Advances in Clinical and Experimental Medicine

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Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 1, January-February, p. 105–114

Publication type: review article

Language: English

Deficiencies and Excessive Human Complement System Activation in Disorders of Multifarious Etiology

Niedobory oraz nadmierna aktywacja układu dopełniacza człowieka w chorobach o różnorodnej etiologii

Dorota Tichaczek-Goska1,

1 Department of Biology and Medical Parasitology, Wroclaw Medical University, Wroclaw, Poland

Abstract

Complement is an integral part of the immune system protecting the host organism against invasion and proliferation of various microorganisms. It is also involved in the removal of the body’s own damaged and altered cells. Activation of the complement system is a very precise process and it is strictly controlled by regulatory proteins present in both plasma and at host cells’ surfaces. C3 protein plays a major role in the complement activation and generation of immune responses. Deficiencies of the C3 and other complement components, so-called early and late complement proteins, contribute to the emergence of recurrent bacterial, viral and fungal infections. The low level of mannose-binding lectin is also important. This protein plays a protective role in the early stages of infection and in the control of inflammation. Its deficit is one of the most common reasons for human immunodeficiency, observed in microbial infections as well as in autoimmune diseases such as rheumatoid arthritis. On the other hand, the excessive activation of complement proteins is often discovered to be the reason for many diseases. These include e.g. autoimmune diseases, Alzheimer’s syndrome, schizophrenia, atypical hemolytic-uremic syndrome, angioedema, macular degeneration, and Crohn’s disease.

Streszczenie

Układ dopełniacza jest integralnym elementem odporności chroniącym organizm gospodarza przed wnikaniem i rozprzestrzenianiem różnorodnych drobnoustrojów. Bierze również udział w usuwaniu uszkodzonych i zmienionych komórek własnych organizmu. Aktywacja układu dopełniacza odznacza się precyzją i podlega ścisłej kontroli ze strony białek regulatorowych, znajdujących się zarówno w osoczu, jak i na komórkach makroorganizmu. Główną rolę w aktywacji komplementu i reakcjach odpornościowych odgrywa białko C3. Niedobory zarówno tego składnika, jak i pozostałych, tzw. wczesnych oraz późnych białek dopełniacza, sprzyjają pojawianiu się nawracających zakażeń bakteryjnych, wirusowych oraz grzybiczych. Duże znaczenie w podatności organizmu na choroby zakaźne mają również małe stężenia lektyny wiążącej mannozę. Białko to pełni ważną rolę ochronną we wczesnych stadiach zakażenia oraz regulacji procesu zapalnego. Z jednej strony jego deficyt to jeden z najczęściej występujących wśród ludzi niedoborów odporności, obserwowany zarówno w zakażeniach drobnoustrojami, jak i w chorobach autoimmunologicznych, np. reumatoidalnym zapaleniu stawów. Z drugiej strony, stale odkrywa się choroby i zespoły objawów, których podłoża upatruje się w nadmiernej aktywacji komplementu. Należą do nich m.in. choroby autoimmunizacyjne, zespół Alzheimera, schizofrenia, atypowy zespół hemolityczno-mocznicowy, obrzęk naczynioruchowy, zwyrodnienie plamki żółtej czy zespół Leśniowskiego-Crohna.

Key words

complement protein deficiencies, complement regulation, bacterial infections, MBL, C3 protein

Słowa kluczowe

niedobory białek dopełniacza, regulacja dopełniacza, zakażenia bakteryjne, MBL, białko C3

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