Lecture 6 - Innate Immunity (Complement)

Question 1

What is the complement system?

Answer 1

The complement system is a group of soluble (mostly) proteases that circulate in the blood or other fluids.

Question 2

What is a protease?

Answer 2

A protease is an enzyme that performs proteolysis (breaking down proteins).

Question 3

Where are complement proteins mostly produced?

Answer 3

Complement proteins are mostly produced in the liver.

Question 4

What system sets off a chain reaction that helps to amplify inflammation and clear pathogens?

Answer 4

Complement System

Question 5

What are the three key mechanisms of complement action?

Answer 5

• Increasing Vascular Permeability and Chemotaxis
• Destroying Pathogen Cell Membranes
• Increasing Recognition of Pathogens and Facilitating Phagocytosis (Opsonization)

Question 6

What is opsonization?

Answer 6

Opsonization is the coating of the surface of a pathogen by antibody and/or complement that makes it more easily ingested by phagocytes.

Question 7

What process is defined as the internalization of particular matter by cells by a process of engulfment, in which the cell membrane surrounds the material, eventually forming an intracellular vesicle containing the ingested material?

Answer 7

Phagocytosis

Question 8

What are three complement pathways?

Answer 8

Classical, Alternative, and Lectin

Question 9

What is common between all three complement pathways?

Answer 9

All pathways generate a C3 convertase, which cleaves C3, leaving C3b bound to the microbial surface and releasing C3a.

Question 10

What triggers the lectin pathway?

Answer 10

The lectin pathway is triggered by PRRs (mannose-binding lectin and ficolins) that circulate in the blood recognizing and binding carbohydrates on pathogen surfaces.

Question 11

What triggers the classical pathway?

Answer 11

The classical pathway is triggered by C1q directly interacting with the pathogen surface or with antibodies bound to the surface.

Question 12

Which complement pathway can connect adaptive and innate immunity?

Answer 12

Classical Pathway

Question 13

What triggers the alternative pathway? When can this occur?

Answer 13

The alternative pathway is triggered by C3 undergoing spontaneous hydrolysis. This can occur once C3b has been produced by one of the other complement pathways and can occur spontaneously in plasma by specific convertases.

Question 14

How are alternative convertases stabilized?

Answer 14

Alternative convertases are stabilized by neutrophils (Properdin).

Question 15

You are a physician treating a patient with a complement deficiency. Which one of the following types of pathogens would be most difficult for this patient’s immune system to clear?

• Extracellular Parasite
• Intracellular Virus
• Extracellular Bacteria
• Intracellular Parasite

Answer 15

Extracellular Bacteria

Question 16

True or False?:

There are two different C3 convertases.

Answer 16

False

There are many different C3 convertases.

Question 17

How does the complement system cause inflammation?

Answer 17

C3a and C5a act on blood vessels to increase vascular permeability and cell-adhesion molecules. This increased permeability allows increased fluid leakage from blood vessels and etravasation of immunoglobulin and complement molecules. As well, migration of macrophages and lymphocytes is increased.

Question 18

What happens when C3a and C5a are present in large amounts?

Answer 18

Anaphylactic Shock

Question 19

True or False?:

Complement receptors connect complement-tagged pathogens to effector cells.

Answer 19

True

Question 20

What do C3aRs and C5aRs on granulocytes do?

Answer 20

They stimulate release of proinflammatory cytokines and granule components from basophils, eosinophils, neutrophils, and mast cells.

Question 21

How do complement pathways lead to an increase in phagocytosis?

Answer 21

C3 cleavage leaves C3b on bacterium surfaces. Since phagocytes have C3bRs, the presence of C3b increases their ability to phagocytose.

Question 22

What happens when only C3b binds to CR1 (a C3bR)? How is this rectified?

Answer 22

When only C3b binds to CR1, bacteria are not phagocytoses. C5a can activate macrophages to phagocytose.

Question 23

What is created by complement factors to cause pathogen lysis?

Answer 23

Membrane-Attack Complex

Question 24

What do complement-regulatory proteins do?

Answer 24

Complement-regulatory proteins prevent complement activation from proceeding under normal/basal conditions. They prevent the appearance of C3 convertase and promote the disappearance of C3 convertase.

Question 25

What is responsible for negative regulation of complement activity?

Answer 25

Complement-Regulatory Proteins

Question 26

A study compared the genetics of two strains of mice, one susceptible (white) and one resistant (black) to infection. Analyses of genomes showed that the susceptible strain had deletion in the gene that coded for C5a. The mice of each strain were infected with C. albicans. Viral load was later determined. What are the results and what can you conclude from the figure below?

Answer 26

Results: The resistant strain had a lower viral load than the susceptible strain.

Conclusions: C5a plays a role in fighting off C. albicans.