Cellular and genetic requirements for graft-versus-host reactivity

The immune response is an important component of vertebrate's defense to infectious agents. Vertebrates with an ill-developed immune system generally die before reaching the reprodyctive age. In man this is examplified by children with hereditary severe combined immunodeficiency disease. Immunity is based upon the capacity of lymphocytes to recognize antigens and to make them harmless. This can be done in two ways: via a humoral immune response and via a cellular or cellmediated immune response. These two limbs of the immune system are based upon two types of lymphocytes: B and T lymphocytes. The bone marrow-derived B lymphocytes are the progenitors of plasma cells which secrete humoral products, i.e. the antigenspecific antibodies. The thymus-derived or T lymphocytes are responsible for cell-mediated immunity. Humoral immunity can be transferred from immune to non-immune individuals by means of serum, whereas cell-mediated immune responses can only be transferred to non-immune individuals by means of lymphocytes. Recognition of an antigen by aT lymphocyte will trigger that cell to mount a specific immune response without the release of antibodies. Examples of cell-mediated immune responses are the defense to viruses (e.g., measles, mumps) and the resistance to intracellularly growing bacteria (e.g., Listeria monocytogenes). Furthermore, delayed type hypersensitivity (e.g., the Mantoux reaction in humans infected with tubercle bacilli) and graft rejection (e.g., rejection of a kidney transplant) are caused by cell-mediated immune responses. Recent studies reveal that for optimal activation of the cell-mediated immune system not only the foreign antigen must be recognized by the T lymphocytes, but also a self-component. These self-components are cell surface markers which can be different for different individuals of a certain species. They are called histocompatibility antigens. Each individual of a certain species can mount an extremely strong cell-mediated immune response against those histocompatibility antigens of most other individuals of that species. This often occurs after organ and tissue transplantation when donor and recipient are genetically unrelated.