Резюме
Михальчук М.В., Галкін О.Ю., Дуган О.М. Особливості регуляції біосинтезу IgE та молекулярні механізми IgE-залежних реакцій.
В оглядовій статті проведено аналіз сучасних наукових даних щодо молекулярних механізмів синтезу IgE та особливостей IgE-залежних імунних реакцій. Узагальнено сучасні наукові дані щодо: особливостей будови та регуляції біосинтезу IgE (у тому числі особливості будови IgE, механізмів перемикання біосинтезу IgE та його регуляції) та сучасні уявлення про молекулярні механізми IgE-залежних реакцій (зокрема розглянуто особливості участь IgE у захисті макроорганізму від паразитів, будову та біологічні функції високо- та низькоафінного рецепторів IgE, антиген-залежні ефекти IgE та IgE-опосередковані алергічні реакції). ІgЕ містяться тільки у організмі ссавців, тому є доволі пізнім з еволюційної точки зору ізотипом імуноглобулінів. У нормі імуноглобулін класу Е міститься у організмі в дуже малих кількостях (від 10 до 400 нг/мл). Накопичується в основному в тканинах слизових оболонок, шкірі, зв’язується за рахунок Fcе-рецепторів з поверхнею тучних клітин, базофілів, еозинофілів, нейтрофілів. Індукція синтезу IgE відбувається після безпосереднього контакту антигену з мембраноасоційованими формами IgE. Регуляція синтезу відбувається за допомогою інтерлейкіну 4. IgE зумовлює поверхневу експресію обох специфічних рецепторів: високоафінного FcеRI та низькоафінного FcеRIІ/CD23. FcеRI являє собою мультимерний імунний рецептор, який відіграє найважливішу роль у розвитку алергічних IgE-опосередкованих реакціях. Низькоафінний рецептор FcеRII/CD23 відіграє важливу роль в регулюванні реакцій IgE: він взаємодіє із IgE, CD11c, CD18, CD21/CR2, CD47, CD51, CD61. Імуноглобулін Е відіграє також важливу роль у імунній відповіді проти гельмінтних інвазій.
Ключові слова: IgE, молекулярні механізми біосинтезу, алергія, IgE-залежні реакції.
Резюме
Михальчук Н.В., Галкин А.Ю., Дуган А.М. Особенности регуляции биосинтеза IgE и молекулярные механизмы IgE-зависимых реакций.
В обзорной статье проведен анализ современных научных данных о молекулярных механизмах синтеза IgE и особенностей IgE-зависимых иммунных реакций. Обобщены современные научные данные об: особенностях строения и регуляции биосинтеза IgE (в том числе особенности строения IgE, механизмы переключения биосинтеза IgE и его регуляции) и современные представления о молекулярных механизмах IgE-зависимых реакций (в частности, рассмотрены особенности участие IgE в защите макроорганизма от паразитов, строение и биологические функции высоко- и низкоаффинного рецепторов IgE, антиген-зависимые эффекты IgE и IgE-опосредованные аллергические реакции). IgЕ содержатся только в организме млекопитающих, поэтому является довольно поздним с эволюционной точки зрения изотипом иммуноглобулинов. В норме иммуноглобулин класса Е содержится в организме в очень малых количествах (от 10 до 400 нг/л). Накапливается в основном в тканях слизистых оболочек, коже, связывается за счет Fcе-рецепторов с поверхностью тучных клеток, базофилов, эозинофилов, нейтрофилов. Индукция синтеза IgE происходит после непосредственного контакта антигена с мембраноассоциированными формами IgE. Регуляция синтеза происходит с помощью интерлейкина 4 IgE приводит поверхностную экспрессию обоих специфических рецепторов: высокоаффинного FcеRI и низкоаффинного FcеRII/CD23. FcеRI представляет собой мультимерный иммунный рецептор, который играет важнейшую роль в развитии аллергических IgE-опосредованных реакциях. Низкоаффинный рецептор FcеRII/CD23 играет важную роль в регулировании реакций IgE: он взаимодействует с IgE, CD11c, CD18, CD21/CR2, CD47, CD51, CD61. Иммуноглобулин Е играет также важную роль в иммунном ответе против гельминтных инвазий.
Ключевые слова: IgE, молекулярные механизмы биосинтеза, аллергия, IgE-зависимые реакции.
Summary
Mykhalchuk M.V., Galkin O.Yu., Dugan O.M. Peculiarities of regulation of IgE biosynthesis and molecular mechanisms of IgE-dependent reactions.
In a review article were analyzed the current scientific data on the molecular mechanisms of synthesis of IgE and IgE-dependent features of immune responses. We summarized the current scientific evidence about: features of the structure and regulation of biosynthesis of IgE (including structural features of IgE, IgE switching mechanisms of biosynthesis and its regulation) and current ideas on the molecular mechanisms of IgE-dependent reactions (in particular, the features of the participation of IgE in the protection of the microorganism against parasites and biological functions of high and low affinity IgE receptor, antigen-dependent effects of IgE and IgE-mediated allergic reactions). IgE is found only in mammals, so is quite late immunoglobulin isotyp from an evolutionary point of view. Normally, the immunoglobulin class E contained in the body in very small quantities (10 to 400 ng/L). Accumulates mainly in the tissues of the mucous membranes, skin, communicates through Fcе-receptor with the surface of mast cells, basophils, eosinophils, neutrophils. Induction of IgE synthesis occurs after the direct contact with the membrane forms IgE. Regulation of synthesis occurs via the interleukin 4 IgE causes the surface expression of both specific receptors: high-affinity FcеRI and low affinity FcеRII/CD23. FcеRI is a multimeric immune receptor, which plays a crucial role in the development of IgE-mediated allergic reactions. Low affinity receptor FcеRII/CD23 plays an important role in regulating responses IgE: it reacts with IgE, CD11c, CD18, CD21/CR2, CD47, CD51, CD61. IgE also plays an important role in the immune response against helminth invasions.
Key words: IgE, the molecular mechanisms of biosynthesis, allergy, IgE-dependent reactions.
Рецензент: д.мед.н., проф. І.В. Лоскутова

УДК 57.083.322+ 571.27

Національний технічний університет України «Київський політехнічний інститут» (Київ)

Национальный технический университет Украины "Киевский политехнический институт" (Киев)

National Technical University of Ukraine "Kyiv Polytechnic Institute" (Kyiv)

alexfax@list.ru, alexfbt@mail.ua, biotech@kpi.ua

In 1921 as a result of experiments of German scientists S. Prausnitz and H. Kustner it been shown correlation between allergy and unidentified serum factor. These factor was named  as “regain” by A.F. Coca in 1925. Only in the 1966-67 American researchers K. Ishizaka, T. Ishizaka, M. Hornbrook [2] and in Sweden investigators Н. Bennich and C. Johansson [3] identified a new class of antibodies, which was defined by the World Health Organization as immunoglobulin E (IgE). IgE is a class of antibody which is present only in mammals, and is a monomeric glycoprotein with 190 kDa molecular mass. IgE Fc-fragment has twice the molecular weight compared to the Fc-fragment of IgG (100 kDa), due to the additional 100 amino acid residues (contains additional four CH-domain). Immunoglobulin E is synthesized mainly in the lymphoid tissue of the skin, respiratory tract, intestines and lymph nodes that drain it. The main function of IgE is associated with defense against helminths and protozoa parasites. IgE plays an important role in hypersensitivity type I, which is manifested by various allergic diseases such as allergic asthma, allergic rhinitis, food allergy, atopic dermatitis, anaphylaxis, etc.

Given the clinical significance of IgE is an important study of the mechanisms of synthesis of this class of IgE and IgE-dependent immune responses, which play an important role in the development of allergy and defense against parasites.

The aim of the work was to analyze the current scientific data on the molecular mechanisms of synthesis of IgE and IgE-dependent features of immune responses. Work carried out in accordance with scientific research plan of the National Technical University of Ukraine “Kyiv Polytechnic Institute” and is a fragment of the search topic “Comparative characterization and optimization methods epitop mapping antigens of protein nature”.

In a review article were analyzed the current scientific data on the molecular mechanisms of synthesis of IgE and IgE-dependent features of immune responses. We summarized the current scientific evidence about: features of the structure and regulation of biosynthesis of IgE (including structural features of IgE, IgE switching mechanisms of biosynthesis and its regulation) and current ideas on the molecular mechanisms of IgE-dependent reactions (in particular, the features of the participation of IgE in the protection of the microorganism against parasites and biological functions of high and low affinity IgE receptor, antigen-dependent effects of IgE and IgE-mediated allergic reactions).

IgE is found only in mammals, so is quite late immunoglobulin isotyp from an evolutionary point of view. Normally, the immunoglobulin class E contained in the body in very small quantities (10 to 400 ng/L). Accumulates mainly in the tissues of the mucous membranes, skin, communicates through Fcε-receptor with the surface of mast cells, basophils, eosinophils, neutrophils. Induction of IgE synthesis occurs after the direct contact with the membrane forms IgE.

Regulation of synthesis occurs via the interleukin 4 (IL-4). IgE causes the surface expression of both specific receptors: high-affinity FcεRI and low affinity FcεRII/CD23. FcεRI is a multimeric immune receptor, which plays a crucial role in the development of IgE-mediated allergic reactions. Low affinity receptor FcεRII/CD23 plays an important role in regulating responses IgE: it reacts with IgE, CD11c, CD18, CD21/CR2, CD47, CD51, CD61. IgE also plays an important role in the immune response against helminth invasions.

The point of initiation of synthesis of IgE-antibody is antigen recognition by  membrane-associated form of immunoglobulin E, which is expressed on the surface of B cells. However, for the further proliferation of B cells and their differentiation into IgE-secretory plasma cells required two additional signals: CD40 and CD40L interaction and signal molecules as IL-4 or IL-13, which direct recombination into the genome of Cε, resulting ε-chain transcribed. A large number of T-helper (Th) type II (Th2), can induce both signals. Thus, the antigen was subjected to proteolytic cleavage by peptide fragments further associated with molecules of major histocompatibility complex class II (MHC II) and transported to the surface of B cells. Specific T cells that carry MHC II with antigenic determinants recognize and bind antigen. This results in transient expression CD40L on T cells. CD40L/CD40 interaction activates B7-1/B7-2 (CD80/CD86) receptors on B cells and stimulates B cells to proliferate. The binding of B7 to CD28 on T cells activates T cells, which begin to produce IL-4 and other cytokines and thus cause the differentiation of B cells into plasma cells. Mast cells, basophils and eosinophils, effector cells of IgE are produce Th2 type cytokines, including IL-4. In addition, CD40L mast cells and basophils can induce synthesis of IgE. However, IgE synthesis involves the synthesis of Th2-type cytokines. IgE response against this antigen are regulated predominantly Th2-cells. In contrast, interferon-γ inhibits the immune response to Th2-type and synthesis of IgE.

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References

1.     Litman, G.W. Rast, J.P. and Fugmann, S.D. (2010), “The origins of vertebrate adaptive immunity”, Nat. Rev. Immunol., vol. 10, no. 8, pp. 3-14.

2.     Marchalonis, J.J., Whitfield, G.K. and Schluter, S.F. (2003), “Rapid evolutionary emergence of the combinatorial recognition repertoire”, Integr. Comp. Biol., vol. 43, no. 2, pp. 347-359.

3.     Schluter, S.F., Bernstein, R.M., Bernstein, H., et al. (1999), “'Big Bang' emergence of the combinatorial immune system”, Dev. Comp. Immunol., vol. 23, no. 2, pp. 107-111.

4.     Galkin, O.Yu. (2013), “Development of improved methods of extraction and purification of human IgE”, Research Bulletin of National Technical University of Ukraine “Kyiv Polytechnic Institute”, vol. 3, pp. 18-23.

5.     Flajnik, M.F. (2002), “Comparative analyses of immunoglobulin genes: suprises and portents”, Nat. Rev. Immunol., vol. 2, no. 9, pp. 688-698.

6.     Johansson, S.G., Bennich, H. and Wide, H. L. (1968), “A new class of immunoglobulin in human serum”, Immunol., vol. 14, no. 2, pp. 265-272.

7.     Rowe, D.S., Teckett, L., Bennich, H., et al. (1970), “A reach standard for human serum immunoglobulin E”, Bull. World Health Org., vol. 42, p. 535.

8.     Bennich, H.H., Ishizaka, K. and Johansson, S.G. (1968), “Immunoglobulin E: a new class of human immunoglobulin”, Immunochem., vol. 15, no. 3, pp. 323-324.

9.     Johnstone, A. and Turner, M. (1997), Immunochemistry 2: A Practical Approach, IRL Press, Oxford: 1997, UK.

10.   David, J., Natalie, M., O’Connor, B., et al. (2004), “Transcription of Ig germline genes in single human B cells and the role of cytokines in isotype determination”, J. Immunol., vol. 173, no. 7, pp. 4529-4538.

11.   Robinson, D.S. (2000), “Th-2 cytokines in allergic disease”, Br. Med. Bull., vol. 56, no. 4, pp. 956-968.

12.   Worm, M. and Henz, B. (1997), “Molecular regulation of human IgE synthesis”, J. Mol. Med. (Berl.), vol. 75, no. 6, pp. 440-447.

13.   Hendrix, S. and Nitsch, R. (2007), “The role of T helper cells in neuroprotection and regeneration”, J. Neuroimmunol., vol. 184, no. 1-2, pp. 100-112.

14.   Beth, A., Scott, C. and Jardetzky, G. (2000), “Structure of the human IgE-Fc Cε3-Cε4 reveals conformational flexibility in the antibody effector domains”, Immunity, vol. 13, no. 3, pp. 375-385.

15.   Untersmayr, E., Bises, G., Stark, P., et al. (2010), “The high affinity IgE receptor FcεRI is expressed by human intestinal epithelial cells”, PLoS ONE, vol. 5, no. 2, pp. e9023.

16.   Yamaguchi, M., Sayama, K., Yano, K., et al. (1999), “IgE enhances Fcε receptor I expression and IgE-dependent release of histamine and lipid mediators from human umbilical cord blood-derived mast cell: synergistic effect of IL-4 and IgE on human mast cell Fcε receptor I expression and mediator release”, J. Immunol., vol. 162, no. 9, pp. 5455-5465.

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