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Questions and Answers
What is the primary function of the Membrane Attack Complex (MAC)?
What is the primary function of the Membrane Attack Complex (MAC)?
Which antibody class is characterized as pentameric?
Which antibody class is characterized as pentameric?
What role do splenic macrophages play in immune complex (IC) clearance?
What role do splenic macrophages play in immune complex (IC) clearance?
What is the composition of the Fab region of an antibody?
What is the composition of the Fab region of an antibody?
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How are polymeric immunoglobulins such as IgA and IgM held together?
How are polymeric immunoglobulins such as IgA and IgM held together?
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Which type of bacteria is more susceptible to lysis by the Membrane Attack Complex (MAC)?
Which type of bacteria is more susceptible to lysis by the Membrane Attack Complex (MAC)?
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What is one of the primary functions of the complement system?
What is one of the primary functions of the complement system?
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What structure does the Membrane Attack Complex (MAC) specifically perforate?
What structure does the Membrane Attack Complex (MAC) specifically perforate?
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Which statement accurately describes the relationship between Gram negative bacteria and the Membrane Attack Complex?
Which statement accurately describes the relationship between Gram negative bacteria and the Membrane Attack Complex?
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What advantage does opsonization provide to the immune system?
What advantage does opsonization provide to the immune system?
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Which of the following functions is considered the most important function of the complement system?
Which of the following functions is considered the most important function of the complement system?
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What is the effect of opsonins on the immune response?
What is the effect of opsonins on the immune response?
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Which process is NOT directly facilitated by the complement system?
Which process is NOT directly facilitated by the complement system?
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What is the primary role of C3b in complement activation?
What is the primary role of C3b in complement activation?
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Which of the following opsonins directly enhances phagocytosis of pathogens?
Which of the following opsonins directly enhances phagocytosis of pathogens?
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Which receptor binds specifically to C3b during the opsonization process?
Which receptor binds specifically to C3b during the opsonization process?
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Why are encapsulated pathogens typically resistant to phagocytosis?
Why are encapsulated pathogens typically resistant to phagocytosis?
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What does the term 'fixation' of complement refer to?
What does the term 'fixation' of complement refer to?
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What is the composition of the C1 complex in the classical pathway of complement activation?
What is the composition of the C1 complex in the classical pathway of complement activation?
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Which immunoglobulin is considered the most efficient at activating the classical complement pathway?
Which immunoglobulin is considered the most efficient at activating the classical complement pathway?
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What is required for C1q to activate the classical pathway?
What is required for C1q to activate the classical pathway?
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In terms of pathway activation, what is the similarity between the Lectin and Classical pathways?
In terms of pathway activation, what is the similarity between the Lectin and Classical pathways?
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What initiates the formation of the Membrane Attack Complex (MAC)?
What initiates the formation of the Membrane Attack Complex (MAC)?
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What is the role of anaphylatoxins like C5a and C3a in the immune response?
What is the role of anaphylatoxins like C5a and C3a in the immune response?
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Which of the following molecules forms a cylindrical pore in membranes during the MAC formation?
Which of the following molecules forms a cylindrical pore in membranes during the MAC formation?
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Which event marks the final step in the formation of the Membrane Attack Complex?
Which event marks the final step in the formation of the Membrane Attack Complex?
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What role does C5 convertase play in the complement cascade?
What role does C5 convertase play in the complement cascade?
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Which component initiates the assembly of the Membrane Attack Complex (MAC)?
Which component initiates the assembly of the Membrane Attack Complex (MAC)?
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What attracts neutrophils during the complement cascade?
What attracts neutrophils during the complement cascade?
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What does the lectin pathway of complement activation use to detect pathogens?
What does the lectin pathway of complement activation use to detect pathogens?
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Which serine proteases are involved in the cleavage of C4 and C2 in the lectin pathway?
Which serine proteases are involved in the cleavage of C4 and C2 in the lectin pathway?
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How is C3 convertase generated in the complement system?
How is C3 convertase generated in the complement system?
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Which pathway of complement activation is triggered by the binding of C1 to antibodies?
Which pathway of complement activation is triggered by the binding of C1 to antibodies?
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Which component of the complement system is more directly involved in the opsonization of pathogens?
Which component of the complement system is more directly involved in the opsonization of pathogens?
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What is the primary outcome of a C3 deficiency in the complement system?
What is the primary outcome of a C3 deficiency in the complement system?
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Which receptor functions as a B cell coreceptor?
Which receptor functions as a B cell coreceptor?
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What is a key function of the C3a receptor in the complement system?
What is a key function of the C3a receptor in the complement system?
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Which receptors are involved in phagocytosis and have a role in cell adhesion?
Which receptors are involved in phagocytosis and have a role in cell adhesion?
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What secondary condition can arise from deficiencies in late complement components?
What secondary condition can arise from deficiencies in late complement components?
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What function do complement control proteins serve?
What function do complement control proteins serve?
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Which of the following is NOT a role of complement split products?
Which of the following is NOT a role of complement split products?
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Which of the following complement receptors is known for its role in leukocyte adhesion?
Which of the following complement receptors is known for its role in leukocyte adhesion?
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Study Notes
Complement System Overview
- The complement system comprises over 20 plasma and cell surface proteins interacting with each other.
- Complement components are typically denoted by uppercase "C" followed by a number (e.g., C1, C2, C3).
- Complement activation is triggered by pattern recognition during inflammation and trauma.
- Sequential proteolytic activation of zymogens (inactive precursors) generates active "split products."
- Split products are identified by suffixes (e.g., C3a and C3b are split products of C3).
Learning Objectives
- Differentiate the three complement activation pathways.
- Explain the biological properties of complement activation split products.
- Describe the regulation of complement activation and its products in host resistance to infection, inflammation, and immunopathology.
- Discuss the effects of deficiencies and defects in complement regulation.
Introduction to the Complement System
- The complement system is composed of over 20 proteins interacting; these proteins are crucial for the immune system.
- Complement components are numbered sequentially with uppercase "C" as a prefix (e.g., C1, C2, C3).
- Complement is activated by pattern recognition during infection or injury.
- Proteolytic activation of inactive precursors generates active "split products".
- These split products are denoted with suffixes (e.g., C3a and C3b are split products of C3).
Functions of the Complement System
- Identifies pathogens as a signal to the immune system.
- C3 activation leads to the generation of C3a and the opsonin C3b.
- Recruits phagocytes (C5a) and activates mast cells (C3a/C5a).
- Kills pathogens by creating pores in their membranes (C5b6789(n)).
Complement Pathways
- Alternative pathway—spontaneous activation (continuously active).
- Lectin pathway—triggered by plasma lectins binding to microbial surface carbohydrates.
- Classical pathway—activated by antibodies (IgG or IgM) bound to antigens.
Overview of Complement Functions
- Membrane Attack Complex (MAC): Gram-negative bacteria are more susceptible to lysis by MAC than Gram-positive bacteria.
- Opsonization and Phagocytosis: The coating of pathogens with complement factors enhances phagocytosis.
- Inflammation: Complement split products promote inflammation/recruitment of immune cells.
Antibody Structure Review
- Fab region – binds antigen.
- Fc region – binds complement and Fc receptors on cells.
- Heavy chains (2) - composed of CH1, hinge, CH2, and CH3 domains.
- Light chains (2) - composed of VL and CL domains.
- Antigen binding sites contain hypervariable regions.
- Hinge regions confer flexibility.
Antibody Classes
- Monomeric: IgD, IgE, and IgG.
- Dimeric: Secretory IgA (sIgA).
- Pentameric: IgM (5 Fc regions).
- Polymeric (IgA and IgM) held together by the J chain.
Immune Complex Formation
- Immune complexes (Ab-Ag) form when antibodies bind to antigens.
- Complement can be activated by immune complexes.
- Immune complexes bind to complement receptors on RBCs and are transported to the spleen and liver.
- Splenic macrophages and Kupffer cells remove immune complexes from RBCs.
Immune Complex Elimination
- Immune Complexes (ICs) bind to complement receptors (CR1) on RBCs and are transported to the spleen and liver.
- Splenic macrophages and Kupffer cells bind to Fc receptors (FcRs) of ICs.
- ICs are removed from RBC surfaces via phagocytosis.
Regulation of Complement Activation
- Properdin (Factor P): stabilizes C3 convertase.
- Factor H: inactivates C3b by cleaving it to iC3b.
- Decay-accelerating factor (DAF): disrupts C3 convertase (C3bBb).
- Properdin (Factor I): inactivates C3b, C4b.
- Membrane cofactor protein (MCP): promotes the inactivation of C3b and C4b.
- CD59 prevents the formation of the membrane attack complex (MAC).
Pathologic Effects of Complement
- Tissue damage resulting from excessive complement activation, in bacterial infections.
- Intravascular thrombosis leading to ischemic injury in tissues.
- Formation of immune complexes in autoimmune diseases (e.g., systemic lupus erythematosus, vasculitis, glomerulonephritis).
- Pathological effects of complement deficiencies or defects in regulation (e.g., increased susceptibility to recurrent infections, hereditary angioedema).
Pathological effects of Complement Deficiencies
- C3 deficiency: most severe; leads to increased susceptibility to recurrent bacterial infections.
- Deficiencies in terminal complement components (C5-C9) result in insufficient MAC formation and higher risk of infections by Neisseria.
- Deficiency in factors D and P (alternative pathways) leads to higher risk of Neisseria infections.
Hereditary Angioedema (HAE)
- Deficiency in C1-inhibitor leads to unregulated bradykinin production.
- Results in edema and vasodilation/inflammation.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Genetic defect in the PIGA gene affecting GPI-anchored proteins.
- Deficiency in complement regulators (CD55, CD59) on RBCs leads to lysis and hemolytic anemia.
Complement Receptors
- Complement receptor 1 (CR1): binds to C3b, C4b and facilitates phagocytosis and clearance of immune complexes.
- Complement receptor 2 (CR2): B cell co-receptor; binds iC3b, and is crucial for the immune response.
- Complement receptor 3 (CR3: MAC-1): binds iC3b and other ligands promoting phagocytosis and leukocyte adhesion.
- Complement receptor 4 (CR4): similar functions to CR3.
- C3a receptor: chemotaxis and mast cell degranulation.
- C5a receptor: chemotaxis and mast cell degranulation.
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Description
Test your knowledge on the complement system and antibody functions with this quiz. Explore the roles of the Membrane Attack Complex, immunoglobulins, and the immune response dynamics. Ideal for students studying immunology or related fields.