neuroimmunology Flashcards
Major functions of innate immune system (3)
- Complement cascade
- Identify/remove foreign substances
- Activate adaptive immune system
Which parts of the complement cascade are Opsonisins
C1q and C3b
Which parts of the complement cascade bind to GPCR?
C3a and C5a
Describe innatue immune system>
Innate immune system.
The innate immune system, also known as non-specific immune system and first line of defense, is a subsystem of the overall immune system that comprises the cells and mechanisms that defend the host from infection by other organisms or objects in a non-specific manner.
· – Evolutionarily very old
· – Major functions – recruit immune cells to sites of infection
· Activation of the complement cascade
· Identification and remove of foreign substances
· Activation of the adaptive immune syste
How does opsonisation work?
Foreign cells are tagged with complement molecules (C3b) which are recognised by host receptors (CR1) to induce phagocytosis.
What do anaphylatoxins do?
Regulation of inflammatory cytokines, neuroprotective/degenerative effects (C3a, C5a)
Describe C3a signal transduction
AKT–> MAPK–> NFKB–> cytokine release and cell proliferation of immune cells
Describe Recruitment of membrane attack complex (MAC)
C5 binds C6 and 7–> binds to membrane. C8 binds to complex, c9 binds to complex and polymerizes. End product is a pore
What are two roles of the complement system in the CNS?
Removal of dying neurons
Removal of excess synapses
What is complement cascade
collection of proteins floating around in the blood that causes a series of (cascades) of reactions to help remove pathogens (e.g. bacteria) – before activation of the adaptive immune system.
> Also – recruits immune cells like macrophages etc, to the sites of infection and/or damage (e.g. cellular debris) to induce inflammatory responses.
How can C3 be made from C4?
C3 convertase
What is a positive regulator of the alternative pathway
fB
Tell me about complement and CNS developement.
found in develpoing CNS, and upregulated during neural developements,
has roles in removing dying neurons
and removing excess synapses
describe opsonisation process at neuronal memnraes
draw me
Evidence of synaptic pruning in eyes
c1q died and is seen near nerve terminal in photos.
then in knockout of c1q they still miantained these connections,
What happens in absence of C3aR in MND model
Worsening of symptoms. Indicates that C3a may be protective.
Why might C3a be neuroprotective?
Astrocytes C3aR release neurotrophic factors which bind to TrKs present on neurons to aid in their viability and differentiation
Where is c5 made
both MN and microglia, broken into c5a and c5b,
receptor also on surface of motorneuron,( not in wild type)
What happens to C5a in MND?
upregulated, meaning
c5a stimulates gliosis,
recruiting and activate glial cell, recruits receptor to recuit immune cells
when you atcivate C5ar1, create cytokines, further dricing inflammatory
it just all becomes more and more upregualted
CD88 ablation…
Increases survival rate and slows motor neuron loss, doesnt prevent tho
MND mice lacking C5aR1 have…
Reduced microglia and monocyte mRNA levels. Reduced cytokines
Where is C5a and C5aR1 upregulated in MND?
fast twitch skeletal muscles,
Macrophages and helper T cells in muscle express c5ar1
seen bc withoutthese there were less immune cells
These additional peripheral effects may help explain some of the increased
movements in the SOD1G93A mice where we have pharmacologically blocked
C5aR1
descrbe ying and yanh of complement activation
draw
