immunology : rheumatoid arthritis and SLE

Question 1

what type of hypersensitivity is SLE

Answer 1

type 3 , complexes of dna and anti dna antibodies becoming localised causing inflammation in skin and can be all organs and tissues!

Question 2

what is the prevalence of sle Europeans to afro carib, gender and age

Answer 2

more common in afro-carrib, gender bias females 10 times more likely and in females normally in 30s/40s

Question 3

Name some clinical features of sle

Answer 3

• Any organ/tissue
• Common patterns
– Skin (diverse patterns, photosensitivity, alopecia)
– Joints (non-erosive arthritis and tendinitis)
– Sicca symptoms (salivary, lacrimal, genital tract)
– Glomerulonephritis (several patterns: mesangial,
membranous and peripheral)
– Neurological: CNS, eye, peripheral nervous system

Question 4

what is the main issue that triggers off sle

Answer 4

abnormal apoptosis which exposes nuclear antigens, which act as damps activate innate response

Question 5

list the antibodies formed when abnormal apoptosis occurs

Answer 5

Antinuclear autoantibodies
– (ANA): multiple components
• Anti-dsDNA
• Anti-histone
• Antibodies to extractable nuclear antigens (ENA)
– Anti-Ro/Anti-La (RNA processing)
– Anti-RNP/Anti-Sm (spliceosome)
• Rheumatoid factor
• Anti-cardiolipin antibodies

Question 6

how do the antibodies cause injury in sle

Answer 6

direct cytoxicity e.g autoimmune haemolytic anemia and thrombocytopenia,

immune complex forms and deposits in the skin or the kidney tissues

Trigger pro-inflammatory response in cells carrying Fc
gamma receptors
• Promote NK cell activation and/or cytotoxicity

Question 7

why in SLE is there an excess alpha IFN production

Answer 7

because the complexes fool the immune system into thinking there is a viral infection. (psuedo viral) a ifn is response to this

Question 8

Immune system in sle

Answer 8

neutrophil activate, alpha ifn increase and complement consumption increases

Question 9

what does abatacept do in sle

Answer 9

blocks cd86 and cd 26 by acting as ctla-4. so no second signal no activation

Question 10

what hypersensitivities does RA involve

Answer 10

2,3,4

Question 11

What is diff between ra and osteoarthritis

Answer 11

RA is inflammation around joint with bone erosion, osteoarthritis is wear and tear.

Question 12

who does ra affect more men or women

Answer 12

females more 3 to one

Question 13

what’s the aetiology of RA

Answer 13

Systemic autoimmune disease of unknown aetiology

Question 14

describe why RA is a chronic inflammatory condition and what you can observe in inflamed joint

Answer 14

extensive angiogenisis, b and t cells (type iv), hyperplasic synovial lining, macrophages, dendrites, osteoblasts and fibroblasts

Question 15

what do fibroblast and macrophages produce

Answer 15

chemokines to attract more cells to joints ccl2 ccl5 il8

cytokine tnf, il1,il6

MMP-1, -3 and -9(enzymes metalloproteinases eats collagen etc)

Question 16

comment on gene predisposal to RA

Answer 16

hla dr1/hladr4, responsible for antigen presentation to t cell, genetic risk no more than 15%

Question 17

What are risk factors(enviromental) for RA

Answer 17

smoking, infections such as ebv

Question 18

what is a marker for RA not rheumatoid factor, that also has a great specificity for RA

Answer 18

Anti-citrullinated protein antibody
cyclic citrullinated peptide (CCP)

May predict erosive disease

Question 19

what evidence supports involvement of t cells in RA pathogenisis

Answer 19

associations of RA with HLA DR1/4, ra and hiv together makes ra better because less cd4 t cells. il2 activates RA, synovial histology and synovial t cells activation and cytokines

Question 20

In RA what happens to synovial membrane

Answer 20

Thickening of the synovial lining layer
– proliferation of fibroblast-like synoviocytes
• Angiogenesis
• Influx of mononuclear cells
(T and B cells and monocytes)
• Production of cytokines, chemokines
and matrix metalloproteinases

Question 21

Direct cell contact between activated T cells and

monocytes induces

Answer 21

IL-1β production

Question 22

Direct cell contact between T cells and FLS induces

Answer 22

MMP

production

Question 23

• Direct cell contact between T cells and FLS induces

Answer 23

MCP1 production

Question 24

• Main autoantibody associated with RA

Answer 24

rheumatoid factor-Non-specific and non-pathogenic
• Diagnosis
• 80% RA patients are RF+
• Present in sera many months before disease is
apparent

Question 25

Problem with T cell hypothesis for RA

Answer 25

No evidence of an autoantigen
Putative Autoantigens include:
• superantigen
• heat shock proteins

and more

Question 26

what do osteoclast do to bones in RA

Answer 26

eat away at bone

Question 27

why is Balance Between Pro-inflammatory and

Anti-inflammatory Mediators important

Answer 27

because in inflammmation e.g RA pro inflammation tfna and il1b and others dominate anti inflammatory so therapeutics tries to restore balance

Question 28

how do they attempt to treat RA

Answer 28

souluble recptors to bind tfna so it can’t cause proinflammatory state and monoclonal antibodies