Complement (Exam 1) Flashcards
Where are complement proteins primarily produced
liver
spleen
macrophages
What do complement components consist of
Proteins C1-C9
Factors B, D, and P
Numerous inhibitors of the pathway
What are the two proteolytic fragments seen in complement
B fragment
A gragment
Generally B fragment is what
larger and biologically active
Generally A fragment is what
smaller, not biologically active
What is needed to induce a classical complement pathway
antibody bound to specific antigen on pathogen surface
What is needed to induce alternative complement pathway
pathogen surface creates local environment conducive to complement activation
What will occur in all 3 complement pathways once activated
induces inflammation
lyse certain infectious agents
opsonize infectious agents
clear immune complexes
What is activated by all three complement pathways
C3
What complement pathway involves antibodies and what antibodies are involved
classical
IgG and IgM
Which of the complement pathways are involved in innate immunity
Lectin and alternate
Which of the complement pathways are involved in adaptive immunity
classical
What initiates the alternate pathway
spontaneous lysis of C3 causing C3b to bind and initiate pathway
What complement proteins are common to both alternate and classical pathways
C3b, C3a, C5a, MAC
How many molecules of IgG and IgM need to be bound to C1 to initiate classical pathway
1 IgM
2 IgG
What form are IgG and IgM secreted in
IgG: monomer
IgM: pentamer
What is needed to form C3 convertase
C4b and C2a
Briefly outline the process in which C3 is cleaved into proteolytic fragments
C4 is cleaved into C4a and C4b—C4b binds to surface
C2 is then cleaved into C2a and C2b. C2a binds to C4b to create C3 convertase
C3 is converted to C3a and C3b. C3b remains on cell surface
What classes are C3b and C3a
C3b opsonin
C3a anaphylotoxin
What are the functions of C5a and C5b
C5a: anaphylotoxin and chemotaxis
C5b: initiates MAC formation
What must be present to form C5 convertase
C4b, C2a, C3b
What protein is inadequate in a MAC deficiency
any protein from C5-C9
Which type of fragment will acquire enzyme activity
B fragments
What are the a fragments of complement known as
anaphylatoxins
What complement effector is involved in opsonization
C3b
What does C3b bind to
pathogen to help the phagocyte opsonize more efficiently
What complement effector is involved in clearance of immune complexes
C3b
What complement effectors are chemotactic
C3a and C5a
What complement effectors are part of the membrane attack complex
C5-C9
What are the opsonins
C3b and IgG
What is opsonization
antibody binds to antigen on bacteria via IgG and goes to a phagocyte
What receptors does opsonization occur through
complement receptors
What do immune complexes trigger
type 3 hypersensitivity reactions and inflammation
How are immune complexes made soluble
C3b disrupts the complexes to make them soluble
What role do RBCs play in clearance of immune complexes
C3b on immune complexes can bind to the C1 receptor on RBCs and be taken to the liver and spleen where they will be removed
When will antigen and antibody be higher during an infection
antigen higher at beginning
antibody higher at end
What will the zone of equivalence show
high levels of immune complexes
How will autoimmune disorders affect C3b
large amount of immune complexes which will exhaust the available C3b
once C3b is used. Will cause immune complexes to build up and become trapped
What can occur if C3b is unavailable
immune complexes can become trapped and initiate an immune response
What will occur after immune complexes become trapped in autoimmune disorders
initiate an immune response which will activate complement and cause a lot of inflammation
What are examples of anaphylatoxins
C3a and C5a
What is the action of anaphylatoxins
can bind directly to complement receptors on mast cells and basophils to cause degranulation without IgE
What are the major results of anaphylatoxins
increase in vascular permeability and phagocytosis
What type of infection is MAC critical in
Neisseria infections
A patient has recurrent infections of meningitis, what complement is likely lacking
C5-C9 any of these
What allows MAC to attack Neisseria
has lipooligosaccharide which is less bulky than LPS
A patient presents with repeated infections of Neisseria meningitidis. What could be causing this
MAC deficiency
What is the function of the C1 (C1 INH) inhibitor protein
inhibits C1r and C1s serine protease activity to turn off complement
What is the function of decaying accelerating factor (DAF)
blocks formation of C3 convertase. Displaces Bb from C3b
What pathway does C1 inhibitor affect
classical pathway, inhibits
What is the distribution of DAF
leukocytes, epithelial cells, endothelial cells
What is the function of CD59
blocks C9 binding and prevents formation of MAC
What is the distribution of CD59
blood cells
endothelial cells
epithelial cells
What proteins if inhibited would affect the classical pathway
C1q, C1r, C1s, C4 and C2
What would be seen in a classical pathway deficiency
increased immune complex diseases and increased infections with pyogenic bacteria
What pathway would a deficiency in C3 affect
both pathways. No complement can occur
What would be seen in a C3 defienciency
recurrent bacterial infections and immune complex disease
What pathway would a deficiency in C5-C9 affect
both pathways
What would be seen in an individual with C5-C9 deficiency
recurrent meningococcal and gonococcal infections
What will be seen in an individual with a deficiency in C1-INH
hereditary angioedema: overuse of C1, C4, and C2, edema at mucosal surfaces
What is deficient in hereditary angioedema
C1-INH
How can hereditary angioedema be treated
frozen plasma
