Advertisement Upgrade to remove ads

complement

a series of serum and membrane expressed proteins involved in the effector role of the immune response to pathogens
synthesized in the liver and by cells involved in the inflammatory response

complement functions

key role in defense against many foreign invaders
production of opsonins (proteins that facilitate phagocytosis)
production of anaphylatoxins
direct killing of organisms
enhancing antigen-specific immune responses
maintaining homeostasis

complement activation pathways

involves a cascade of successive components
enhances a small initiating signal
components are cleaved into activated fragments
fragments induce intense inflammatory responses to eliminate infectious agents

classical pathway

antigen-antibody complexes are main activators of this pathway
activated by the formation of soluble Ag-Ab complexes or binding of Ab (IgM or IgG) to Ag on target cell
C-reactive protein binds to the surface of many bacteria and is also an activator
only gets activated when the antigen is bound; free antibody doesn't bind complement

classical pathway components

major components labeled C with a number
when a component is cleaved in the process of activation, it fragments receive an additional letter, a or b
cleavage products often bind to form an active enzyme

activation effectiveness

IgM is more effective at activating complement than IgG
C1q binds to CH3 domain of IgM and CH2 domain of IgG; both require at least two adjacent Fc regions
activation of the thiol-ester bond and covalent attachment to antigen; causes thiol-ester bond to change form and attaches to the antigen which causes C1q to change form and get activated
when C1q gets activated, C1r gets activated

classical pathway mechanism

C1s undergoes proteolytic cleavage to form C4 and C2
C4 and C2 are cleaved into C4a, C4b, C2a, and C2b
C4b and C2b combine to form C4b2b which is a C3 convertase
antibody must be present for this to happen; distinguishing difference between this pathway and the others

lectin pathway

antibody independent pathway which makes it part of the innate immunity response
components are designated by abbreviations and numbers i.e. MASP-1
activated by mannose-binding lectin to mannose residues on foreign surface

lectin pathway mechanism

binding of MBP activates MASP-1 and MASP-2 (membrane protein associated serine proteases) that cleave and activate C4 and C2
cleaved C4 and C2 generate C3 convertase
converges with the classical pathway at activation of C3

alternative pathway

antibody independent pathway which makes it part of the innate immunity response; does not require Ag-Ab complex formation
designated by letters i.e. B, D, and P
initiated by foreign cell surface proteins
produces active C3 and C5 convertase
active C3 is generated spontaneously
host cells regulate the progression

membrane attack complex formation

classical, lectin, and alternative pathways form C3 convertase
C3 convertase cleaves C3 to C3b which then forms C5 convertase
C5 convertase cleaves C5 to C5b which binds to C6, C7, C8, and C9
involves a lot of binding
gram positive bacteria have a thick membrane and are resistant to this unless there is a lysozyme present

activation of C3

cleavage of C3 is a critical step in all three pathways
C3 convertase splits C3 into C3a (anaphylatoxin that promotes inflammation) and C3b; C3b continues in the sequential activation of successive components
C3b fixation to surface leads to opsonization and immune complex clearance by binding to CR1 on phagocytic cells

activation of C5

cleavage of C5 produces C5a which is released into the the fluid phase as a potent anaphylatoxin, and C5b which binds to the cell surface for binding the terminal complement components

terminal sequence

components include C5b, C6, C7, C8, and C9; all components are common for all pathways
bind to each other to form membrane attack complex (MAC) which forms a hole in the cell causing water to burst in
results in cell lysis

direct roles of complement

elimination of pathogen via opsonization and phagocytosis
bacteriolysis of membrane, lipid-bilayer of any gram negative bacteria, enveloped viruses, or infected host cells
promoting acute inflammation which results in protection or hypersensitivity reactions

acute inflammation

complement activation on bacterial cell surface releases anaphylatoxins C3a, C4a, and C5a; leads to histamine release
C5a binds to phagocyte's cell receptors
phagocytes increase in random cell movement (chemokinesis)
pseudopod formation
directional cell movement (chemotaxis)

regulation of complement activity

suicide substrate mechanism in which an inhibitor forms a covalent bond with the active site of the enzyme; C1 inhibitor binds to C1r and C1s
proteolytic digestion of the active fragments into smaller inactive fragments; digestion of C4b and C3b by factor I
inhibition of association of complement components; inhibition of MAC formation by CD59
mechanisms in our body eliminate binding proteins and break them down further so they don't attack our own cells

complement deficiency

C1q, C1r, C1s, C4, or C2 deficiency results in suboptimal C3b from alternative pathway
causes increased risk to pyogenic bacteria and a lupus-like immune complex disease

complement deficiency

C3 deficiency results in no C3
causes recurrent infections with pyogenic bacteria and Neisseria; immune complex disease

complement deficiency

C5, C6, C7, or C8 deficiency results in no MAC
causes Neisseria infections, but no immune complex disease

complement deficiency

C1INH deficiency results in an increase in C2a, C4a, and bradykinin
causes hereditary angioneurotic edema

complement deficiency

factor B or properdin deficiency results in no alternate pathway
causes Neisseria infections

complement deficiency

DAF or CD59 deficiency results in increased sensitivity of host cells to the lytic effects of the host's complement activity
causes paroxysmal nocturnal hemoglobulinuria; patient has MACs that poke holes in their own cells causing blood in the urine

Please allow access to your computer’s microphone to use Voice Recording.

Having trouble? Click here for help.

We can’t access your microphone!

Click the icon above to update your browser permissions above and try again

Example:

Reload the page to try again!

Reload

Press Cmd-0 to reset your zoom

Press Ctrl-0 to reset your zoom

It looks like your browser might be zoomed in or out. Your browser needs to be zoomed to a normal size to record audio.

Please upgrade Flash or install Chrome
to use Voice Recording.

For more help, see our troubleshooting page.

Your microphone is muted

For help fixing this issue, see this FAQ.

Star this term

You can study starred terms together

NEW! Voice Recording

Create Set