Rheumatoid Arthritis

Question 1

RA is a complex dz involving numerous cell types, name them.

Answer 1

Macrophages, T cells, B cells, fibroblasts, chondrocytes, neutrophils, mast cells, and dendritic cells

Question 2

Several genes are implicated in the susceptibility to RA and severity of dz including what?

Answer 2

Class II major histocompatibility complex genes, PTPN22, and peptidylarginine deiminases

Question 3

What can be present for many years before the onset of clinical arthritis?

Answer 3

Evidence of AI, including high serum levels of auto antibodies such as RH factor and anticitrullinated protein antibodies

Question 4

T/F: Adaptive and innate immune responses in the synovium have been implicated in the pathogenesis of RA.

Answer 4

True

Question 5

Cytokine networks involving TNF, IL-6, and many other factors participate in disease perpetuation, what does this mean?

Answer 5

They can be targets for therapeutic agents

Question 6

Bone and cartilage destruction are primarily mediated by?

Answer 6

Osteoclasts and fibroblast-like synoviocytes, respectively

Question 7

Do genes play a key role in susceptibility to RA as well as dz severity?

Answer 7

Yup, you betcha

Question 8

Class II major histiocompatibility genes, especially ones containing a specific 5 AA seqyence in the hypervariable region of what are the most prominent genetic association for RA?

Answer 8

HLA-DR4

Question 9

What are the two new defined genetic associations that suggest that the associations in RA are complex and involve many genes?

Answer 9

PTPNN22 and PAD14

Question 10

Is there an etiologic link between viruses, retroviruses, bacteria, and mycoplasma with RA?

Answer 10

No but they have been associated (not linked)

Question 11

Is a single specific RA pathogen?

Answer 11

Probs not

Question 12

Repeated inflammatory stress, especially through specialized receptors that recognize common molecules produced by pathogens, in a genetically susceptible individual might contribute to what?

Answer 12

Breakdown of tolerance and subsequent autoimmunity

Question 13

Can evidence of AI be present in RA many years before the onset of clinical RA

Answer 13

Yes

Question 14

Autoantibodies such as RFs and anticitrullinated protein ABs are commonly associated with?

Answer 14

RA

Question 15

Autoantibodies in RA can do what?

Answer 15

Recognize joint antigens such as T II collagen or systemic antigens such as glucose phosphate isomerase

Question 16

Autoantibodies can potentially contribute to synovial inflammation through several mechanisms, including what?

Answer 16

Local activation of complement

Question 17

The synovium in RA is marked by what? what cells will be there?

Answer 17

Intimal lining hyperplasia and sublining infiltration with mononuclear cells especially CD4+ T cells, macrophages, and B cells

Question 18

What does intimal lining FLS display?

Answer 18

Unusually aggressive features

Question 19

Macrophages in the intimal lining are what?

Answer 19

Highly activated and produce many cytokines

Question 20

Lymphocytes can do what two things in RA?

Answer 20

Diffusely infiltrate the subliming or form lymphoid aggregates with germinal centers

Question 21

Sublining CD4+ T cells may display what?

Answer 21

The memory cell pheno type

Question 22

Synovial B cells and plasma cells in RA exhibit evidence of what?

Answer 22

Antigen driven maturation and antibody protection

Question 23

Dendritic cells can potentially present antigens to T cells, where does this happen?

Answer 23

Synovial germinal centers

Question 24

Mast cells produce what?

Answer 24

Small molecule mediators of inflammation

Question 25

Neutrophils are rarely present in RA synovium but can be abundant where?

Answer 25

Synovial effusions

Question 26

RA synovial effusions contain what?

Answer 26

Neutrophils and mononuclear cells

Question 27

Immune complexes that contain autoantibodies such as and what can they do?

Answer 27

RFs or anticitrullinated protein antibodies that can fix complement, leading to the generation of chemoattractants

Question 28

Small molecule mediators of inflammation such as what are present in RA synovial fluid?

Answer 28

Prostaglandins and leukotrienes

Question 29

What has been implicated in the pathogenesis of RA?

Answer 29

Several subsets of T cells

Question 30

High or low levels of T cell cytokines are present in RA synovium?

Answer 30

Low

Question 31

Name a few T cell cytokines that are present in RA synovium and how do they get there?

Answer 31

IFN gamma, IL17; produced by TH1 and TH17 cells

Question 32

Regulatory T cell function might be low in RA synovium, what does this mean?

Answer 32

uncontrolled activation of other T cells

Question 33

Contribution of T cells to synovial inflammation can be through what?

Answer 33

Antigen-independent mechanisms such as direct cell-cell contact with macrophages

Question 34

Macrophage and fibroblast cytokines are abundant where in RA?

Answer 34

RA synovium

Question 35

Cytokine networks include what proinflammatory cytokines that can help perpetuate synovial inflammation?

Answer 35

IL1, TNF, IL6, IL15, IL18, GMCSF, and IL33

Question 36

Chemokines that recruit inflammatory cells into the joint are commonly produced by what?

Answer 36

Macrophages and fibroblasts

Question 37

Antiinflammatory cytokines such as IL-1Ra and IL10 are produced where, what is the problem with this?

Answer 37

Produced in rheumatoid synovium, amounts may be insufficient to suppress proinflammatory cytokine function or production

Question 38

Complex intracellular signaling mechanisms regulate what in RA synovium?

Answer 38

Cytokine production and actions

Question 39

What are the pathways that may be therapeutic targets for RA tx?

Answer 39

NFkB, MAP kinase, AP1, JAK, Syk + more

Question 40

What reactive species can contribute to the toxic environment that damages cells and increases inflammation in RA?

Answer 40

Reactive oxygen and nitrogen

Question 41

Deficiencies in what cell processes can contribute to the accumulation of cells in rheumatoid synovium?

Answer 41

Cell death and apoptosis

Question 42

Abnormalities of what key regulatory gene can enhance accumulation of cells in a joint?

Answer 42

p53 TSG

Question 43

Inducing apoptosis can potentially do what?

Answer 43

Suppress synovial inflammation and joint destruction

Question 44

Angiogenesis is what kind of process in RA that does what?

Answer 44

Dynamic process that provides nutrients to expanding synovium

Question 45

Angiogenic factors such as IL8, FGF, and VEGF does what?

Answer 45

Can enhance blood vessel proliferation in the synovium

Question 46

Microvascular endothelium in the synovium expresses what?

Answer 46

Adhesion molecules that guide circulating cells into the joint under the influence of chemoattractants

Question 47

Cartilage degradation and bone destruction in RA are mediated by what? (simple answer)

Answer 47

Distinct mechanisms and cell types

Question 48

Several classes of proteases including what are produced by intimal lining cells in RA, especially FLS

Answer 48

MMPs, Serine proteases, cathepsins, and aggrecanases

Question 49

What can invade and damage the cartilage in RA?

Answer 49

Synovial lining cells, especially FLS

Question 50

Bone destruction is mediated by osteoclasts that are activated under the influence of what?

Answer 50

RANKL and other cytokines produced by RA synovium