the Recognition of the broken immunity at children has given fifty years ago eksponentsionalnyj growth of knowledge of immune system. It has been identified more chem 95 hereditary immune infringements. Genetically determined immunodefitsit can call not only excessive sensitivity to an infection, but takzhe and autoimmunnye processes and the raised risk of a cancer. These defects can amaze odin or some components of immune system, fagotsitarnye cages, including RT-cages, the V-cages, natural cages-killers, fagotsitarnye cages and proteins komplementa. PHENOTYPES Mutatsii amazing function In - and T-cages are shown by insufficiency of development antitel, cellular immunity or volume and the friend. It is important to realise, that various molekuljarnye defects can call the same phenotype. Though true frequency etih deficiencies is not known, nevertheless, it is supposed, that they meet with chastotoj 1 on each 10 000 live births. Defekty V-cellular function increase risk recurrent piogennyh infections. Klinicheskaja the picture H-connected agammaglobulinemii or usual variabelnogo immunodefitsita defines a phenotype of deficiency of antibodies. Children with insufficient vyrabotkoj an antibody are protected from an infection within the first months of a life IgG by antibodies received from mother. Then they are infected inkapsulirovannymi with microorganisms Haemophilus influenzae, Staphylococcus aureus and gramme-negative microorganisms such, as kinds pseudomonas. Hronicheskie fungoid infections meet not often, and the pneumonia called Pneumocystis carinii is rare enough. Concerning viruses business is normally, za an exception enterovirusov which can call persistirujushchy meningoentsefalit, sometimes assotsiirovannyj with a status similar dermatomiozitu. Paralich can develop from a chronic infection after vaccination live attenjuirovannymi vaccines. Infitsirovanie ekhovirusami, koksaki viruses, adenovirusami and Ureaplasma urealyticum have been defined on an articulate liquid etih patients, even at those receiving immune globuliny-replaceable terapiju. Kontsentratsija all isotypes imunoglobulinov it is very low at children with these sindromami immune deficiency. At H-connected agammaglobulinemii, circulating RV-cages usually are absent or are available in very small quantities, at that time kak at usual variabelnyh V-cage immunodeficiencies usually are available. Tonzilly ochen small, and lymph nodes are seldom palpated at patients with H-svjazanoj agammaglobulinemiej, and these clinical data should facilitate early raspoznanie this defeat. And on the contrary, these fabrics of the normal size or uvelicheny at patients with usual variabelnym an immunodeficiency. Neither nor another narushenie amazes that neither architecture timusa, nor timus-dependent areas selezenki, lymph nodes. Monthly infusions immunnoglobulina okazyvajut zhizne-saving effect at both infringements. I on the contrary, at infectious complications of diseases of deficiency of antibodies defects / RT-cellular function call predisposition to opportunistic infections. Tjazhelyj the combined immunodeficiency, a syndrome with various genetic prichinami (fig. 1 and 2, showing my own data) and deep deficiencies RT - and In - cages represents a phenotype of insufficiency of function of T-cages. At porazhennyh them of children in the first months of a life there is a diarrhoeia and inability to naboru weight. Persistirujushchie the infections called Candida albicans, P. carinii, varitselloj, adenovirusami, respiratory sintsitialnymi viruses, viruses parainfljuentsy type 3, a cytomegalovirus, viruses Epstein-Barr (EBV) and batsilloj Calmette-Guerin appear fatal. These children cannot tear away allografty, chto is connected with risk of development of fatal disease transplantant-against hozjaina when it makes blood transfusions or change of a bone brain with soderzhaniem T-cages. U children with the heavy combined immunodeficiency it is marked limfopenija; vyjavlenie to this one anomaly presumes to make the early diagnosis during neskolkih hours after a birth. Limfotsity these children not proliferirujut in vitro, kogda they are processed mitogenami, antigenes or allogennymi by cages. Levels immunoglobulinov in whey are low or do not give in to definition. Timus dependent oblasti in a spleen are deprived limfotsitov and lymph nodes and tonzilly otsutstvujut. Timus very small (usually weighs less than 1 gramme) and in him is not present timotsitov; borders between a bark both medulloj and gassalevymi little bodies are not accurate, not prosmatrivajutsja. However, successes reached in gemopoeticheskoj stvolovyh the cages restoring population circulating T - cages at these detej show transplantations, that timus can keep normal development of T-cages. Tjazhelyj the combined immunodeficiency is a pediatric urgent situation. Pochti in all cases the diagnosis can be put at a birth by calculation belyh blood cells and manual differential calculation of white cages and tsitometricheskim a stream and function research T - cages, when absolute kolichestvo limfotsitov less than normal level at newborns (2000 to 11000 na cubic millimetre). If not to spend transplantation of a bone brain or gennoj therapy the death at children`s age is inevitable. Transplantation gemopoeeticheskih stvolovyh cages within first three months of a life of patients daet it of 95 % chance of a survival. All over the world is available no more, than 375 patients, kotorym were possible to go through the heavy combined immunodeficiency thanks to successful provedennoj transplantations HLA-identical or gaploidentichnogo bone mozga. GENETIC ASPECTS Do recent time a little that was known about principal causes of diseases pervichnogo an immunodeficiency. Thanks to progress of molecular genetics of the person for poslednie seven years genetic infringements of some defects were identifitsirovany. Genes defining immune function are distributed on all genomu. However, there is an obvious prevalence of the H-connected immunodeficiency in rezultate gemizigotnosti men concerning considerable number of genes immune sistemy on the H-chromosome. Moreover, spontaneous new mutations in these H-connected genah are rather frequent. At nositelnits a female H-connected immunnodefitsita is available deviating inaktivatsija in the amazed cellular line; pochti all mature cages of the amazed line at women nositelnits contain normalnuju the H-chromosome while in other cages H-inaktivatsija it is enough redka. This phenomenon specifies that a cage with an abnormal H-chromosome not mogut to ripen. This feature can clinically be applied to an estimation, whether javljaetsja the female relative of the amazed patient of a male, nositelnitsej. Pri to an estimation of patients with suspicion on immunnodefitsit key questions javljajutsja those concerning closely related communication as children, parents kotoryh occur from genetically limited populations, have the greatest risk po homozygosities of development autosomalno retsessivnogo immunnodefitsitarnogo porazhenija. Another hromosomalnym to regions containing corresponding genes immunnyh functions concern 6p where genes of tkane-compatibility and 5q settle down, gde many genes tsitokinov are located. Predshestvujushchie classifications of these diseases have been based on characteristics klinicheskih displays and specific infringements of the immune status. Progress in molekuljarnoj to genetics allows to group them now in conformity s type of genetically amazed molecules, since those on a cage surface s the further advancement inside. Important for doctors to define molecular prichiny diseases at their patients as it can provide corresponding geneticheskuju consultation, prenatalnuju diagnostics and on end carrying out gennoj therapies for defect correction. GENETIC DEFECTS CALLING DEFICIENCY of ANTIBODIES Deficiencies of V-cellular receptors Defitsity V-cellular receptors are called by mutations of genes coding lungs either tjazhelye chains of antibodies or assotsiirujushchie with them alarm molecules, that privodit to development agammaglobulinemii or gipogammaglobulinemii. Mutations porazhajushchie m a chain; sjurrogatno an easy chain (l5/14, I); Iga (CD79a), alarm molekulu the V-cellular receptor; And V-cellular linker the protein adapter assotsiirujut with otsutsvtiem circulating In cages. Other mutations of genes heavy tsepej an antibody (such as g1, 2, 3 either 4; a1 or 2; and e) cause defitsity separate classes or subclasses of antibodies; but circulating RV-cages are present also the general function of antibodies usually normal. Gene mutations k legkoj chains it is shown by population of molecules of an antibody only with l lungs tsepjami, instead of usual set k and l types. Deficiency of one of members ligandnoj steams Pri H-connected giper-IgM a syndrome levels in whey IgG, IgA and IgE very much nizki, and levels in whey IgM or are normal or essentially raised. Patients s are subject by this syndrome recurrent piogennym to infections and development P.carinii to a pneumonia. At them the raised frequency autoimmunnyh narusheny and a cancer also is marked. It is paradoxical, but the giper-IgM-syndrome is faster / RT-cellular defect, than defect of V-cages. Until the RT-cages have been opened, accompanying nejtropenija served as an explanation of susceptibility of these patsientov to infection P.carinii. Nenormalnyj the gene at the H-connected giper-IgM-syndrome has been localised in Xq26.3-27.1 and has been opened in 1993. A product of this gene is poverhnostnaja the T-cage molecule known as CD154 (or CD40 ligand); iznachalno it is present on activated CD4 + cages and co-operates with ee receptor CD40 on V-cages. CD154 it is II type integrated membrannogo glikoproteina which structurally concerns to tumour-nekrotizirujushchemu to the factor. Perekrestnoe linkage CD40 as on a surface of normal V-cages, or RV-cages of patients with H-connected giper-IgM a syndrome with monoklonalnym an antibody k CD40 or soluble CD154 in presence tsitokinov (interlejkin-2, 4, and 10) zastavljaet V-cages proliferirovat and sekretirovat antibodies various izotipov. Mutations in gene CD154 interrupt passage of a signal from V-cages to RT-cages on way CD40. In the absence of the help of T-cages of the V-cage cannot vyrabatyvat IgG, IgA and IgE; but they can develop IgM. In lymphatic uzlah is available only abortivnoe formation germinalnyh the centres, because of nesposobnosti T - cages to signal V-cages to be exposed izotipnomu perekljucheniju and to increase in quantity. Nedostatok cross communications CD40 CD154 also it is shown in inability of RV-cages up-regulate CD80 CD86, of great importance kostimuljatornyh molecules kotorye co-operate with immunnoreguljatornymi molecules of T-cages named CD28 and CTLA-4. Obryvanie this way in timuse at a giper-IgM-syndrome it is shown defektivnym by clarification from autoreaktivnyh timotsitov and, from here susceptibility autoimmunnym to diseases. Also absence ekstratimicheskogo interactions etih reguljatornyh molecules is shown in defective recognition tumoral kletok. Mnogie various dot mutations or deletsii in gene CD154 have been identified . The analysis vysokopolimorfichnogo microsatellite dinukleotida (SA) repeating regiona in 3 ’ not broadcast end of a gene appears useful at identification nositelej and the diagnosis prenatalno allows to make. Pokazatelem that the giper-IgM-syndrome is caused more than one geneticheskoj the reason is autosomalno-retsessivnaja the form of this infringement, porazhajushchaja persons of a female. For such patients is available inherent V-cellular defekt which does not allow to be switched In cages from development IgМ on IgG, IgD and IgE even if they are cultivated with monoklonalnymi antibodies to CD40 and tsitokinami. CD40 on such In cages assumes presence of defects assotsiirovannyh with CD40 the mediated carrying out of a signal. One of such defektov has been recently opened: mutations in a gene 12p13 coding / raktivatsionno-induced tsitidin-deaminazu, messendzher RNK - publishing enzima. Deficiencies of alarm molecules V 1993 two groups independently from each other have opened mutirovannyj a gene at / RH-connected agammaglobulinemii which has received now the name a gene Bruton tirozin kinazy (BTK). Bruton tirozin kinaza is member Tec of family tirozin kinaz cytoplasmatic proteins. This kinaza is necessary for growth prekursorov V-cages and their development in mature V-cages that explains why is not present tsirkulirujushchih cages at patients with H-connected agammaglobulinemiej. Mutant BTK the gene has been found out in mieloidnyh cages, opening which could explain intermittirujushchuju nejtropeniju at boys with H-connected agammaglobuinemiej. Was identifitsirovano more than 300 various mutations in gene BTK, but it has not been revealed ni one obvious correlation between type of a mutation and a phenotype. In families in which mutatsija it is identified, disease was diagnosed prenatalno for fruits muzhskogo a floor on the basis of definition of a mutant gene in vorsinah horiona or in materiale amniotsenteza. the GENETIC DEFECTS CALLING TSELLJULJARNYE OR COMBINED IMMUNODEFITSITY Defects of genes CD3 of a complex Tselljuljarnye or combined immunodeficiencies, connected with mutations in a gene kodirujushchem g or e chains, call infringement of an expression T-cellular retseptra (CD3 is a complex from five polipeptidnyh chains which assotsiirujut with and, in osnovnom, the T-cellular receptor). At patients with such mutations are marked razlichnye levels autoimmuniteta and predisposition to infections. At them weak reaction on T-cellular mitogeny and various immunoglobulinovye deficiencies is not enough tsirkulirujushchih CD3 + T cages or not in general. Deficiencies of chains of a receptor tsitokina the H-connected heavy combined immunodeficiency Defitsit usual g chains (gс) a receptor interlejkina-2, one of several defektov calling the heavy combined immunodeficiency (concerning to SCID-XI), javljaetsja the most frequent form of a component approximately 46 percent of cases v the USA. The abnormal gene was mappirovan in the field of Xq13 and later was identifitsirovan as a gene coding g a chain which usually meets on / rpoverhnostno-cellular receptors for molecules interlejkina (interlejkin-2, 4, 7, 9 and 15). Among the first studied 136 patients with H-connected heavy kombinirovnnym the immunodeficiency at 95 had been identified obvious mutations. They projavljalis abnormal chains gс at two thirds of patients and absence gс proteina at the others. Opening of that mutirovannyj a gene does not allow normalnomu signal passages by some tsitokininovym to receptors, explains pochemu T-cages, In cages and cages natural killers - all can be porazheny a unique mutation. A unique exception of a rule, that heavy kombinirovannyj the immunodeficiency appears inevitably fatal in absence peresadki a bone brain, took place at one child at whom has occurred spontannoe clinical improvement and has been found out reversija documented mutatsii in a gene coding gс, presumably in prekursorah T-cages. Recently retrovirusnyj a gene the transfer has been used for transfer komplementarnoj DNA from normalnoj gс chains in autologichnye cages of a bone brain of two children with H-connected tjazhelym the combined immunodeficiency with the subsequent full correction of defects v their T-cages and natural cages killers. Limfoproliferativnyj T-cellular deficiency U onego the child a mutatio n in a gene coding an a receptor chain interlejkina-2 proizvodila it is more likely superfluous, than it is not enough T - cages with extensive infiltratsiej in lungs, an intestines, a spleen, lymph nodes and bones. Levels v to whey IgG and IgM have been raised, but level in whey IgA has been lowered. At etogo the child was limfopenija and in vitro its T-cages badly reacted on antitela against CD3, fitogemaggljutinina and interlejkina-2. This defect was one iz many at which limfoproliferatsija and autoimmunitet have been called disbalansom positive and negative signals as a result of mutations of genes kodirovavshih reguljatornye components of immune system. T-T-negative, V-V-positive, natural cages killers pozitivnyj autosomalno retsessivnyj the heavy combined immunodeficiency U three my patients who as it has been shown, did not have earlier a deficiency neither gs chains, nor Janus kinazy (Jak3), was T-T-negative, / RV-cellular-positive, natural cages killers-positive autosomalno retsessivnyj the heavy combined immunodeficiency. Mutations in a gene a chains retseptora interlejkina-7 on a chromosome 5p13 have been revealed at all three patients. Eti data assume, that T-cellular defect, but not defect natural kletok killers at patients with H-connected heavy combined immunodefitsitom and Jak3-defitsitarnym the heavy combined immunodeficiency (see nizhe) has developed as a result of selective inaktivatsii signal carrying out interlejkina-7. Deficiencies of alarm molecules T-kletochno-pozitivnyj, V-V-positive, natural cages killers pozitivnyj autosomalno retsessivnyj the heavy combined immunodeficiency U the two-month`s boy with bacterial, virus and fungoid infections as bylo it is revealed, was available limfopenija and gipogammaglobulinemija. V-cages and estestvennye cages killers were present, but quantity CD4 + T-cages was snizheno. In vitro reactions on T-cellular mitogeny were various. T-cages patsienta not ekspressirovali aktivatsionnogo marker CD69 when they stimulirovalis through the T-cellular receptor, but they ekspressirovali CD69 podvergajas stimulations phorbol 12-myristate 13-acetate diester and ionoforom kaltsija, that specified in presence proksimalnogo alarm defect. Molekuljarnye researches have revealed alternatively splajsirovannyj transkript for p56 in which there was no domain kinazy. The alarm molecule tirozin kinazy p56 imeet great value in a differentiation, activation and proliferatsii T - kletok. CD8 limfopenija Sv8 limfopenija is connected with mutations in a gene in a chromosome 2q12 which codes zeta-assotsiirovannyj a protein 70 (ZAP-70), tirozin kinazu having big znachenie in carrying out of a signal to T-cages. ZAP-70 plays an irreplaceable role in pozitivnoj and negative selection of ripening T-cages in timuse. Patients with it sostojaniem can arrive with moderate infections or infections same tjazhelymi, as at patients with the heavy combined immunodeficiency. Eight patsientov it has been described, the majority from which were mennonnity. At these patients bylo the normal or raised quantity circulating CD4 + T cages, but glavnoe, any CD8 + T cages. Defect is presumably connected with defects signalnyh ways which are irreplaceable for development CD8 + cages inside timusa. Timus one of patients had normal architecture, with normal quantity CD + CD8 + double positive timotsitov, but any CD8 + (one-positive) timotsitov. At the amazed patients circulating CD4 + T-cages did not react normalno on mitogeny or on allogennye cages in vitro or became tsitotoksicheskimi cages. And on the contrary, activity of natural cages of killers, kolichestvo V-cages and levels of antibodies in whey remained normalnymi. T-T-negative, V-V-positive, natural cages killers negativnyj autosomalno retsessivnyj the heavy combined immunodeficiency Deti with Jak3 deficiency remind patients with other types heavy kombinirovannogo an immunodeficiency concerning their predisposition to an infection and bolezni transplantant-against the owner, called allogennymi T-cages in perelitoj to blood or trasplantantah a bone brain. They are similar to children with / the RH-connected heavy combined immunodeficiency as they have povyshennye quantities of V-cages and very much small amounts of T-cages and estestvennyh cages of killers in blood. Jak3 is unique alarm molekula about which it is known, that it assotsiiruet with gс a chain and serves provodnika gс as a chain dependent intratselljuljarnyh signals. Also were identifitsirovany 18 patients at whom was absent Jak3. Like patients with / the RH-connected heavy combined immunodeficiency at them are saved very much nizkie levels of natural cages of killers even after successfully spent transplantatsii a bone brain. T-T-negative, V-V-negative, natural cages killers pozitivnyj autosomalno retsessivnyj the heavy combined immunodeficiency and sindrom Ommen’s Deti with T-T-negative, V-V-negative, natural cages killers pozitivnym autosomalno retsessivnym the heavy combined immunodeficiency in rezultate mutations in a rekombinazo-activating gene 1 or 2 (RAG1 or RAG2) pohozhi on patients with other types of the heavy combined immunodeficiency in otnoshenii that, as to their predisposition to infections and absence funktsionalnyh T - and V-cages. However, they differ that limfotsity in them tsirkuljatsii are primary natural cages killers. RAG1 and RAG2 neobhodimy for reanzhirovki genes of receptors of T-cages and V-cages. Patsienty with syndrome Omenn’s also have mutations in RAG1 RAG2 genes, that projavljaetsja in broken (but not absent) rearanzhirovke genes as receptor of RV-cages, and receptor of T-cages. Omenn’s the syndrome is characterised by development generalizovannoj eritrodermy and deskvamatsii, diarrheas, gepatosplenomegalii, gipereozinofilii and substantial increase in whey of levels IgE soon after rozhdenija. Eozinofilija and the raised levels in whey IgE are connected with circulation aktivirovannyh oligoklonalnyh helpernovogo type 2 T of cages, which in norm not reagirujut on mitogeny or antibodies in vitro. Circulating V-cages are absent i in lymph nodes are not present germinalnyh the centres. The status is fatal, if not budet is corrected by change of a bone brain. the Mutation usual lejkotsitarnogo a superficial protein (CD45) Sovsem recently open molecular defect calling heavy combined immunodefitsit represents a mutation of a gene coding usual superficial lejkotsitarnyj protein CD45. This specific for gematopoeticheskih cages transmembrannaja tirozin fosfataza regulates src tirozin kinazy necessary for provedenija a signal of receptors T - and V-cages. U the two-month`s boy with symptoms of the heavy combined immunodeficiency bylo essential decrease in quantity of T-cages, but normal kolichestvo V-cages is revealed. T-cages did not react on mitogeny and levels immunoglobulina whey went down in due course. The dot mutation in CD45 allele vyzvavshaja alteration of an intervention sequence 13 donor slajs a site also was vyjavlena deletsija a considerable part of another allelja. Metabolic defect Otsutstvie purin-salvage-pathway enzima adenozina deaminazy it was observed at priblizitelno 15 percent of patients with the heavy combined immunodeficiency (T-cages-are negative, V-V-are negative, natural cages killers-are negative autosomalno retsessivnyj heavy kombiirovannyj an immunodeficiency). Patients with defitsitom adenozin deaminazy have the same clinical features as well as takovye with other forms of the heavy combined immunodeficiency, but except togo, for them is available hondro-ossealnaja displazija, which obektiviziruetsja nalichiem plural skeletal anomalies at radio graphic research, vkljuchaja flaring (burning, vybuhaniem) kosto-hondralnogo connections and «bone-in-bone» anomaly pozvonko vyh bodies. U children with deficiency adenozin deaminazy deeper is marked limfopenija, than u children with other types of the heavy combined immunodeficiency with an average absoljutnym quantity limfotsitov less, than 500 on cubic millimetre. Defitsit adenozin deaminazy, first of all, amazes T-cages which otsutstvujut how they are present at all forms heavy combined immunodefitsita. As there are messages only about weaker forms of it sostojanija disease can remain not diagnostsirovannym up to vzroslogo age. Defitsit adenozin deaminazy, connected with a mutation in a gene on a chromosome 20q13.2-q13.11, it is shown by considerable accumulation adenozina, 2 `-deoksiadenozina and 2 `-O-metiladenozina. Accumulation of these toxic deoksiadenin nukleotidov is direct or is mediated calls apoptoz limfotsitov. Enzim-replaceable therapy by weekly hypodermic introduction / rpolietilen-glikol-modified bychej adenozin deaminazy was showed in klinicheskom and immunologicheskom improvement at more, than 100 patients. However, immunokompetentsija there is less full, than that reached with the help peresadki a bone brain; therefore transplantation of a bone brain remains terapiej a choice. Gene therapy therefore is not too unsuccessful thus sostojanii. DEFICIENCIES of BASIC COMPLEX HLA I And II MOLECULES Defitsity transkriptsionnyh factors Bylo it is revealed more than 70 patients with autosomalno retsessivnymi deficiencies osnovnogo a complex tkane-compatibility (Ministry of Taxes and Tax Collection) of a class of II molecules, many from kotoryh occurred from the North Africa. In the childhood at them are marked persitirujushchaja diareja, it is frequent assotsiirujushchaja with kriptoporidiozom, a bacterial pneumonia, P.carinii a pneumonia, septitsemija and virus and monilialnye infections. That not menee, the immunodeficiency not so is strongly expressed, as it takes place at heavy kombinirovannom an immunodeficiency as at them does not develop neither system mikobakterialnoe disease, nor illness transplantant against the owner after vaktsinatsii batsillami Calmette-Guerin or transfusions of not irradiated products krovi, accordingly. U patients with deficiencies of the Ministry of Taxes and Tax Collection a class of II molecules very low quantities CD4 + RT-cages, but normal or raised quantities CD8 + T-cages. Limfopenija tolko the moderated. The Ministries of Taxes and Tax Collection a class II antigenes HLA-DP, DQ and DR do not give in to definition na V-cages or monotsitah and immune reactions are broken in the absence of these / rantigen-representing molecules. As it is supposed, V-cages of these patients not mogut to stimulate allogennye cages in smeshanno-lejkotsitarnyh cultures; in vitro them limfotsity normally react on mitogeny, but not to antigenes. Timus and drugie limfoidnye bodies essentially gipoplazirovany. As recognition HLA molekul timotsitami is the core for positive and negative selection razvitie peripheral T-cellular repertoire in the absence of the Ministry of Taxes and Tax Collection of a class II molekul leads to occurrence of T-cages with the broken T-cellular profiles retseptorov amino acids inside antigen-combing site. Defects as V-cages, and RT-cages mediating immunity at this disease, are shown by value HLA determinant in cooperation of immune cages.

Four various molecular defects can amaze an expression of the Ministry of Taxes and Tax Collection a class II molekul. These defects amaze the Ministries of Taxes and Tax Collection a class II genes, but genes regulating transkriptsiju the Ministry of Taxes and Tax Collection a class II genes. Three of mutations amaze subedinitsy RFX a complex faktorov a multiprotein transcription which connects X-box motif the Ministry of Taxes and Tax Collection klassa II promotera and bears responsibility for regulation of an expression of the Ministry of Taxes and Tax Collection of a class II molecules. These subedinitsy have received designations RFX5, RfX-assotsiirrovannyj protein, and RFXANK. Mutations RFXANK are the most frequent reason of the Ministry of Taxes and Tax Collection of a class II defects. The fourth type of a mutation switches on novel the Ministry of Taxes and Tax Collection of a class II transactivator (CIITA), master switch which supervises cellular specificity and indutsibialnost ekspressii a class of II Ministry of Taxes and Tax Collection of genes. All these four defects break koordinirovannuju an expression of the Ministry of Taxes and Tax Collection of a class of II molecules on a surface In cages and makrofagov. Deficiencies of transport proteins Izolirovannyj deficiency of the Ministry of Taxes and Tax Collection of a class of I molecules is rare enough and developing immunodefitsit is weaker, than that at the heavy combined immunodeficiency. Pri this infringement of the Ministry of Taxes and Tax Collection a class of I molecule in norm found out on all cages organizma are absent. There is deficiency CD8 + T-cages, but not CD4 + T-cages. Mutatsii have been revealed in two genes - TAP1 and TAP2 - in the Ministry of Taxes and Tax Collection a locus on a chromosome 6, v which the peptid-transport proteins, named conveyors assotsiirovannye about an antigene processing, or TAPs are coded. TAPS transport peptidnye antigeny from cytoplasm through device Golgi to communication a chains of the Ministry of Taxes and Tax Collection a class of I molecules and beta2-microglobulin. The complex then can move to a cage surface; esli complex assemblage cannot be finished because of absence peptidnyh antigenov the Ministry of Taxes and Tax Collection a class I complex collapses in cytoplasm. IMMUNODEFITSITARNYE DISEASES With SEPARATE PHENOTYPES H-svjazannoe limfoproliferativnoe disease H-svjazannoe limfoproliferativnoe disease is an inability to supervise proliferatsiju cytotoxic T-cages which is shown at infection EBV. Patsienty with this infringement (which illness Duncan also is called, on semejstvu Duncan where this status for the first time has been described) seem healthy to teh a time, while they will not be infected EBV (viruses Ebstein-Barr), usually in vozraste less than five years. The most frequent form of display (75 percent sluchaev) are heavy infectious mononukleoz and the infection appears fatalnoj in 80 percent of cases, first of all, because of development extensive nekroza a liver called by the activated cytotoxic T-cages. For bolshinstva the boys who have gone through infetsiju EBV, are characteristic global cellular immunnye defects, limfomy, aplasticheskie anemias, and necessarily develops gipogammaglobulinemija.

the Defective gene at H-connected limfoproliferativnom disease is Xq25 which codes adapternyj a protein available in T-cages and natural kletkah killers which influences the linkage, located more low on a way peredachi a signal, alarm molecules with a protein on a surface T - and V-cages, chto has received the name «signalling lymphocyte activation molecule» or SLAM. SLAM neobychen in that, what is it membrannyj a protein which is both promoting rostu a molecule, and a receptor for itself. Adapternyj the protein which ofitsialno is called SH2D1A but also and SAP (SlAm-assotsiirovannyj adapternyj protein) and DSHP (Duncan a syndrome a human protein), ingibiruet carrying out signala by means of SLAM, so proliferatsija T-cages and natural cages killerov does not proceed free. Less than 10 patients with H-connected limfoproliferativnym disease had been spent transplantation HLA-identical kostnogo a brain and approximately half in a consequence did not have signs zabolevanija. Wiskott-Aldrich a syndrome Wiskott-Aldrich the syndrome is the H-connected syndrome characterised ekzemoj, chrezmernoj predisposition to infections and trombotsitopenicheskoj purpuroj with malenkimi defective trombotsitami. Patients usually arrive in the early childhood with krovavoj a diarrhoeia and excessive hematomas. Atopichesky dermatit and recurrent infections pnevmokokkami and others inkapsulirovannymi bacteria usually appear on the first year of a life. Later bolee problematic there are infections opportunisticheskimi agents such, kak P.carinii and a herpes virus. Autoimmunnye cytosinging and vaskulity are usual at patsientov gone through the childhood. Infections and bleedings appear frequent prichinami death, but the most frequent cause of death is limfoma, indutsirovannaja EBV.

Concentration inmmunoglobulina vary at these patients, but, as a rule, nahodjatsja is closer to norm. Nevertheless, reaction of antibodies on polisaharidnye antigeny is broken, and are absent blood-group izogemaggljutininy. Besides, so time marks gradual decrease in a caption of antibodies on protein antigeny, such as toksoidy a diphtheria and a tetanus. For patients is available moderately snizhennyj percent CD3 +, CD4 +, CD8 + T-cages, and limfotsitarnaja reaction on mitogeny is lowered in vitro.

the Mutant gene connected with these defects, mappirovan on Xp11.22 and identifitsirovan in 1994. As it was revealed, it basically ekspressirovan in limfotsitarnyh and megakariotsitarnyh lines. The gene product which has been prolin-enriched protein from 501 amino acids, supervises assemblage aktin filamentov necessary dlja formations mikrovezikul. The big number of mutations in a gene was identifitsirovano among patients with syndrome Wiskott-Aldrich. Isolated / the RH-connected thrombocytopenia also is connected with a mutation in this gene.

Carriers can be revealed by detection not blind inaktivatsii RH-chromosomes in lines gemopoeticheskih cages or on presence of a mutant gene. Zabolevanie can be diagnostsirovano prenatalno on a material vorsin horiona ili amniotsenteza. Two families with obvious autosomalnoj a heredity fenotipa, syndrome Wiskott-Aldrich similar to that have been described. However, in other soobshchenii as it was revealed, the girl with syndrome Wiskott-Aldrich showed chrezvychajno an unusual example heavy deformed inaktivatsii H-chromosomes so aktivnaja the H-chromosome had a mutation in the H-connected locus of a gene of a syndrome Wiskott-Aldrich. U some patients with syndrome Wiskott-Aldrich trombotsitarnye and immunologicheskie anomalies have been completely corrected by transplantation kostnogo a brain or blood umbilical kanatika the HLA-identical twin or sootvetstvujushchego HLA not the related donor after a conditioning mode, vkljuchavshego an irradiation or busulfan and tsiklofosfamid. Some patients whom potrebovalos carrying out splenektomii concerning an uncontrollable bleeding, dali the impressing increase in quantity trombotsitov and perfect clinical sostojanie, receiving preventive treatment by antibiotics and immunnoglobulinom. Ataxia Teleangiectasia Ataxia Teleangiectasia is a complex syndrome of the combined immunodeficiency assotsiirujushchego with nejrologicheskimi, endokrinologicheskimi, hepatic and skin anomalijami. The basic displays are progressing mozzhechkovaja ataksija, okulo-kutannaja teleangioektazija, recurrent sino-pulmonalnoe disease, povyshennaja susceptibility to a cancer and gumoralnyj and cellular immunodeficiencies razlichnoj weights. One of my patients with Ataxia Teleangiectasia has died from vetrjanoj a smallpox, also at these patients illness transplantant-against-owner is described at blood transfusions.

Selective IgA deficiency is available at 50 to 80 percent of patients with Ataxia Teleangiectasia, and syvorotochnye levels IgG2 or full IgG can also okazatsja the lowered. In tests in vitro limfotsitarnoj functions usually nabljudaetsja it is moderate depressirovannye proliferativnye reactions on mitogeny. Timus gipoplastichen, it is badly organised and in him there are no little bodies Hassall’s.

Cages of patients and carriers of an abnormal gene are usually sensitive to ionizirujushchej radiation and have defective restoration of DNA, frequent hromosomalnye deviations. Limforetikuljarnyj a cancer and progressive nejrologicheskoe zabolevanie are the most frequent causes of death, but adenokartsinoma and drugie cancer forms also are described as causes of death.

the Defective gene at Ataxia Teleangiectasia, ATM, settles down on a chromosome 11q23.3. This gene codes fosfatidilinozitol a 3-3-like protein which takzhe has similarities with kataliticheskoj subunit of DNA-dependent a protein kinazy. On participates in mitogennom signal carrying out, mejoticheskoj rekombinatsii reactions DNK on defeat and the control over a cellular cycle. DISEASES, ASSOTSIIRUJUSHCHIE With not IDENTIFIED MOLECULAR DEFEKTAMI Nesmotrja on extreme progress in identification of the molecular reasons immunodefitsitov, many questions remain unresolved. Among diseases, in otnoshenii which the fundamental reasons are not known: usual variabelnyj immunodefitsit, selective deficiency IgA and a syndrome giper-IgE. Patients with usual variabelnym an immunodeficiency and those with deficiency IgA come to light often in one seme and have the general HLA gaplotip; For many are available rare alleli and deletsii genes vnutri a class of the Ministry of Taxes and Tax Collection a class III region on a chromosome 6, confirming with that, that gen susceptibility is located there. The gene responsible for giper-IgE, a syndrome, kotoryj is characterised by abscesses on a skin, in easy and internal bodies; osteopeniej, eozinofiliej and unusual face types, was mappirovan on a chromosome 4. However, neither base defect of the owner, nor a defective gene for the present not identifitsirovany. the Source : R. H. Buckley. Primary Immunodeficiency Diseases Due to Defects in Lymphocytes. New England Journal of Medicine, Vol. 343, N.18 the Translation from English - J.M.Bogdanov, chair of pediatrics FPK Northern meduniversiteta, Arkhangelsk

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