Complement System Flashcards
What is innate immunity?
non-specific immune response
-genetically determined
-include mucous secretion, complement proteins, and certain white blood cells (neutrophils & macrophages)
What is adaptive immunity?
specific to antigen/pathogen
-contain lymphocytes and small number of genetically encoded proteins that are able recognize and deactivate specific antigens
What are the two main functions of the complement system?
membrane perturbation and inflammation
What is oponsization?
it is a part of membrane perturbation
-coats the membrane of pathogens to promote the removal of pathogens
-also leads to the assembly of the membrane attack complex on pathogen membrane that will lead to lysis
How does the complement system enhance inflammatory response?
release anaphylatoxins that promote cell activation or migration to an inflammatory site (chemotaxis)
When is the complement system activated?
in innate immunity
What are the three ways the complement system can be activated?
C3 turnover, natural Abs, and lectins
What does C3 turnover do?
engage the alternative pathway
What do Natural Abs do?
engage the classical pathway
What do lectins do?
bind to carbohydrates on target and engages the lectin pathway
What replaces natural Abs in adaptive immunity?
specific Abs
What three immune functions are triggered by the complement system?
-phagocytosis
-inflammation
-membrane attack
What has the most important opsonizing activity in phagocytosis?
C3b
What are the chemotactically attracting neutrophils and macrophages in inflammation?
anaphylatoxins C3a and C5a
What is inflammation?
local response to cellular injury that is marked by capillary dilation, leukocytic infiltration, redness, heat, and pain
-serves to eliminate damaged tissue
What is the wheal and flare response?
reaction that occurs during type 1 allergic reactions
-swelling produced by release of serum into the tissues (wheal) and redness of skin, resulting from dilation of blood vessels (flare)
What triggers the classical pathway?
activation of C1-complex
What is the mannose-binding lectin pathway?
homologous to the classical pathway
-uses the opposins: mannose binding lectin and ficolin (NOT C1q)
How does the alternative pathway differ from other pathways?
does not rely on pathogen-binding antibodies
is the alternative pathway always activated?
yes- at a low level
what is the central component of the complement system?
complement fixation
what is complement fixation?
C3 cleaved into C3a and C3b
C3b tags bacteria for destruction
C3a recruits phagocytes
What are the three major components of the classical pathway?
(this is hard to word)
C1, C2, and C4
What ion is the classical pathway dependent on?
magnesium
What is the C1 complex?
complex of C1q, C1r, and C1s
-heads can bind to constant regions of immunoglobulin molecules or directly to the pathogen surface
-cause conformational change in C1r which cleaves and activates C1s
Steps of the classical pathway:
-activated C1 cleaves C4 to C4a and C4b, which binds to microbial surface
-C4b binds C2, which is cleaved by C1 to C2a and C2b, forming C4b2a
-C4b2a is a C3 convertase that cleaves C3 to C3a and C3b, which binds to microbial surface or the convertase surface
How many C3 molecules can one C4b2a cleave?
up to 1000
*amplification effect
What are all three pathways (classical, mannose binding, and alternative) dependent on?
C3 convertase
What are the two serine proteases associated with mannan-binding lectin complex?
MASP-1 and 2
Who is the hottest in the friend group?
Haley
Who is the silliest little goose in the friend group?
Trick question… Alli and Molly
Who always skips class?
Dom and Adam
Who are the two best roomies ever?
Grace and Gracie
When the mannan-binding lectin binds to bacterial surfaces, what happens?
the serine proteases become activated and then activate the complement system
-cleaves C4 and C2
What is C4b2a?
C3 convertase
What four proteins are involved in the alternative pathway of the complement system?
C3, factor B, factor D, and properdin
What are the steps of the alternative pathway?
-C3b deposited by classical or lectin pathway C3 convertase
-C3b binds to factor B
-bound factor B is cleaved by plasma protease factor D into Ba and Bb
-C3bBb complex is C3 convertase, cleaving many C3 molecules to C3a and C3b
What triggers the alternative pathway?
covalent binding of C3b to pathogen or cell surface
What is Factor B cleaved into?
Ba and active protease Bb
what are the terminal complement components that form the membrane attack complex?
C5b, C6, C7, C8, C9
What is the C3 convertase of the alternative pathway?
C3bBb
What are the steps of the membrane attack complex?
-C5b binds to C6 and C7
-C5b67 complex binds to membrane via C7
-C8 binds to the complex and inserts into the cell membrane
-C9 molecules bind to the complex and polymerize
-10-16 molecules of C9 bind to and form a pore in the membrane
need to know: there are pre-made proteins (C9) that allow you to make a pore in cells
What does activation of complement cause on the surface of the microorganism?
deposition of C3b
What binds to C3b to start the process of phagocytosis?
CR1 receptor on phagocytes
if just C3b is bound to CR1 receptor, does phagocytosis occur?
no
*C3b is regulated on whether it will cause phagocytosis or not
What causes the activation of the phagocytes?
binding to C5a
What helps to regulate complement activation?
series of proteins that help to protect the host cell from accidental damage
what does CD59 do?
prevents formation of membrane-attack complex on autologous or allogenic cells
What helps to block the creation of excess C3 convertase and C3b?
DAF
-blocks the association of Factor B with C3b as well as accelerating dissociation of Bb from C3b
what does DAF do?
stops formation of new C3b
Is disrupting the complement system okay?
no, it can cause many different disease
What is paroxysmal nocturnal hemoglobinurina?
acquired disorder that results in premature death and impair production of blood cells
-RBC, leukocytes, and platelets
-affects both sexes equally
-deficiency in DAF protein
What is a treatment for paroxysmal nocturnal hemoglobinurina?
therapeutic inhibition of C5
Eculizumab
-humanized recombinant murine monoclonal antibody
-antibody binds to C5 near the cleavage site and prevents its cleavage into C5b and C5a
What is atypical hemolytic uremic syndrome?
-chronic uncontrolled activation of complement system
-multiple blood clots form throughout the body
-mutation in Factor H, Factor I, or membrane cofactor protein
What is hereditary angioedema?
-recurrent attacks of severe swelling
-3 types
What causes type I hereditary angioedema?
mutation in gene that makes C1 inhibitor protein
-deficiency in C1
What causes type II hereditary angioedema?
mutation in gene that makes C1 inhibitor protein
-atypical C1 protein that is less capable to suppressing activation of complement system
What causes type III hereditary angioedema?
often due to mutation in Factor XII gene
