Transpl Immunol 2002 Aug 01;102-3:91-100. doi: 10.1016/s0966-3274(02)00054-0.

The complexity of immune and alloimmune response.

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Alloimmune response induced by foreign histoincompatible alloantigens is a complex phenomenon possessing mechanisms, characteristics to innate and adoptive immune response. It is also modified by various immunregulating exocrine and autocrine factors. Starting the new time period of functional genomics the knowledge of human genes'' structure needs a more clear insight not only about the function and contribution of genes but their historical background, origin and importance in the phylogenesis. Comparative immunology comes into focus of interest helping to understand the complexity of immune and alloimmune response. It is almost unbelievable that immune functions as phagocytosis and cytokine production like IL-1 and TNF have already emerged 700 million years ago in starfishes and sponges. Functions--including recruitment of coelomocytes, killing of micro-organisms by lysosome-like enzyme activity, opsonization by complement analogous proteins and oxidative burst function--remained unchanged during phylogenesis and could be found not only in insects but in mammals as well as representatives of innate immunity. The importance of these molecules is reflected in homology of conservative regions. One of the biggest evolutionary steps happened 500 million years ago when fish developed a jaw in the Placoderms species. This fact led to the development of gut associated immune system. The system was the basis to create the genetic material for recombination and mutation to establish variability and diversity of proteins, as immunoglobulins. It is interesting to lean how diversity of immunglobulins in sharks is insured by joining of blocks of V, D, J and C genes, in contrast to humans, where those genes are located on different chromosome regions. These differences are associated with an immediate production of specific immunglobulin or a slower one combined with immunologic memory. Similar development could be found in T cell antigen specific receptors, too. Concerning the establishment of adoptive immunity by emergence of genetic recombination, which allowed the production of a huge diversity of specific antigen binding proteins, another structure developed parallel from the histoglobin molecule. This protein was created to catch peptide particles which split from the proteins originating from microorganisms, viruses or foreign cell compartments. The cave-like groove capturing the different peptides represented a huge variability. These histocompatibility molecules emerged from this ancient structure for more than 300 million years ago. The genetic family responsible for their synthesis became the most complex gene family including many other genes involved in the immune response. The polymorphic character of the histocompatibility protein is responsible for the capture of the relevant peptides fitting best to the allotype-determined groove. In certain species the same function could be filled by different ancient molecules with the same success. Dendritic cells and their importance in differentiation and antigen presentation became in the focus of interest in the last decade. They have lymphoid and myeloid origin, mature and less differentiated subtypes with characteristic CD markers and cytokine profile. Their function and origin from the stem cell subpopulation is an important example how nature influences the development of immunity to the accommodation and survival to the always changing environment. The new molecular techniques will help to get closer to understand the function of genes regulating immune response and modify them.

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Genes referenced: ago1b LOC115919910