, allowi ng differentiation-maturation of cells during embryogenesis (action of stem cell factor (SFC), IL-3, IL-7, and activation cascade), serve ev en later as a functional prerequisite for an adaptive immune response to antigen. As a result, this attempt to classify primary immunodefici encies by differentiation periods (when they become evident most marke dly in terms of their function) has an inherent logical limitation. So me 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 w hy the developmental differentiation scheme is bound to turn, in the f uture, into an immunodeficiency classification by localization of gene mutations and their incidence in time, e.g., increased mutation incid ence during proliferation following cell stimulation by antigen stimul i.