Immunology

Question 1

What are the 3 groups of immune mediated diseases which affect the joints?

Answer 1

1) Rheumatoid arthritis
2) Juveline arthritis
3) Spondyloarthritis

Question 2

What is Rheumatoid arthritis?

Answer 2

chronic, inflammatory disorder

Question 3

Which tissues does Rheumatoid arthritis target?

Answer 3

1) synovial lining of joints
2) bursae
3) tendon cheaths
4) cartilage
5) bone

Question 4

What are the characteristic antibodies for Rheumatoid arthritis?

Answer 4

1) RF (Rheumatoid factor)

2) ACPA (anti-cyclic citrullinated peptide)

Question 5

Are males or females more susceptible to Rheumatoid arthritis?

Answer 5

females

Question 6

What is the role of HLA in Rheumatoid arthritis?

Answer 6

DR4 subtypes of DRB1 alleles may bind pathogenic epitopes (particualrly thsoe containing citrulline) and alter negative selection in the thymus

Question 7

What is PTPN22?

Answer 7

Protein Tyrosine Phophatase Lyp in RA; active in hematopoetic tissues

Question 8

What is PADI4?

Answer 8

Peptidyl Arginine Deiminase type IV in RA; enzyme whcih converts arganine to citrulline

Question 9

What is the series of events in the immunobiology of RA?

Answer 9

1. acute initiating events (tissue damaeg)
2. synovial fibroblasts stimulated by damage
3. innate immune system activated
4. stimulation of adaptive immune responsive

Question 10

Which types of T-cells are activated in the adaptive immunity of RA?

Answer 10

CD4+ Th1 and Th17

CD8+

Question 11

How do Th17 cells enhance inflammation in RA?

Answer 11

produce cytokines which suppress Treg cells

Question 12

Which bacterium are Th17 cells important in providing defense against intracellular bacteria?

Answer 12

M. tuberculosis

Question 13

What is the Rheumatoid factor?

Answer 13

IgM anti-IgG with specificity to the Fc region of IgG

Question 14

What is citrullination?

Answer 14

post-translational modification of arganine

Question 15

What is the purpose of citrullination?

Answer 15

HLA-DR4 molecules preferentially bind to citrullinated peptides

Question 16

What is the anti-cyclic citrullinated peptide (ACPA)?

Answer 16

measures IgG antibodies in RA

Question 17

What does a positive ACPA test in early RA predict?

Answer 17

more severe disease with development of erosive arthritis sooner

Question 18

What is the role of IL-1 in RA?

Answer 18

activates monocytes/macrophages to cause inflammation

Question 19

What is IL-1Ra?

Answer 19

IL-1 receptor antagonist; produced constitutively and during inflammation and binds but does not activate IL-1 receptor

Question 20

What is the role of TNF-alpha in RA?

Answer 20

inflammation; fever and macrophage activation

Question 21

Which factors do monoclonal antibodies target in RA therapies?

Answer 21

1) TNK-alpha
2) IL-6 receptor
3) B cells

Question 22

Which factors do TNF-receptors target in RA therapies?

Answer 22

TNF-alpha

Question 23

Which factors do receptor antagonists target in RA therapies?

Answer 23

IL-1

Question 24

Which factors do CTLa4-Ig fusion proteins target in RA therapies?

Answer 24

CD80/86

Question 25

What is Juvenile Idiopathic Arthritis?

Answer 25

chronic arthritis occurring before 16 yo; unknown cause

Question 26

Is there a gender preference in Juvenile Idiopathic Arthritis?

Answer 26

NO

Question 27

What is the pathogenesis of Juvenile Idiopathic Arthritis?

Answer 27

Th1 mediate inflammation

Question 28

What are the autoantibodies in Juvenile Idiopathic Arthritis?

Answer 28

1) RA 2) ACPA 3) ANA

Question 29

What is the synovial inflammation of Juvenile Idiopathic Arthritis?

Answer 29

1) mononuclear cells (B, T, macrophages, dendritic cells) | 2) T cells (CD4+ Th1)

Question 30

Which cytokines are released in Juvenile Idiopathic Arthritis?

Answer 30

1) IL-1 2) IL-6 3) TNF-alpha

Question 31

What is spondyloarthritis?

Answer 31

heterogenous group of inflammatory diseases which include spinal and peripheral joint arthritis

Question 32

Why do only a subset of HLA-B27 positive individuals (5%) develop disease?

Answer 32

HLA-B27 is a class I HLA molecule . While most individuals with SpA are B27 positive, not all B27 positive individuals develop disease

Question 33

What are the immune abnormalities in SpA?

Answer 33

1) increased macrophages/monocytes 2) upregulation of TLR2 and TLR4 3) infiltration of synovium with CD8+ T cells 4) presence of TNF-alpha, IL-1 5) responsive to anti-TNF treatment

Question 34

What serve as targets for immune based therapy?

Answer 34

inflammatory cytokines