Lecture 3: innate immunity: complement and interferon

Question 1

Complement cells are

Answer 1

A group of blood plasma (and inflammatory fluid) proteins
5 to 10% of plasma proteins
Mostly produced in the liver by hepatocytes
To a lesser extent by macrophages and mast cells
Part of the innate immune system
Also, a bridge between innate and adaptive immunity

Question 2

Cascade is

Answer 2

• Complement factors act like a cascade of enzymes (like clotting)
• C3 is a central protein

Question 3

Actions of complement

Answer 3

Lysis of bacteria, cells and viruses
Promotion of phagocytosis (opsonization)
Triggers inflammation
Removes damaged cells

Question 4

Complement activation

Answer 4

There are three different pathways by which complement activation occurs:
Alternative Pathway
Lectin Pathway
Classical Pathway
Microbes activate complement by the lectin and alternative pathways
Antibodies stimulate activation by the classical pathway

Question 5

Activation of Complement - Alternate Pathway

Answer 5

C3 is constantly spontaneously breaking down into C3a and C3b
C3b is the active form of the molecule.
When C3b binds to mammalian cell walls, it is rapidly destroyed.
When C3b binds to bacterial cells:
When C3b binds to mammalian cell walls, it is rapidly destroyed
C3b continues to be active and the complement system progresses

Question 6

Activation of Complement - Lectin Pathway

Answer 6

Soluble pattern-recognition molecules called lectins bind to sugars on the surface of bacteria, protozoa or fungi
These sugar arrangements are not found on mammalian cells
Examples of soluble pattern-recognition molecules
Mannose-binding lectin (MBL), and Ficolins
Binding activates lectin and triggers a cascade which leads to breakdown of C3 to C3a and C3b

Question 7

Activation of Complement - Classical Pathway

Answer 7

Occurs later in infections because antibody has to be produced
Very effective in activating complement
Antibody binds to antigen on the pathogen
Bound antibody triggers the classical pathway
Activates C1
Triggers the activation of C3

Question 8

Consequences of Activation

Answer 8

Activation of C3
C3 and C4 fragments bind to the surface of the pathogen
These are recognized by receptors on macrophages and neutrophils.
The pathogen is bound and phagocytosed (opsonization)
Some fragments attract phagocytes.
Particularly neutrophils and macrophages
Other fragments stimulate mast cells to degranulate.
Release of histamine makes capillaries leaky - proteins and immune cells can reach the site more easily.
Formation of the Membrane Attack Complex (MAC) or Terminal Complement Complex (TCC)
A group of proteins that insert themselves into the cell membrane to create a hole through it

Question 9

Interferon is and produced by

Answer 9

Innate immunity against viral infections
Produced by
Some dendritic cells
Fibroblasts
Other
Cells recognize viruses using Pattern Recognition Receptors
Produce interferon.

Question 10

Interferon production is

Answer 10

immediate
Minutes
Acts locally on infected and NON-INFECTED cells.
Inhibits virus production by changing cell metabolism.
Can stimulate apoptosis
Programmed cell death

Question 11

Significance of interferon

Answer 11

Innate protection against viruses
Interferon used int therapy
Antiviral
Recombinant feline interferon used to treat:
Dogs with parvovirus or distemper?X
Cats with FeLV? Yes
Some live vaccines trigger rapid production of interferon.
May give partial early protection.