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FC sawv cev rau qhov tshuaj tiv thaiv dab tsi?

Muab lo rau  Cuaj hlis 24, 2020, Kho los ntawm Jason, Qeb  
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Cov tshuaj tiv thaiv kab mob yog dab tsi?
FC antibody yog dab tsi?
1. Kev Txhais Tau
2. Fc Sau
3. Qhia Tawm Thib
Dab tsi yog Fc receptor sawv rau?
FC sawv cev rau qhov tshuaj tiv thaiv dab tsi?

xaus

Cov crystallizable fragment (Fc antibody tau) yog qhov rov qab ntawm tshuaj tiv thaiv, uas cuam tshuam nrog cov cell receptors hu ua Fc receptors thiab qee cov protein ntawm kev ua kom tiav. Cov yam ntxwv no tso cai rau cov tshuaj tiv thaiv kab mob ua kom lub cev tiv thaiv kab mob.

Hauv IgG, IgA thiab IgD antibody isotypes, the Fc antibody tau yog tsim los ntawm ob qho tib si protein fragments muab tau los ntawm qhov thib ob thiab thib peb qhov tseem ceeb ntawm ob txoj hlua hnyav ntawm lub tshuaj tiv thaiv; IgM thiab IgEFc cheeb tsam muaj peb txoj saw hlau hnyav (CH domains 2-4) hauv txhua txoj saw polypeptide. Cov Fc cheeb tsam ntawm IgG muaj qhov chaw khaws cia zoo N-glycosylation site. Glycosylation ntawm Fc fragments yog qhov tseem ceeb rau Fc receptor-mediated ua haujlwm.

Cov tshuaj tiv thaiv kab mob yog dab tsi?

Antigen vs Antibody
Antigen vs Antibody

Antibodies yog immunoglobulins, uas yog globulins uas muaj cov tshuaj tiv thaiv kab mob (Ab) lossis cov qauv tshuaj thiab zoo ib yam li cov tshuaj tiv thaiv kab mob. Feem ntau, nws yog peptide saw qauv tsim los ntawm ob lub teeb pom kev zoo ib yam thiab ob qhov hnyav hnyav zoo ib yam txuas nrog los ntawm interchain disulfide bonds.

Cov tshuaj tiv thaiv kab mob tuaj yeem faib ua tsib pawg, uas yog immunoglobulin G (IgG) thiab immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin D (IgD) thiab immunoglobulin E (Lus qhia). Thiab cov tshuaj tiv thaiv kab mob yog tsim los ntawm thaj tsam sib txawv Fab thiab qhov tseem ceeb Fc. Fab tuaj yeem khi antigen, thiab Fc tuaj yeem khi rau Fc receptors. Coj IgG ua piv txwv. IgG feem ntau taug kev hauv ntshav thiab khi rau Fc receptors nyob rau saum npoo ntawm lub cev tiv thaiv kab mob. Nws yuav ua haujlwm los txhawb kev tiv thaiv kab mob hauv lub cev thiab tiv thaiv kev nkag mus rau cov kab mob.

FC antibody yog dab tsi?

1. Lus txhais

Fc receptors tuaj yeem khi rau IgFc cov khoom tawg ntawm lub ntsej muag ntawm tes. Cov receptors uas khi rau txawv immunoglobulins (IgA, IgE, IgM, thiab IgG) tau sau ua ke hu ua FcRs, uas koom nrog hauv kev tswj hwm thiab ua tiav cov tshuaj tiv thaiv kab mob tiv thaiv kab mob.

Feem ntau hais lus, FcRs txuas cov cheeb tsam cuam tshuam los ntawm kev tiv thaiv kab mob tshwj xeeb thiab lub cev tiv thaiv kab mob hauv nruab nrog cev (cov qog mast, neutrophils, monocytes thiab macrophages). Qhov tseem ceeb dua, cov lus teb ua rau mob no cuam tshuam nrog kev tswj hwm lub cev los ntawm kev puas tsuaj ntawm cov nqaij. Tom qab kev sib khi rau Fc thaj tsam ntawm cov tshuaj tiv thaiv kab mob kom qhib txoj hauv kev taw qhia, cov kab mob tiv thaiv kab mob yuav pib ua cov lus teb tiv thaiv kab mob, xws li: cov tshuaj tiv thaiv kab mob-tsim cov xov tooj ntawm tes, qhov ua rau mob hnyav, lossis cov tshuaj tiv thaiv kab mob-tiv thaiv cell-mediated cytotoxicity (ADCC) thiab lwm yam kev tua lub hom phiaj ntawm tes.

Fc receptor yog tus txais rau c-terminus ntawm Fc ib feem ntawm immunoglobulin. Tom qab immunoglobulin (Ig) khi rau antigen, lub Fc thaj tsam ntawm cov tshuaj tiv thaiv kab mob yog allosteric thiab khi rau Fc tus neeg txais ntawm daim nyias nyias ntawm tes los tsim ntau yam kev lom. Cov nyhuv ntawm antigen-tshuaj tiv thaiv nyuaj ntawm lub xovtooj yog txhua yam kho tau los ntawm Fc tus txais. Yog li ntawd, fc cov tshuaj tiv thaiv kab mob ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob thiab nws txoj cai. Txhua hom Ig nws muaj nws tus coj Fc receptor.

2. Fc Sau

Txoj haujlwm ntawm ob qhov sib txuas ntawm antigen ntawm cov tshuaj tiv thaiv kab mob zoo ib yam, thiab lawv nyob ntawm qhov kawg ntawm ob txhais caj npab hu ua antigen-binding fragments (Fab antibody). Tus tuav ntawm "Y" hu ua crystalline fragment (FC), thiab qab zib tau khi rau FC. Fc (crystallizable fragment) suav nrog: 2 CH2, 2 CH3 (IgA, IgD, IgG), tag nrho ntawm 4 tus thawj, lossis 2 CH2, 2 CH3, 2 CH4 (IgM, IgE), tag nrho ntawm 6 Cov qauv muaj feem.

3. Luv Lus Qhia Txog

Los ntawm kev siv Fab'2 cov tshuaj tiv thaiv kab mob thiab P, c cov neeg tsis muaj qhov tsis txaus los nkag siab lub luag haujlwm ntawm fc tiv hauv kev nkag mus ntawm macrophages. Kev tshawb fawb siv Fab'2 anti-GBM cov tshuaj tiv thaiv kab mob ua rau pom tias Fc cheeb tsam yuav tsum tau siv nyob rau hauv autoantibody-dependent thiab ntxiv-ywj siab macrophage infiltration.

Kev siv IgG thiab Fc thooj los kho cov nas tiv thaiv kab mob ua kom tsis muaj teeb meem loj zuj zus glomerulonephritis tuaj yeem txo qhov kev loj hlob ntawm tus kab mob thiab txo qis kev nkag mus ntawm macrophages thiab T cells. Fcγ receptor (Fc '/R) -deficient nas tau siv los kawm txog kev cuam tshuam ntawm kev khi ntawm cov tshuaj tiv thaiv kab mob Fc/FcγR rau tus neeg txais khoom ntawm kev nkag mus ntawm cov qog nqaij hlav hauv glomerulonephritis. Piv nrog NZB/NZW cov nas tsis tu ncua, FcγR tsis muaj peev xwm lupus-nquag nas tau txo qis kev tsim lub hli thiab txhim kho kev muaj sia nyob, tab sis qib ntawm kev tiv thaiv kab mob tsis sib xws thiab ua kom zoo dua qub ntxiv. Qhov no zoo ib yam nrog cov txiaj ntsig ntawm kev tshawb fawb yav dhau los uas tsis muaj qhov xav tau ntxiv hauv kev tiv thaiv kab mob glomerulonephritis, qhia tias Fc/FcγR ua kom sib haum macrophage nkag mus rau hauv lub cev tiv thaiv kab mob nephritis.

Tsis-crescent nephritis nrog tsis xws luag nyob rau hauv anti-GBM thiab FcRγ chains yog tus yam ntxwv los ntawm kev nce ciaj sia taus thiab txo nephritis. Lwm cov kev tshawb fawb tau pom tias FcRγ cov nas tsis muaj peev xwm tau tiv thaiv los ntawm kev puas tsuaj ntsig txog neutrophil thaum ntxov, tab sis tom qab ntawd dhau los ua proteinuria nrog macrophage nkag mus, nrog los ntawm kev tsim lub hli. FcγRIIB tus neeg txais khoom koom nrog hauv "txheej txheem tshuaj tiv thaiv kab mob", uas ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv ib puag ncig. Cov nas tsis muaj peev xwm nyob rau hauv qhov kev txwv tsis pub tuaj yeem yooj yim nce mus rau cov ntshav hauv ntshav thiab crescentic glomerulonephritis tom qab kev tiv thaiv kab mob rau bovine hom IV collagen kab mob.

Glomerulonephritis tshwm sim thaum tsis muaj C3 tso, thiab kev hloov pauv ntawm cov qog nqaij hlav es tsis txhob siv B cells los ntawm FcγRIIB-cov nas tsis muaj peev xwm kuj tseem tuaj yeem ua rau glomerulonephritis, qhia tias kev nkag siab T cells ua lub luag haujlwm tseem ceeb ntawm no. Lupus-prone to murine FcγRIIB tus txhawb nqa polymorphism cuam tshuam nrog kev tsim cov tshuaj autoantibodies.

Dab tsi yog Fc receptor sawv rau?

Rau cov cell nrog nws tus txais, thaum cov tshuaj tiv thaiv khi rau lub antigen, lub cell yuav ua haujlwm tshwj xeeb hauv qab no:

  1. Prophage muaj Fc receptors rau IgG, thiab neutrophils suav rau feem ntau ntawm polymorphonuclear leukocytes muaj Fc receptors rau IgG thiab IgA. Cov antigens feem ntau raug ntes thiab nqos los ntawm cov tshuaj tiv thaiv uas khi rau antigens thiab qee zaum tsis muaj cov tshuaj tiv thaiv kab mob (cytophilic antibodies).
  2. Feem ntau ntawm B cells (ntau dua 80%) muaj Fc receptors rau IgG. Thiab lawv tsis sib txawv hauv cov cell tsim cov tshuaj tiv thaiv kab mob, thiab tuaj yeem ua haujlwm tau los ntawm kev khi rau antigen-antibody complexes kom tso tawm cov tshuaj tiv thaiv kab mob tsim tawm ntawm tes.
  3. Kwv yees li 10% ntawm T cells muaj Fc receptors, uas feem ntau ua raws li kev tiv thaiv kab mob tiv thaiv cov cell, tab sis lub luag haujlwm ntawm Fc receptors hauv cov hlwb no tseem tsis meej. Hauv tib neeg lub cev, cov cell uas muaj Fc receptors rau IgM yog cov pabcuam pabcuam rau B cells, thiab cov cell uas muaj receptors rau IgG ua haujlwm li inhibitory cells.
  4. Thaum IgE uas khi rau Fc tus neeg txais ntawm mast cells txuas ntxiv rau lub antigen, cov qog mast tuaj yeem tso tawm yam uas ua rau "ua rau mob sai sai".
  5. Qee cov tsis-lymphocytic cells (NK cells) tuaj yeem khi rau Cheeb Tsam FC ntawm IgG uas khi rau cov qog nqaij hlav cancer thiab cov qe sib txawv, thiab cuam tshuam cov hlwb no. Qhov tshwm sim no hu ua antibody-dependent cell-mediated cytotoxicity (Antibody dependent cell-mediated cytotoxicity). Hauv kev tiv thaiv kab mob, cov hlwb nrog Fc tus txais feem ntau suav nrog B cells, tua cov cell, thiab macrophages.

FC sawv cev rau qhov tshuaj tiv thaiv dab tsi?

Txawv Ig subclasses cuam tshuam nrog ntau hom cell los ntawm tsev neeg nyuaj ntawm Fc cov neeg txais ntawm lub xovtooj ntawm tes. Kev sib raug zoo, kev faib tawm ntawm tes, qauv, thiab kev cuam tshuam lom ntawm cov Fc receptors nrog Ig kuj txawv. Thaum FcR khi rau IgFc ntu, nws yuav xa cov cim tshwj xeeb rau sab hauv thiab ua rau ntau yam lus teb ntawm tes. Cov lus teb no nyob ntawm hom FcR, hom xov tooj, lub xeev ua kom lub xov tooj, cov lus teb raug nqi, tus lej txais tos koom nrog, tus txais txais kev sib txuas sib txuas, thiab lwm yam sab nraud uas cuam tshuam rau Fc thooj ntawm cov tshuaj tiv thaiv.

Tus txheeb ze sib npaug ntawm cov neeg txais kev tiv thaiv (FcγRⅡ) thiab qhib kom ua (FcγRI thiab FcγRⅢ) FcRs qhia los ntawm leukocytes thiab parenchymal cells yog tus tswj hwm tseem ceeb ntawm cov lus teb tshwm sim los ntawm kev tso tshuaj tiv thaiv kab mob thiab lub ntsiab tus txiav txim ntawm tus kab mob kev raug mob.

Ob tus nas thiab tib neeg IgG receptors thiab FCγRs yog cov tswv cuab ntawm Ig superfamily. Nws tau muab faib ua peb hom, suav nrog kev sib raug zoo FcγRI (CD64), uas tuaj yeem khi rau monomeric IgG; low-affinity FcγRⅡ (CD32) thiab FcγRⅢ (CD16), uas tsuas yog cuam tshuam nrog IgG complexes. Kev hloov pauv ntawm ntau cov noob thiab alleles thiab xaiv cov kev sib txuas ntawm mR-NA tau ua rau muaj ntau yam sib txawv ntawm FcγR hom, thiab lawv cov transmembrane thiab thaj tsam cytoplasmic muaj qhov sib txawv, ua rau muaj kev sib txawv ntawm lub cev. Qhov sib txawv ntawm qhov sib txawv no tseem xav txog tus kheej FClrR hom thiab IgG subclass (tshwj xeeb yog tib neeg IgGl thiab IgG2) kev muaj peev xwm los sib txawv yog txawv. Qhov kev qhia ntawm FcγRs sib txawv nrog lub xeev ntawm kev ua haujlwm ntawm tes thiab tswj hwm los ntawm cytokines.

IgE Fc receptors (FcεR) tau muab faib ua ob hom, suav nrog kev sib raug zoo FcεRI (ib tus tswv cuab ntawm Ig superfamily) thiab kev sib raug zoo qis FcεRⅡ (CD23, tus tswv cuab ntawm tsev neeg cov lus qhia serum). Qhov kawg tau muab faib rau saum npoo ntawm ntau yam ntawm hematopoietic cells, suav nrog B cells, uas yog tus coj txais rau CD21 (ua kom tau txais tus lej 2, CR2, uas koom nrog hauv kev tswj hwm qhov pib ntawm B cell receptor signaling). Tib neeg FcεRⅠReceptors yog cov tswv cuab ntawm Ig superfamily uas tuaj yeem khi monomeric lossis multimeric IgAl thiab IgA2, thiab tau nthuav dav dav hauv ntau lub cell.

Cov qauv glycosylation sib txawv ua rau muaj cov qauv sib txawv. Tib neeg mesangial hlwb nthuav tawm cov pob txha tshiab IgA receptor uas txawv ntawm CD89. Nws txoj kev khi rau IgA ua rau pom kev qhia ntawm cytokines thiab chemokines, kev nthuav dav ntawm tes, thiab kev sib txuas ntawm cov lej sib txawv. Soluble FcRs tau txais los ntawm kev tso tawm ntawm cov khoom tiv thaiv proteolytic ntawm lub xov tooj ntawm tes lossis xaiv cov khoom sib txuas ntawm mRNA tsis muaj thaj chaw sib kis. Lawv koom nrog hauv kev tswj hwm kev tiv thaiv kab mob (uas yog, qhov cuam tshuam ntawm Ig cov khoom lag luam hauv vitro), thiab tseem tuaj yeem muaj kev kho mob zoo rau qhov ua tsis tau zoo los ntawm tshuaj tiv thaiv.

xaus

FC antibody tau khi rau FC receptors, tso cov tshuaj tiv thaiv kom ua tiav lub cev tiv thaiv kab mob thiab pab peb tawm tsam cov neeg txawv teb chaws tuaj. Nws tuaj yeem pom qhov ntawd FC antibody tau ua lub luag haujlwm tsis hloov pauv hauv tib neeg lub neej thiab kev noj qab haus huv.

Xav kawm paub ntau ntxiv txog antigens thiab cov tshuaj tiv thaiv kab mob? Nyeem Monoclonal-thiab-polyclonal-antibodies.

References

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