Immunhi nyos llapotok

1. Immunhi�nyos �llapotok 2005. �pr. 4.

2. Immundeficienci�ra utal� t�netek Az immunrendszer sejtjeinek, sejtfelsz�ni molekul�inak, szab�lyoz� komponenseinek nem megfelelo muk�d�se immunhi�nyos �llapotot eredm�nyez, ami cs�kkent v�dekezo k�pess�ggel j�r. A k�rosodott immunrendszeru gyermekek �ltal�ban s�lyos bakteri�lis fertoz�sektol szenvednek, melyek hossz� ideig fenn�llnak, visszat�rnek, vagy sz�vodm�nyeket okoznak. Ha ak�r gyermekn�l, ak�r felnottn�l s�lyos vagy ritka fertoz�sek ism�tlodnek, f�lmer�l az immunhi�nyos rendelleness�g gyan�ja. Az olyan k�rokoz�kkal val� fertozod�s, melyek norm�lisan nem beteg�tik meg az embereket (p�ld�ul Pneumocystis, Cytomegalov�rus, Candida, Mycobacterium) az immunrendszert �rinto probl�m�ra utal. A fertoz�s fajt�ja t�mpontot jelent az immunhi�ny t�pus�nak meg�llap�t�s�hoz. Ha a fertoz�seket bizonyos extracellul�ris bakt�riumok okozz�k, pl. Streptococcus, az ok val�sz�nuleg a B-limfocit�k el�gtelen antitesttermel�s�ben keresendo. A v�rusok, gomb�k vagy intracellul�ris k�rokoz�k (pl. Pneumocystis) okozta s�lyos fertoz�sek �ltal�ban a sejtes immunit�s �rintetts�g�re utalnak. A Staphylococcus �s Escherichia coli okozta bakteri�lis fertoz�sek �ltal�ban azt jelzik, hogy a fagocitasejt funkci�k s�r�ltek. A Neisseria bakt�rium fertoz�sei gyakran a komplementrendszer zavarait jelzik. Az �letkor: 6 h�napos kor elott a fertoz�sek �ltal�ban T-limfocita rendelleness�get jeleznek; idosebb gyermekekn�l a fertoz�sek �ltal�ban az antitesttermel�s �s a B-limfocit�k zavarait jel�lik. A felnottkorban megjeleno immunhi�ny ritk�n �r�klodo; sokkal val�sz�nubb ok lehet bizonyos v�rusfertoz�s vagy m�s �llapotok, mint cukorbetegs�g, rosszult�pl�lts�g, veseel�gtelens�g �s rosszindulat� daganat. arc- �s homlok�reg-gyullad�s, id�lt f�lfertoz�s, id�lt h�rgrut, t�dogyullad�s. Ny�lkah�rty�k hajlamosak a fertoz�sekre. A sz�j�reg gomb�s fertoz�se, a sz�jpen�sz, a sz�jfek�lyekkel �s �nyfertoz�sekkel egy�tt, a k�rosodott immunrendszer korai t�nete lehet. A szemek gyullad�sa (konjunktivitisz, k�toh�rtya-gyullad�s), hajhull�s, s�lyos ekc�ma (borgyullad�s) �s a kit�gult, t�redezett bor alatti kapill�risok szint�n felvetik az immunk�rosod�s lehetos�g�t. Az em�sztorendszer fertoz�sei hasmen�shez �s tests�lycs�kken�shez vezethetnek Mivel az immunhi�nyos �llapotok nagyon fiatal gyermekekn�l gyakran �r�kletesek, ez�rt a csal�d m�s gyermek tagjain�l megjeleno visszat�ro fertoz�sek fontos t�mpontot jelentenek. arc- �s homlok�reg-gyullad�s, id�lt f�lfertoz�s, id�lt h�rgrut, t�dogyullad�s. Ny�lkah�rty�k hajlamosak a fertoz�sekre. A sz�j�reg gomb�s fertoz�se, a sz�jpen�sz, a sz�jfek�lyekkel �s �nyfertoz�sekkel egy�tt, a k�rosodott immunrendszer korai t�nete lehet. A szemek gyullad�sa (konjunktivitisz, k�toh�rtya-gyullad�s), hajhull�s, s�lyos ekc�ma (borgyullad�s) �s a kit�gult, t�redezett bor alatti kapill�risok szint�n felvetik az immunk�rosod�s lehetos�g�t. Az em�sztorendszer fertoz�sei hasmen�shez �s tests�lycs�kken�shez vezethetnek Mivel az immunhi�nyos �llapotok nagyon fiatal gyermekekn�l gyakran �r�kletesek, ez�rt a csal�d m�s gyermek tagjain�l megjeleno visszat�ro fertoz�sek fontos t�mpontot jelentenek.

3. Elso primer immunhi�nyos esetle�r�s 1950. Addig a hasonl� betegek fertoz�s �ldozatai lettek. D�nto �tt�r�st jelentett az antibiotikumos kezel�s lehetos�ge az 1940-es �vektol. Knock out egerekkel v�gzett vizsg�latok nagyban seg�tik a a kutat�stElso primer immunhi�nyos esetle�r�s 1950. Addig a hasonl� betegek fertoz�s �ldozatai lettek. D�nto �tt�r�st jelentett az antibiotikumos kezel�s lehetos�ge az 1940-es �vektol. Knock out egerekkel v�gzett vizsg�latok nagyban seg�tik a a kutat�st

4. Az immunrendszer sejtjeinek, sejtfelsz�ni molekul�inak, szab�lyoz� komponenseinek hi�nya vagy nem megfelelo muk�d�se. Elsodleges: g�n hi�ny vagy hib�s muk�d�s. A k�rosod�s term�szete att�l f�gg, hogy az immunrendszer mely pontj�n k�vetkezik be a k�rosod�s. Eg�r modell: nude-meztelen eg�r, t�musz hi�nya.Az immunrendszer sejtjeinek, sejtfelsz�ni molekul�inak, szab�lyoz� komponenseinek hi�nya vagy nem megfelelo muk�d�se. Elsodleges: g�n hi�ny vagy hib�s muk�d�s. A k�rosod�s term�szete att�l f�gg, hogy az immunrendszer mely pontj�n k�vetkezik be a k�rosod�s. Eg�r modell: nude-meztelen eg�r, t�musz hi�nya.

5. Elsodleges T-sejt okozta immunhi�ny ? A velesz�letett T-sejt hi�ny a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�solja ? A cellul�ris immunv�lasz k�rosod�sa �ltal�ban egy�ttj�r DTH �s citotoxicit�si funkci� zavar�val ? No az �rz�kenys�g az intracellul�ris patog�n, v�rus-, protozoa-, gomba fertoz�sek ir�nt ? A T-sejt funkci� kies�s miatt k�rosodik az ellenanyagtermel�s; a humor�lis immunv�lasz is

7. A velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�soljaA velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�solja

8. DiGeorge szindr.: 3-4. garat�vet �rinto korai magzati fejlod�si rendelleness�g, nem alakul ki t�musz �s mell�kpajzsmirigy DiGeorge szindr.: 3-4. garat�vet �rinto korai magzati fejlod�si rendelleness�g, nem alakul ki t�musz �s mell�kpajzsmirigy

9. A velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�soljaA velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�solja

11. A velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�soljaA velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�solja

13. A velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�soljaA velesz�letett T-sejt hi�nya a cellul�ris �s humor�lis immunv�laszt egyar�nt befoly�solja

14. Adenozin-deamin�z (ADA) vagy purin-nukleozid-foszforil�z (PNP) deficiencia. Molecular Medicine: Gene Therapy for Adenosine Deaminase DeficiencyThe DiseaseAdenosine deaminase deficiency is one of the causes of severe combined immunodeficiency (SCID), a group of hereditary diseases in which lymphocytes fail to develop normally. Affected individuals are deficient in all functions of the immune system. SCID is rare, with a frequency of about one in a million. Because of the profound defect in immune function, infants with this disease are susceptible to recurrent infections by various organisms, including viruses, bacteria, fungi, and protozoans. Unless treated, these infections are usually fatal within two years. Molecular and Cellular Basis About 20% of SCID cases result from genetic deficiencies in the enzyme adenosine deaminase, which catalyzes the deamination of adenosine and deoxyadenosine. In the absence of adenosine deaminase, deoxyadenosine accumulates, resulting in corresponding increases in the concentration of deoxyadenosine triphosphate (dATP). High levels of dATP are toxic to proliferating cells because dATP inhibits the enzyme ribonucleotide reductase, which is required for synthesis of all four deoxyribonucleoside triphosphates. Consequently, increased concentrations of dATP block DNA synthesis. Although all cells have adenosine deaminase, a deficiency in its activity is particularly toxic to lymphocytes, because they lack what other types of cells have: additional enzymes that degrade dAMP, thereby preventing dATP accumulation. Thus, a deficiency in adenosine deaminase specifically blocks lymphocyte replication and prevents the development of a functional immune system. Adenozin-deamin�z (ADA) vagy purin-nukleozid-foszforil�z (PNP) deficiencia. Molecular Medicine: Gene Therapy for Adenosine Deaminase Deficiency

15. Somatic Therapy for SCID (1990)Severe Combined Immunodeficiency Disease (SCID) is due to a defective gene for Adenosine Deaminase (ADA). A retrovirus, which is capable of transferring it's DNA into normal eukaryotic cells (transfection), is engineered to contain the normal human ADA gene. Isolated T-cell stem line cells from the patient are exposed to the retrovirus in cell culture, and take up the ADA gene. Reimplantation of the transgenic cells into the patient's bone marrow establishes a line of cells with functional ADA, which effecitvely treats SCID.

19. Back in 1988 the gene responsible for A-T was mapped to chromosome 11. The subsequent identification of the gene proved difficult; it was 7 more years until the human ATM gene was cloned. The diverse symptoms seen in A-T reflect the main role of ATM, which is to induce several cellular responses to DNA damage. When the ATM gene is mutated, these signaling networks are impaired, and so the cell does not respond correctly to minimize the damage. Some of the ATM-dependent signaling pathways are found in yeast. Because these pathways appear to be conserved throughout evolution, they are likely to be central to the DNA damage response. Research into finding an effective therapy for A-T sufferers is likely to be helped by harnessing the power of yeast genetics, which allows more rapid and systematic study of the pathways affected by an ATM mutation. Back in 1988 the gene responsible for A-T was mapped to chromosome 11. The subsequent identification of the gene proved difficult; it was 7 more years until the human ATM gene was cloned. The diverse symptoms seen in A-T reflect the main role of ATM, which is to induce several cellular responses to DNA damage. When the ATM gene is mutated, these signaling networks are impaired, and so the cell does not respond correctly to minimize the damage. Some of the ATM-dependent signaling pathways are found in yeast. Because these pathways appear to be conserved throughout evolution, they are likely to be central to the DNA damage response. Research into finding an effective therapy for A-T sufferers is likely to be helped by harnessing the power of yeast genetics, which allows more rapid and systematic study of the pathways affected by an ATM mutation.

22. Figure 11.10. Immunoelectrophoresis reveals the absence of several distinct immunoglobulin isotypes in serum from a patient with X-linked agammaglobulinemia (XLA). Serum samples from a normal control and from a patient with recurrent bacterial infection caused by the absence of antibody production, as reflected in an absence of gamma globulins, are separated by electrophoresis on an agar-coated slide. Antiserum raised against whole normal human serum and containing antibodies against many of its different proteins is put in a trough down the middle; each antibody forms an arc of precipitation with the protein it recognizes. The position of each arc is determined by the electrophoretic mobility of the serum protein; immunoglobulins migrate to the gamma globulin region of the gel. The absence of immunoglobulins in a patient who has X-linked agammaglobulinemia is shown in the photograph at the bottom, where several arcs are missing from the patient's serum (upper set). These are IgA, IgM, and several subclasses of IgG, each recognized in normal serum (lower set) by antibodies in the antiserum against human serum proteins. Photograph from the collection of the late C.A. Janeway Snr. Figure 11.10. Immunoelectrophoresis reveals the absence of several distinct immunoglobulin isotypes in serum from a patient with X-linked agammaglobulinemia (XLA). Serum samples from a normal control and from a patient with recurrent bacterial infection caused by the absence of antibody production, as reflected in an absence of gamma globulins, are separated by electrophoresis on an agar-coated slide. Antiserum raised against whole normal human serum and containing antibodies against many of its different proteins is put in a trough down the middle; each antibody forms an arc of precipitation with the protein it recognizes. The position of each arc is determined by the electrophoretic mobility of the serum protein; immunoglobulins migrate to the gamma globulin region of the gel. The absence of immunoglobulins in a patient who has X-linked agammaglobulinemia is shown in the photograph at the bottom, where several arcs are missing from the patient's serum (upper set). These are IgA, IgM, and several subclasses of IgG, each recognized in normal serum (lower set) by antibodies in the antiserum against human serum proteins. Photograph from the collection of the late C.A. Janeway Snr.

24. In a normal immune response to a new antigen, B cells first produce IgM antibody. Later, the B cells switch to produce IgG, IgA and IgE, antibodies that protect tissues and mucosal surfaces more effectively. In the most common form of HIM there is a defect in the gene TNFSF5, found on chromosome X at q26. This gene normally produces a CD40 antigen ligand (CD154), a protein on T cells which binds to the CD40 receptor on B and other immune cells. Without CD154, B cells are unable to receive signals from T cells, and thus fail to switch antibody production to IgA and IgG. The absence of CD 40 signals between other immune cells makes individuals with HIM susceptible to infections by opportunistic organisms such as Pneumocystis and Cryptosporidium species. Treatment of HIM mainly consists of regular IV replacement of the missing IgG antibodies and prompt treatment of infections. Long lasting immunity, however, cannot be maintained without a bone marrow transplant, which is done when a suitable donor is available. In a normal immune response to a new antigen, B cells first produce IgM antibody. Later, the B cells switch to produce IgG, IgA and IgE, antibodies that protect tissues and mucosal surfaces more effectively. In the most common form of HIM there is a defect in the gene TNFSF5, found on chromosome X at q26. This gene normally produces a CD40 antigen ligand (CD154), a protein on T cells which binds to the CD40 receptor on B and other immune cells. Without CD154, B cells are unable to receive signals from T cells, and thus fail to switch antibody production to IgA and IgG. The absence of CD 40 signals between other immune cells makes individuals with HIM susceptible to infections by opportunistic organisms such as Pneumocystis and Cryptosporidium species. Treatment of HIM mainly consists of regular IV replacement of the missing IgG antibodies and prompt treatment of infections. Long lasting immunity, however, cannot be maintained without a bone marrow transplant, which is done when a suitable donor is available.

25. Photographs courtesy of R. Geha and A. Perez-Atayde. Photographs courtesy of R. Geha and A. Perez-Atayde.

31. X-kapcsolt SCID X-kromosz�m�hoz k�t�tt, fi�kban h�romszor gyakoribb Jelei az elso �leth�napokban megmutatkoznak, kezel�s n�lk�l egy �ven bel�l let�lis Perif�ri�s v�r: T-, B+ IL-2R g�n mut�ci�ja IL-2R ? k�z�s jel�tvivo l�nc: IL-2, IL-15, IL-7, IL-9

32. - Nem szintetiz�l�dik az IL-2R gamma l�nca- K�z�s gamma l�nc: IL-4R, IL-7R, IL-9R, IL-11R, IL-15R X-linked SCID mutation database (IL2RGbase) Database of Mutations Causing Human X-Linked SCIDData on mutations in any of the eight exons may be retrieved by clicking on the exon of interest in the image below, or by clicking on one of the following hyperlinks.Exon 1Exon 2Exon 3Exon 4Exon 5Exon 6Exon 7Exon 8Large Deletions IL2RG exons and intervening sequences. cDNA numbers are relative to the initiation of transcription. Abbreviations: B, Box 1/Box 2 domain; C, conserved cysteine; TM, transmembrane region; W, WSXWS box.X-linked SCID mutation database (IL2RGbase) Database of Mutations Causing Human X-Linked SCIDData on mutations in any of the eight exons may be retrieved by clicking on the exon of interest in the image below, or by clicking on one of the following hyperlinks.Exon 1Exon 2Exon 3Exon 4Exon 5Exon 6Exon 7Exon 8Large Deletions IL2RG exons and intervening sequences. cDNA numbers are relative to the initiation of transcription. Abbreviations: B, Box 1/Box 2 domain; C, conserved cysteine; TM, transmembrane region; W, WSXWS box.

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43. Janeway Fertoz�s lezajl�sa eg�szs�ges �s immundeficiens szervezetben. Term�szetes immunrendszer hi�ny�ban (pl. k�rosodott fagocita funkci�k) a k�rokoz�k korl�tlanul szaporodnak a szervezetben. Norm�lis term�szetes immunv�lasz �s k�rosodott adapt�v immunit�s eset�n szint�n k�rosodott az antig�n elimin�ci�. Janeway Fertoz�s lezajl�sa eg�szs�ges �s immundeficiens szervezetben. Term�szetes immunrendszer hi�ny�ban (pl. k�rosodott fagocita funkci�k) a k�rokoz�k korl�tlanul szaporodnak a szervezetben. Norm�lis term�szetes immunv�lasz �s k�rosodott adapt�v immunit�s eset�n szint�n k�rosodott az antig�n elimin�ci�.

44. Inheritance of severe combined immunodeficiency How is SCID inherited? X-linked SCID is caused by an altered gene found on the X-chromosome, so the disorder usually affects only boys. In some cases, the disease appears 'out of the blue', following a genetic change in the unfertilised egg. In others, the affected boy inherits SCID from his carrier mother. A carrier woman has a one-in-four chance of having an affected son, and a one-in-four chance of having a carrier daughter. Recessive inheritance If two parents are both carriers of a genetic condition with a recessive inheritance pattern, there is a one-in-four chance that each child will be affected. So on average, one-quarter of their children will be affected. There is also a one-in-two chance that each child will be an unaffected carrier, like the parents. Examples of genetic conditions that show a recessive pattern of inheritance are cystic fibrosis, sickle-cell disease, Tay-Sachs disease and phenylketoneuria. How is SCID inherited? X-linked SCID is caused by an altered gene found on the X-chromosome, so the disorder usually affects only boys. In some cases, the disease appears 'out of the blue', following a genetic change in the unfertilised egg. In others, the affected boy inherits SCID from his carrier mother. A carrier woman has a one-in-four chance of having an affected son, and a one-in-four chance of having a carrier daughter. Recessive inheritance If two parents are both carriers of a genetic condition with a recessive inheritance pattern, there is a one-in-four chance that each child will be affected. So on average, one-quarter of their children will be affected. There is also a one-in-two chance that each child will be an unaffected carrier, like the parents. Examples of genetic conditions that show a recessive pattern of inheritance are cystic fibrosis, sickle-cell disease, Tay-Sachs disease and phenylketoneuria.