Immunodeficiency diseases underscore the critical role of the immune system's cells and molecules in maintaining overall protection against disease. Primary immunodeficiency diseases, stemming from over 300 distinct inherited genetic defects, encompass a spectrum from severe SCID conditions affecting T cells and B cells to milder defects impacting the production of specific immunoglobulin classes or complement components. The most severe SCID cases obstruct the development of all hematopoietic lineages, T and B cells, or T cells alone, which in turn impairs antibody production due to the essential roles of helper T cells in many antibody responses. Advances in early screening now enable the detection of most SCID forms at birth, allowing for infection prevention and timely initiation of therapies. Some of these defects can now be corrected through bone marrow or HSC transplantation, with gene therapy emerging as a promising avenue.

Other primary immunodeficiencies that affect narrower aspects of the immune system, such as antibodies or complement components, may be more readily managed by replacing the missing immune protein through intravenous administration of immunoglobulins or complement components. However, reduced B or T cell counts can result in immune dysregulation, explaining the paradox of immunodeficiency coinciding with autoimmunity. More clearly defined are the mechanisms behind severe autoimmune conditions like APECED and IPEX, which arise from defects in self-tolerance within the thymus or in the generation of regulatory T cells.

Secondary, or acquired, immunodeficiencies occur due to factors that negatively affect immune responses over the course of life, such as malnutrition, immunosuppressive drug treatments, or HIV infection. Various aspects of HIV epidemiology and biology have contributed to its significant global impact. For instance, HIV can be transmitted...