Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems are distinct from each other in humans - thymus-dependent cell-mediated immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus lymphoid organ of rabbits, like the bursa of Fabricius, represents a central lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that phagocytosis killing of catalase-positive microorganisms employ oxidative burst. Bone marrow transplantation (BMT) proved life saving in severe combined immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a complicating aplastic anemia launching BMT as a treatment of many diseases. Now 75 fatal diseases have been cured by myeloablative BMT. BMT also cured experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell) transplants cured these diseases. Autoimmune diseases and lethal glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2-year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem cells (stromal cells) was effective treatment for a form of collagen-vascular disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an opsonin that activates the complement system when mutated and at low levels in blood, opens a door to frequent infections throughout childhood and adult life. This new immunodeficiency is based on genetic mutations that involve a native defense system.