Transfer of blood cells between humans, called transfusion, is the oldest form of transplantation in clinical medicine. The major barrier to transfusion is the presence of allogeneic blood group antigens, the prototypes of which are the ABO antigens (Fig. 1). These antigens are expressed on red blood cells, endothelial cells, and many other cell types. ABO antigens are carbohydrates on membrane glycoproteins or glycosphingolipids; they contain a core glycan that may be enzymatically modified by addition of either of two types of terminal sugar residues. There are three alleles of the gene encoding the enzyme that adds these sugars: one encodes an enzyme that adds N-acetylgalactosamine, one that adds galactose, and one that is inactive and cannot add either. Therefore, depending on the alleles inherited, an individual may be one of four different ABO blood groups: Blood group A individuals have N-acetylgalactosamine added to the core glycan; blood group B individuals have a terminal galactose; blood group AB individuals express both terminal sugars on different glycolipid or glycoprotein molecules; and individuals with blood group O express the core glycan without either of the terminal sugars.

Fig1. ABO blood group antigens. A, Chemical structure of ABO antigens. B, Figure shows the antigens and antibodies present in people with the major ABO blood groups.

Individuals are tolerant of the blood group antigens they express, but make antibodies specific for the antigens they do not express. Thus, type A individuals make anti-B anti bodies, type B individuals make anti-A antibodies, O group individuals make both anti-A and anti-B, and type AB individuals do not make anti-A or anti-B antibodies. These anti bodies are called natural antibodies because they are made in the absence of the antigen. They are likely produced by B cells in response to antigens of intestinal microbes, and the antibodies cross-react with ABO blood group antigens. Because the blood group antigens are sugars, they do not elicit T cell responses that drive isotype switching, and the antibodies specific for A or B antigens are largely IgM. The preformed antibodies react against transfused blood cells expressing the target antigens and activate complement, which lyses the red cells; the result may be a severe trans fusion reaction, characterized by a strong systemic inflammatory response, intravascular thrombosis, and kidney damage. This problem is avoided by matching blood donors and recipients so there are no antigens on the donor cells that can be recognized by preformed antibodies in the recipient, a standard practice in medicine.

Blood group antigens other than the ABO antigens also are involved in transfusion reactions, and these usually are less severe. One important example is the RhD antigen, which is a red cell membrane protein expressed by about 90% of people. Pregnant women who are RhD-negative can be immunized by exposure to RhD-expressing red cells from the baby during childbirth if the baby inherited the RhD gene from the father. The mother will produce anti-RhD antibodies that can cross the placenta during subsequent pregnancies and attack Rh-positive fetal cells, causing hemolytic disease of the fetus and newborn.

Hematopoietic stem cell transplantation is being used increasingly to correct hematopoietic defects, to restore bone marrow cells damaged by irradiation and chemotherapy for cancer, and to treat leukemias. Either bone marrow cells or, more often, hematopoietic stem cells mobilized in a donor’s blood are injected into the circulation of a recipient, and the cells home to the marrow. T he transplantation of hematopoietic stem cells poses many special problems. Before transplantation, some of the bone marrow of the recipient has to be destroyed to create space to receive the transplanted stem cells, and this depletion of the recipient’s marrow inevitably causes deficiency of blood cells, including immune cells, resulting in potentially serious immune deficiencies before the transplanted stem cells generate enough replacement blood cells. The immune system reacts strongly against allogeneic hematopoietic stem cells, so successful trans plantation requires careful HLA matching of donor and recipient. HLA matching also prevents rejection of transplanted stem cells by NK cells, which are inhibited by recognition of self MHC molecules . If mature allogeneic T cells are transplanted with the stem cells, these mature T cells can attack the recipient’s tissues, resulting in a clinical reaction called graft-versus-host disease. When the donor is an HLA-identical sibling (as in about 80% of cases), this reaction is directed against minor histocompatibility antigens. The same reaction is exploited to kill leukemia cells (so-called graft-versus leukemia effect), and hematopoietic stem cell transplantation is now commonly used to treat leukemias resistant to chemotherapy. NK cells in the marrow inoculum may also contribute to the destruction of leukemia cells.

Despite these problems, hematopoietic stem cell transplantation is a successful therapy for a wide variety of diseases affecting the hematopoietic and lymphoid systems.

مواضيع ذات صلة

Hypersensitivity Disorders Caused by Immune Responses : Clinical Syndromes and Therapy

Activation of Mast Cells and Secretion of Mediators

Activation of Th2 Cells and Production of IgE Antibody

Prevention and Treatment of Graft Rejection

Monocytes–Macrophages: Host Defense Functions: Phagocytosis

Mononuclear Phagocyte System

Immune Mechanisms of Graft Rejection

Induction of Immune Responses Against Transplants

Transplantation Antigens

Glycans and Immunity

Immune Responses Against Transplants

Cancer Immunotherapy : Stimulation of Host Antitumor Immune Responses by Vaccination With Tumor Antigens