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Questions and Answers
What is complement?
What is complement?
What is a zymogen?
What is a zymogen?
A protein that is activated on proteolytic cleavage by a protease.
What is an opsonin?
What is an opsonin?
An antibody or other substance that binds to foreign microorganisms or cells, making them more susceptible to phagocytosis.
What are anaphylatoxins?
What are anaphylatoxins?
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What is degranulation?
What is degranulation?
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What are mast cells?
What are mast cells?
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What are basophils?
What are basophils?
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What is the membrane attack complex?
What is the membrane attack complex?
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What does C3 convertase do?
What does C3 convertase do?
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What is the function of C5 convertase?
What is the function of C5 convertase?
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What initiates the classical pathway of complement activation?
What initiates the classical pathway of complement activation?
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What initiates the lectin pathway of complement activation?
What initiates the lectin pathway of complement activation?
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What is the difference between the alternative pathway and the classical pathway?
What is the difference between the alternative pathway and the classical pathway?
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What are phagocytosis-enhancing components?
What are phagocytosis-enhancing components?
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Where are most complement components synthesized?
Where are most complement components synthesized?
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Why are patients with deficiencies in C3 susceptible to infections?
Why are patients with deficiencies in C3 susceptible to infections?
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What are the three major pathways of complement activation?
What are the three major pathways of complement activation?
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What binds to microbial surfaces to initiate the lectin pathway?
What binds to microbial surfaces to initiate the lectin pathway?
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What is the role of factor B in the alternative pathway?
What is the role of factor B in the alternative pathway?
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What do C3b molecules bound to microbial surfaces do?
What do C3b molecules bound to microbial surfaces do?
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How is C5 convertase formed in the alternative pathway?
How is C5 convertase formed in the alternative pathway?
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What does the C3bBbC3b complex do?
What does the C3bBbC3b complex do?
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How does C5b work?
How does C5b work?
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CR1 receptors on phagocytes bind to complement-opsonized microbial cells.
CR1 receptors on phagocytes bind to complement-opsonized microbial cells.
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Where do most complement reactions take place?
Where do most complement reactions take place?
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What happens if C6 and C7 binding occurs on a noncellular surface?
What happens if C6 and C7 binding occurs on a noncellular surface?
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The membrane attack complex introduces large pores in the microbial cell membrane.
The membrane attack complex introduces large pores in the microbial cell membrane.
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What is the role of CD21 (CR2) in B cell function?
What is the role of CD21 (CR2) in B cell function?
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What can C3b form bonds with?
What can C3b form bonds with?
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Study Notes
The Complement System Overview
- Complement consists of serum and membrane proteins that play crucial roles in immune response, pathogen recognition, and elimination.
- It functions through three main pathways: classical, lectin, and alternative.
Key Terms and Definitions
- Complement: A protein group essential in innate and adaptive immunity, facilitating pathogen elimination.
- Zymogen: Inactive precursor proteins activated by proteolytic cleavage.
- Opsonin: Substances that increase phagocytosis by marking pathogens for destruction.
- Anaphylatoxins (C3a and C5a): Fragment products that cause mast cell degranulation, smooth muscle contraction, and increased vascular permeability.
- Degranulation: Release of contents from mast cells, contributing to inflammation.
- Mast Cells: Cells that release histamines, promoting inflammatory responses.
- Basophils: Leukocytes that produce histamine during immune responses.
Complement Pathways and Their Initiation
- Classical Pathway: Activated by antibody-antigen complexes and involves complement components C1, C4, and C2.
- Lectin Pathway: Initiated by mannose-binding lectin binding to microbial surfaces, activating C2 and C4.
- Alternative Pathway: Starts by the spontaneous hydrolysis of C3, independent of antibodies, leading to C3 convertase formation.
Enzyme Complexes and Their Functions
- C3 Convertase: Enzyme that cleaves C3 into C3a (inflammatory mediator) and C3b (opsonin).
- C5 Convertase: Enzyme complex formed from C3 convertase, cleaving C5 into C5a and C5b, leading to the formation of the membrane attack complex (MAC).
Complement Components and Their Synthesis
- Most complement proteins are synthesized in the liver by hepatocytes.
- Key Components: Include initiators (C1q, MBL), convertase activators, opsonins, anaphylatoxins, MAC, complement receptors, and regulatory proteins.
Differential Pathway Details
-
Classical Pathway:
- Activated by IgM/IgG binding to multivalent antigens.
- Results in the formation of active serine proteases that cleave C3.
-
Lectin Pathway:
- Initiated by lectins binding to carbohydrates on pathogens.
- Uses MASP-2 for the cleavage of C2 and C4 to form C3 convertase.
-
Alternative Pathway:
- Activates C3bBb complex providing C3 convertase activity.
- Amplified through continuous C3 hydrolysis.
Opsonization and Phagocytosis
- Complement proteins (C3b and C4b) bind to microbial cells, enhancing phagocytosis through opsonization.
- C3b facilitates the clearance of immune complexes by either phagocytosis or hepatic clearance.
Regulatory Proteins
- Protect host cells from complement-mediated damage.
- Examples include Factor I, which degrades C3b, and CD59, which inhibits MAC formation on host cells.
Significance of C3
- Central component across all complement pathways.
- Deficiencies in C3 can lead to increased susceptibility to both gram-positive and gram-negative bacteria due to impaired opsonization.
Pathway Comparisons
- Similarities: All pathways converge to generate C3 convertases.
- Differences: Initial activation differs; classical and lectin pathways depend on antibodies or lectins, while alternative pathway activation is spontaneous.
Overall Functions of the Complement System
- Promotes inflammation and enhances immune efficiency via opsonization, chemotaxis, and direct lysis of pathogens through MAC formation.
- Essential for clearing immune complexes and defective cells, contributing to overall homeostasis and immune surveillance.### Activation of Complement Pathways
- Alternative pathway activated in the presence of bacteria through binding of properdin to bacterial surfaces.
- All three complement pathways converge at the formation of C5 convertase, crucial for cleaving C5 into C5a and C5b.
- Classical and lectin pathways’ C5 convertase composition: C4b2a3b; alternative pathway composition: C3bBbC3b.
C5 Fragment and Membrane Attack Complex (MAC)
- C5b is the larger fragment, generated on target cell surfaces, providing binding sites for MAC components.
- C5b rapidly becomes inactive unless stabilized by C6 binding.
- Membrane attack complex formation occurs when C5b binds to C6 and C7, triggering C7 to insert into microbial membranes, leading to cell death.
Consequences of MAC Release
- Released MACs can cause lysis of nearby innocent bystander cells.
- MAC formation prevents osmotic integrity in target cells, resulting in cellular death.
Functions of Complement Components
- The MAC (C5b-C9) is responsible for lysing bacterial cells and disrupting cell membranes.
- C3b and C4b facilitate opsonization, marking pathogens for destruction by immune cells.
- Anaphylatoxins C3a and C5a induce inflammation and chemotaxis through their receptors on leukocytes.
Interface Between Innate and Adaptive Immunity
- C3b and C4b, along with their fragments, augment antibody responses and enhance immunologic memory by interacting with immune complexes.
- MBL, C1q, and complement components C3, C4, and C5a boost antigen presentation, influencing T cell potential.
Immune Response Phases
- Complement components play roles in the clearance of immune complexes and apoptotic cells, especially during the contraction phase of immune responses.
- CD46 promotes the induction of regulatory T cells, essential for maintaining immune homeostasis.
Complement Receptors and Immune Complex Handling
- CR1 (CD35) binds to C3b, C4b, C1q, and MBL, facilitating the clearance of immune complexes via erythrocyte transport to the liver for phagocytosis.
- Phagocyte CR1 receptors mediate binding to complement-opsonized microbes, leading to receptor-mediated phagocytosis and pro-inflammatory molecule secretion.
C3b Breakdown and B Cell Activation
- C3b is broken down by endogenous proteases into iC3b, C3d, and C3dg, each recognized by CD21 (CR2).
- CD21 functions as part of the B cell co-receptor complex, enhancing B cell activation by binding C3d and lowering the antigen concentration required for effective activation.
Summary of Key Concepts
- C3b forms bonds with antigens irrespective of its breakdown products, aiding in B cell activation through simultaneous binding with C3d and B-cell receptor.
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Test your knowledge of the complement system with these flashcards covering key definitions and concepts. Each term is designed to help you understand the interactions and functions of proteins in both innate and adaptive immunity. Perfect for students studying immunology or related subjects.