Immunology Chapter 5 Flashcards

Questions and Answers

What is complement?

A group of serum and cell membrane proteins (correct)

A non-protein molecule

A type of antibody

A type of pathogen

What is a zymogen?

A protein that is activated on proteolytic cleavage by a protease.

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?

Split products C3a and C5a of complement that mediate degranulation of mast cells and basophils. Signup and view all the answers

What is degranulation?

The release of the contents of mast cell granules. Signup and view all the answers

What are mast cells?

Cells that release chemicals (such as histamine) that promote inflammation. Signup and view all the answers

What are basophils?

Circulating leukocytes that produce histamine. Signup and view all the answers

What is the membrane attack complex?

The complex of complement components C5-C9 that mediates cell lysis by creating a membrane pore. Signup and view all the answers

What does C3 convertase do?

Cleaves C3 into C3a and C3b. Signup and view all the answers

What is the function of C5 convertase?

Cleaves C5 to C5a and C5b. Signup and view all the answers

What initiates the classical pathway of complement activation?

Antibody bound to antigen. Signup and view all the answers

What initiates the lectin pathway of complement activation?

The binding of mannose-binding lectin to mannose-containing peptidoglycans. Signup and view all the answers

What is the difference between the alternative pathway and the classical pathway?

The alternative pathway is initiated by spontaneous hydrolysis of C3, while the classical pathway requires antibody-antigen complexes. Signup and view all the answers

What are phagocytosis-enhancing components?

Opsonins that bind to microbial cells to enhance their uptake by phagocytes. Signup and view all the answers

Where are most complement components synthesized?

In the liver by hepatocytes. Signup and view all the answers

Why are patients with deficiencies in C3 susceptible to infections?

C3b acts to opsonize pathogens, facilitate clearance of immune complexes, and form the C5 convertase. Signup and view all the answers

What are the three major pathways of complement activation?

Classical pathway, lectin pathway, alternative pathway. Signup and view all the answers

What binds to microbial surfaces to initiate the lectin pathway?

Mannose-binding lectin (MBL). Signup and view all the answers

What is the role of factor B in the alternative pathway?

Factor B is cleaved to Bb and Ba, forming the alternative pathway C3 convertase. Signup and view all the answers

What do C3b molecules bound to microbial surfaces do?

Recruit factor B and amplify the concentration of the C3 convertase. Signup and view all the answers

How is C5 convertase formed in the alternative pathway?

By the addition of C3b to the alternative pathway C3bBb C3 convertase complex. Signup and view all the answers

What does the C3bBbC3b complex do?

C3bBbC3b cleaves C5, which goes on to form the membrane attack complex (MAC). Signup and view all the answers

How does C5b work?

C5b binds to the serum protein C6, forming a complex that interacts with the cell membrane. Signup and view all the answers

CR1 receptors on phagocytes bind to complement-opsonized microbial cells.

True Signup and view all the answers

Where do most complement reactions take place?

Surfaces of microbial cells or immune complexes in the fluid phase of the body. Signup and view all the answers

What happens if C6 and C7 binding occurs on a noncellular surface?

The hydrophobic binding sites will be unable to anchor the complex and it is released. Signup and view all the answers

The membrane attack complex introduces large pores in the microbial cell membrane.

True Signup and view all the answers

What is the role of CD21 (CR2) in B cell function?

CD21 binds to C3d fragment, bringing the B cell receptor into proximity for enhanced activation. Signup and view all the answers

What can C3b form bonds with?

C3b can form bonds with antigens and is not affected by the breakdown products. Signup and view all the answers

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.