Blood defense system – Proposal for a new concept of an immune system against blood borne pathogens comprising the liver, spleen and bone marrow

Blood‐borne pathogen (BBP) infections can rapidly progress to life‐threatening sepsis and must therefore be promptly eliminated by the host's immune system. Intravascular macrophages of the liver sinusoid, splenic marginal zone and red pulp and perisinusoidal macrophage protrusions in the bone marrow (BM) directly phagocytose BBPs in the blood as an innate immune response. The liver, spleen and BM thereby work together as the blood defence system (BDS) in response to BBPs by exerting their different immunological roles. The liver removes the vast majority of these invading organisms via innate immunity, but their complete elimination is not possible without the actions of antibodies. Splenic marginal zone B cells promptly produce IgM and IgG antibodies against BBPs. The splenic marginal zone transports antigenic information from the innate to the adaptive immune systems. The white pulp of the spleen functions as adaptive immune tissue and produces specific and high‐affinity antibodies with an immune memory against BBPs. The BM works to maintain immune memory by supporting the survival of memory B cells, memory T cells and long‐lived plasma cells (LLPCs), all of which have dedicated niches. Furthermore, BM perisinusoidal naïve follicular B cells promptly produce IgM antibodies against BBPs in the BM sinusoid and the IgG memory B cells residing in the BM rapidly transform to plasma cells which produce high‐affinity IgG antibodies upon reinfection. This review describes the complete immune defence characteristics of the BDS against BBPs through the collaboration of the liver, spleen and BM with combined different immunological roles.