Ch. 13 Book Questions Flashcards
Which of the following functions of antibodies does NOT require Fc receptors specific for IgG?
a. Phagocytosis of antibody opsonized antigens by neutrophils
b. Antibody mediated cellular cytotoxicity by NK cells
c. Antibody mediated feedback inhibition of B cells
d. Neonatal immunity mediated by maternal antibodies transported through the placenta
e. Neutralization of tetanus toxin by anti-tetanus antibodies
e. Neutralization of tetanus toxin by anti-tetanus antibodies
Neutralization of microbes and toxins requires binding of antibody and no other effector functions. Neutrophils and macrophages utilize IgG Fc receptors (FcγR1 and FcγRII) to phagocytose IgG-opsonized antigens. Antibody feedback inhibition of B cells is mediated by FcγRIIB on the B cell. Neonatal immunity depends on transplacental transport of IgG via the neonatal Fc receptor (FcRn)
Which of the following events initiates activation of the alternative complement pathway?
a. C1q binding to a microbial surface
b. Spontaneous cleavage of C3 to C3b
c. Complement receptor 1 (CR1) binding of C3b
d. Factor I cleavage of C3
e. Mannose-binding lectin (MBL) binding to a microbial surface
b. Spontaneous cleavage of C3 to C3b
The alternative pathway is initiated when C3b, generated by spontaneous cleavage of C3 in the fluid phase, covalently binds to a cell surface. C1q is required for initiation of the classical pathway. It does not bind directly to cell surfaces but rather to the constant regions of two Ig molecules, which may be bound to cell surface antigens. Factor I is a protease that cleaves C3b and C4b and regulates both alternative and classical pathways. CR1 on phagocytes binds C3b-opsonized microbes. Mannose-binding lectin (MBL) binds to mannose on microbial surfaces to initiate the lectin pathway.
Children with C3 deficiency are at high risk for serious bacterial and fungal infections. Which of the following explains the importance of C3 in defense against these microbes?
a. Fragments of C3 generated by both classical and alternative pathway C3 convertases serve as important opsonins for phagocytosis of the microbes
b. Fragments of C3 generated only by the classical pathway C3 convertase serve as important opsonins for phagocytosis of the microbes
c. Fragments of C3 generated only by the alternative pathway C3 convertase serve as important opsonins for phagocytosis of the microbes
d. Fragments of C3 generated by both classical and alternative pathway C3 convertases bind to microbes and serve as ligands recognized by activating receptors on NK cells
e. Fragments of C3 generated by both classical and alternative pathway C3 convertases serve as important stimulants of helper T cell cytokine secretion
a. Fragments of C3 generated by both classical and alternative pathway C3 convertases serve as important opsonins for phagocytosis of the microbes
All three complement activation pathways (classical, alternative, and lectin) generate C3 convertases, which are multi-protein enzyme complexes that cleave C3 into C3a and C3b. C3b binds covalently to microbial surfaces, and acts as an opsonin that binds to complement receptor 1 (CR1) on phagocytes. This opsonization role of C3b is essential for clearance of many pathogens. C3a has proinflammatory properties, including chemoattraction of leukocytes and endothelial activation. C3 fragments do not play a role in NK cell recognition of microbes, nor do they stimulate T cell cytokine production.
A 15 year old boy with a history of multiple episodes of severe abdominal pain is found to have evidence of intravascular hemolysis, including hemoglobinuria and an elevated reticulocyte count. Further workup included flow cytometry of his red blood cells, and showed a lack of cell surface GPI (glycosyl-phosphatidyl-inosityl)-linked proteins. A diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) was made. What is the basis of the loss of red blood cells (RBCs) in this patient?
a. Phagocytosis of RBCs by splenic macrophages is increased because normally GPI linked proteins inhibit phagocytes
b. RBCs are unusually sensitive to complement-mediated lysis because of the lack of C1 inhibitor (C1 INH), which normally regulates C1r and C1s activity in the classical pathway of complement
c. RBCs are unusually sensitive to complement lysis because of the lack of CD59, which normally inhibits membrane attack complex formation on host cells, and CD55 (decay accelerating factor), which normally inhibits the formation of C3 convertases on host cells
d. RBCs are unusually sensitive to complement lysis because of the lack of complement receptor 1 (CR1), which normally promotes Factor I mediated cleavage of C3b and C4b on host cells
e. RBCs are unusually susceptible to osmotic lysis because GPI linked proteins normally serve as ion transport channels in the RBC membrane
c. RBCs are unusually sensitive to complement lysis because of the lack of CD59, which normally inhibits membrane attack complex formation on host cells, and CD55 (decay accelerating factor), which normally inhibits the formation of C3 convertases on host cells
CD59 (and CD55) are GPI-linked complement regulatory proteins that are normally present in RBC membranes, and are missing in PNH, leaving patients at risk for episodic bouts of compliant mediated hemolysis. GPI linked proteins on RBCs are not known to influence phagocytosis, nor are they components of ion transport channels. Although CR1 does regulate complement activation on host cells, it is not a GPI linked protein and would not be missing in this patient. C1 INH is not a GPI linked protein, and CI INH deficiency causes another disease, called hereditary angioneurotic edema.
All of the following are accurate statements about neonatal immunity EXCEPT:
a. Transfer of maternal IgG across the placenta is mediated by an Fc receptor structurally similar to class I MHC.
b. IgA is absorbed in the gut from breast milk and re-secreted by the infant into the bronchial mucosa.
c. IgA secretion into breast milk involves transport through breast epithelial cells, and is dependent on the poly-Ig receptor.
d. Transport of IgG across the neonatal intestinal epithelium is mediated by an Fc receptor structurally similar to class I MHC.
e. Loss of maternal antibodies is partly responsible for increased frequency of infections in infants at about 6 months of age.
b. IgA is absorbed in the gut from breast milk and re-secreted by the infant into the bronchial mucosa.
IgA is secreted into breast milk via poly-Ig receptor-mediated transcellular transport, but it is not reabsorbed in the infant’s gut. Rather, IgA remains in the lumen of the alimentary canal as a defense against intestinal microbes. IgG from breast milk is reabsorbed into the circulation from the gut lumen by the class I MHC-like neonatal Fc receptor (FcRN). This same receptor also mediates transplacental transport of IgG. Passive immunity mediated by maternal antibodies wanes with time; at about 6 months, infants have a nadir of circulating antibodies because maternal antibodies are depleted and antibodies produced by the infant have not reached maximal levels. This nadir corresponds to a period of increased susceptibility to infections, which is even more exaggerated in children with immunodeficiency diseases.
