A branch of immunotherapies of profound importance is that of organ, tissue, and cell transplantation. So too are the profound immunological challenges presented in such therapies. All of the considerations of innate and adaptive immunity come into play with homograph (aka allograph) transplantation, that is transplantation from one donor to another of the same species (humans for this discussion) but with different genetic (genotype) makeup. Between the basic immunologic tenet of “self-versus-non-self” to the anamnestic (memory) response of the immune system, success with homographic transplantation needs intricate blood typing, cellular (receptor), and genetic matching of donor and recipient.
Organ failure (heart, liver, kidneys, etc.) is not unusual in humans, no less tissue injury and destruction by dermatological diseases (autoimmune and otherwise, e.g., accidents, and particularly, burns). So, the need to reduce (suppress) the immune system’s natural reaction to a “foreign transplant” was an obvious necessity in homographic transplantation. Immunosuppressive drugs, from steroids to the strongest immunotherapeutic agents, proved capable of doing the job of controlling the immune response. The introduction of the immunosuppressant drug cyclosporine in 1983 revolutionized
transplant medicine. But needless to say, these drugs would also reduce the patient’s fundamental (T cell, B cell, etc.) defenses against other non-self-invader, particularly opportunistic infectious agents.
Isoantigens (blood antigens or HLA complex, all slightly different in individuals) are present in some members of the human species (subset) and not others. Transfusion (blood) or transplantation of isoantigens into a donor without isoantigens will produce an immune antibody response (alloimmunity with alloantibodies) and result in a blood transfusion reaction or graft rejection (Type II cytotoxic hypersensitivity reaction, from Blog #9). So, it is critical that donor blood types and isoantigens are properly matched with recipients.
The discovery of isoantigens led to a more dynamic form of transplantation, namely bone marrow transplant. Given that the bone marrow is a principal site of stem cell, blood cell, and immune cell development, its value in providing a “new” immune system to a qualified recipient (i.e., isoantigen match) becomes obvious in treating autoimmune diseases and cancers. Bone marrow transplants may use cells from your own body (autologous transplant) or from a donor (allogeneic transplant). In either case, with a proper donor, the stem cells will yield a new, hopefully revitalized and disease-free immune system. By combining these newly developed immunotherapeutic procedures, new treatment modalities including xenotransplantation may be viable alternatives to allogeneic transplantation. Recently, a pig heart genetically modified by CRISPR-Cas9 was successfully implanted in a 57-year-old male. As of the writing of this blog, after 2 months postop the patient was doing well.
Discussion Questions:
Control of a natural immune reaction to a “foreign transplant” is an obvious necessity in homographic transplantation. What was the original immunosuppressant drug to control such a reaction and can you name some additional drugs used currently?
The discovery of isoantigens created the field of bone marrow transplantation. How is this technology used today in the treatment of autoimmune diseases and cancers?
Comments