How Complement Activity is regulated?

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Complement activity is carefully regulated by serum levels of complement components, natural decay of the activated fragments, serum protease inhibitors, and specific complement inhibitors.

CI inhibitor (C1INH) is a plasma protein which dissociates activated Clr and Cls from Clq, limiting the active time of the complex. It blocks spontaneous activation of CI also.

Several inhibitory proteins such as C4 binding protein (C4Bp), Factor H etc. dissociate the C3 and C5 convertases and promote degradation of C4b and C3b by Factor I. C4Bp and decay accelerating factor (DAF) occupy C2 binding place and prevent C2 binding with C4, an essential step in the activation process of complement system.

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Certain enzymes like carboxy peptidases in serum destroy the anaphylactic and chemotactic activities of C3a, C4a and C5a fragments and block formation of MAC on host cells. Factors H, I and P regulate activity of C3bBb according to the requirement.

MAC can detach from the target cell and cause damage to the neighboring healthy cells through its binding. To prevent damage through this mechanism, certain serum proteins known as “S proteins” bind with the detached units to prevent their binding with the healthy cells.

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