Complement System Flashcards
The major humoral effector mechanism of immune resposne
complement system
Which is the only antibody-dependent complement activation pathway?
Classical (alternative and lectin are antibody-INdependent)
activation of complement system results in the generation of these 4 major immunobiological activities
- anaphylatoxins
- chemoattractants/chemotaxis
- Memembrane attack complex (MAC attack!)
- Opsonins
Which pathway is considered a pathogen associate molecular pathway? (PAMP?)
Mannose binding lectin pathway, which minds to a terminal mannose
what is the humor effector mechanism initiated by?
Soluble molecules (classical requires antibody, connecting it to adaptive immune system)
anaphylaxis
acute systemic inflammatory response
these factors induce smooth muscle contraction and degranulation of mast cells and basophils
Anaphylatoxins
These factors act on neutrophils and monocytes to direct their migration to the antigenic stimulus
Chemoattractants/chemotoxins (C5)
This complex produces holes in the membranes of bacterial pathogens and cells, and is comprised of which molecules?
Membrane attack complex. Made up of C5b, C6, C7, C8, C9n
The major opsonin of the complement system
C3b (a little on C4b)
All three pathways converge at which step to form what?
Converge at C3b to then activate membrane attack complex
Activator of C1q
IgM (secretes as pentamer) and IgG
Serine proteases when activated
C1r and C1s
3 major plays of Classical pathway
C1, C4, C2
How many of the globular heads of C1q must bind to the Fc portions of antibodies on bacteria?
2 globular heads out of 6.
C3 convertase of classical pathway
C4b2a (C4b + C42a)
the bond C4b makes with surface of bacteria
labile thioester bond
C3b has same opsinon function as
IgG
C3 convertase of classical pathway (C4b2a) function as an enzyme
cleaves C3 to generate C3b (large) and C3a (small)
Alternative pathway is activated by a small amount of
C3b (can be generated from lectin or classical pathway)
Mannose binding lectin pathway has overall structural homology to C1q, except that it binds to
terminal mannose sugar of bacteria
Two molecules associated with MBL structure and 2 important properties
MASP-1, MASP-2
1) antibody independent
2) like C1r and C1s, they are serine proteases
In alternative pathway, C3b bound to bacteria provides a binding site for
Factor B
Major players in alternative pathway
Factor B and D
This factor circulate in its active form and cleaves B into Bb
Factor D
C3 convertase of alternative pathway
C3bBb
In addition to binding to bacteria to instigate the alternative pathway, what else can C3b do?
Acts as an opsonin and can bind with C3 convertases
C5 convertases
Classical/MBL: C4b2a3b
Alternative: C3bBb3b
final step in complement cascade
C5 convertases activity
Cleave C5 into C5a and C5b
Binds to antigen surface and begins formation of MAC
C5b
What is most important deficiency in complement pathway
C3
Promote the movement of leukocytes from blood into soft tissue and changes blood flow so that increase adhesion molecules are expressed
Anaphylatoxins
Deficiency of MAC is only a problem when dealing with this one type of bacteria
Nysteria
Recurrent infections from C3 deficiecny
Pyogenic Infection (looks similar to C3b deficiency)
Properdin is a stimulatory regulatory molecule found in solution (soluble) that stabilizes which complex?
C3bBb (C3 convertase of alternative pathway)
C1 inhibitior (C1-INH) stops complement activation at which stage?
C1 activation: dissociates C1q from (C1r+C1s)
individuals that lack C1-INH develop this serious condition
Hereditary Angioneurotic Edema (usually see the accumulation of fluids in the larynx)
C4 -binding protein (C4BP) inhibits which stage of complement activation?
Classical and Mannose C3 convertase.
Dissociates C4b2a —> (C4b + C2a)
Cofactor for Factor I
C4BP
degrades C4b and C3b using C4BP or H as cofactor by proteolysis
Factor I
Why does Factor I cleave C4b and C3b?
so that those molecules wont re react with C2a and Bb respectively
An increase in [C3b] circulating is due to a deficiency in this
Factor I (cleaves C3b)
Dissociates alternative pathway C3 convertase into C3b and Bb
Factor H
Two types of regulatory molecules/ inhibitors in complement pathway
soluble (found in solution) and membrane associate (found on human cell membranes)
3 regulatory membrane bound molecules
- DAF (decay accelerating factor)
- CD59
- MCP (membrane co-factor protein)
Disease associated with absence of DAF and CD59
Paroxysmal Nocturnal Hemoglobinuria = destruction of RBC
DAF and CD59 are bound to membrane by
GPI linkages
DAF and CD59 protect against
Membrane attack complex (MAC)
Why can’t RBC block MAC formation?
Not nucleated (nucleated cells have regulatory protective mechanism and can also repair damage to cell membrane)
Receptor for C3b and C4b
CR1
Interaction of CR1 with its ligands stimulate
phagocytosis, erythrocyte transport of immune complexes and promotes C3b and C4b decay
how do CR1 on RBCs work?
Bind to immune complex in blood and eliminates it through the spleen; RBC returns to circulation
Main Fc receptor that promotes phagocytosis
Fc gamma R1 (for antibody IgG1)
Fc receptor binds to
Fc portion of an antibody that is bound to an antigen
Fc gammaR1 receptor for which antibody
IgG
Fc epsilonR1 is receptor for which antibody
IgE
Fc epsilonR1 is found on what cells
mast cells and basophils
Fc gammaR1 is found on what cells
phagocytic cells (macrophages and neutrophils)
