Question 1

In the alternative pathway, C3b can bind to which of the following?
I. To C3bBb
II. To factor B
III. The microbe cell surface

A) I only
B) III only
C) I and II
D) II and III
E) I, II, and III

I, II, and III

Accepted Answer

C3b can bind to the microbial cell surface and either act as an opsonin, or bind to factor B. Factor D can then cleave B to Ba and Bb to form C3bBb, which is the C3 convertase of the alternative pathway. When more C3 is cleaved, the resultant C3b can bind to C3bBb to form the alternative pathway C5 convertase (C3bBb3b), leading to subsequent formation of the MAC complex.

Question 2

The role that C3d plays in the immune response to pathogens is:&#10;A) Activation of B cells&#10;B) Activation of CD4 and CD8 T cells&#10;C) Activation of the alternative pathway&#10;D) Activation of inhibitory factors of the complement pathways

Accepted Answer

C3d is a degradation product of C3. C3d bound to antigen can bind to the complement receptor-2 (CR2) on the surface of B cells, and in conjunction with a BCR binding to antigen, can lead to B cell activation. This step is a key component in connecting complement pathway activation with the adaptive immune response.

Question 3

Which of the following are methods by which the C3 complement component can be cleaved?
I. Factor D
II. C3 convertase
III. Spontaneous cleavage

A) I only
B) III only
C) I and II
D) II and III
E) I, II, and III

II and III

Accepted Answer

Factor D cleaves factor B into Ba and Bb components. C3 can be cleaved by C3 convertases of any of the three complement pathways (C3bBb of the alternative pathway or C4b2a of the classical or lectin pathways). C3 is also cleaved spontaneously because it is a volatile molecule, and then C3b either binds to hydroxyl or amino groups on a nearby pathogen or is rapidly inactivated by reacting with water.

Question 4

The role that C3bBb3b plays in the complement pathway is to:&#10;A) Cleave C2 to C2a and C2b&#10;B) Cleave C3 to C3a and C3b&#10;C) Cleave C4 to C4a and C4b&#10;D) Cleave C5 to C5a and C5b

Accepted Answer

C3bBb3b is the C5 convertase of the alternative pathway. Therefore, it cleaves C5 into C5a and C5b. C5a acts as a chemoattractant, and C5b is the first component in the membrane attack complex (MAC), which creates the pore in the cell surface of the pathogen.

Question 5

What is the role of C9 in the complement pathways?&#10;A) Creates pore&#10;B) C3 convertase&#10;C) C5 convertase&#10;D) Binds to antibodies on microbe surface

Accepted Answer

C9 binds to C5b678 and polymerizes with other C9 components to create a barrel-shaped pore through the surface of the microbe. The pore can lead to osmotically-induced lysis of the microbe, and multiple pores can be created in a single microbe. C9 does not act as a C3 convertase or a C5 convertase, and does not bind to antibodies. The C3 convertases are C3bBb (alternative) and C4b2a (classical/lectin). The C5 convertases are C3bBb3b (alternative) and C4b2a3b (classical/lectin). C1 is the only component that binds to antibodies on the surface of the pathogen.

Question 6

Which component is common to all three complement pathways?&#10;A) C1&#10;B) C2&#10;C) C3&#10;D) C4

Accepted Answer

C1 is unique to the classical pathway, while C2 and C4 are part of both the lectin and classical pathways. The C3, C5, and MAC components are common to all three pathways. All pathways involve the formation of a C3 convertase and a C5 convertase to cleave those components, respectively, into active fragments that lead to MAC formation. So based on the answer options available, C3 is the common component.

Question 7

Patients with paroxysmal nocturnal hemoglobinuria lack which complement regulatory components on the host cell surfaces?&#10;A) Factor H and Factor I&#10;B) Decay accelerating factor (DAF) and CD59&#10;C) Membrane cofactor protein (MCP) and C1INH&#10;D) Homologous restriction factor (HRF) and properdin

Accepted Answer

Patients with paroxysmal nocturnal hemoglobinuria have a mutation in the PIG-A gene of hematopoietic cells. This defect leads to a mutant version of the glycosylphosphatidylinositol protein (GPI), which serves as a membrane anchor for surface proteins. As a result, blood cells lack the surface proteins DAF and CD59 that inhibit complement activation on host cells, and cells are lysed inappropriately, leading to red cell hemolysis and anemia.

Question 8

Which of the following components can act as an opsonin?&#10;A) C1q&#10;B) C3b&#10;C) C4a&#10;D) C5b

Accepted Answer

C3b and C4b can both act as opsonins, binding directly to the surface of the microbe to enhance phagocytosis. Phagocytes have complement receptors on the cell surface that bind to C3b or C4b for a tighter bond prior to phagocytosis. C1q is the first component of the classical pathway and binds to antibodies on the surface of a pathogen, but does not enhance phagocytosis. C4a and the other smaller components from cleavage of inactive components act as chemoattractants, but not as opsonins. C5b serves as the anchor to begin formation of the MAC pore complex, and does not function as an opsonin.

Question 9

Which of the following complement components acts as a chemoattractant?&#10;A) C2a&#10;B) C3a&#10;C) C4b&#10;D) C5b

Accepted Answer

C3 is cleaved to C3b and C3a. C3b binds to the pathogen surface and acts as an opsonin or binds to factor B to begin formation of the C3 convertase. C3a acts as a chemotactic agent to attract other immune cells to the site of infection. C4b and C2a combine to form the C3 convertase of the classical and lectin pathways and do not serve as chemoattractants. C5 is cleaved into C5b and C5a, with C5a acting as a chemoattractant, while C5b begins the MAC formation.

Question 10

Which of the complement pathways requires antibodies for activation?
I. Lectin pathway
II. Alternative pathway
III. Classical pathway

A) I only
B) III only
C) I and II
D) II and III
E) I, II, and III

Accepted Answer

Only the classical complement pathway requires antibody production for activation. After antibodies bind to the surface of the pathogen, the globular heads of C1q can bind to the Fc portions of either IgG or IgM. This binding activates the C1r/s components. C1s is a serine protease, which can cleave C4 and C2, leading to the formation of the classical pathway C3 convertase, followed by formation of C5 convertase and MAC.

Deck 11: Complement