Rheumatoid Arthritis

Question 1

a group of disorders highly variable in their phenotypic expression. they all have the presence of localized and/or systemic inflammation in common, which results in characteristic musculoskeletal system and internal organ damage. clinical and pathologic features are determined by the initiating stimuli

Answer 1

inflammatory rheumatic diseases

Question 2

does this describe acute or chronic inflammatory rheumatoid diseases:
- initiating force is often recognizable, endogenous or exogenous
- it is self-limiting but flares may occur upon re-exposure
- e.g. gout

Answer 2

acute

Question 3

does this describe acute or chronic inflammatory rheumatoid diseases:
- initiating force is often remote and no longer recognizable by the time the disease phenotype is well established and diagnosis is made
- self-amplifying autoimmune response driven by self-antigens
- e.g. rheumatoid arthririts, SLE

Answer 3

chronic

Question 4

does this describe acute or chronic inflammatory rheumatoid diseases:
has an inhibitory loop thus the immune response gets rid of the initiator

Answer 4

acute

Question 5

does this describe acute or chronic inflammatory rheumatoid diseases:
has an inhibitory loop, but also has an auto-amplifying loop - inflammation occurs because there is damage and then more damage occurs

Answer 5

chronic

Question 6

pathogenesis of inflammation: what are the pro-inflammatory cytokines that are involved with endothelial activation

Answer 6

TNF-alpha and IL-1beta

Question 7

pathogenesis of inflammation: this cytokine produced by infected monocyte-macrophages skew the lymphocyte response towards Th1 cells (which generates the Th1 cytokines IL-2, IFN-gamma and TNF-alpha) that are associated with activating macrophage killing functions and protecting against invading intracellular pathogens.

Answer 7

IL-12

Question 8

pathogenesis of inflammation: the presence of ____ during the initial response induces the differentiation of Th2 lymphocytes which generate Th2 cytokines (IL-4, IL-5, IL-6 and IL-10). these cytokines have their predominant function in activating B cells and generating antibodies

Answer 8

IL-4

Question 9

pathogenesis of inflammation: a new subset of helper T cells that develop in the presence of the cytokine TGF-gamma and IL-6 have recently been described. These cells are termed ____ cells because of their characteristic secretion of IL-17. they appear to be critically inclined in recruiting granulocytes, protecting against certain types of bacteria and generating chronic inflammation and autoimmunity

Answer 9

Th17

Question 10

pathogenesis of inflammation: this pathway is activated when antibody binds to its specific antigen. it induces inflammatory cell recruitment and activation.

Answer 10

classical complement pathway

Question 11

pathogenesis of inflammation: what are examples of myelopmonocytic cells

Answer 11

neutrophils and macrophages

Question 12

pathogenesis of inflammation: although ________ cells have numerous effector pathways that function to rid the host of foreign invaders, some of these effector mechanisms can damage healthy tissue if released in large amounts. these include free radical species generated during the respiratory burst, as well as a variety of secretory products contained in the granules of these inflammatory cells

Answer 12

myelomonocytic cells

Question 13

pathogenesis of inflammation: what are some of the products contained in the granules of myelomonocytic cells, where when liberated into the extracellular medium, they can have damaging effects on normal connective tissues

Answer 13

cathepsins, elastase and collagenase.

Question 14

pathogenesis of inflammation: activation of the myelomonocytic cell effector function that results in tissue damage comes from what

Answer 14

complement pathway and immunoglobulin Fc gamma receptors

Question 15

pathogenesis of inflammation: these cells are capable of killing target cells. when target cell destruction exceeds the capacity for renewal, impaired tissue function can result. as with other lymphocyte functions, this effector function is activated only on ligation of the T-cell receptor by a specific peptide

Answer 15

cytotoxic T lymphocytes (CD8+ T cells)

Question 16

pathogenesis of inflammation: what are the two mechanisms that T lymphocytes use to kill target cells

Answer 16

• Fas/Fas-ligand pathway (FasL present on activated lymphocytes binds to the Fas receptor on target cells and activates target cell apoptosis)
• release of cytotoxic T-lymphocyte secretory granules (contains two classes of proteins: one called perforin that allows water, salt and protein to enter the rage cells cytoplasm and also granzyme that targets a number of critical cellular substrates and activates the process of apoptosis within the target cell)

Question 17

pathogenesis of inflammation: the destruction of antibody-coated target cells by natural killer cells is called __________ and occurs when the Fc receptor of a natural kill cell binds to the Fc portion of the surface bound antibody. an example is the photosensitive skin disease that occurs in patients with SLE who possess the Rho antibody

Answer 17

antibody-dependant cellular cytotoxicity (ADCC)

Question 18

pathogenesis of inflammation: in response to inflammatory mediators including cytokines and T cells, cells in tissues ordinarily unrelated to the immune response can alter their from and function to support a chronic inflammatory response. this is known as

Answer 18

host tissue differentiation

Question 19

this is a chronic systemic inflammatory disease characterized by:
- persistent symmetric inflammation of multiple peripheral joint
- proliferation of the synovial linings of diarthrodial joints
- untreated can lead to progressive joint destruction, disability and premature death

Answer 19

rheumatoid arhtritis

Question 20

true or false: rheumatoid arthritis is more common in women

Answer 20

true

Question 21

RA is a systemic autoimmune disease in which the abnormal activation of B cells, T cells and ______ (innate/adaptive) immune effectors causes damage to the patients own tissues

Answer 21

innate

Question 22

although the cause of RA is unknown, what are some theories regarding the ethology of RA

Answer 22

• environmental factors
• microbial infections
• trauma to the joint, increased physical stress
• genetic factors (MHC class II alleles e.g. HLA-DR4)

Question 23

what are some factors related to the initiation of RA

Answer 23

• genetic factors (MHC class ll alleles: PAD12, 14, etc)
• environmental factors (smoking, infection)
• autoantibodies (both rheumatoid factor and ACPAs can be present int he serum of patients years before disease onset making them valuable diagnostic markers)

Question 24

what are some factors related to the propagation of RA

Answer 24

• citrullination (PAD enzymes mediate the conversion of arginine to citrulline)
• cytokines (TNF-alpha is an important upstream mediator in the propagation of the RA inflammatory process)

Question 25

if pathways downstream of TNF-alpha are inhibited with soluble TNF-alpha receptor or monoclonal antibodies to TNF-alpha, will this result in benefit or worsening of the patient

Answer 25

benefit! inhibiting TNF-alpha is good! because TNF-alpha is what does the damage

Question 26

among the five PAD enzyme family members, which two are the most strongly implicated in RA pathogenesis

Answer 26

PAD 2 and 4

Question 27

mechanism of inflammation and joint destruction: CD4+ T cells become activated by antigen-presenting cells (APCs) through interactions between the T-cell receptor and class II MHC-peptide antigen (signal 1) with co stimulation through the _______ pathway, as well as other pathways

Answer 27

CD28-CD80/86

Question 28

mechanism of inflammation and joint destruction: synovial CD4+ cells differentiate into ____ and ____ cells, each with their own distinctive cytokine profile

Answer 28

Th1 and Th17

Question 29

mechanism of inflammation and joint destruction: _____ cells activate B cells, some of which are destined to differentiate into auto-antibody producing plasma cells.

Answer 29

Th cells

Question 30

mechanism of inflammation and joint destruction: _____ stimulate synovial macrophages and fibroblasts to secrete pro inflammatory mediators among which is TNF-alpha

Answer 30

T effector cells

Question 31

mechanism of inflammation and joint destruction: TNF-alpha has a critically important function in regulating the balance between bone destruction and formation. it up regulates the expression of dickkopf-1 (DKK-1) which can then internalize ___ receptors on osteoblast precursors. ___ is a soluble mediator that promotes osteoblastogenesis and bone formation

Answer 31

Wnt

Question 32

what are the four stages of pannus formation

Answer 32

1. initiation phase - some change in synovial lining
2. immune response phase - hyperplasia of synovium
3. inflammatory phase - oxygen radicals, arachidonic acid and lysosomes destroy synovial tissue
4. destruction phase - synovial lining invades and destructs the bone

Question 33

what are some clinical presentations of RA

Answer 33

• morning stiffness in joints lasting at least 1 hr before improvement
• soft-tissue swelling of three or more joints symmetrically distributed (hands wrists, feet, hips, knees and shoulders)
• demineralization and erosion of involved joints and bones by synovial inflammation
• ongoing inflammation leads to joint deformity

as the disease progresses
- decrease ability to climb stairs, opening jars and doors
- decreased precise movements of fingers
- depression
- weight loss

Question 34

this is when the joints in the wrist and hand shift so that the fingers bend towards the ulna bone on the outside of the forearm

Answer 34

ulnar drift

Question 35

this is a medical condition in which the finger is flexed at the proximal interphalangeal joint (PIP) and hyper-extended at the distal interphalangeal joint (DIP)

Answer 35

boutinniere deformity

Question 36

how is RA diagnosed

Answer 36

• X-rays
• positive for rheumatoid factor isotopes (IgM, IgG and IgA)
• positive for anti-cyclic citrullinated peptide (anti-CCP)