Effector mechanisms of humoral immunity Flashcards
What are the four general functions of an antibody?
- Neutralization of microbes and toxins
- Antibody-mediated opsonization and phagocytosis
- Antibody-dependent cell-mediated cytotoxicity
- Activation of classical complement pathway
Which Fc receptor(s) mediate antibody-mediated opsonization and phagocytosis?
Fc gamma receptors, especially RI (CD64) on phagocytes
Which Fc receptor mediates antibody-dependent cell-mediated cytotoxicity?
Fc gamma RIIIA (CD16) on NK cells
Describe six general functions of Fc receptors.
- Opsonization/phagocytosis
- Antibody-dependent cell-mediated cytotoxicity
- Degranulation
- Feedback inhibition of various cellular responses
- Complement activation
- Antigen uptake by antigen-presenting cells
Which Fc receptor mediates eosinophil degranulation?
Fc epsilon RI
Which Fc receptor inhibits various cellular responses, including BCR signaling?
Fc gamma RIIB (CD32)
What are the functions of CR1 (CD35)?
- Phagocytosis
- Clearance of immune complexes
- Dissociation of C3 convertases by acting as cofactor for cleavage of C3b, C4b
What are the functions of CR2 (CD21)?
- Co-receptor for B cell activation
- Trapping of antigens in the germinal center
Note: CR2 is receptor for EBV
What are the function(s) of CR4 (CD?
Phagocytosis
Which ligand(s) bind CR1 (CD35)?
C3b > C4b > iC3b
Which ligand(s) bind CR2 (CD21)?
C3d, C3dg > iC3b
Which ligand(s) bind CR3 (Mac-1, CD11b/CD18)?
iC3b, ICAM-1, microbes
Which ligand(s) bind CR4 (Gp 150/95, CD11c/CD18)?
iC3b
What is the function of C1 esterase inhibitor?
Inhibits proteolytic activity of C1r, C1s, and MASP2
Inhibits kallikrein
What is the pathophysiology of hereditary angioedema?
Increased breakdown of C4 and C2, leading to formation of C2 kinin, which causes edema
Impaired inhibition of kallikrein and factor XII, which promote increased formation of bradykinin
Patients with C1, C2, or C4 deficiency are at increased risk for which disease?
Systemic lupus erythematous, potentially due to decreased clearance of immune-complexes, leading to the development of autoantibodies and/or decreased clearance of apoptotic bodies containing fragmented DNA
What is the most common complement deficiency?
C2 deficiency
Patients with late complement deficiencies are at increased risk for which infection?
Neissseria
What is the function of CD59?
Inhibits formation of MAC on host cells by inhibiting addition of C9 to C5b-C8
What is the pathophysiology of paroxysmal nocturnal hemoglobinuria?
Deficiency in phosphatidylinositol glycosyltransferase-A (PIG-A,) which is required to form protein-lipid linkages (GPI anchors) on CD59 and DAF, resulting in unregulated complement activation on the surfaces of erythrocytes, leading to recurrent bouts of intravascular hemolysis
What is the function of decay-accelerating factor (DAF)?
Displaces C2a from C4b and Bb from C3b, leading to dissociation of C3 convertases
What is the function of Factor I?
Degrades C3b and C4b in the presence of cofactors, including MCP, CR1, Factor H, C4BP
Which products are generated by degradation of C3b?
iC3b (inactive C3b), C3d, C3dg
What are the cofactors for Factor I?
MCP
CR1
Factor H
C4BP
What is the function of properdin?
Stabilizes C3 convertase, C3bBb, in the alternative pathway
What is the function of Factor D?
Helps cleave Factor B to form C3bBb
What is the clinical consequence of Factor I deficiency?
Depletion of C3 due to unregulated formation of C3 convertase, resulting in increased infections
C3 glomerulonephritis
What is the function of factor H?
Binds C3b and displaces Bb
Cofactor for factor I-mediated cleavage of C3b
What is the function of C4-binding protein (C4BP)?
Binds C4b and displaces C2
Cofactor for factor I-mediated cleavage of C4b
What is the function of membrane cofactor protein (MCP)?
Cofactor for factor I-mediated cleavage of C3b and C4b
Which laboratory findings are associated with HAE type I?
Low C4
Low C1 INH
Low C1 INH FXN
Normal C1q
Which laboratory findings are associated with HAE type II?
Low C4
Normal or high C1 INH
Low C1 INH FXN
Normal C1q
Which laboratory findings are associated with HAE type III?
Normal C4
Normal C1 INH
Normal C1 INH FXN
Normal C1q
Which laboratory findings are associated with AAE type 1?
Low C4
Low C1 INH
Low C1 INH FXN
Low C1q
Which laboratory findings are associated with AAE type II?
Low C4
Normal C1 INH
Low C1 INH FXN
Low C1q
Anti-C1 INH Ab present
Which cell surface receptor does EBV use to enter cells?
CR2 (CD21)
Which complement receptor is a co-receptor for B cells?
CR2 (CD21)
Which membrane proteins inhibit C3 convertase?
Membrane cofactor protein (MCP)
CR1
Decay-accelerating factor (DAF)
Factor J
C4 binding protein (C4BP)
Which plasma protein serves as a cofactor for factor I-mediated cleavage of C3b?
Factor H
Which plasma protein serves as a cofactor for factor I-mediated cleavage of C4b?
C4 binding protein (C4BP)
What is the function of CD59?
Inhibition of MAC formation
What are five effector functions of complement?
1) Opsonization and phagocytosis of microbes
2) Clearance of immune complexes
3) Recruitment and activation of leukocytes by C5a, C3a
4) Cell lysis via membrane attack complex
5) B cell activation via CR2
What are three ways microbes evade complement?
1) Thick cell walls
2) Recruitment of host complement regulatory proteins
3) Expression of proteins that inhibit complement activation
What are three examples of microbes recruiting host complement regulatory proteins?
1) Expression of sialic acids that recruit Factor H
2) HIV expression of GP41, which binds Factor H
3) HIV incorporation of DAF, CD59 when budding from host cell
