Complement System Flashcards
define the innate immune system
-genetically determined and nonspecific
what are the elements of the innate immune system
mucous secretions, complement proteins, and neutrophils, macrophages, and dendritic cells
define the adaptive immune system
involves B cells and T cells containing a small number of genetically encoded proteins that combine to produce an enormous variety of proteins capable of recognizing and deactivating anitgens
which immune system do you acquire and which are you born with
acquire- adaptive
born with- innate
what are the functions of the complement system
- alters the membrane of pathogens and cellular debris
- enhance the inflammatory response via release of anaphylatoxins that promote cell activation or migration to an inflammatory site
what does opsonization promote
the removal of particles via complement receptors on host cells
what is the function of opsonization
leads to assembly of the membrane attack complex on pathogens and lysis
how does the complement system work in innate immunity
complement system becomes activated on a target such as apoptotic cells, tissue debris or pathogens
what are the mechanisms in which the complement system works with innate immunity
-natural, spontaneous turnover (tick over) of C3 engages the alternative pathway
- binding to the target of naturally occurring antibodies engages the classical pathway
- binding of lectins to carbohydrates on the target engages the lectin pathway
what are natural antibodies replaces with in adaptive immunity
specific antibodies
what immune functions does complement trigger
phagocytosis
inflammation
membrane attack
how does phagocytosis work in complement
by opsonizing antigens. C3b has most important opsonizing activity
how does inflammation work in complement
by chemotactically attracting macrophages and neutrophils
how does membrane attack work in complement
by rupturing cell wall of bacteria
what is inflammation
a local response to cellular injury that is marked by capillary dilation, leukocytic infiltration, redness, heat, and pain
- serves as a mechanism initiating the elimination of noxious agents and of damaged tissue
what happnes in a type 1 allergic reaction
swelling is produced by the release of serum into the tissues (wheal) and redness of the skin resulting from the dilation of blood vessels (flare)
what is the classical pathway triggered by
activation of the C1 complex
- antigen: antibody complex
how does the lectin pathway start
mannose-binding lectin or ficolin binds carbohydrates on pathogen surfaces
what is the mannose-binding lectin pathway homologous to but how is it different
the classical pathway but uses opsonins such as MBL and ficolin instead of C1q
what is the alternative pathway activated by
at a low level, from the spontaneous C3 hydrolysis due to the breakdown of the internal thioester bond
- pathogen surfaces
what does the alternative pathway not rely on
pathogen-binding antibodies like the other pathways
what molecules does the classical pathway use
C1q, C1r, C1s, C4, C2
what molecules does the lectin pathway use
MBL/ficolin, MASP-2, C4, C2
what molecules does the alternative pathway use
C3, B, D
what does C3 convertase do
cleaves C3 into C3a and C3b
what do C3a and C5a do
they are peptide mediators of inflammation, phagocyte recruitment
what does C3b do
binds to complement activators of phagocytes, opsonizes pathogens and removal of immune complexes
what do C5b, C6, C7, C8, and C9 do
MAC, lysis of certain pathogens and cells
what does the classical pathway of complement involve the cleavage of
C2 C4 and C3
what is the C1 complex made of
C1q C1r and C1s
describe C1q
composed of 6 identical subunits with globular heads and long collagen-like tails. the tails combine to binds to two molecules each of C1r and C1s to form the complex
what is the opsonization mechanism
- activated C1s cleaves C4 to C4a and C4b which binds to microbial surface
- C4b then binds C2 which is cleaved by C1s to C2a and C2b forming the C4b2a complex
- C4b2a is an active C3 convertase cleaving C3 into C3a and C3b which binds to microbial surface or to the convertase itself
- one molecule of C4b2a can cleave up to 1000 molecules of C3 to C3b. many C3b molecules binds to the microbial surface
what does mannan binding lectin form a complex with
serine proteases that resemble the complement C1 complex
describe the MBL complex
forms clusters of 2-6 carbohydrate binding heads around a central collagen stalk. MASP1 and MASP2 are associated with the complex
what is another term for C4b2a and what does it lead to
C3 convertase, leads to the generation of C5 convertase
what does C5 convertase do
cleaves C5 into C5a and C5b
what pathways share the same biological activities and the same regulatory proteins
the lectin pathway and the classical pathway
what is the mechanism of the alternative pathway
-C3b deposited by classical or lectin pathway C3 convertase to a pathogen or cell surface
-C3b binds factor B
- bound factor B is cleaved by plasma protease factor D into Ba and Bb
- C3bBb complex is a C3 convertase cleaving many C3 molecules to C3a and C3b
what does C3b lead to
the MAC complex
what forms the pore on membrane surface
C9
how is the MAX complex pore formed (mechanism)
-C5b binds to C6 and C7
- C5b67 complexes binds to membrane via C7
- C8 binds to the complex and inserts into the cell membrane
- C9 molecules binds to the complex and polymerize
- C9 binds each other to form a pore in the membrane
how does opsonization and phagocytosis occur via activation of complement
-C3b is deposited on surface of the microorganism by MBL and/or alternative pathway
- C3b binds to CR1 on the surface of phagocytes
- C5a binds and activates the cell to phagocytose microorganisms
what step do the alternative pathway, lectin pathway and classical pathway converage at
C3 convertase
what regulates complement activation
a series of proteins that act on different stages of the complement cascade, dissociating the complex or catalyzing the degradation of complement proteins
what regulates the alternative pathway C3 convertase
DAF, CR1, MCP, and factor H
what does DAF do
displaces Bb from C3b and C2b from C4b thereby preventing C3 convertase
what does MCP do
dissociates C3 convertases and factor 1cleaves
what is paroxysmal nocturnal hemoglobinurina
acquired disorder that results in premature death and impaired production of blood cells
what blood cells does PNH effect
RBCs, leukocytes, and platelets
who is usually affected by PNH
both sexes equally diagnoses in young adulthood
what is the mechanism of PNH
deficiency in DAF protein
what does Eculizumab do and what is it used for
used for PNH and blocks C5 convertase
what is atypical hemolytic uremic syndrome
results from chronic uncontrolled activation of the complement system
what happens in atypical hemolytic uremic syndrome
mutliple blood clots form throughout body in small blood vessels which can lead to stroke, heart attack, kidney failure, and death
what is the mechanism of atypical hemolytic uremic syndrome
mutations in factor H, factor I, or membrane cofactor protein
what is the most common functional defect in atypical hemolytic uraemic syndrome and age related macular degeneration
reduced cofactor activity (MCP or factor H) for C3b
what is hereditary angioedema
recurrent attacks of severe swelling
what is the type 1 form of hereditary angioedema
deficiency of C1
what is the type 2 form of hereditary angioedema
an atypical C1 protein that is less capable of suppressing activation of the complement system
what is type 3 form of hereditary angioedema
due to mutations in factor 12 gene
what is the mechanism of C1 inhibitor deficiency in hereditary angioedema
factor 12a and plasmic cause prekallifrein to be converted into lakkikrein which converts high molecular weight kininogen to bradykinin which results in vasodilation, smooth muscle contraction and edema
