What are some of the mutations that may block activation or effector functions of both mature CD4+ T cells and B cells, and what are the clinicopathologic consequences of these mutations?

-defects in various genes involved in B cell maturation and activation or in T-B cell collaboration. mutations in genes encoding receptors for B cell growth factors or costimulators that play a role in T cell–B cell interactions. Causes Common variable immunodeficiency (CVID) is a heterogeneous group of disorders that are characterized by poor antibody responses to infections and reduced serum levels of IgG, IgA, and sometimes IgM. -mutations in the transcription factors that normally induce class II MHC expression. Causes bare lymphocyte syndrome a disease caused by a failure to express class II major histocompatibility complex (MHC) molecules. The disease is manifested by a profound decrease in CD4+ T cells because of defective maturation of these cells in the thymus and poor activation of the cells in peripheral lymphoid organs. -mutations affecting various signaling pathways or cytokines and receptors involved in differentiation of naive T cells into effector cells. affected patients show severe T cell deficiency or deficiency in particular arms of T cell–mediated immunity, such as in Th1. -genetic disorders in which cytotoxic CD8+ T cells and NK cells are unable to kill virus-infected target cells. causes Hemophagocytic lymphohistiocytosis (HLH) syndromes characterized by systemic, sometimes life-threatening, activation of immune cells including macrophages, usually in response to infections. -mutations in the gene encoding perforin as well as mutations in genes that encode proteins involved in granule exocytosis. These mutations result in persistent infections, usually viral, and excessive production of IFNγ by T cells and NK cells, which in turn causes excessive macrophage activation