Rheumatoid Arthritis Flashcards
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
inflammatory rheumatic diseases
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
acute
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
chronic
does this describe acute or chronic inflammatory rheumatoid diseases:
has an inhibitory loop thus the immune response gets rid of the initiator
acute
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
chronic
pathogenesis of inflammation: what are the pro-inflammatory cytokines that are involved with endothelial activation
TNF-alpha and IL-1beta
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.
IL-12
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
IL-4
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
Th17
pathogenesis of inflammation: this pathway is activated when antibody binds to its specific antigen. it induces inflammatory cell recruitment and activation.
classical complement pathway
pathogenesis of inflammation: what are examples of myelopmonocytic cells
neutrophils and macrophages
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
myelomonocytic cells
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
cathepsins, elastase and collagenase.
pathogenesis of inflammation: activation of the myelomonocytic cell effector function that results in tissue damage comes from what
complement pathway and immunoglobulin Fc gamma receptors
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
cytotoxic T lymphocytes (CD8+ T cells)
pathogenesis of inflammation: what are the two mechanisms that T lymphocytes use to kill target cells
- 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)
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
antibody-dependant cellular cytotoxicity (ADCC)
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
host tissue differentiation
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
rheumatoid arhtritis
true or false: rheumatoid arthritis is more common in women
true
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
innate
although the cause of RA is unknown, what are some theories regarding the ethology of RA
- environmental factors
- microbial infections
- trauma to the joint, increased physical stress
- genetic factors (MHC class II alleles e.g. HLA-DR4)
what are some factors related to the initiation of RA
- 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)
what are some factors related to the propagation of RA
- 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)
