Final (SLE AND MS)

Question 1

SLE is different than RA because its a ___________ autoimmune disease

Answer 1

systemic

Question 2

SLE affects what population more?

Answer 2

women
ethic

Question 3

What are 5 common themes of SLE?

Answer 3

1. auto-reactive B cells
2. anti-nucleic acid auto-Ab
3. pDCs
4. TLR7/9
5. IFN-a

Question 4

where are auto-reactive B cells made in SLE?

Answer 4

extra-follicular B cell activation

Question 5

How are anti-nucleic acid auto-Ab made in SLE?

Answer 5

cell damage from mutations exposes nucleic acids

Question 6

How are pDCs involved in SLE?

Answer 6

DNA/RNA released from damaged cells is recognized by pDCs TLR7/9 activating them

Question 7

How is TLR-7/9 involved in SLE?

Answer 7

recognizes released DNA/RNA from cell damage

Question 8

How is IFN-a involved in SLE?

Answer 8

produced by activated pDCs when their TLRs recognize RNA/DNA from damaged cells
**all nucleated cells have IFN-a receptors

Question 9

What is the SLE loop?

Answer 9

production IFN-a from activated pDCs activates formation of auto-reactive B cells and anti-nucleic acid auto-Abs

Question 10

What induces the formation of auto-reactive B cells and anti-nucleic acid auto-Abs in SLE?

Answer 10

secretion of IFN-a

Question 11

What is the entry criteria for SLE?

Answer 11

positive ANA

Question 12

What is ANA?

Answer 12

antibodies against nuclear material

Question 13

What are 3 ANAs in SLE?

Answer 13

1. anti-dsDNA
2. anti-histamine
3. anti-Smith (RNA)

Question 14

What is the clinical criteria for SLE?

Answer 14

fever
nephritis
seizures

Question 15

What is the SLE flare?

Answer 15

waxing and waning of SLE symptoms

Question 16

During the SLE flare what is elevated?

Answer 16

anti-DNA Ab
TLR-9 activated pDCs
IFN-a
* increased risk of nephritis and cardiac events

Question 17

What is the immunological criteria for SLE?

Answer 17

decreased C3 and C4
increased anti-dsDNA & anti-Smith Ab

Question 18

What does it mean when C3 and C4 is low?

Answer 18

less complement activation = less tagging and clearance = more chance for B cells to encounter DNA/RNA and produce auto-Ab

Question 19

What is the best immunological marker for SLE?

Answer 19

anti-Smith Ab

Question 20

What are 3 possible sources of DNA/RNA that activates pDCs in SLE?

Answer 20

1. cell damage + LL37 + TLR-7 + pDCs
2. RNA/DNA Ab internalized by pDCs
3. loss of function of DNASE1L3

Question 21

What is the regular function of DNASE1L3?

Answer 21

breaks down DNA/RNA from apoptosed cells

Question 22

How does the loss of function of DNASE1L3 play a role in SLE?

Answer 22

large DNA/RNA from apoptosed cells cannot be broken down resulting in activation of pDCs (TLR-9/7) = IFN-a secretion

Question 23

What gene makes SLE a monogenic disease?

Answer 23

DNASE1L3

Question 24

Belimumab is an anti-BAFF treatment for SLE. How does it work?

Answer 24

prevents auto-reactive B cells from leaving the spleen
(BAFF is a B cell survivial signal)

Question 25

Anifrolumab is a ant-IFNRA treatment for SLE. How does it work?

Answer 25

prevents mDCs from signaling to B cells to create auto-reactive B cells

Question 26

Vocolsporin is a anti-Cal & synaptopin protecting drug. How does it work?

Answer 26

prevents transcription of NFAT = decreased T cells and cytokine production
protects podocytes (kidney filatration cells) *stabalizes cytoskeleton

Question 27

What is multiple sclerosis?

Answer 27

neuroinflammatory disease caused by immune complexes infiltrating the blood brain barrier

Question 28

What is the clinical manifestation of MS?

Answer 28

lesions on CNS caused by immune complex mediated inflammation

Question 29

What cells cause damage to the myelin sheath in MS?

Answer 29

CD8+ T cells and Ab attach to attract other immune cells

Question 30

What are the 3 types of MS?

Answer 30

1. relapsing-remitting
2. secondary progressive
3. primary progressive

Question 31

What is relapsing-remitting MS?

Answer 31

waxing and waning of symptoms
* increased inflammation and demylenation when waxing

Question 32

Where are lesions on brains seen and by what imaging?

Answer 32

NMR
white matter

Question 33

What is secondary progressive MS?

Answer 33

waxing and waning but overtime recovery is eventually not possible

Question 34

What is primary progressive MS?

Answer 34

never experience remission (directly to progressive disease)

Question 35

What does it mean that the brain is immune privileged?

Answer 35

there is typically not immune responses there

Question 36

Where does immune response initiate in MS?

Answer 36

outside of CNS CD8+ T cells are activated then cross BBB

Question 37

Natalizumab is an anti-alpha4-beta1 integrin binding drug for MS. How does it work?

Answer 37

blocks CD8+ T cells from crossing the BBB = improved RR MS

Question 38

What are B cell’s role in MS?

Answer 38

make auto-Ab that bind to myelin to make macrophages eat mylein

Question 39

Ocrelizumab is an anti-CD20 therapy. How does it work for MS?

Answer 39

absence of CD20 induces B cell death = less auto-B cells and Ab

Question 40

S1P Modulators are drugs for MS. How?

Answer 40

prevents auto-reactive T cells from leaving the thymus

Question 41

Anti-IFN-B is a drug for MS. How?

Answer 41

limits inflammatory response

Question 42

What is EBV role in MS?

Answer 42

creates auto-reactive B cells against myelin which then presents to T cells making then auto-CD8+ T cells against myelin

Question 43

What is EBVs role in MS via molecular mimicry?

Answer 43

EBV viral protein sequences mimic human myelin proteins and thereby induce autoimmunity against myelin and CNS antigens

Question 44

What is a unique way auto-Ab are made in SLE?

Answer 44

B cell activation occurs outside of SLT (thanks to increased pDCs and IFN)