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Effector mechanisms of humoral immunity Flashcards

1
Q

What are the four general functions of an antibody?

A
  1. Neutralization of microbes and toxins
  2. Antibody-mediated opsonization and phagocytosis
  3. Antibody-dependent cell-mediated cytotoxicity
  4. Activation of classical complement pathway
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2
Q

Which Fc receptor(s) mediate antibody-mediated opsonization and phagocytosis?

A

Fc gamma receptors, especially RI (CD64) on phagocytes

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3
Q

Which Fc receptor mediates antibody-dependent cell-mediated cytotoxicity?

A

Fc gamma RIIIA (CD16) on NK cells

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4
Q

Describe six general functions of Fc receptors.

A
  1. Opsonization/phagocytosis
  2. Antibody-dependent cell-mediated cytotoxicity
  3. Degranulation
  4. Feedback inhibition of various cellular responses
  5. Complement activation
  6. Antigen uptake by antigen-presenting cells
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5
Q

Which Fc receptor mediates eosinophil degranulation?

A

Fc epsilon RI

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6
Q

Which Fc receptor inhibits various cellular responses, including BCR signaling?

A

Fc gamma RIIB (CD32)

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7
Q

What are the functions of CR1 (CD35)?

A
  1. Phagocytosis
  2. Clearance of immune complexes
  3. Dissociation of C3 convertases by acting as cofactor for cleavage of C3b, C4b
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8
Q

What are the functions of CR2 (CD21)?

A
  1. Co-receptor for B cell activation
  2. Trapping of antigens in the germinal center

Note: CR2 is receptor for EBV

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9
Q

What are the function(s) of CR4 (CD?

A

Phagocytosis

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10
Q

Which ligand(s) bind CR1 (CD35)?

A

C3b > C4b > iC3b

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11
Q

Which ligand(s) bind CR2 (CD21)?

A

C3d, C3dg > iC3b

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12
Q

Which ligand(s) bind CR3 (Mac-1, CD11b/CD18)?

A

iC3b, ICAM-1, microbes

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13
Q

Which ligand(s) bind CR4 (Gp 150/95, CD11c/CD18)?

A

iC3b

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14
Q

What is the function of C1 esterase inhibitor?

A

Inhibits proteolytic activity of C1r, C1s, and MASP2
Inhibits kallikrein

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15
Q

What is the pathophysiology of hereditary angioedema?

A

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

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16
Q

Patients with C1, C2, or C4 deficiency are at increased risk for which disease?

A

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

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17
Q

What is the most common complement deficiency?

A

C2 deficiency

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18
Q

Patients with late complement deficiencies are at increased risk for which infection?

A

Neissseria

19
Q

What is the function of CD59?

A

Inhibits formation of MAC on host cells by inhibiting addition of C9 to C5b-C8

20
Q

What is the pathophysiology of paroxysmal nocturnal hemoglobinuria?

A

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

21
Q

What is the function of decay-accelerating factor (DAF)?

A

Displaces C2a from C4b and Bb from C3b, leading to dissociation of C3 convertases

22
Q

What is the function of Factor I?

A

Degrades C3b and C4b in the presence of cofactors, including MCP, CR1, Factor H, C4BP

23
Q

Which products are generated by degradation of C3b?

A

iC3b (inactive C3b), C3d, C3dg

24
Q

What are the cofactors for Factor I?

A

MCP
CR1
Factor H
C4BP

25
What is the function of properdin?
Stabilizes C3 convertase, C3bBb, in the alternative pathway
26
What is the function of Factor D?
Helps cleave Factor B to form C3bBb
27
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
28
What is the function of factor H?
Binds C3b and displaces Bb Cofactor for factor I-mediated cleavage of C3b
29
What is the function of C4-binding protein (C4BP)?
Binds C4b and displaces C2 Cofactor for factor I-mediated cleavage of C4b
30
What is the function of membrane cofactor protein (MCP)?
Cofactor for factor I-mediated cleavage of C3b and C4b
31
Which laboratory findings are associated with HAE type I?
Low C4 Low C1 INH Low C1 INH FXN Normal C1q
32
Which laboratory findings are associated with HAE type II?
Low C4 Normal or high C1 INH Low C1 INH FXN Normal C1q
33
Which laboratory findings are associated with HAE type III?
Normal C4 Normal C1 INH Normal C1 INH FXN Normal C1q
34
Which laboratory findings are associated with AAE type 1?
Low C4 Low C1 INH Low C1 INH FXN Low C1q
35
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
36
Which cell surface receptor does EBV use to enter cells?
CR2 (CD21)
37
Which complement receptor is a co-receptor for B cells?
CR2 (CD21)
38
Which membrane proteins inhibit C3 convertase?
Membrane cofactor protein (MCP) CR1 Decay-accelerating factor (DAF) Factor J C4 binding protein (C4BP)
39
Which plasma protein serves as a cofactor for factor I-mediated cleavage of C3b?
Factor H
40
Which plasma protein serves as a cofactor for factor I-mediated cleavage of C4b?
C4 binding protein (C4BP)
41
What is the function of CD59?
Inhibition of MAC formation
42
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
43
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
44
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

Immunology (10 decks)

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