What complement fragment initiates the Mac?

What complement fragment initiates the Mac?

Assembly of the MAC (Fig. 18.12) is initiated when the complement protease C5 convertase cleaves C5 into C5a and C5b. Complement protein C6 then binds to C5b, and this complex binds to complement C7 forming a larger complex.

What is the role of Mac during complement activation?

Antibody-mediated complement activation leads to MAC deposition on the surface of infected cells. Assembly of the MAC leads to pores that disrupt the cell membrane of target cells, leading to cell lysis and death. The MAC is composed of the complement components C5b, C6, C7, C8 and several C9 molecules.

What does complement cascade cause?

The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex.

Is the complement system bad?

However, harmful inappropriate or excessive complement activation can lead to tissue injury with serious consequences including death. This is normally avoided by a number of circulating (C1 inhibitor, factor H, C4b-binding protein) and membrane-associated (CD46, CD55, CR1, CD59) complement regulators [6].

What activates alternative complement pathway?

The alternative pathway is one of three complement pathways that opsonize and kill pathogens. This pathway is activated by viruses, fungi, bacteria, parasites, cobra venom, immunoglobulin A, and polysaccharides and forms an important part of the defense mechanism independent of the immune response.

What does MAC complex do?

The membrane attack complex (MAC) is an important innate immune effector of the complement terminal pathway that forms cytotoxic pores on the surface of microbes.

What is the major physiologic role of complement 1 CR1?

CR1 (Complement Receptor 1, CD35) is a membrane receptor for C3b and C4b expressed on erythrocytes, leukocytes and podocytes. It plays an important role in removal of immune complexes and pathogens coated with C3b and C4b.

What activates the complement cascade?

The complement system activates through a triggered-enzyme cascade. In such a cascade, an active complement enzyme generated by cleavage of its zymogen precursor then cleaves its substrate, another complement zymogen, to its active enzymatic form.

What do anaphylatoxins do?

The C3a, C4a and C5a components are referred to as anaphylatoxins: they cause smooth muscle contraction, vasodilation, histamine release from mast cells, and enhanced vascular permeability. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals.

What are the consequences of complement activation?

Its activation results in three major potential outcomes for microbes: cell lysis upon assembly and insertion of the terminal membrane attack complex (MAC), complement mediated opsonization, and the release of anaphylatoxins that enhance local inflammation.

What does cdcd59 do in complement activation?

CD59 regulates complement activation cascade at the final step, inhibiting formation of membrane attack complex (MAC). This protein, being anchored to the cell membrane via glycosyl phosphatidyl inositol (GPI), is expressed ubiquitously on cells which are in contact with body fluids containing components.

What does CD59 bind to in MAC complexes?

CD59 binds to C8 in MAC and prevents incorporation of pore-forming poly-C9. CD59 may also bind to C9 in partially assembled MAC complexes. The term ‘homologous restriction factor’ is a misnomer because CD59 can protect cells against ‘non-host’ complement, albeit to varying degrees.

What is CD59 in red blood cells?

Similar to CD55, CD59 is a GPI-anchored membrane protein [74], expressed on red blood cells (RBC). It regulates the terminal step in the complement system by inhibiting MAC formation [73,74].

What is cdcd59 and why is it important?

CD59 is responsible for binding complement components C8 and C9 and preventing formation of membrane attack complex to protect cells from complement damage. Individuals who lack CD59 are typically ill with neuropathy, strokes, and episodes of Coombs-negative hemolysis.