neuroimmunology

Question 1

Major functions of innate immune system (3)

Answer 1

1. Complement cascade
2. Identify/remove foreign substances
3. Activate adaptive immune system

Question 2

Which parts of the complement cascade are Opsonisins

Answer 2

C1q and C3b

Question 3

Which parts of the complement cascade bind to GPCR?

Answer 3

C3a and C5a

Question 4

Describe innatue immune system>

Answer 4

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

Question 5

How does opsonisation work?

Answer 5

Foreign cells are tagged with complement molecules (C3b) which are recognised by host receptors (CR1) to induce phagocytosis.

Question 6

What do anaphylatoxins do?

Answer 6

Regulation of inflammatory cytokines, neuroprotective/degenerative effects (C3a, C5a)

Question 7

Describe C3a signal transduction

Answer 7

AKT–> MAPK–> NFKB–> cytokine release and cell proliferation of immune cells

Question 8

Describe Recruitment of membrane attack complex (MAC)

Answer 8

C5 binds C6 and 7–> binds to membrane. C8 binds to complex, c9 binds to complex and polymerizes. End product is a pore

Question 9

What are two roles of the complement system in the CNS?

Answer 9

Removal of dying neurons

Removal of excess synapses

Question 10

What is complement cascade

Answer 10

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.

Question 11

How can C3 be made from C4?

Answer 11

C3 convertase

Question 12

What is a positive regulator of the alternative pathway

Answer 12

fB

Question 13

Tell me about complement and CNS developement.

Answer 13

found in develpoing CNS, and upregulated during neural developements,

has roles in removing dying neurons
and removing excess synapses

Question 14

describe opsonisation process at neuronal memnraes

Answer 14

draw me

Question 15

Evidence of synaptic pruning in eyes

Answer 15

c1q died and is seen near nerve terminal in photos.

then in knockout of c1q they still miantained these connections,

Question 16

What happens in absence of C3aR in MND model

Answer 16

Worsening of symptoms. Indicates that C3a may be protective.

Question 17

Why might C3a be neuroprotective?

Answer 17

Astrocytes C3aR release neurotrophic factors which bind to TrKs present on neurons to aid in their viability and differentiation

Question 18

Where is c5 made

Answer 18

both MN and microglia, broken into c5a and c5b,

receptor also on surface of motorneuron,( not in wild type)

Question 19

What happens to C5a in MND?

Answer 19

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

Question 20

CD88 ablation…

Answer 20

Increases survival rate and slows motor neuron loss, doesnt prevent tho

Question 21

MND mice lacking C5aR1 have…

Answer 21

Reduced microglia and monocyte mRNA levels. Reduced cytokines

Question 22

Where is C5a and C5aR1 upregulated in MND?

Answer 22

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

Question 23

descrbe ying and yanh of complement activation

Answer 23

draw