Complement Flashcards
What is complement system?
‘Complementary’ system
Hepatically synthesized plasma proteins that play a role in INNATE immunity & inflammation.
MAC against gram -ive bacteria
MAC (Membrane attack complex) defends against which type of bacteria?
Gram -ive bacteria
Gram +ive bacteria have thick peptidoglycan outer layer which prevents insertion of the MAC into the cell membrane
What are the various pathways to complement activation?
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
IgG complex with antigen to activate complement is which pathway?
Classic pathway
starts from C1 and continues
Which pathway activates complement by C3b?
Alternative pathway
starts from C3b and continues
Functions of complement
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
C3b function
Opsonization (↑ phagocytosis)
(binds to lipopolysaccharides on bacteria)
Helps clear immune complexes
C3a, C4a function
Anaphylaxis
mast cell activators
C5a function
Anaphylaxis
(mast cell activators)
Neutrophil chemotaxis
Which part of complement is MAC?
MAC are terminal events
C5b-to-C9
Deficiency of C5-C9 can lead to increased susceptibility to which organisms?
recurrent NEISSERIA (gonococci, meningococci) infections
b/c ↓MAC
Terminal complement deficiencies (C5–C9)
↑ risk of severe, recurrent pyogenic sinus & respiratory tract infections is due to which compliment protein deficiency?
Early complement deficiencies (C1-C4 esp C3 deficiency)
↑ susceptibility to type III hypersensitivity reactions is seen in which complement disorder?
C3 deficiency
Angioedema due to unregulated activation of kallikrein is seen in which complement regulatory protein deficiency?
C1 esterase inhibitor deficiency
ACE inhibitors are contraindicated in which complementary regulatory protein deficiency?
C1 esterase inhibitor deficiency
(ACE inhibitors inhibit bradykinin degradation resulting in ↑ plasma bradykinin)
C1 esterase inhibitor deficiency also ↑ bradykinin (vasodilation, ↑ tissue permeability and edema)
Complement-mediated lysis of RBCs & paroxysmal nocturnal hemoglobinuria is seen in which complementary regulatory protein deficiency?
CD55 (DAF) deficiency
decay-accelerating factor
Which complementary regulatory protein deficiency is characterized by ↑ bradykinin & ↓ C4 levels?
C1 esterase inhibitor deficiency
C1 esterase inhibitor deficiency leads to which condition?
Hereditary angioedema due to unregulated activation of kallikrein → ↑ bradykinin & ↓ C4 levels
Which drugs are contraindicated in C1 esterase inhibitor deficiency? Why?
ACE inhibitors
(ACE inhibitors inhibit bradykinin degradation resulting in ↑ plasma bradykinin)
C1 esterase inhibitor deficiency also ↑ bradykinin (vasodilation, ↑ tissue permeability and edema)
Opsonization is main function of which complement?
C3b
Anaphylaxis (mast cell activation) is main function of which complement?
C3a
C4a
C5a
MAC is cytolysis by which complements?
C5b - 9
C5b, C6, C7, C8 C9
Which test is used to to screen for activation of the classical complement pathway?
CH50 Blood Test
Adult reference range is 42 to 95 U/mL
↑ risk of SLE is associated with which complement deficiency disorder?
Early complement deficiencies (C1-C4)
↓ 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).
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)
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)
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)
Atypical venous thrombosis (eg, Budd-Chiari syndrome; portal vein, cerebral, or dermal
thrombosis) are features of which complement disorder?
Paroxysmal nocturnal hemoglobinuria
What is the confirmatory test for paroxysmal nocturnal hemoglobinuria?
Flow cytometry
will show ↓ expression of a protein called glycophosphatidylinositol (GPI) anchor proteins on RBCs
What are examples of complement regulatory protein deficiencies?
C1 esterase inhibitor deficiency
Paroxysmal nocturnal hemoglobinuria
What are examples of complement protein deficiencies?
Early complement deficiencies (C1-C4)
Terminal complement deficiencies (C5–C9)
Early complement deficiencies (C1-C4) are at an increased risk for which autoimmune disorder?
SLE
b/c C3b function includes immune complex clearance
Increased susceptibility to recurrent Neisseria infections are due to which complement?
Terminal complement deficiencies (C5–C9)
MAC
