Immunology: MCQs with answers (explained) on Complement Pathway

The complement pathway, a cornerstone of immunology, encompasses distinct types, functions, and disease implications that intricately shape our immune responses. Comprising three main pathways – classical, lectin, and alternative – this system orchestrates a dynamic interplay of interactions to bolster our defenses against infections. The classical pathway is triggered by antigen-antibody complexes, while the lectin pathway responds to pathogen-specific carbohydrates. The alternative pathway, on the other hand, offers a rapid, antibody-independent response. These pathways collectively contribute to opsonization, inflammation, and the formation of membrane attack complexes that eliminate threats. Understanding the complement pathway is pivotal, as deficiencies or dysregulations can lead to various diseases, such as Paroxysmal Nocturnal Hemoglobinuria (PNH) and autoimmune disorders. 

Multiple Choice Questions on Complement Pathway and Immune Response 

1) Complements are the proteins that are involved in the clearance of antigens/bacteria. 

Which of the following pathway is involved in the adaptive immune response?
a) Alternative Pathway
b) Classical Pathway
c) Lectin Binding Pathway
d) All of the above

2) In the classical pathway, the antibody activated the C1 complex consisting of the C1q, C1r & C1s subunits. 

Which of the following subunit binds to the antibody?
a) C1q
b) C1r
c) C1s
d) All of the above

3) Which of the following isotype antibody is a potent activator of the classical complement pathway?
a) IgM
b) IgA
c) IgE
d) IgG

4) Which of the following C1 subunit has the catalytic activity that cleaves C4 and C2 complement proteins?
a) C1q
b) C1r
c) C1s
d) None of the above

5) In the classical pathway, which of the following complement complex serve as C3 convertase
a) C4aC2a
b) C4bC2b
c) C4bC2a
d) C4aC2b

6) In the classical pathway, after the proteolysis of the C3 complement pathway.

Which component is cleaved by C4bC2aC3b and initiates the formation of membrane attack complex?
a) C5
b) C6
c) C7
d) C8

7) The alternative pathway is activated in response to antigens but does not require antibody interaction. The following proteins are the component of the alternative pathway, except?
a) C3
b) Factor B
c) Factor D
d) Properdin

8) C3 undergo spontaneous hydrolysis to form C3a and C3b, but they have a short half before encountering the carbohydrate bacterial antigens only. 

Which of the following carbohydrate moieties are present in the mammalian cells to inactivate C3b?
a) Mannose-6-phosphate
b) Sialic acid
c) Sphingosine
d) None of the above

9) Which of the following process is required for the formation of a C3 convertase that amplifies complement activation?
a) C3b must bind to foreign antigens
b) Factor B must bind to C3b for its proteolysis by Factor D
c) Properdin must bind to the C3bBb complex for stabilization
d) All of the above

10) Certain microorganisms such as Salmonella, Listeria, Neisseria, and Cryptococcus consist of specific carbohydrate moieties on the surface antigen that activate
a) Alternative Pathway
b) Classical Pathway
c) Lectin Binding Pathway
d) All of the above

11) The membrane attack complex consists of five different complement proteins C5, C6, C7, C8, and C9. 

Which of the following subunits bind to the surface and provide a binding site for a subsequent component?
a) C5a
b) C5b
c) C6a
d) None of the above

12) Which of the following complement proteins polymerizes to form a perforin-like structure that stabilizes membrane attack complex?
a) C6
b) C7
c) C8
d) C9

13) Which of the following component of complement proteins enhances inflammation (anaphylatoxin)?
a) C3a
b) C5a
c) Both of the above
d) None of the above

14) Which of the following complement component facilitate opsonization and phagocytosis?
a) C3a
b) C3b
c) C5a
4) C5b

15) Which of the complement receptor activate phagocytosis by binding to C3b & C4b coated particles
a) CR1
b) CR2
c) CR3
d) CR4

16) Which of the following complement receptor activate a humoral response by promoting the trapping of an antigen-antibody complex?
a) CR1
b) CR2
c) CR3
d) CR4

17) The deficiency of the complement proteins (C1q, C1q, C1s) or the complement receptors leads to the accumulation of immune complexes resulting in SLE or vasculitis. 

The deficiency affects which of the following complement pathway?
a) Alternative pathway
b) Lectin binding pathway
c) Classical pathway
d) None of the above

18)  Lack of complement proteins; factor D and properdin leads to recurrent bacterial infection. 

Which of the following pathways is affected in this condition?
a) Alternative pathway
b) Classical pathway
c) Lectin binding pathway
d) None of the above

19) Erythrocytes express the complement receptor help that transports and clear the immune complex from circulation. 

Which of the following complement receptors is expressed in the erythrocytes?
a) CR4
b) CR2
c) CR3
d) CR1

20) Paroxysmal Nocturnal Hemoglobinuria is the condition that manifests as increased fragility of erythrocytes, leading to chronic hemolytic anemia, pancytopenia, and venous thrombosis. 

Which of the following options is associated with PNH?
a) Deficiency of complement protein C9
b) Deficiency of Factor D
c) Deficiency of DAF
d) Deficiency of complement receptor

Multiple Choice Answer:

1- b) Classical Pathway. the classical pathway of the complement system is closely linked to the adaptive immune response through the interaction between antibodies and antigens. Antibodies (IgM or IgG) bind to antigens on the surface of pathogens or other foreign substances during the initiation of the classical pathway.

2- a) C1q, The first component of the classical pathway is the C1 complex, which consists of three subunits: C1q, C1r, and C1s. When antibodies bind to antigens, the Fc (constant) region of the antibody interacts with the C1q component of the C1 complex, and C1r and C1s act as protease (enzyme).

3- a) IgM, is a crucial initiator of the classical pathway of the complement system.

4- c)C1s. C1s subunit cleaves complement protein C4 into C4a and C4b fragments and also cleaves C2 into C2a and C2b fragments.

 
5- b)C4bC2b, enzyme complex C1s-C4b-C2b, known as the C3 convertase.

6- a)C5
7- a)C3. The alternative pathway can be spontaneously activated on pathogen surfaces without the need for antibody-antigen complexes. It is initiated by the spontaneous hydrolysis (splitting) of complement protein C3 within the bloodstream.

8- b)Sialic acid

The carbohydrate moieties present in mammalian cells to inactivate C3b are sialic acids. Sialic acids are negatively charged carbohydrates that are found on the surface of mammalian cells and play a role in preventing the uncontrolled activation of the complement system. They provide a mechanism for regulating the complement cascade and preventing excessive inflammation and tissue damage. Sialic acids on mammalian cell surfaces can help to inactivate C3b by binding to it and preventing its further activity, thus protecting the body's own cells from complement-mediated damage.

9- d)All of the above

The formation of a C3 convertase that amplifies complement activation involves multiple steps and components. Each of the processes mentioned in the options is required for the complete formation and stabilization of the C3 convertase complex:

a) C3b must bind to foreign antigens: This is an important step in the complement cascade. When C3b binds to foreign antigens or surfaces, it initiates the alternative pathway of complement activation.

b) Factor B must bind to C3b for its proteolysis by Factor D: This is a key step in the alternative pathway. Factor B binds to the C3b molecule bound to a foreign surface, and then it is cleaved by Factor D, resulting in the formation of the C3 convertase C3bBb.

c) Properdin must bind to the C3bBb complex for stabilization: Properdin is a plasma protein that stabilizes the C3 convertase (C3bBb) complex, preventing its rapid decay and allowing continued activation of the complement cascade.

All of these processes are essential for the formation and amplification of the C3 convertase, which is a central component in the alternative pathway of complement activation.

10- c)Lectin Binding Pathway

Certain microorganisms such as Salmonella, Listeria, Neisseria, and Cryptococcus consist of specific carbohydrate moieties on the surface antigens that activate the complement system. These carbohydrate moieties can trigger complement activation through pathways such as the lectin pathway, leading to the immune response against these pathogens. The complement system plays a crucial role in identifying and eliminating these microorganisms through opsonization, inflammation, and other immune mechanisms

11- b)C5b

Among the options provided, the subunit that binds to the surface and provides a binding site for a subsequent component in the formation of the membrane attack complex (MAC) is C5b. C5b serves as the initial component that binds to the target cell membrane. Subsequent components, including C6, C7, C8, and C9, then assemble onto this complex to form the complete MAC.

12- d)C9

C9 is the complement protein that polymerizes and forms a pore-like structure within the cell membrane during the assembly of the membrane attack complex (MAC). This perforin-like structure allows ions and water to enter the target cell, leading to cell lysis and destruction. C9 molecules assemble in a circular pattern, creating a stable pore that disrupts the integrity of the cell membrane and contributes to the cytolytic activity of the MAC.

13- c)Both of the above

C3a as an Anaphylatoxin

When the complement system is activated, C3 is cleaved into two fragments, C3a and C3b. C3a acts as an anaphylatoxin by binding to receptors on mast cells and basophils, triggering the release of histamine and other inflammatory mediators from these cells. Histamine causes vasodilation, increased vascular permeability, and smooth muscle contraction. This leads to the characteristic symptoms of inflammation, including redness, swelling, and increased blood flow to the affected area. C3a also attracts and activates immune cells, such as neutrophils and eosinophils, to the site of inflammation.

C5a as an Anaphylatoxin:

C5a is generated when C5 is cleaved during the complement cascade. Like C3a, C5a functions as an anaphylatoxin by binding to receptors on mast cells, basophils, and other immune cells. Binding of C5a to these receptors triggers the release of histamine and other pro-inflammatory substances, intensifying the inflammatory response. C5a attracts various immune cells to the site of inflammation, including neutrophils, monocytes, and macrophages. This accumulation of immune cells helps combat pathogens and clear cellular debris.

14- b)C3b. C3b fragments can covalently bind to the pathogen's surface or other nearby surfaces, promoting opsonization and phagocytosis.

15- a)CR1

Complement Receptor 1 (CR1), also known as CD35, is a receptor found on various immune cells, including phagocytes like macrophages and neutrophils. CR1 binds to complement-coated particles, such as those opsonized with C3b and C4b. This binding enhances phagocytosis by facilitating the recognition and uptake of these particles by phagocytic cells. CR1 plays a significant role in enhancing the clearance of opsonized pathogens and immune complexes, thus contributing to the immune response against infections and other immune challenges. 

16- b)CR2

Complement Receptor 2 (CR2), also known as CD21, is primarily found on B cells and certain subsets of T cells. CR2 plays a crucial role in the humoral immune response by promoting the trapping of antigen-antibody complexes, especially those that are opsonized by complement fragments (C3d). When B cells encounter an antigen-antibody complex, CR2 binds to the C3d portion of the complex. This interaction enhances the activation of B cells, leading to stronger immune responses, including increased antibody production and memory cell generation. CR2 is also involved in the germinal center reaction, where B cells undergo affinity maturation and class switching to produce more effective antibodies.

17- c)Classical pathway

Deficiencies in components of the classical pathway of the complement system, such as C1q, C1r, or C1s, can lead to impaired clearance of immune complexes. The classical pathway is initiated by antigen-antibody complexes, and its activation helps to eliminate these complexes from circulation. In SLE and certain vasculitis conditions, the immune complexes are not efficiently cleared, leading to their accumulation and deposition in tissues, which contributes to inflammation and tissue damage. This accumulation of immune complexes is a hallmark of these autoimmune diseases.

18- a)Alternative pathway

The alternative pathway of the complement system is primarily responsible for initiating the complement cascade in the absence of specific antibody-antigen complexes. Properdin is a key stabilizing factor that helps in the stabilization of the alternative pathway C3 convertase (C3bBb) complex, which is crucial for amplifying the complement response. Factor D is involved in the activation of the alternative pathway by cleaving factor B to its active form, allowing it to bind to C3b and initiate the formation of the C3 convertase.

Lack of factor D and properdin can impair the proper functioning of the alternative pathway, which is essential for the innate immune response against bacterial infections. Without these components, the alternative pathway's ability to efficiently recognize and eliminate bacterial pathogens is compromised, leading to recurrent bacterial infections.

19- d)CR1

Complement Receptor 1 (CR1), also known as CD35, is found on various cell types, including erythrocytes. CR1 plays a significant role in the immune response by binding to complement-coated particles, such as immune complexes. In the context of erythrocytes, CR1 helps transport immune complexes from circulation to the liver and spleen, where they can be cleared by phagocytic cells. This process contributes to the removal of immune complexes and prevents their accumulation in circulation, which is important for maintaining immune homeostasis and preventing autoimmune reactions.

20- c)Deficiency of DAF

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired disorder of the hematopoietic stem cells. It is characterized by the absence or deficiency of certain cell surface proteins, particularly those that are involved in regulating the complement system. One of the key features of PNH is the increased sensitivity of erythrocytes to complement-mediated lysis, leading to chronic hemolytic anemia.

The condition is associated with the deficiency of complement regulatory proteins, particularly Decay-Accelerating Factor (DAF, also known as CD55) and membrane inhibitor of reactive lysis (MIRL, also known as CD59). These proteins help protect cells, including erythrocytes, from complement-mediated lysis.