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234 Cards in this Set
- Front
- Back
what are the 3 criteria for a disease to be AI
|
presence of an immune reaction to a self Ag
the reaction is not secondary to tissue damage but is the primary pathology absence of another well defined cause of the disease |
|
what are the autoreactive cells in type 1 DM
|
T cells
|
|
what are T cells reactive against in MS
|
CNS Myelin
|
|
what are T cells reactive against in SLE
|
DNA, platelets, RBCs, and protein-phospholipid complexes
|
|
what is the target of T cells in Goodpasture's syndrome
|
the basement membrane of lung and kidneys
|
|
what protein generates the self Ags that test developing T cells for AI
|
AIRE
|
|
what disease is caused by a mutation in the AIRE gene
|
AI polyendocrinopathy
|
|
what are the second signals that are missing that lead to T cell anergy
|
CD28 which binds to the B7 receptors on APCs
|
|
why does a lack of second signals lead to anergy
|
1) activation of ubiquitin ligases and proteolytic degredation of receptor-assoc signaling proteins
2) CTLA-4(binds B7) and PD-1 bind to the cells and inhibit them when they are not opposed by CD28 activation |
|
what does a mutation in the CTLA4 gene lead to
|
AI endocrine diseases
|
|
what do regulatory T cells express on there surface that gives them their fx
|
CD25(the alpha chain of IL2 receptor)
Foxp3(a transcription factor of the forkhead family) |
|
disease caused by a foxp3 mutation
|
IPEX(immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
|
|
what is the cytokine that is req for maintenance of regulatory T cell
|
IL2
|
|
what disease are assoc with CD25 polymorphism
|
MS
|
|
what do regulatory T cells express that suppresses lymph activation and effector cell fx
|
IL10 and TGF-beta
|
|
what is the receptor on T cells that activates deletion by activation-induced cell death
|
Bim which activates the mitochondrial pathway
|
|
what receptors are involved in deletion by the death receptor pathway in autoreactive T cells
|
Fas(CD95) binds to FasL(homologous to TNF) on the activated lymph
|
|
how can self reactive B cells be deleted
|
They bind FasL from activated T cells to their Fas receptor
|
|
what disease is caused by a mutation in Fas
|
AI lymphoproliferative syndrome
|
|
what are the immune-privileged sites
|
testis, eye, and brain
|
|
what are the genes most assoc with AI
|
HLA genes
|
|
what diseases are assoc with a mutation in PTPN22
|
RA
type 1 DM and several other AI |
|
what is the most frequently implicated gene in AI
|
PTPN-22
|
|
what is the fx of PTPN22
|
protein phosphatase that inhib the action of lymph protein kinases
|
|
what disease is assoc with NOD2
|
crohns disease
|
|
what is the fx of NOD2
|
it is a cytoplasmic sensor of microbes
|
|
what genes are assoc with MS
|
IL2 receptor(CD25)
IL7 alpha chain |
|
what causes B cells to decrease Ab production when there are Ags around
|
An IgG bound to an Ag attaches to a B cell Fc receptor for IgG
|
|
what bugs cause polyclonal B cell activation which results in production of autoantibodies
|
EBV and HIV
|
|
how can inf protect from AI
|
they promote low level IL2 production that is essential for maintaining regulatory T cells
|
|
what are Th1 AI responses characterized by
|
macrophage-rich inflammation
production of Abs that activate complement and bind to Fc receptors to inc destruction |
|
characteristics of a Th17 AI response
|
Neutrophil and monocyte rich
|
|
what do the systemic AI diseases tend to involve
|
BVs and connective tissues
they are often called collagen vascular diseases |
|
what are the principal tissues effected by SLE
|
skin, joints, kidney, and serosal membranes
|
|
what group is at highest risk for SLE
|
Women of child-bearing age
|
|
what races are at highest risk for SLE
|
blacks and latinos
|
|
what are the 4 groups of ANAs in SLE
|
Abs to DNA
Abs to histones Abs to nonhistone proteins bound to DNA Abs to nucleolar Ags |
|
what type of Abs are suggested by homogeneous or diffuse nuclear staining in a nuclear flourescence test
|
Abs to chromatin, Histones, and occasionally dsDNA
|
|
what type of Abs are suggested by rim or peripheral staining patterns in a nuclear fluorescence test
|
dsDNA
|
|
what does a speckled pattern in a nuclear fluorescence test mean
|
Abs to non-DNA nuclear consituents and is not specific
Examples--> SS-A, SS-B, Sm Ag, ribonucleoprotein |
|
what does a nucleolar pattern refer to on a nuclear fluorescence test
|
Abs to RNA
most often occurs in pts with systemic sclerosis(scleroderma) |
|
Abs to what Ags are diagnostic of SLE
|
Smith Ag
dsDNA |
|
what are anti-phospholipid Abs directed against
|
epitopes of plasma proteins that are revealed when they are in complex with phospholipids
ex--> prothrombin, annexin V, Beta2-glycoprotein I, Protein S, and Protein C |
|
why might a pt with SLE have a false positive for syphilis
|
Abs to the phospholipid-Beta2-glycoprotein complex also bind cardiolipin which is used in syphilis serologies
|
|
what are lupus anticoagulant
|
the Abs involved in lupus that interfere with clotting and prolong thromboplastin time
|
|
what are the SEs of lupus anticoagulants
|
clots that cause recurrent spontaneous miscarriages, focal cerebral or ocular ischemia
|
|
secondary antiphospholipid Ab syndrome
|
the disease caused when a pt with SLE also has lupus anticoagulants
|
|
what is primary antiphospholipid syndrome
|
when a pt develops lupus anticoagulants without developing SLE
|
|
what alleles in SLE are assoc with anti-dsDNA, anti-Sm, and antiphospholipid Abs
|
HLA-DQ
|
|
what complement defects are assoc with SLE and why
|
C2, C4, or C1q
the lack of complement inhibs the removal of circulating immune complexes by the mononuclear phagocytic system, thus favoring tissue deposition |
|
what happens when cells that undergo apoptosis dont get cleared by phagocytes
|
their nuclear components can elicit immune responses
|
|
what are the 5 immunological factors that play a role in SLE
|
1)failure of self-tolerance by B cells
2)CD4+ T cells become specific for nucleosomal Ags 3)DNA and RNA may activate B cells by engaging TLRs, which inc Ab production 4)DNA and RNA engage TLRs on dendritic cells and make them produce INF-gamma which activates them and B cells to produce a Th1 response 5)inc production of BAFF to stim B cells |
|
what environmental factors exacerbate SLE
|
1)UV light(stims keratinocytes to produce IL1 and it damages DNA which may allow it to be recognized by TLRs)
2) sex hormones(SLE is worse during menses and pregnancy) |
|
drugs that can exacerbate SLE
|
hydralazine
procainamide D-penicillamine |
|
what do the complexes of Ag and Ab bind to in SLE
|
Fc receptors on B cells and dendritic cells
|
|
what do defects in selfreactivity lead to in the case of Nucleic acids
|
they engage TLRs on B cells and dendritic cells and cause them to produce Austoantibodies(B cells) and INFs(dendritic cells)
|
|
what is the type of hypersensitivity in SLE
|
type 3
|
|
how to ANAs get to their Ags
|
they have to wait for them to be exposed when the cell lyses because they cant cross the cell membrane
|
|
what are hematoxylin bodies
|
nuc of damaged cells that react with ANAs, lose their chromatin pattern, and become homogeneous
|
|
what is an LE cell
|
any phagocytic leukocyte that has engulfed the denatured nuc of an injured cell
|
|
what lymphs are activated in SLE
|
helper T cells and B cells
|
|
what is a characteristic morphology of SLE in BVs
|
an acute necrotizing vasculitis involving capillaries, small arts, and arterioles
|
|
what characterizes the arteritis of SLE
|
fibrinoid deposits in the vessel walls
|
|
What are in the immune complexes that deposit in the kidney made of in SLE
|
DNA
anti-DNA Abs and other Ags such as histones |
|
characteristics of mesangial lupus glomerulonephritis
|
1)mesangial cell proliferation and immune complex deposition without involvement of glomerular capillaries
2)there can be no/slight or moderate inc in mesangial matrix and number of mesangial cells 3)there are always deposits of Ig and complement present |
|
characteristics of glomeruli in focal proliferative glomerulonephritis in SLE
|
crescent formation
fibrinoid necrosis prolif of endothelial and mesangial cells infiltrating leukocytes eosinophilc deposits or intracapillary thrombi there are subendothelial deposits |
|
what is the most severe case of lupus nephritis
|
diffuse proliferative glomerulonephritis
|
|
what fills bowmans capsule in diffuse proliferative glomerulonephritis
|
cellular crescents
|
|
characteristics of membranous glomerulonephritis in SLE
|
diffuse thickening of the capillary walls
predominantly subepithelial |
|
what is a wire-loop lesion
|
subendothelial deposits create a homogeneous thickening of the capillary wall
|
|
what does the erythema in SLE look like histologically
|
vacuolar degeneration of the basal layer of the epidermis
there is variable edema and perivascular inflammation in the dermis |
|
what are the characteristics of joints in SLE
|
nonerosive synovitis with little deformity
|
|
what effects does SLE have on the CNS
|
there are Abs against the synaptic membrane proteins
antiphospholipid Abs cause noninflammatory occlusion of small vessels by intimal prolif |
|
effects of SLE on serosal cavity
|
there is fibrinous exudate on the mesothelial surfaces in acute phases
later they become thickened, opaque, and coated with shaggy fibrous tissue that may lead to obliteration of the serosal cavity |
|
effects of SLE on the heart
|
diffuse leaflet thickening(libman-sacks endocarditis)
|
|
effect of SLE on atherosclerosis
|
immune complexes and antiphospholipid Abs cause endothelial damage
HTN, obesity, and hyperlipidemia are more common in SLE pts |
|
effects of SLE on the spleen
|
Central penicilliary arts may show a concentric intimal and smooth muscle hyperplasia(onion-skin lesions)
|
|
effects of SLE on LNs
|
LNs are enlarged with hyperplastic follicles or even demonstrate necrotizing lymphadenitis
|
|
what are used to tx the SLE exacerbations
|
Corticosteroids
|
|
the most common cause of death in SLE
|
renal failure and intercurrent infections
|
|
what Abs are rarely present in Chronic discoid Lupus erythematosus
|
Abs to dsDNA
|
|
what is deposited at the dermoepidermal junction
|
Ig and C3
|
|
what is the main Ab in subacute cutaneous lupus erythematosus
|
Abs to SS-A
|
|
what gene is assoc with subacute cutaneous lupus erythematosus
|
HLA-DR3
|
|
what systems are rarely involved in drug-induced lupus erythematosus
|
renal and CNS
|
|
What Abs are assoc with drug-induced lupus erythematosus
|
Abs to histones
|
|
what genes are assoc with drug-induced lupus erythematosus
|
HLA-DR4
|
|
characteristics of sjogren syndrome
|
dry eyes(keratoconjunctivitis sicca)
dry mouth(xerostomia) both are due to destruction of the lacrimal and salivary glands due to lymphocytic infiltration and fibrosis |
|
what is the most common syndrome assoc with sjogrens
|
RA
|
|
what are the predominant cells of the infiltrates in sjogrens
|
CD4+ helper T cells and some B cells, incl plasma cells
|
|
why are sjogrens and RA commonly assoc
|
sjogrens pts commonly have Rh factor(an Ab reactive with self-Ag)
|
|
what are the main Abs in sjogrens against
|
nucleoprotein Ags SS-A and SS-B
|
|
what are pts with SS-A in sjogrens more likely to have
|
early disease onset
longer disease duration extraglandular manifestations |
|
what are the genes assoc with sjogrens
|
HLA-DQA1
HLA-DQB1 |
|
what is the suspected initiating trigger of sjogrens
|
viral inf of the salivary glands which cause local cell death and release of tissue self-Ags
|
|
what is the auto-Ag in sjogrens
|
the cytoskeletal protein alpha-fodrin
|
|
what fvirus causes a clinical disease similar to sjogrens
|
HTLV-1
|
|
what are the morphological characteristics of sjogrens
|
periductal and perivascular lymphocytic infiltration
there can be lymphoid follicles and germinal centers in the salivary glands |
|
what group is at the highest risk for sjogrens
|
women between 50 and 60yo
|
|
extraglandular Sx of sjogrens
|
synovitis, diffuse pulmonary fibrosis, and peripheral neuropathy
they are more common pts with SS-A Abs there can be tubulointerstitial nephritis Hyperplastic LNs |
|
how do you Dx sjogrens
|
Biopsy of the lip to examine minor salivary glands
|
|
what cancer is assoc with sjogrens
|
A marginal zone B cell lymphoma
|
|
characteristics of scleroderma
|
1)chronic inflam as a result of AI
2)widespread damage to small blood vessels 3)progressive interstitial and perivascular fibrosis in the skin and mult organs |
|
characteristics of diffuse scleroderma
|
widespread skin involvment at onset
rapid progression and early visceral involvement |
|
characteristics of limited scleroderma
|
skin involvement is confined to the fingers, forearms, and face
visceral involvement is late some pts can develop CREST syndrome |
|
what is CREST syndrome
|
Calcinosis
Raynauds phenomenon esophageal dysmotility sclerodactyly telangiectasia |
|
what cells are implicated in scleroderma
|
CD4+ T cells(Th2 are common)
|
|
what cytokines are involved in scleroderma
|
TGF-beta and IL13 because they stim transcription of genes that encode collagen and other matrix proteins(fibronectin) in fibroblasts
|
|
what Ab is specific for scleroderma
|
Ab for DNA topoisomerase I(anti-Scl 70), assoc with pulmonary fibrosis and periph vascular disease
and anticentromere Ab, assoc with CREST syndrome |
|
what is commonly the initial lesion of scleroderma
|
microvascular disease
|
|
what is a trigger for perivascular fibrosis in scleroderma
|
endothelial injury that causes platelet aggregation causing the release of platelet and endothelial factors(PDGF and TGF-Beta)
|
|
what special features do vascular smooth muscle cells have in scleroderma
|
inc expression of adrenergic receptors
|
|
what morphologic effect does scleroderma have on the skin
|
inc of collagen in the dermis
thinning of the epidermis loss of rete pegs atrophy of the dermal appendages hyaline thickening of the walls of the BVs |
|
what effect does scleroderma have on the alimentary tract
|
progressive atrophy and collagenous fibrous replacement of the muscularis(most prominent at the esophagus)
excess collagenization of the lamina propria and submucosa loss of villi and microvilli in the small intestine lower esophageal dysfx |
|
what are the effects of scleroderma on the musculoskeletal system
|
hypertrophy and hyperplasia of the synovial soft tissue
|
|
what are the Abs reactive to in mixed connective tissue
|
ribonucleoprotein particle-containing U1 ribonucleoprotein
|
|
what vessels are involved in polyarteritis nodosa
|
all types
|
|
what are the 3 criteria for a disease to be AI
|
presence of an immune reaction to a self Ag
the reaction is not secondary to tissue damage but is the primary pathology absence of another well defined cause of the disease |
|
what are the autoreactive cells in type 1 DM
|
T cells
|
|
what are T cells reactive against in MS
|
CNS Myelin
|
|
what are T cells reactive against in SLE
|
DNA, platelets, RBCs, and protein-phospholipid complexes
|
|
what is the target of T cells in Goodpasture's syndrome
|
the basement membrane of lung and kidneys
|
|
what protein generates the self Ags that test developing T cells for AI
|
AIRE
|
|
what disease is caused by a mutation in the AIRE gene
|
AI polyendocrinopathy
|
|
what are the second signals that are missing that lead to T cell anergy
|
CD28 which binds to the B7 receptors on APCs
|
|
why does a lack of second signals lead to anergy
|
1) activation of ubiquitin ligases and proteolytic degredation of receptor-assoc signaling proteins
2) CTLA-4(binds B7) and PD-1 bind to the cells and inhibit them when they are not opposed by CD28 activation |
|
what does a mutation in the CTLA4 gene lead to
|
AI endocrine diseases
|
|
what do regulatory T cells express on there surface that gives them their fx
|
CD25(the alpha chain of IL2 receptor)
Foxp3(a transcription factor of the forkhead family) |
|
disease caused by a foxp3 mutation
|
IPEX(immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
|
|
what is the cytokine that is req for maintenance of regulatory T cell
|
IL2
|
|
what disease are assoc with CD25 polymorphism
|
MS
|
|
what do regulatory T cells express that suppresses lymph activation and effector cell fx
|
IL10 and TGF-beta
|
|
what is the receptor on T cells that activates deletion by activation-induced cell death
|
Bim which activates the mitochondrial pathway
|
|
what receptors are involved in deletion by the death receptor pathway in autoreactive T cells
|
Fas(CD95) binds to FasL(homologous to TNF) on the activated lymph
|
|
how can self reactive B cells be deleted
|
They bind FasL from activated T cells to their Fas receptor
|
|
what disease is caused by a mutation in Fas
|
AI lymphoproliferative syndrome
|
|
what are the immune-privileged sites
|
testis, eye, and brain
|
|
what are the genes most assoc with AI
|
HLA genes
|
|
what diseases are assoc with a mutation in PTPN22
|
RA
type 1 DM and several other AI |
|
what is the most frequently implicated gene in AI
|
PTPN-22
|
|
what is the fx of PTPN22
|
protein phosphatase that inhib the action of lymph protein kinases
|
|
what disease is assoc with NOD2
|
crohns disease
|
|
what is the fx of NOD2
|
it is a cytoplasmic sensor of microbes
|
|
what genes are assoc with MS
|
IL2 receptor(CD25)
IL7 alpha chain |
|
what causes B cells to decrease Ab production when there are Ags around
|
An IgG bound to an Ag attaches to a B cell Fc receptor for IgG
|
|
what bugs cause polyclonal B cell activation which results in production of autoantibodies
|
EBV and HIV
|
|
how can inf protect from AI
|
they promote low level IL2 production that is essential for maintaining regulatory T cells
|
|
what are Th1 AI responses characterized by
|
macrophage-rich inflammation
production of Abs that activate complement and bind to Fc receptors to inc destruction |
|
characteristics of a Th17 AI response
|
Neutrophil and monocyte rich
|
|
what do the systemic AI diseases tend to involve
|
BVs and connective tissues
they are often called collagen vascular diseases |
|
what are the principal tissues effected by SLE
|
skin, joints, kidney, and serosal membranes
|
|
what group is at highest risk for SLE
|
Women of child-bearing age
|
|
what races are at highest risk for SLE
|
blacks and latinos
|
|
what are the 4 groups of ANAs in SLE
|
Abs to DNA
Abs to histones Abs to nonhistone proteins bound to DNA Abs to nucleolar Ags |
|
what type of Abs are suggested by homogeneous or diffuse nuclear staining in a nuclear flourescence test
|
Abs to chromatin, Histones, and occasionally dsDNA
|
|
what type of Abs are suggested by rim or peripheral staining patterns in a nuclear fluorescence test
|
dsDNA
|
|
what does a speckled pattern in a nuclear fluorescence test mean
|
Abs to non-DNA nuclear consituents and is not specific
Examples--> SS-A, SS-B, Sm Ag, ribonucleoprotein |
|
what does a nucleolar pattern refer to on a nuclear fluorescence test
|
Abs to RNA
most often occurs in pts with systemic sclerosis(scleroderma) |
|
Abs to what Ags are diagnostic of SLE
|
Smith Ag
dsDNA |
|
what are anti-phospholipid Abs directed against
|
epitopes of plasma proteins that are revealed when they are in complex with phospholipids
ex--> prothrombin, annexin V, Beta2-glycoprotein I, Protein S, and Protein C |
|
why might a pt with SLE have a false positive for syphilis
|
Abs to the phospholipid-Beta2-glycoprotein complex also bind cardiolipin which is used in syphilis serologies
|
|
what are lupus anticoagulant
|
the Abs involved in lupus that interfere with clotting and prolong thromboplastin time
|
|
what are the SEs of lupus anticoagulants
|
clots that cause recurrent spontaneous miscarriages, focal cerebral or ocular ischemia
|
|
secondary antiphospholipid Ab syndrome
|
the disease caused when a pt with SLE also has lupus anticoagulants
|
|
what is primary antiphospholipid syndrome
|
when a pt develops lupus anticoagulants without developing SLE
|
|
what alleles in SLE are assoc with anti-dsDNA, anti-Sm, and antiphospholipid Abs
|
HLA-DQ
|
|
what complement defects are assoc with SLE and why
|
C2, C4, or C1q
the lack of complement inhibs the removal of circulating immune complexes by the mononuclear phagocytic system, thus favoring tissue deposition |
|
what happens when cells that undergo apoptosis dont get cleared by phagocytes
|
their nuclear components can elicit immune responses
|
|
what are the 5 immunological factors that play a role in SLE
|
1)failure of self-tolerance by B cells
2)CD4+ T cells become specific for nucleosomal Ags 3)DNA and RNA may activate B cells by engaging TLRs, which inc Ab production 4)DNA and RNA engage TLRs on dendritic cells and make them produce INF-gamma which activates them and B cells to produce a Th1 response 5)inc production of BAFF to stim B cells |
|
what environmental factors exacerbate SLE
|
1)UV light(stims keratinocytes to produce IL1 and it damages DNA which may allow it to be recognized by TLRs)
2) sex hormones(SLE is worse during menses and pregnancy) |
|
drugs that can exacerbate SLE
|
hydralazine
procainamide D-penicillamine |
|
what do the complexes of Ag and Ab bind to in SLE
|
Fc receptors on B cells and dendritic cells
|
|
what do defects in selfreactivity lead to in the case of Nucleic acids
|
they engage TLRs on B cells and dendritic cells and cause them to produce Austoantibodies(B cells) and INFs(dendritic cells)
|
|
what is the type of hypersensitivity in SLE
|
type 3
|
|
how to ANAs get to their Ags
|
they have to wait for them to be exposed when the cell lyses because they cant cross the cell membrane
|
|
what are hematoxylin bodies
|
nuc of damaged cells that react with ANAs, lose their chromatin pattern, and become homogeneous
|
|
what is an LE cell
|
any phagocytic leukocyte that has engulfed the denatured nuc of an injured cell
|
|
what lymphs are activated in SLE
|
helper T cells and B cells
|
|
what is a characteristic morphology of SLE in BVs
|
an acute necrotizing vasculitis involving capillaries, small arts, and arterioles
|
|
what characterizes the arteritis of SLE
|
fibrinoid deposits in the vessel walls
|
|
What are in the immune complexes that deposit in the kidney made of in SLE
|
DNA
anti-DNA Abs and other Ags such as histones |
|
characteristics of mesangial lupus glomerulonephritis
|
1)mesangial cell proliferation and immune complex deposition without involvement of glomerular capillaries
2)there can be no/slight or moderate inc in mesangial matrix and number of mesangial cells 3)there are always deposits of Ig and complement present |
|
characteristics of glomeruli in focal proliferative glomerulonephritis in SLE
|
crescent formation
fibrinoid necrosis prolif of endothelial and mesangial cells infiltrating leukocytes eosinophilc deposits or intracapillary thrombi there are subendothelial deposits |
|
what is the most severe case of lupus nephritis
|
diffuse proliferative glomerulonephritis
|
|
what fills bowmans capsule in diffuse proliferative glomerulonephritis
|
cellular crescents
|
|
characteristics of membranous glomerulonephritis in SLE
|
diffuse thickening of the capillary walls
predominantly subepithelial |
|
what is a wire-loop lesion
|
subendothelial deposits create a homogeneous thickening of the capillary wall
|
|
what does the erythema in SLE look like histologically
|
vacuolar degeneration of the basal layer of the epidermis
there is variable edema and perivascular inflammation in the dermis |
|
what are the characteristics of joints in SLE
|
nonerosive synovitis with little deformity
|
|
what effects does SLE have on the CNS
|
there are Abs against the synaptic membrane proteins
antiphospholipid Abs cause noninflammatory occlusion of small vessels by intimal prolif |
|
effects of SLE on serosal cavity
|
there is fibrinous exudate on the mesothelial surfaces in acute phases
later they become thickened, opaque, and coated with shaggy fibrous tissue that may lead to obliteration of the serosal cavity |
|
effects of SLE on the heart
|
diffuse leaflet thickening(libman-sacks endocarditis)
|
|
effect of SLE on atherosclerosis
|
immune complexes and antiphospholipid Abs cause endothelial damage
HTN, obesity, and hyperlipidemia are more common in SLE pts |
|
effects of SLE on the spleen
|
Central penicilliary arts may show a concentric intimal and smooth muscle hyperplasia(onion-skin lesions)
|
|
effects of SLE on LNs
|
LNs are enlarged with hyperplastic follicles or even demonstrate necrotizing lymphadenitis
|
|
what are used to tx the SLE exacerbations
|
Corticosteroids
|
|
the most common cause of death in SLE
|
renal failure and intercurrent infections
|
|
what Abs are rarely present in Chronic discoid Lupus erythematosus
|
Abs to dsDNA
|
|
what is deposited at the dermoepidermal junction
|
Ig and C3
|
|
what is the main Ab in subacute cutaneous lupus erythematosus
|
Abs to SS-A
|
|
what gene is assoc with subacute cutaneous lupus erythematosus
|
HLA-DR3
|
|
what systems are rarely involved in drug-induced lupus erythematosus
|
renal and CNS
|
|
What Abs are assoc with drug-induced lupus erythematosus
|
Abs to histones
|
|
what genes are assoc with drug-induced lupus erythematosus
|
HLA-DR4
|
|
characteristics of sjogren syndrome
|
dry eyes(keratoconjunctivitis sicca)
dry mouth(xerostomia) both are due to destruction of the lacrimal and salivary glands due to lymphocytic infiltration and fibrosis |
|
what is the most common syndrome assoc with sjogrens
|
RA
|
|
what are the predominant cells of the infiltrates in sjogrens
|
CD4+ helper T cells and some B cells, incl plasma cells
|
|
why are sjogrens and RA commonly assoc
|
sjogrens pts commonly have Rh factor(an Ab reactive with self-Ag)
|
|
what are the main Abs in sjogrens against
|
nucleoprotein Ags SS-A and SS-B
|
|
what are pts with SS-A in sjogrens more likely to have
|
early disease onset
longer disease duration extraglandular manifestations |
|
what are the genes assoc with sjogrens
|
HLA-DQA1
HLA-DQB1 |
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what is the suspected initiating trigger of sjogrens
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viral inf of the salivary glands which cause local cell death and release of tissue self-Ags
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what is the auto-Ag in sjogrens
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the cytoskeletal protein alpha-fodrin
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what fvirus causes a clinical disease similar to sjogrens
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HTLV-1
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what are the morphological characteristics of sjogrens
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periductal and perivascular lymphocytic infiltration
there can be lymphoid follicles and germinal centers in the salivary glands |
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what group is at the highest risk for sjogrens
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women between 50 and 60yo
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extraglandular Sx of sjogrens
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synovitis, diffuse pulmonary fibrosis, and peripheral neuropathy
they are more common pts with SS-A Abs there can be tubulointerstitial nephritis Hyperplastic LNs |
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how do you Dx sjogrens
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Biopsy of the lip to examine minor salivary glands
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what cancer is assoc with sjogrens
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A marginal zone B cell lymphoma
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characteristics of scleroderma
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1)chronic inflam as a result of AI
2)widespread damage to small blood vessels 3)progressive interstitial and perivascular fibrosis in the skin and mult organs |
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characteristics of diffuse scleroderma
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widespread skin involvment at onset
rapid progression and early visceral involvement |
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characteristics of limited scleroderma
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skin involvement is confined to the fingers, forearms, and face
visceral involvement is late some pts can develop CREST syndrome |
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what is CREST syndrome
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Calcinosis
Raynauds phenomenon esophageal dysmotility sclerodactyly telangiectasia |
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what cells are implicated in scleroderma
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CD4+ T cells(Th2 are common)
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what cytokines are involved in scleroderma
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TGF-beta and IL13 because they stim transcription of genes that encode collagen and other matrix proteins(fibronectin) in fibroblasts
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what Ab is specific for scleroderma
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Ab for DNA topoisomerase I(anti-Scl 70), assoc with pulmonary fibrosis and periph vascular disease
and anticentromere Ab, assoc with CREST syndrome |
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what is commonly the initial lesion of scleroderma
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microvascular disease
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what is a trigger for perivascular fibrosis in scleroderma
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endothelial injury that causes platelet aggregation causing the release of platelet and endothelial factors(PDGF and TGF-Beta)
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what special features do vascular smooth muscle cells have in scleroderma
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inc expression of adrenergic receptors
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what morphologic effect does scleroderma have on the skin
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inc of collagen in the dermis
thinning of the epidermis loss of rete pegs atrophy of the dermal appendages hyaline thickening of the walls of the BVs |
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what effect does scleroderma have on the alimentary tract
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progressive atrophy and collagenous fibrous replacement of the muscularis(most prominent at the esophagus)
excess collagenization of the lamina propria and submucosa loss of villi and microvilli in the small intestine lower esophageal dysfx |
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what are the effects of scleroderma on the musculoskeletal system
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hypertrophy and hyperplasia of the synovial soft tissue
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what are the Abs reactive to in mixed connective tissue
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ribonucleoprotein particle-containing U1 ribonucleoprotein
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what vessels are involved in polyarteritis nodosa
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all types
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