pathophysiology

Question 1

define rheumatoid arthritis

Answer 1

chronic joint inflammation that can result in joint damage (synovitis)

Question 2

site of inflammation in rheumatoid arthritis

Answer 2

synovium (can affect C1-C2 in spine, but nowhere else in spine)

Question 3

what auto-antibodies is rheumatoid arthritis associated with

Answer 3

rheumatoid factor (IgM vs IgG), anti-cyclic citrullinated peptide (CCP) antibodies

Question 4

define ankylosing spondylitis

Answer 4

chronic spinal inflammation that can result in spinal fusion and deformity (enthesitis with no rheumatoid factor)

Question 5

site of inflammation in ankylosing spondylitis

Answer 5

enthesis (in spine, nucleus pulposus surrounded by annulus fibrosis which inserts into vertebral bone at enthesis)

Question 6

auto-antibodies in ankylosing spondylitis

Answer 6

none (seronegative)

Question 7

4 seronegative spondyloarthropathies

Answer 7

ankylosing spondylitis, Reiters syndrome and reactive arthritis, psoriatic arthritis, enteropathic synovitis

Question 8

define systemic lupus erythematosus

Answer 8

chronic tissue inflammation in presence of antibodies directed against self antigens (immune complexes)

Question 9

locations of inflammation in systemic lupus erythematosus

Answer 9

multi-site, particularly joints, skin and kidney

Question 10

what auto-antibodies are associated with systemic lupus erythematosus

Answer 10

antinuclear antibodies (antigens in nuclear), anti-double stranded DNA antibodies (key SLE antigen in nucleus - histone complexes)

Question 11

5 connective tissue diseases

Answer 11

systemic lupus erythematosus, inflammatory muscle disease (polymositis, dematomyositis), systemic sclerosis, Sjogren’s syndrome, overlap syndromes (mixture of other 4)

Question 12

function of major histocompatibility complex (MHC), and significance

Answer 12

important in recognition of antigens by T cells, with a strong association for susceptibility of rhuematological diseases

Question 13

association between MHC and rheumatoid arthritis

Answer 13

HLA-DR4

Question 14

association between MHC and systemic lupus erythematosus (3 words in SLE)

Answer 14

HLA-DR3

Question 15

association between MHC and ankylosing spondylitis

Answer 15

HLA-B27

Question 16

what do genes withing MHC class I and II regions encode

Answer 16

cell surface proteins

Question 17

function of MHC class I and II molecules

Answer 17

present antigen to T cells

Question 18

MHC class I: cell expression, antigens, T cell recognition and response

Answer 18

expressed on all nucleated cells, endogenous (IC) antigens, recognised by CD8+ T cells (Tc), response of cell killing

Question 19

MHC class II: cell expression, antigens, T cell recognition and response

Answer 19

expressed on APCs, exogenous (EC) antigens, recognised by CD4+ T cells (Th), antibody response

Question 20

what is the peptide-binding site of MHC made up of

Answer 20

walls (a-helicies) and floor (B-pleated sheets)

Question 21

what determines which antigens can bind to MHC

Answer 21

sequence in peptide-binding groove

Question 22

what can T cells only see

Answer 22

antigen-bound to MHC (MHC restriction)

Question 23

pathogenesis of HLA-associated disease

Answer 23

due to peptide antigen (exogenous or self) that is able to bind to HLA molecules and trigger disease (arthritogenic antigen)

Question 24

what does antigen and HLA-B27 in ankylosing spondylitis trigger

Answer 24

CD8+ T cell response

Question 25

what does antigen and HLA-DR4 in rheumatoid arthritis trigger

Answer 25

CD4+ T cell response

Question 26

in ankylosing spondylitis, what does HLA-B27 having an inclination to misfold cause

Answer 26

cellular stress, triggering IL-23 release and IL-17 production by adaptive immune cells (CD4+ Th17 cells) and innate immune cells (CD4-, CD8- (double-negative) T cells in entheses)

Question 27

treatment of ankylosing spondylitis

Answer 27

blockading IL-23 and IL-17