Clinics in Immunology and Allergy最新文献

The chromosomal organization of immunoglobulin genes, and the synthesis of various heavy and light chains to molecules with an infinitive variety of antibody specificities, is discussed. These molecules carry antigenic determinants (epitopes) that may be individual (idiotypes), shared (isotypes and isoallotypes) or polymorphic (allotypes).

Since biological effector functions correlate with epitopes, its determination can be relevant to clinical disease. In particular, in cases of an excessive or a decreased production of immunoglobulins or of incomplete proteins, the determination of isotypes and allotypes will supply information on the abnormality.

Allotypes are genetic markers that are useful for family and population studies, for investigation of paternity, blood stains, zygosity of twins and other identification problems. Testing for antibodies to immunoglobulins is indicated when severe transfusion reactions occur that cannot be explained by blood cell incompatibility.

Research on the association of immunoglobulin alleles with immune response, and their interactive effect with HLA in diseases, is gradually developing. The study of the Ig and HLA systems may contribute to the elucidation of the aetiology of immunological disorders and malignancies.

The HLA region controls the major antigen system responsible for graft rejection and alloimmunization. More fundamental to the immune response, it controls the individual genetic elements regulating the interactions responsible for cellular immune functions. These HLA genetic determinants operate as permissive signals. When appropriate epitopes are available for presenting antigen to T cells, the effect is to facilitate response. If effector cells are activated, immune response is initiated. If suppressor cells are activated, immune response may be inhibited. Another genetic system separate from HLA presumably contains the genetic information that provides diversity for the T cell antigen receptor. Multiple nongenetic factors may also influence the immune response, among them prior alloimmunization via transfusion or pregnancy, viral infections and potentially a variety of other transfusion-related factors.

Exposure to HLA and other tissue antigens has in general no clinical benefits and potential major adverse effects for an immunocompetent patient. Subsequent rejection of grafts of haematopoietic stem cells or of other tissues can result, as well as refractoriness to platelet and granulocyte transfusions. In the setting of profound immune suppression, infusion of viable lymphocytes can result in planned or inadvertent engraftment and a graft versus host reaction. The latter can occur even in the absence of measurable engraftment of haematopoietic cells. The apparent paradoxical effects of blood transfusion in aplastic anaemia, leading to marrow graft rejection, and in renal transplantation, leading to improved graft survival, reflect the lack of knowledge about which factors lead to Ir gene phenomena and which lead to Is gene phenomena. The observation that alloimmunization can result in specific immune suppression raises the exciting prospect of transplantation without the necessity of establishing a general state of immune compromise in the host. Since the effect of alloimmunization from transfusion or other sources is so unpredictable, it is difficult to ascertain whether transfusion is immunosuppressive in healthy individuals. Transfusion-related viral infections can lead to reversible immune compromise; much less is known about the effects of non-viral factors. Of these factors, HLA antigens in unaltered or in soluble form are probably important, but their relation to Ir and Is appears unpredictable.

Evidence for transmission of AIDS via blood products has added to concern about transfusion-related immune suppression. Individuals at highest risk for transfusion-transmitted disease have received heavy exposure to multiple donor blood products. They are expected to exhibit the most pronounced non-specific immunological changes as well. If the aetiologic agent(s) responsible for AIDS can be identified, then the prevalence of seropositivity among those high risk patients can be ascertained and immunological effects unrelate