COMPLEMENT SYSTEM

Question 1

Produces a cascade phenomenon where the product of one reaction is the enzymatic catalyst of the next

Answer 1

Complement system

Question 2

Regulatory proteins

(memorize; refer to mother notes)

Answer 2

1. C1 inhibitor
2. Factor I - cleaves C3b and C4b
3. Factor H - cofactor with I to inactivate C3b; prevents binding of B to C3b
4. C4 binding protein - acts as cofactor with I to inactivate C4b
5. S protein (vitronectin) - prevents attachment of the C5b67 complex to cell membranes
6. CD59 (membrane inhibitor of reactive lysis) - blocks assembly of MAC
7. Homologous Restriction Factor - binds to C8 therefore prevents formation of MAC
8. Decay Accelerating Factor - prevents assembly of C3 convertase

Question 3

Regulatory protein that prevents assembly of C3 convertase:

Answer 3

Decay Accelerating Factor

Question 4

Regulatory protein that binds to C8 therefore prevents the formation of MAC:

Answer 4

Homologous Restriction Factor

Question 5

Regulatory protein that blocks the assembly of MAC

Answer 5

CD59 (Membrane Inhibitor of Reactive Lysis)

Question 6

Regulatory protein that prevents attachment of the C5b67 complex to cell membranes

Answer 6

S protein (vitronectin)

Question 7

Regulatory protein that acts as a cofactor with I to inactivate C4b

Answer 7

C4 binding protein

Question 8

Regulatory protein that cleaves C3b and C4b

Answer 8

Factor I

Question 9

Regulatory protein; cofactor with I to inactivate C3b; prevents binding of B to C3b

Answer 9

Factor H

Question 10

The first activation cascade described; is the main antibody-directed mechanism for triggering complement activation

Answer 10

Classical pathway

Question 11

Recognition unit of classical pathway; Trimolecular structure stabilized by Calcium:

Answer 11

C1

Question 12

a 6 globular structure recognition unit, 2 of which must attach to Fc:

Answer 12

C1q

Question 13

How many IgG molecules are required to attach to an antigen before complement can bind?

Answer 13

2 adjacent molecules

Question 14

How many IgM molecules must attach to antigen before complement can bind?

Answer 14

1 molecule of IgM

Question 15

Activation unit of the classical pathway:

Answer 15

C4
C2
C3

Question 16

Membrane Attack Complex units:

Answer 16

C5, 6, 7, 8, 9
C4b6789 - MAC

Question 17

C3 convertase complex:

Answer 17

C3bBb

Question 18

C5 convertase complex:

Answer 18

C3bBb3b

C5 convertase cleaves C5 and MAC is formed

Question 19

Initiated by microorganisms with mannose:

Answer 19

Lectin pathway

Question 20

Complement units that are anaphylatoxins

Answer 20

C3a
C4a
C5a

Question 21

Complement subunit that increases capillary permeability (Edema)

Answer 21

C2b

Question 22

Complement units that are opsonins

Answer 22

C3b
C4b
C5b

Question 23

Complement unit that acts as a chemotoxin

Answer 23

C5a

Question 24

An ion that stabilizes C1 complex

Answer 24

Calcium (Ca)

Question 25

An ion that stabilizes C3 convertase (C3bBb)

Answer 25

Magnesium (Mg)

Question 26

C1 inhibitor deficiency causes:

Answer 26

Hereditary Angioneurotic Edema (HANE)

Question 27

C1 (q, r, s) deficiency causes:

Answer 27

Lupus-like syndrome

Question 28

C2 deficiency causes:

Answer 28

ATHEROSCLEROSIS 🌟 Lupus-like syndrome Recurrent infections

Question 29

C3 deficiency causes:

Answer 29

GLOMERULONEPHRITIS 🌟 Severe recurrent infections

Question 30

C4 deficiency causes:

Answer 30

Lupus-like syndrome

Question 31

C5, 6, 7, 8 deficiency causes:

Answer 31

Recurrent infections with Neisseria spp.

Question 32

C9 deficiency causes:

Answer 32

N known disease association

Question 33

Decay Accelerating Factor CD59/MIRL Homologous Restriction Factor Deficiency of these factors can cause:

Answer 33

Paroxysmal nocturnal hemoglobinuria

Question 34

Most common complement unit deficiency:

Answer 34

C2

Question 35

Most severe complement unit deficiency:

Answer 35

C3

Question 36

The classical complement pathway is activated by a. most viruses b. antigen-antibody complexes c. fungal cell walls d. mannose in bacterial cell walls

Answer 36

b. antigen-antibody complexes Classical complement pathway activation: 1. Initiated by antigen-antibody (immune) complexes 2. C1q binding to IgG or IgM antibodies 3. Sequential activation of C1r, C1s, C4, C2, C3, C5, C6, C7, C8, and C9 Classical pathway triggers: 1. Immune complexes (antigen-antibody) 2. C-reactive protein (CRP) 3. Pentraxins Other complement pathways: 1. Alternative pathway: activated by microbial surfaces (e.g., fungal cell walls, bacterial LPS) 2. Lectin pathway: activated by mannose-containing structures (e.g., bacterial cell walls) 3. Terminal pathway: common to all pathways, leads to membrane attack complex (MAC) formation Key roles of classical pathway: 1. Antibody-dependent complement activation 2. Opsonization and phagocytosis 3. Inflammation and immune response regulation Viruses can activate complement through: 1. Antibody-dependent neutralization 2. Direct interaction with complement proteins Understanding complement activation helps in: 1. Immunology and infectious disease research 2. Vaccine development and immunotherapy 3. Autoimmune disease and inflammation studies

Question 37

Which of the following is characteristic of complement components? a. Normally present in serum b. Mainly synthesized by B cells c. Present as active enzymes d. Heat stable

Answer 37

a. Normally present in serum Complement components characteristics: 1. Normally present in serum as inactive precursors (zymogens) 2. Synthesized mainly by liver hepatocytes and macrophages 3. Activate in a cascade-like fashion to mediate immune responses 4. Heat labile (not stable), especially when activated Key points: - Complement components are soluble proteins in serum. - Most are synthesized by liver hepatocytes and macrophages. - B cells produce antibodies, not complement components. - Complement activation involves proteolytic cleavage, releasing active fragments. Main functions: 1. Opsonization and phagocytosis 2. Membrane attack complex (MAC) formation 3. Inflammation and immune response regulation 4. Antibody-dependent complement activation

Question 38

All of the following are true of the recognition unit except a. it consists of C1q, C1r, and C1s b. the subunits require calcium for binding together c. binding occurs at the FC region of antibody molecules d. C1q becomes active esterase

Answer 38

d. C1q becomes active esterase Recognition unit (C1 complex) characteristics: 1. Consists of C1q, C1r, and C1s 2. Subunits require calcium ions (Ca2+) for binding 3. Binds to the Fc region of antibody molecules (IgG or IgM) However, C1q itself does not become an active esterase. Instead: - C1r and C1s become active serine proteases upon C1q binding to antibody - Activated C1r cleaves and activates C1s - Activated C1s cleaves and activates C4 and C2 Key points: - C1 complex recognizes and binds to antibody-antigen complexes - Calcium ions stabilize C1q-C1r-C1s interactions - C1 activation initiates classical complement pathway Corrected statement: "The recognition unit (C1 complex) consists of C1q, C1r, and C1s, which require calcium ions for binding together and interact with the Fc region of antibody molecules, leading to activation of C1r and C1s as serine proteases."

Question 39

Which of the following is referred to as C3 convertase? a. C1qrs b. C3bD c. C3bBb d. C4b5a

Answer 39

C. C3bBb

Question 40

Mannose-binding protein in the lectin pathway is most similar to which classical pathway component? a. C3 b. C1rs c. C1q d. C4

Answer 40

c. C1q

Question 41

Which of the following describes the role of properdin in the alternative pathway? a. Stabilization of C3/C5 b. Conversion of B to Bb c. Inhibition of C3 convertase formation d. binding and cleavage of Factor B

Answer 41

a. Stabilization of C3/C5 Properdin (Factor P) role in alternative pathway: 1. Stabilizes C3 convertase (C3bBb) and C5 convertase (C3bBbC3b) 2. Prevents spontaneous dissociation of C3 convertase 3. Enhances alternative pathway activation Properdin does not: b. Convert B to Bb (that's done by Factor D) c. Inhibit C3 convertase formation (it stabilizes it) d. Bind and cleave Factor B (that's done by Factor D) Alternative pathway key steps: 1. Spontaneous C3 hydrolysis 2. Factor B binding to C3b 3. Factor D cleavage of B to Bb 4. C3 convertase (C3bBb) formation 5. Properdin stabilization of C3 convertase Properdin's role is crucial for: 1. Amplifying alternative pathway activation 2. Enhancing microbial clearance 3. Regulating complement-mediated inflammation

Question 42

Which best characterizes the membrane attack complex (MAC)? a. Each pathway uses different factors to form it b. C5 through C9 are not added in any particular order c. One MAC unit is sufficient to lyse any type of cell d. C9 polymerizes to form the transmembrane channel

Answer 42

d. C9 polymerizes to form the transmembrane channel Membrane Attack Complex (MAC) characteristics: 1. Formed by sequential assembly of C5b, C6, C7, C8, and multiple C9 molecules 2. C9 polymerizes to form a transmembrane channel, causing cell lysis 3. Same MAC formation process for all three complement pathways Key points: - MAC formation is the final step in all complement pathways - C5b-C9 assembly creates a stable, ring-shaped transmembrane pore - Osmotic imbalance and cell lysis ensue Incorrect options: a. Each pathway uses the same factors (C5-C9) to form MAC b. C5-C9 assembly occurs in a specific, ordered sequence c. Multiple MAC units are often required for effective cell lysis (especially for larger cells) MAC's role: 1. Lyse pathogens, infected cells, or tumor cells 2. Regulate immune responses and inflammation

Question 43

All of the following represent functions of the complement system except a. decreased clearance of antigen-antibody complexes b. lysis of foreign cells c. increase in vascular permeability d. migration of neutrophils to the tissues

Answer 43

a. decreased clearance of antigen-antibody complexes Complement system functions: 1. Lysis of foreign cells (b) 2. Opsonization and enhanced phagocytosis 3. Increase in vascular permeability (c) 4. Chemotaxis: migration of neutrophils to tissues (d) 5. Clearance of antigen-antibody complexes (not decreased, but enhanced) Complement helps clear immune complexes by: 1. Solubilizing and removing complexes 2. Preventing deposition in tissues 3. Reducing inflammation and tissue damage Incorrect option (a) suggests decreased clearance, which is opposite of complement's role. Additional complement functions: 1. Amplifying immune responses 2. Regulating inflammation 3. Enhancing antibody-mediated immunity Note: Dysregulation of complement can lead to immune complex-mediated diseases, such as systemic lupus erythematosus (SLE).

Question 44

Which if the following is true of the amplification loop in complement activation? a. It is only found in the alternative pathway b. The membrane attack unit is amplified c. C3b is the product that is increased d. Increasing amounts of C1qrs are produced

Answer 44

c. C3b is the product that is increased Amplification loop in complement activation: 1. Found in alternative pathway (and lectin pathway) 2. C3b deposition on microbial surfaces amplifies complement activation 3. C3b binds and activates Factor B, forming C3 convertase (C3bBb) 4. C3 convertase cleaves more C3, increasing C3b deposition Key points: - C3b is the central molecule in the amplification loop - Amplification enhances microbial clearance and immune response Incorrect options: a. Amplification loop is also present in lectin pathway b. Membrane attack unit (MAC) formation is downstream of amplification d. C1qrs is part of classical pathway, not amplified in alternative pathway Amplification loop significance: 1. Enhances microbial clearance and immune response 2. Regulates inflammation and tissue damage 3. Crucial for alternative pathway's role in innate immunity

Question 45

Factor H acts by competing with which of the following for the same binding site? a. Factor B b. Factor D c. C3B d. Factor I

Answer 45

a. Factor B Factor H function: 1. Regulates alternative pathway 2. Competes with Factor B for binding to C3b 3. Inhibits C3 convertase (C3bBb) formation 4. Facilitates Factor I-mediated C3b cleavage Factor H binds to C3b, preventing: 1. Factor B binding and C3 convertase formation 2. Amplification of alternative pathway Incorrect options: b. Factor D cleaves Factor B, but doesn't compete with Factor H c. C3b is the binding target, not competitor d. Factor I cooperates with Factor H, cleaving C3b Key role of Factor H: 1. Regulates alternative pathway activation 2. Prevents excessive complement activation 3. Maintains immune homeostasis Dysregulation of Factor H is implicated in 1. Atypical hemolytic uremic syndrome (aHUS) 2. Age-related macular degeneration (AMD) 3. Complement-mediated diseases

Question 46

A lack of CR1 receptors on RBCs would result in which of the following? a. Decreased binding of C3b to RBCs b. Decreased clearance of immune complexes by the spleen c. Decreased breakdown of C1qrs d. Decreased binding of Factor H

Answer 46

b. Decreased clearance of immune complexes by the spleen CR1 (Complement Receptor 1) function: 1. Binds C3b and C4b on immune complexes 2. Facilitates immune complex clearance by spleen and liver 3. Regulates complement activation on erythrocytes (RBCs) Lack of CR1 on RBCs leads to: 1. Impaired immune complex clearance 2. Increased risk of immune complex-mediated diseases (e.g., SLE) 3. Enhanced complement activation and inflammation Incorrect options: a. CR1 binds C3b, but its absence doesn't decrease C3b binding c. C1qrs breakdown is not directly related to CR1 d. Factor H binding is not primarily mediated by CR1 CR1's role on RBCs: 1. Immune complex transport and clearance 2. Regulation of complement activation 3. Maintenance of immune homeostasis Dysregulation of CR1 is implicated in: 1. Systemic lupus erythematosus (SLE) 2. Immune complex-mediated diseases 3. Complement-related disorders

Question 47

Which best describes the role of CR2 on cell membranes? a. Binds C1qrs b. Acts as co-receptor on B cells for antigen c. Increases clearance of immune complexes d. Binds particles opsonized with C3b

Answer 47

b. Acts as co-receptor on B cells for antigen CR2 (Complement Receptor 2), also known as CD21, acts as a co-receptor on B cells, enhancing B cell activation and antigen response by: 1. Binding C3dg and C3d fragments of C3b 2. Facilitating antigen presentation and recognition 3. Co-stimulating B cell activation with CD19 and CD81 CR2's role as a co-receptor: 1. Amplifies B cell responses to antigens 2. Enhances antibody production and affinity maturation 3. Regulates humoral immunity

Question 48

Which of the following best characterizes hemolytic uremic syndrome? a. It is a rare cause of renal failure in children b. it can be associated with deficiencies in Factor H c. The major cause is the lack of DAF on RBCs d. It is associated with antibody-to-C3 convertase

Answer 48

b. It can be associated with deficiencies in Factor H Hemolytic Uremic Syndrome (HUS) characteristics: 1. Triad: hemolytic anemia, acute kidney injury, and thrombocytopenia 2. Typically follows diarrheal illness (E. coli O157:H7) 3. Complement dysregulation, particularly alternative pathway HUS associations: 1. Deficiencies in Factor H, Factor I, or MCP (Membrane Cofactor Protein) 2. Mutations in genes encoding complement regulators 3. Autoantibodies to Factor H or Factor B Incorrect options: a. HUS is a significant cause of renal failure in children c. Decay-accelerating factor (DAF) deficiency is associated with paroxysmal nocturnal hemoglobinuria (PNH) d. Antibodies to C3 convertase are not a primary cause of HUS

Question 49

The CH50 test measures which of the following? a. Patient serum required to lyse 50% of sensitized sheep RBCs b. Functioning of both the classical and alternative pathways c. Genetic deficiencies of any of the complement components d. Functioning of the lectin pathway only

Answer 49

a. Patient serum required to lyse 50% of sensitized sheep RBCs CH50 (Complement Hemolytic Activity of 50%) test measures: 1. The amount of patient serum needed to lyse 50% of sensitized sheep RBCs 2. Complement-mediated hemolysis, reflecting classical pathway function This test: 1. Quantifies complement activity 2. Detects deficiencies or dysfunction in classical pathway components (C1-C9) 3. Useful for diagnosing complement-related disorders

Question 50

Which of the following would be most effective in preventing bystander lysis of RBCs? a. C1-INH b. Factor B c. DAF d. Factor H

Answer 50

c. DAF (Decay-Accelerating Factor) DAF (CD55) prevents bystander lysis by: 1. Accelerating decay of C3 convertase (C4b2a) 2. Blocking amplification loop 3. Regulating classical pathway on host cells DAF's role: 1. Protects host cells (RBCs, endothelial cells) from complement damage 2. Prevents bystander lysis and autoimmune hemolysis Other options: a. C1-INH regulates classical pathway initiation, not bystander lysis b. Factor B is part of alternative pathway, not directly preventing bystander lysis d. Factor H regulates alternative pathway, but less effective on RBCs DAF's significance: 1. Paroxysmal nocturnal hemoglobinuria (PNH) treatment 2. Atypical hemolytic uremic syndrome (aHUS) management 3. Complement-related disease therapies

Question 51

A decreased CH50 level and a normal AH50 level indicate which deficiency? a. Decrease in components in the lectin pathway only b. Decrease in components in the alternative pathway only c. Decrease in components of both classical and alternative pathways d. Decrease in components of the classical pathway

Answer 51

d. Decrease in components of the classical pathway CH50 (Classical pathway Hemolytic Activity of 50%) measures classical pathway function (C1-C9). AH50 (Alternative pathway Hemolytic Activity of 50%) measures alternative pathway function. Decreased CH50 with normal AH50 indicates: 1. Classical pathway defect or deficiency 2. Normal alternative pathway function Classical pathway components: 1. C1q, C1r, C1s 2. C2, C4 3. C3-C9 (shared with alternative pathway) Deficiencies in classical pathway components (e.g., C1q, C2, C4) would decrease CH50. Normal AH50 suggests: 1. Intact alternative pathway 2. No deficiency in alternative pathway components (e.g., Factor B, Factor D) Clinical implications: 1. Suspect classical pathway-related disorders (e.g., SLE, rheumatoid arthritis) 2. Investigate C1-C4 component deficiencies 3. Differentiate from alternative pathway-related diseases

Question 52

Which best describes the role of an anaphylatoxin? a. Coats cells to increase phagocytosis b. Attracts WBCs to the area of antigen concentration c. Increases production of interleukin-1 d. Increases permeability of blood vessels

Answer 52

d. Increases permeability of blood vessels Anaphylatoxins (C3a, C4a, and C5a) are complement fragments that: 1. Increase vascular permeability 2. Cause smooth muscle contraction 3. Enhance histamine release from mast cells 4. Contribute to anaphylaxis and inflammation Key effects: 1. Vascular leakage and edema 2. Smooth muscle contraction (bronchospasm) 3. Increased mucus production 4. Enhanced inflammatory cell recruitment Other options: a. Opsonization (coating cells) is mediated by C3b, not anaphylatoxins b. Chemotaxis (attracting WBCs) is primarily mediated by C5a c. Interleukin-1 (IL-1) production is indirectly influenced by anaphylatoxins Anaphylatoxins play roles in: 1. Allergic reactions and anaphylaxis 2. Inflammatory diseases (e.g., asthma, arthritis) 3. Immune complex-mediated disorders

Question 53

Which best describes the role of Factor H? a, Acts with DAF to break down C3b b. Prevents binding of Factor B to C3b c. Binds to the C5C6C7 complex d. binds to C1q to shut down the classical pathway

Answer 53

b. Prevents binding of Factor B to C3b Factor H: 1. Regulates alternative pathway 2. Binds to C3b, preventing Factor B binding 3. Facilitates Factor I-mediated C3b cleavage 4. Inhibits C3 convertase (C3bBb) formation Key functions: 1. Regulates alternative pathway amplification 2. Prevents excessive complement activation 3. Protects host cells from complement damage Incorrect options: a. DAF (Decay-Accelerating Factor) breaks down C3 convertase, while Factor H regulates alternative pathway c. C5b-9 (Membrane Attack Complex) formation is not directly regulated by Factor H d. C1q is part of classical pathway, not regulated by Factor H Factor H's significance: 1. Atypical hemolytic uremic syndrome (aHUS) management 2. Complement-related disease therapies 3. Immune system regulation and homeostasis

Question 54

A lack of C1-INH might result in which of the following conditions? a. Paroxysmal nocturnal hemoglobinuria b. Hemolytic uremic syndrome c. Hereditary angioedema d. Increased bacterial infections

Answer 54

c. Hereditary angioedema C1-INH (C1 inhibitor) deficiency leads to: 1. Unregulated classical pathway activation 2. Excessive generation of bradykinin 3. Increased vascular permeability Hereditary Angioedema (HAE) characteristics: 1. Recurrent episodes of edema 2. Swelling of face, extremities, and airways 3. Abdominal pain and gastrointestinal symptoms Other options: a. Paroxysmal Nocturnal Hemoglobinuria (PNH) is related to DAF (Decay-Accelerating Factor) deficiency b. Hemolytic Uremic Syndrome (HUS) is often associated with complement alternative pathway dysregulation d. Increased bacterial infections are more related to deficiencies in terminal complement components (C5-C9) C1-INH's role: 1. Regulates classical pathway initiation 2. Inhibits C1r and C1s activation 3. Prevents excessive complement activation

Question 55

Which would be most effective in measuring an individual complement component? a. CH50 assay b. Radial immunodiffusion c. AH50 assay d. Lytic assay with liposome

Answer 55

b. Radial immunodiffusion Radial immunodiffusion (RID) is a precise method for measuring individual complement component levels, including: 1. Antigen-antibody complex formation 2. Quantitative measurement of complement proteins Advantages: 1. High sensitivity and specificity 2. Accurate quantification 3. Wide dynamic range Other options: a. CH50 assay measures classical pathway function (C1-C9), not individual components c. AH50 assay measures alternative pathway function (Factor B-C9), not individual components d. Lytic assay with liposomes evaluates complement-mediated lysis, not individual component levels RID is ideal for: 1. Diagnosing complement deficiencies 2. Monitoring complement levels in diseases (e.g., SLE, rheumatoid arthritis) 3. Researching complement-related disorders Other methods for measuring individual complement components include: 1. ELISA (Enzyme-Linked Immunosorbent Assay) 2. Western blot 3. Immunoelectrophoresis