Advances in Immunology: 103
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Our knowledge of its effects on cytokines was recently extended by the demonstration that it inhibited production of tumour necrosis factor and interleukin 6 induced by staphylococcal enterotoxin B by neutralising the enterotoxin. Intravenous immunoglobulin has been shown to modulate complement activation in several animal models, and this may be important in human dermatomyositis.
Recent data indicate that intravenous immunoglobulin may have an inhibitory effect on C1 as well. Intravenous immunoglobulin is relatively safe for clinical use, but it is prepared from humans, and, although it is treated to inactivate viruses, no full guarantee against infectious transmission can be given. Because of these aspects, as well as high costs and, most important, the lack of data from controlled clinical trials, treatment with intravenous immunoglobulin should continue to be restricted to treating idiopathic thrombocytopenic purpura, Kawasaki disease, steroid resistant dermatomyositis, and probably a few selected patients with acquired haemophilia, intractable asthma, myasthenia gravis, and Guillain-Barre syndrome.
In recent years interest in infectious diseases has increased because of problems concerning infections in immunocompromised patients, increasing occurrence of drug resistant strains of many microorganisms, and the effects of the HIV epidemic. Vaccination remains an essential component of preventive medicine. It is well established that an effective vaccine is the most cost effective tool to control an infectious disease. It can lead to virtual eradication of an infectious disease—such as smallpox—or to a pronounced reduction in the incidence of a disease with almost complete arrest of transmission—as with polio and measles.
These effects show the importance of continuing effective vaccination programmes. Priority should be given to the study of vaccines and development of new vaccines. Several of our most effective vaccines are still based on empirical findings. Recent developments have been possible because of our increased knowledge of microbial pathogenesis and the immune system.
Capsular polysaccharides are often poor immunogens, and vaccines based on them fail to induce immunological memory, particularly in children. Vaccines based on chemical coupling of capsular polysaccharides to protein carriers have proved to be valuable, like the Haemophilus influenzae type b polysaccharides coupled to tetanus toxoid. In this form it becomes a T cell dependent antigen and induces immunological memory, resulting in a considerable decrease in the disease in children under 5 years old.
Whole cell vaccines are used extensively—for example, suspensions of killed Bordetella pertussis organisms, usually incorporated in combined vaccines against diphtheria and tetanus as well. Although these vaccines have been effective, adverse effects can occur and the safety of whole cell pertussis vaccine in particular has been questioned. Studies have identified four main pertussis antigens that induce formation of protective antibodies: On the basis of this information, acellular pertussis vaccines have been developed and have shown excellent protection in extensive clinical trials, 35 36 presenting a major advance in vaccine technology.
Local administration of antigen usually results in a systemic response by the immune system, but local responses do occur, particularly with the mucosal immune system. This is one of the most active fields of basic immunology and is of particular importance in the development of new vaccines. An essential feature is how antigen should be delivered to ensure an optimal and selective response by the mucosal immune system. The techniques being tested include nasal immunisation, 39 expression of selected recombinant protein on the surface of oral commensal bacteria, 40 oral vaccination with attenuated recombinant enterobacteria like Vibrio cholerae, 41 42 and new delivery systems for oral vaccines.
In recent years there has been renewed interest in tuberculosis, and new information has come from recombinant DNA technology. Insufficient knowledge of mechanisms of protective immunity and the basis for the pathogen's characteristic dormancy and reactivation are major problems, but new technologies have opened up new avenues for the development of vaccines. Recent developments suggest that we may be able to develop vaccines against a wider range of conditions than just infectious diseases.
Malignancies, allergies, and autoimmune diseases are promising candidates for the development of vaccines. Skip to main content. We use cookies to improve our service and to tailor our content and advertising to you. More info Close You can manage your cookie settings via your browser at any time.
To learn more about how we use cookies, please see our cookies policy Close. Education And Debate Recent Advances: Clinical immunology BMJ ; doi: Article Related content Metrics Responses Peer review. Abstract Summary points The genetic basis for many types of hereditary immunodeficiency has now been found, allowing more precise diagnosis and giving hope for future treatments Manipulation of proteins that regulate complement activation has exciting therapeutic implications, such as ameliorating the hyperacute rejection of xenografts Deficiencies in complement regulators have been implicated in several types of kidney disease, and soluble complement receptor 1 may be useful in future treatments Intravenous immunoglobulin is now used to treat several systemic inflammatory conditions, and its effects include modulating proinflammatory cytokines and complement activation Use of new technologies is allowing development of more effective vaccines and avoidance of adverse effects such as found with whole cell pertussis vaccine.
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. Complement The complement system is composed of more than 30 proteins and is an important part of the humoral host defence system. Fig 1 Kidney glomeruli from pigs aged weeks with hereditary deficiency of factor H and membranoproliferative glomerulonephritis type II. Intravenous immunoglobulin Intravenous immunoglobulin has been used in replacement therapy for patients with immunoglobulin deficiency and in specific passive immunisation against certain infectious diseases.
CLINICAL USE Intravenous immunoglobulin is relatively safe for clinical use, but it is prepared from humans, and, although it is treated to inactivate viruses, no full guarantee against infectious transmission can be given. Infection and vaccines In recent years interest in infectious diseases has increased because of problems concerning infections in immunocompromised patients, increasing occurrence of drug resistant strains of many microorganisms, and the effects of the HIV epidemic.
Immunologist ; 3: J Clin Invest ; Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. In vivo transfer of GPI-linked complement restriction factors from erythrocytes to the endothelium. Science ; Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nature Med ; 1: Tissue expression of human complement inhibitor, decay-accelerating factor, in transgenic pigs—A potential approach for preventing xenograft rejection.
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Transplantation ; Enzymatic removal of alphagalactosyl epitopes from porcine endothelial cells diminishes the cytotoxic effect of natural antibodies. Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis.
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Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation. Cellular expression of the C5a anaphylatoxin receptor C5aR: J Immunol ; N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation.
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J Exp Med ; C5a-induced expression of P-selectin in endothelial cells. Enhancement by the complement membrane attack complex of tumor necrosis factor-alpha-induced endothelial cell expression of E-selectin and ICAM Saadi S , Platt JL. Transient perturbation of endothelial integrity induced by natural antibodies and complement. Complement-mediated regulation of tissue factor activity in endothelium. Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.
Crry and CD59 regulate complement in rat glomerular epithelial cells and are inhibited by the nephritogenic antibody of passive Heymann nephritis. The effects of soluble recombinant complement receptor 1 on complement-mediated experimental glomerulonephritis. J Am Soc Nephrol ; 5: Variable region-connected, dimeric fraction of intravenous immunoglobulin enriched in natural autoantibodies. J Autoimmun ; 8: In vitro inhibition of tumour necrosis factor-alpha and interleukin-6 production by intravenous immunoglobulins. Br J Haematol ; Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG intravenous immunoglobulin.
Eur J Immunol ; Update on the use of intravenous immune globulin in the treatment of patients with inflammatory muscle disease. J Clin Immunol ; Regulation of complement activity by immunoglobulin. Effect of immunoglobulin isotype on C4 uptake on antibody-sensitized sheep erythrocytes and solid phase immune complexes. Qi M , Schifferli JA.
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Inhibition of complement activation by intravenous immunoglobulins. Arthritis Rheum ; Inhibition of complement-mediated red cell lysis by immunoglobulins is dependent on the IG isotype and its Cl binding properties. Scand J Immunol ; Intravenous polyclonal immunoglobulins in autoimmunity and transplantation. Xenobiotica ; 3: Use of intravenous immunoglobulin to delay xenogeneic hyperacute rejection—in vivo and in vitro evaluation. Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation.
HCV infection in patients with primary defects of immunoglobulin production. Clin Exp Immunol ; High-dose intravenous gamma globulin therapy: How does it work?
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Malignancies, allergies, and autoimmune diseases are promising candidates for the development of vaccines. Intravenous immunoglobulin is relatively safe for clinical use, but it is prepared from humans, and, although it is treated to inactivate viruses, no full guarantee against infectious transmission can be given. The same residues of mouse IgG1 are also involved in FcRn binding, except that Tyr is replaced by histidine. It has long been known that a defect in the glycosylphosphatidylinositol anchor—with consequent lack of CD55 and CD59 on cell membranes—is associated with paroxysmal nocturnal haemoglobinuria, and animal studies have shown that blocking of complement regulatory proteins on endothelial cells leads to vascular leakage. CLINICAL USE Intravenous immunoglobulin is relatively safe for clinical use, but it is prepared from humans, and, although it is treated to inactivate viruses, no full guarantee against infectious transmission can be given. These roles include the maintenance of IgG levels and the delivery of antigen in the form of immune complexes to degradative compartments within cells.
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The same residues of mouse IgG1 are also involved in FcRn binding, except that Tyr is replaced by histidine. Multitasking by Exploitation of Intracellular Transport Functions: The Many Faces of FcRn. Schematic representation of FcRn-mediated recycling of IgG in a polarized cell such as an endothelial cell.
IgGs are taken into the cell by fluid phase and enter early endosomes. The pH of the early endosome is permissive for FcRn binding, and binding of the IgG to FcRn results in recycling or transcytosis, not shown and salvage from lysosomal degradation. Conversely, unbound IgG enters the lysosome and is degraded. Images of live cells were acquired and processed as described in.
The first frame for each dataset is arbitrarily labeled 0 s, although the frames shown were taken at different times after the start of the chase period.