Mini-review: defense strategies and immunity-related genes

The immune system is of crucial importance in defense against infection. It has to cope with a large number of different pathogens that relentlessly develop new ways to avoid recognition or elimination. Yet most infections are cleared. Immune-system genes must evolve to keep pace with increasingly sophisticated evasion by pathogens. In this article we examine features of human defense genes that reflect the demands imposed by such intense selection. Key examples are MHC and KIR genes, where features such as polygeny and polymorphism facilitate the comprehensive logistics needed to counteract infection.     

Immune complex diseases

Immune complex diseases (ICD) include different diseases of infectious and noninfectious origin in the pathogenesis of which the leading role belongs to immune complexes circulating in the blood stream. Three variants of the ICD course are distinguished: fulminant, acute, and chronic. The main morphological manifestation of ICD is vasculitis (in the fulminant course--microangiothrombopathy) and its consequences in the form of various circulation disorders. Renal glomeruli are frequently involved (glomerulonephritis). Immunopathologic reactions in the form of hypersensitivity reaction or inhibition of immune response are important in ICD.     

Autoimmunization and autoimmune diseases]

Autoimmunization is understood as a type of immune reactions to the unchanged autoantigens only. Autoimmune processes can be subdivided into the physiological ("sanitary" and regulatory) and pathological ones. Physiological processes are of importance in supporting natural immunological tolerance while pathological processes develop on the basis of the physiological ones in presence of various defects of suppressive mechanisms of the immune system. Pathological processes are the basis of the autoimmune diseases and diseases with secondary autoimmune disturbances. The distinction between organo-specific and organo-nonspecific autoimmune diseases can be taken as their preliminary tentative classification.     

Fractalkine and inflammatory diseases]

The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.     

复杂性状疾病的系统生物学研究

复杂性状疾病,即多基因病,其发生发展是基因,蛋白质,代谢分子,环境等众多因素相互作用的结果,仅仅从基因或蛋白等单层次研究已不能解释其发病规律。系统生物学的出现为从整体出发研究复杂性状疾病提供了新的视角和机会。本文主要介绍系统生物学概况和在复杂性状疾病研究中的应用。     

Immune complex mediated diseases.

Immune complexes formed in the circulation are believed to be the principal pathogenetic agents in certain human diseases, notably in various forms of glomerulonephritis and arteritis. Criteria for the recognition of immune complex deposits in tissue are discussed and recently developed sensitive methods that detect circulating immune complexes are reviewed. In addition, the evidence implicating certain antigens and causative agents in human immune complex mediated glomerulonephritis and arteritis is evaluated.     

Biosorption with extracorporeal use of heterologous spleen in the complex treatment od suppurative-septic diseases]

The search for new methods in the control of purulent infection is highly topical nowadays. For this purpose a complex of intensive therapy is suggested involving hemosorption via the patient's blood perfusion through porcine heterospleen. By literature and experimental data this technique is not inferior in efficacy to the use of the donor spleen. The spleen is removed conventionally, in modification of the authors. The results of the hemosorption analysed on 82 procedures performed in 1989-1990 justify employment of the above hemosorption in view of its efficacy, availability, simplicity.     

Prion diseases and blood transfusion]

Prion diseases are lethal disorders, some of which are transmissible by infectious route. Experimental data concerning neuroinvasion indicate that there is a viremia during the migration of the prion agent to the central nervous system. The possibility of accidental transmission via blood products and therefore potential transfusion risk thus arises. The analysis of experimental and epidemiological data available at present contributes to the following conclusion: the potential and theoretical risk for contamination from blood products is not null but mathematically very low, there is no indisputable experimental proof for that risk via systemic route and no case is definite and the risk is probably linked to leukocytes, and especially B lymphocytes. These conclusions are reassuring but nevertheless justify strict epidemiological survey and a reasonable discussion for each transfusion. Some groups of people have to be excluded from blood donors.     

Immunosuppressive drugs and autoimmune diseases]

Only a few immunosuppressive drugs can be used today. These are: corticosteroids, azathioprine, cyclophosphamide, ciclosporine A, accessorily chlorambucil and methotrexate. They all have different actions on immune responses. The use of these drugs has completely changed the prognosis of autoimmune diseases such as systematic lupus erythematous, polyartheritis nodosa, Wegener's granulomatosis. Nevertheless treatment of other autoimmune diseases, such as type I insulin-dependent diabetes mellitus or multiple sclerosis, has been inconclusive.     

Malassezia related diseases]

The genus Malassezia is now divided into eleven species. Different species initiate or aggravate different skin diseases. In seborroheic dermatitis, M. restricta play an important role, while in atopic dermatitis, M. globosa and/or M. restricta are major cutaneous microflora. M. globosa is a causative species of tinea versicolor, and this species is also a causative species of malassezia folliculitis. We should therefore obtain better knowledge of the ecological and pathogenic roles of malassezia.     

Central tolerance and autoimmune diseases]

Central tolerance is established by the repertoire selection of immature T lymphocytes in the thymus, avoiding autoimmune responses to self-antigens. Differential ligand-TCR interactions that result in positive and negative selection initiate differential intracellular signals that, in turn, lead to the survival-or-death decision of immature thymocytes. TCR signal dysregulation due to the mutation of ZAP-70 or defective apoptosis of autoreactive thymocytes due to the deficiency of pro-apoptotic protein Bim impair tolerance and cause autoimmunity. Thymic repertoire selection also induces the development of CD25(+)CD4(+) regulatory T cells, which play important roles for maintaining peripheral tolerance. Furthermore, the establishment of central tolerance requires the development of thymic medulla that is mediated by the activation of NF-kappaB signaling pathway, promiscuous expression of tissue-specific self-antigens by medullary epithelial cells that is regulated by AIRE, and cortex-to-medulla migration of developing thymocytes that is regulated by CCR7-mediated chemokine signals.     

Organ-specific autoimmune diseases and cytokines]

Changes in serum levels of cytokines in organ-specific autoimmune diseases were reviewed. Serum levels of IL-12, critical for the development of Th1 cells, were increased in thyrotoxic patients with Hashimoto's thyroiditis and Graves' disease. Serum levels of IL-5, secreted from Th2 cells, were increased in thyrotoxic patients with Graves' disease, but not in thyrotoxic patients with Hashimoto's thyroiditis. In patients with IDDM, serum levels of Th1 cytokines (IFN-gamma and IL-2) were increased but serum levels of Th2 cytokines (IL-4 and IL-10) were not increased. These findings suggest that measuring the serum concentration of various cytokines is useful to analyze Th1/Th2 balance in autoimmune diseases.     

DNA repair and related diseases]

DNA-repair is a complex enzymatic process which enables all living cells to withstand the deleterious and mutagenic effects of most genotoxic agents. Defective DNA-repair is caused by mutations involving genes which encode the enzymes responsible for recognition and excision of DNA lesions. Some of these genes have been identified in humans. Several severe human diseases are caused by defective DNA repair affecting the entire genome (e.g. xeroderma pigmentosum and trichotiodystrophy) or only actively transcribed genes (Cockayne's syndrome). Some of these conditions are associated with extremely high rate of cancer.