IMMUNOLOGY & SEROLOGY (TopnotcherQT) > COMPLEMENT SYSTEM > Flashcards
COMPLEMENT SYSTEM Flashcards
memorization
Produces a cascade phenomenon where the product of one reaction is the enzymatic catalyst of the next
Complement system
Regulatory proteins
(memorize; refer to mother notes)
- C1 inhibitor
- Factor I - cleaves C3b and C4b
- Factor H - cofactor with I to inactivate C3b; prevents binding of B to C3b
- C4 binding protein - acts as cofactor with I to inactivate C4b
- S protein (vitronectin) - prevents attachment of the C5b67 complex to cell membranes
- CD59 (membrane inhibitor of reactive lysis) - blocks assembly of MAC
- Homologous Restriction Factor - binds to C8 therefore prevents formation of MAC
- Decay Accelerating Factor - prevents assembly of C3 convertase
Regulatory protein that prevents assembly of C3 convertase:
Decay Accelerating Factor
Regulatory protein that binds to C8 therefore prevents the formation of MAC:
Homologous Restriction Factor
Regulatory protein that blocks the assembly of MAC
CD59 (Membrane Inhibitor of Reactive Lysis)
Regulatory protein that prevents attachment of the C5b67 complex to cell membranes
S protein (vitronectin)
Regulatory protein that acts as a cofactor with I to inactivate C4b
C4 binding protein
Regulatory protein that cleaves C3b and C4b
Factor I
Regulatory protein; cofactor with I to inactivate C3b; prevents binding of B to C3b
Factor H
The first activation cascade described; is the main antibody-directed mechanism for triggering complement activation
Classical pathway
Recognition unit of classical pathway; Trimolecular structure stabilized by Calcium:
C1
a 6 globular structure recognition unit, 2 of which must attach to Fc:
C1q
How many IgG molecules are required to attach to an antigen before complement can bind?
2 adjacent molecules
How many IgM molecules must attach to antigen before complement can bind?
1 molecule of IgM
Activation unit of the classical pathway:
C4
C2
C3
Membrane Attack Complex units:
C5, 6, 7, 8, 9
C4b6789 - MAC
C3 convertase complex:
C3bBb
C5 convertase complex:
C3bBb3b
C5 convertase cleaves C5 and MAC is formed
Initiated by microorganisms with mannose:
Lectin pathway
Complement units that are anaphylatoxins
C3a
C4a
C5a
Complement subunit that increases capillary permeability (Edema)
C2b
Complement units that are opsonins
C3b
C4b
C5b
Complement unit that acts as a chemotoxin
C5a
An ion that stabilizes C1 complex
Calcium (Ca)
An ion that stabilizes C3 convertase (C3bBb)
Magnesium (Mg)
C1 inhibitor deficiency causes:
Hereditary Angioneurotic Edema (HANE)
C1 (q, r, s) deficiency causes:
Lupus-like syndrome
C2 deficiency causes:
ATHEROSCLEROSIS 🌟
Lupus-like syndrome
Recurrent infections
C3 deficiency causes:
GLOMERULONEPHRITIS 🌟
Severe recurrent infections
C4 deficiency causes:
Lupus-like syndrome
C5, 6, 7, 8 deficiency causes:
Recurrent infections with Neisseria spp.
C9 deficiency causes:
N known disease association
Decay Accelerating Factor
CD59/MIRL
Homologous Restriction Factor
Deficiency of these factors can cause:
Paroxysmal nocturnal hemoglobinuria
Most common complement unit deficiency:
C2
Most severe complement unit deficiency:
C3
The classical complement pathway is activated by
a. most viruses
b. antigen-antibody complexes
c. fungal cell walls
d. mannose in bacterial cell walls
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
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
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
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
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.”
Which of the following is referred to as C3 convertase?
a. C1qrs
b. C3bD
c. C3bBb
d. C4b5a
C. C3bBb
Mannose-binding protein in the lectin pathway is most similar to which classical pathway component?
a. C3
b. C1rs
c. C1q
d. C4
c. C1q
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
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
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
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
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
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).
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
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
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
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
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
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:
- Immune complex transport and clearance
- Regulation of complement activation
- Maintenance of immune homeostasis
Dysregulation of CR1 is implicated in:
- Systemic lupus erythematosus (SLE)
- Immune complex-mediated diseases
- Complement-related disorders
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
b. Radial immunodiffusion
Radial immunodiffusion (RID) is a precise method for measuring individual complement component levels, including:
- Antigen-antibody complex formation
- 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
