Lecture 5: Regulation of Complement Flashcards
Recall the overview of the complement activation.
What are opsonization and opsonins?
Recall the receptors for complement proteins.
CR1-mediated phagocytosis is enhanced by _____ and ____________.
C5a
specific IgG bound to microbe
What are immune complexes and how are they cleared from the bloodstream?
Immune complexes are formed between antibody and antigen. It is removed from circulation through the action of complement. Many molecules of C3b are bound covalently to the complex. These bound-C3b binds to the receptor CR1 on erythrocyte surfaces. These are then brought to the spleen and liver where the phagocytic cells remove the immune complex.
Describe the process of B cell activation through complement proteins.
C3b is bound to the pathogen surface. It is then cleaved by factor I and MCP, releasing the C3f fragment and leaves iC3b on the surface. iC3b is then cleaved by factor I and CR1, releasing C3c and leaves C3dg bound to the surface.
C3dg is then recognized by the CR2 receptor (along with recognition of the antigen by BCR) leading to B cell activation.
C3a and C5a are ________________. Describe it.
They are anaphylatoxins which causes systemic inflammation. They bind to C3a and C5a receptors found on mast cells, endothelial cells, and phagocytes. This induces tumor necrosis factor-alpha (TNF-alpha) and histamine release by mast cells - causing leakage of blood vessels and migration of leukocytes.
Note: C5a is also a powerful chemoattractant - acting on neutrophils and monocytes (C5aR)
Recall the regulatory proteins of complement activation.
Describe the mechanism of inhibiting C1 activation.
Displaces C1r/s and MASP-2, inhibiting activation of C1q and MBL
Describe the mechanism of the inhibition of C3 convertase.
In the classical/lectin pathway, DAF/MCP/CR1 displaces C2b from the C3 convertase.
In the alternative pathway, the DAF/CR1 displaces Bb form the C3 convertase.
Describe the mechanism of factor I-mediated cleavage of cell-associated C3b.
As well as iC3b, the factor I mediated cleavage also produces the breakdown products C3d and C3dg that also binds to CR on phagocytes and B cells.
Describe the regulation of MAC formation.
Recall the other functions of complement.
Describe the mechanism of the inhibition of C5 convertase.
Recall on how microbes evade complement system.
Mention diseases of complement deficiencies.
Recall the stages at which complement actovoty is regulated.
