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Immunology - First Aid > Complement > Flashcards

Complement Flashcards

1
Q

What is complement system?

A

‘Complementary’ system

Hepatically synthesized plasma proteins that play a role in INNATE immunity & inflammation.

MAC against gram -ive bacteria

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2
Q

MAC (Membrane attack complex) defends against which type of bacteria?

A

Gram -ive bacteria

Gram +ive bacteria have thick peptidoglycan outer layer which prevents insertion of the MAC into the cell membrane

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3
Q

What are the various pathways to complement activation?

A

Classic pathway

  • (IgM/ IgG mediated) antigen-antibody complexes
  • C1

Alternative pathway

  • Spontaneous & microbial surfaces
  • ↑ C3b

Lectin pathway

  • Mannose, other sugars on microbial surface
  • starts from C1-like complex
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4
Q

IgG complex with antigen to activate complement is which pathway?

A

Classic pathway

starts from C1 and continues

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5
Q

Which pathway activates complement by C3b?

A

Alternative pathway

starts from C3b and continues

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6
Q

Functions of complement

A

C3b

  • opsonization (↑ phagocytosis)
  • helps clear immune complexes

C3a, C4a
- anaphylaxis

C5a

  • anaphylaxis
  • neutrophil chemotaxis

C5b-to-C9
cytolysis by MAC

Opsonins

  • C3b & IgG are 1° opsonins in bacterial defense
  • ↑ phagocytosis

Inhibitors
prevent complement activation on self cells (RBCs)
- DAF decay-accelerating factor (CD55)
- CI esterase inhibitor

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7
Q

C3b function

A

Opsonization (↑ phagocytosis)
(binds to lipopolysaccharides on bacteria)

Helps clear immune complexes

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8
Q

C3a, C4a function

A

Anaphylaxis

mast cell activators

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9
Q

C5a function

A

Anaphylaxis
(mast cell activators)

Neutrophil chemotaxis

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10
Q

Which part of complement is MAC?

A

MAC are terminal events

C5b-to-C9

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11
Q

Deficiency of C5-C9 can lead to increased susceptibility to which organisms?

A

recurrent NEISSERIA (gonococci, meningococci) infections

b/c ↓MAC

Terminal complement deficiencies (C5–C9)

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12
Q

↑ risk of severe, recurrent pyogenic sinus & respiratory tract infections is due to which compliment protein deficiency?

A

Early complement deficiencies (C1-C4 esp C3 deficiency)

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13
Q

↑ susceptibility to type III hypersensitivity reactions is seen in which complement disorder?

A

C3 deficiency

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14
Q

Angioedema due to unregulated activation of kallikrein is seen in which complement regulatory protein deficiency?

A

C1 esterase inhibitor deficiency

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15
Q

ACE inhibitors are contraindicated in which complementary regulatory protein deficiency?

A

C1 esterase inhibitor deficiency

(ACE inhibitors inhibit bradykinin degradation resulting in ↑ plasma bradykinin)

C1 esterase inhibitor deficiency also ↑ bradykinin (vasodilation, ↑ tissue permeability and edema)

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16
Q

Complement-mediated lysis of RBCs & paroxysmal nocturnal hemoglobinuria is seen in which complementary regulatory protein deficiency?

A

CD55 (DAF) deficiency

decay-accelerating factor

17
Q

Which complementary regulatory protein deficiency is characterized by ↑ bradykinin & ↓ C4 levels?

A

C1 esterase inhibitor deficiency

18
Q

C1 esterase inhibitor deficiency leads to which condition?

A

Hereditary angioedema due to unregulated activation of kallikrein → ↑ bradykinin & ↓ C4 levels

19
Q

Which drugs are contraindicated in C1 esterase inhibitor deficiency? Why?

A

ACE inhibitors

(ACE inhibitors inhibit bradykinin degradation resulting in ↑ plasma bradykinin)

C1 esterase inhibitor deficiency also ↑ bradykinin (vasodilation, ↑ tissue permeability and edema)

20
Q

Opsonization is main function of which complement?

A

C3b

21
Q

Anaphylaxis (mast cell activation) is main function of which complement?

A

C3a

C4a

C5a

22
Q

MAC is cytolysis by which complements?

A

C5b - 9

C5b, C6, C7, C8 C9

23
Q

Which test is used to to screen for activation of the classical complement pathway?

A

CH50 Blood Test

Adult reference range is 42 to 95 U/mL

24
Q

↑ risk of SLE is associated with which complement deficiency disorder?

A

Early complement deficiencies (C1-C4)

25
Q

↓ haptoglobin & dark urine are features of which complement disorder?

A

Paroxysmal nocturnal hemoglobinuria
(complement-mediated intravascular hemolysis)

Acquired PIGA gene mutation prevents the formation of glycosylphosphatidylinositol (GPI) anchors for complement inhibitors (self-protectors), such as decay-accelerating factor (DAF/CD55 deficiency) and membrane inhibitor of reactive lysis (MIRL/CD59).

26
Q

What is the gene defect in paroxysmal nocturnal hemoglobinuria?

A

Acquired PIGA gene mutation

Acquired PIGA gene mutation →
↓ glycosylphosphatidylinositol (GPI) anchors for complement inhibitors:
- ↓ decay-accelerating factor (DAF/CD55 deficiency)
- ↓ membrane inhibitor of reactive lysis (MIRL/CD59 deficiency)

27
Q

In paroxysmal nocturnal hemoglobinuria, an acquired PIGA gene defect can lead to which deficiencies?

A

DAF decay-accelerating factor (CD55 deficiency)

MIRL membrane inhibitor of reactive lysis (CD59 deficiency)

Acquired PIGA gene mutation →
↓ glycosylphosphatidylinositol (GPI) anchors for complement inhibitors:
- ↓ decay-accelerating factor (DAF/CD55 deficiency)
- ↓ membrane inhibitor of reactive lysis (MIRL/CD59 deficiency)

28
Q

Why is paroxysmal nocturnal hemoglobinuria a misnomer?

A

paroxysmal
(can also be chronic not just periodic)

nocturnal
(can happen in daytime also)

hemoglobinuria
(damage to WBC & platelets also)

29
Q

Atypical venous thrombosis (eg, Budd-Chiari syndrome; portal vein, cerebral, or dermal
thrombosis) are features of which complement disorder?

A

Paroxysmal nocturnal hemoglobinuria

30
Q

What is the confirmatory test for paroxysmal nocturnal hemoglobinuria?

A

Flow cytometry

will show ↓ expression of a protein called glycophosphatidylinositol (GPI) anchor proteins on RBCs

31
Q

What are examples of complement regulatory protein deficiencies?

A

C1 esterase inhibitor deficiency

Paroxysmal nocturnal hemoglobinuria

32
Q

What are examples of complement protein deficiencies?

A

Early complement deficiencies (C1-C4)

Terminal complement deficiencies (C5–C9)

33
Q

Early complement deficiencies (C1-C4) are at an increased risk for which autoimmune disorder?

A

SLE

b/c C3b function includes immune complex clearance

34
Q

Increased susceptibility to recurrent Neisseria infections are due to which complement?

A

Terminal complement deficiencies (C5–C9)

MAC

Immunology - First Aid (15 decks)

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