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Rheum Key Points > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

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

A

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

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2
Q

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

A

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

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3
Q

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

A

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

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4
Q

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

A

True

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5
Q

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

A

They can be targets for therapeutic agents

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6
Q

Bone and cartilage destruction are primarily mediated by?

A

Osteoclasts and fibroblast-like synoviocytes, respectively

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7
Q

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

A

Yup, you betcha

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8
Q

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?

A

HLA-DR4

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9
Q

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

A

PTPNN22 and PAD14

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10
Q

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

A

No but they have been associated (not linked)

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11
Q

Is a single specific RA pathogen?

A

Probs not

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12
Q

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

A

Breakdown of tolerance and subsequent autoimmunity

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13
Q

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

A

Yes

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14
Q

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

A

RA

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15
Q

Autoantibodies in RA can do what?

A

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

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16
Q

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

A

Local activation of complement

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17
Q

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

A

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

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18
Q

What does intimal lining FLS display?

A

Unusually aggressive features

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19
Q

Macrophages in the intimal lining are what?

A

Highly activated and produce many cytokines

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20
Q

Lymphocytes can do what two things in RA?

A

Diffusely infiltrate the subliming or form lymphoid aggregates with germinal centers

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21
Q

Sublining CD4+ T cells may display what?

A

The memory cell pheno type

22
Q

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

A

Antigen driven maturation and antibody protection

23
Q

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

A

Synovial germinal centers

24
Q

Mast cells produce what?

A

Small molecule mediators of inflammation

25
Q

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

A

Synovial effusions

26
Q

RA synovial effusions contain what?

A

Neutrophils and mononuclear cells

27
Q

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

A

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

28
Q

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

A

Prostaglandins and leukotrienes

29
Q

What has been implicated in the pathogenesis of RA?

A

Several subsets of T cells

30
Q

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

A

Low

31
Q

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

A

IFN gamma, IL17; produced by TH1 and TH17 cells

32
Q

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

A

uncontrolled activation of other T cells

33
Q

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

A

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

34
Q

Macrophage and fibroblast cytokines are abundant where in RA?

A

RA synovium

35
Q

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

A

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

36
Q

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

A

Macrophages and fibroblasts

37
Q

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

A

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

38
Q

Complex intracellular signaling mechanisms regulate what in RA synovium?

A

Cytokine production and actions

39
Q

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

A

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

40
Q

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

A

Reactive oxygen and nitrogen

41
Q

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

A

Cell death and apoptosis

42
Q

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

A

p53 TSG

43
Q

Inducing apoptosis can potentially do what?

A

Suppress synovial inflammation and joint destruction

44
Q

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

A

Dynamic process that provides nutrients to expanding synovium

45
Q

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

A

Can enhance blood vessel proliferation in the synovium

46
Q

Microvascular endothelium in the synovium expresses what?

A

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

47
Q

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

A

Distinct mechanisms and cell types

48
Q

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

A

MMPs, Serine proteases, cathepsins, and aggrecanases

49
Q

What can invade and damage the cartilage in RA?

A

Synovial lining cells, especially FLS

50
Q

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

A

RANKL and other cytokines produced by RA synovium

Rheum Key Points (7 decks)

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