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
Q

What is the function of properdin?

A

Stabilizes C3 convertase, C3bBb, in the alternative pathway

26
Q

What is the function of Factor D?

A

Helps cleave Factor B to form C3bBb

27
Q

What is the clinical consequence of Factor I deficiency?

A

Depletion of C3 due to unregulated formation of C3 convertase, resulting in increased infections
C3 glomerulonephritis

28
Q

What is the function of factor H?

A

Binds C3b and displaces Bb
Cofactor for factor I-mediated cleavage of C3b

29
Q

What is the function of C4-binding protein (C4BP)?

A

Binds C4b and displaces C2
Cofactor for factor I-mediated cleavage of C4b

30
Q

What is the function of membrane cofactor protein (MCP)?

A

Cofactor for factor I-mediated cleavage of C3b and C4b

31
Q

Which laboratory findings are associated with HAE type I?

A

Low C4
Low C1 INH
Low C1 INH FXN
Normal C1q

32
Q

Which laboratory findings are associated with HAE type II?

A

Low C4
Normal or high C1 INH
Low C1 INH FXN
Normal C1q

33
Q

Which laboratory findings are associated with HAE type III?

A

Normal C4
Normal C1 INH
Normal C1 INH FXN
Normal C1q

34
Q

Which laboratory findings are associated with AAE type 1?

A

Low C4
Low C1 INH
Low C1 INH FXN
Low C1q

35
Q

Which laboratory findings are associated with AAE type II?

A

Low C4
Normal C1 INH
Low C1 INH FXN
Low C1q
Anti-C1 INH Ab present

36
Q

Which cell surface receptor does EBV use to enter cells?

A

CR2 (CD21)

37
Q

Which complement receptor is a co-receptor for B cells?

A

CR2 (CD21)

38
Q

Which membrane proteins inhibit C3 convertase?

A

Membrane cofactor protein (MCP)
CR1
Decay-accelerating factor (DAF)
Factor J
C4 binding protein (C4BP)

39
Q

Which plasma protein serves as a cofactor for factor I-mediated cleavage of C3b?

A

Factor H

40
Q

Which plasma protein serves as a cofactor for factor I-mediated cleavage of C4b?

A

C4 binding protein (C4BP)

41
Q

What is the function of CD59?

A

Inhibition of MAC formation

42
Q

What are five effector functions of complement?

A

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
Q

What are three ways microbes evade complement?

A

1) Thick cell walls
2) Recruitment of host complement regulatory proteins
3) Expression of proteins that inhibit complement activation

44
Q

What are three examples of microbes recruiting host complement regulatory proteins?

A

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