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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?

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
↓ haptoglobin & dark urine are features of which complement disorder?
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
What is the gene defect in paroxysmal nocturnal hemoglobinuria?
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
In paroxysmal nocturnal hemoglobinuria, an acquired PIGA gene defect can lead to which deficiencies?
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
Why is paroxysmal nocturnal hemoglobinuria a misnomer?
paroxysmal (can also be chronic not just periodic) nocturnal (can happen in daytime also) hemoglobinuria (damage to WBC & platelets also)
29
Atypical venous thrombosis (eg, Budd-Chiari syndrome; portal vein, cerebral, or dermal thrombosis) are features of which complement disorder?
Paroxysmal nocturnal hemoglobinuria
30
What is the confirmatory test for paroxysmal nocturnal hemoglobinuria?
Flow cytometry | will show ↓ expression of a protein called glycophosphatidylinositol (GPI) anchor proteins on RBCs
31
What are examples of complement regulatory protein deficiencies?
C1 esterase inhibitor deficiency Paroxysmal nocturnal hemoglobinuria
32
What are examples of complement protein deficiencies?
Early complement deficiencies (C1-C4) Terminal complement deficiencies (C5–C9)
33
Early complement deficiencies (C1-C4) are at an increased risk for which autoimmune disorder?
SLE | b/c C3b function includes immune complex clearance
34
Increased susceptibility to recurrent Neisseria infections are due to which complement?
Terminal complement deficiencies (C5–C9) MAC

Immunology - First Aid (15 decks)

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