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Clinical immunology is a rapidly expanding specialty, and new developments have implications for many doctors since patients with immunological diseases are treated by general practitioners and by clinicians in various specialties. We will therefore consider recent advances in clinical immunology with regard to immunodeficiency, complement, treatment with intravenous immunoglobulin, and infection and vaccines.
Immunodeficiency
Recent developments in the study of genetically determined immunodeficiency have broadened our understanding of the immune system and, in doing so, have extended the possibilities for treatment. The initial description of isolated humoral immunodeficiency, Bruton's agammaglobulinaemia, showed the consequences of insufficient antibody production-repeated attacks of severe infections against which antibodies are the main protection. Cellular immunodeficiency leads to another pattern of infections, and severe combined immunodeficiency-in which both arms of the immune system are affected-implies severe early disease usually leading to death within the first or second year of life. The different types of severe combined immunodeficiency are heterogeneous in their genetic basis (recessive or sex linked) and the basic mechanisms involved, and to some extent in clinical appearance. It is in our knowledge of the basic mechanisms that we have seen the greatest developments. 1
COMMUNICATION BETWEEN CELLS
Development of immune responses requires extensive signalling between cells-such as between the antigen presenting cell and responding T cells that produce interleukins, signal substances essential for inducing the required proliferation and differentiation of lymphocytes. The basic reaction is between the specific T cell antigen receptor and processed antigen in the groove of HLA molecules on the surface of the antigen presenting cell. In addition CD4 or CD8 molecules are involved. Recent studies of the hyper IgM immunodeficiency-immunoglobulin deficiency with increased IgM-have shown the fundamental importance of secondary signals provided by other adhesion molecules. CD40 is a surface antigen on B cells that reacts with a ligand (CD40L) present on activated T cells. The interaction between them is synergised by co-stimulatory signals to drive proliferation and differentiation of B cells. In patients with X linked hyper IgM immunodeficiency, expression of CD40L on activated T cells is incomplete because of several distinct mutations of the gene coding for CD40L. 2 The signals required for switching immunoglobulin class from IgM to IgG are not generated so that a secondary immune response cannot develop, resulting in...