Lecture 5 - Innate immunity: Immediate response to infection Flashcards
Describe the steps of the inflammatory response:
Surface wound introduces bacteria which activates resident effector cells to secrete cytokines
Vasodilation and increased vascular permeability allow fluid, protein, and inflammatory cells to leave blood and enter tissue
Infected tissue becomes inflamed causing redness, heat, swelling, and pain
How do innate and adaptive immune responses differ?
innate response works at the local level whereas adaptive immune response has a greater systemic effect and forms memory
How do barriers prevent pathogens from crossing epithelia and colonizing tissue?
They act as mechanical barriers
They have chemical properties such as pH and antimicrobial enzymes that make them tough to move past
Microbiome compete with the pathogen reducing their virulence
What are some chemical barriers to entry on the skin?
Fatty acids and antimicrobial peptides
What is the complement system?
Soluble proteins constitutively made in the liver that are present in the blood lymph and extracellular fluids and are involved in the first wave of immunity.
What do complement proteins do?
One of the fastest responses of the body they mark pathogens for destruction.
Why is the bacterial capsule so important to their defence against the complement protein?
It prevents the attachment of complement proteins and therefore prevent phagocytosis
How does the complement protein mark the pathogen?
zymogens are circulating in blood (circulating inactive complement).
Complement cleavage is triggered by bacterial cell surface thus activating it
Infection triggers activation and cascade of enzymatic reactions
One fragment binds to the bacterium while the other attracts phagocyte in that direction
Complement fragments meet and this induces phagocytosis
What form do complement proteins circulate?
Zymogen form which means inactive form.
What does C3b do and what does C3a do?
C3a recruits phagocytes
C3b tags for phagocytosis (complement fixation)
What bond does inactive C3 have?
Thioester bond and this bond is stabilized within hydrophobic interior
What happens when C3 is cleaved?
C3b exposes thioester bond to hydrophilic environment
How does C3b work?
C3b exposes thioester bond to hydrophilic environment which reacts with hydroxyl and amino groups on pathogen’s surface.
What are the 3 pathways for complement activation?
Classical (antigen binding complement)
Alternative (pathogen surface creates environment for complement activation)
Lectin pathway (Mannose-binding lectin binds to pathogen surface)
All 3 pathways recruit C3 activation into C3a and C3b
Which of the 3 complement activation pathways are considered a part of both innate and adaptive immune responses?
The classical pathway (the antigen specific pathway)
At the start of infection which complement is activated?
Alternative pathway
Where is inactive C3 made?
In the liver
What is the first step of the C3 activation pathway?
In plasma close to microbial surface thioester bond of C3 spontaneously hydrolyses at low frequency iC3.
What is the pathway of Complement activation?
Inactive C3 is produced in liver
Inactive C3 is hydrolysed spontaneously near the surface of a microbe forming the product iC3
iC3 binds factor B
Serine protease factor D cleaves B and produces soluble C3 convertase aka iC3Bb which activates more C3 molecules by cleaving C3 into C3a and C3b
C3b fragments bind to pathogen surfaces
What can C3b that is bound to pathogen surfaces do?
It can bind to factor B to facilitate cleavage by factor D
What are the 2 convertases produced by the C3 complement system?
iC3Bb and the alternative C3 convertase
What does the alternative C3 convertase do?
It produces a feedback loop creating more C3a and C3b complexes which provide a rapid bacterial coating
What are the 2 broad categories of complement control proteins?
Plasma proteins that interact with C3b attached to microbial surfaces
Membrane proteins on human cells that prevent complement fixation on host cell surface
What measure is taken to ensure that complements are attached only to pathogens and not human cell surfaces?
Regulatory proteins