Autoimmune Flashcards
1
Q
Principal mechanism of central tolerance
A
antigen-induced deletion of self-reactive lymphocytes in central lymphoic organs
2
Q
___ is often the first manifestation of SS
A
Puffy Fingers
3
Q
___ of the muscularis may develop in gut in SS
A
Progressive atrophy and collagenous fibrous replacement
4
Q
2 ANA’s virtually unique to SS
A
Anti-Scl 70 (topo1) and Anticentromere Ab
5
Q
4 environmental factors implicated in SLE
A
UV, Cigarrettes, Sex hormones, Drugs (procainamide, hydralazine)
6
Q
Ab’s for dsDNA and Smith antigen
A
Specific for SLE
7
Q
Ab’s in Limited vs Diffuse SS
A
Limited: Anti-centromere; Diffuse: Anti-Scl-70
8
Q
Ab’s to __ and __ are specific for SLE
A
dsDNA and Smith antigen
9
Q
About half of SS deaths are attributable to
A
Renal failure
10
Q
Acute cellular rejection is typically accompanied by clinical signs of
A
renal failure
11
Q
Acute cellular transplant rejection primarily involves
A
Tubules and Interstitium
12
Q
Acute GVHD causes epithelium necrosis in 3 principal organs
A
Liver, Skin, Gut
13
Q
Acute humoral rejection mainly effects
A
Graft vasculature
14
Q
Acute humoral transpant rejection is dx by
A
Staining for C4d
15
Q
Advanced Sclerosing Lupus Nephritis (VI) is characterized by
A
Complete sclerosis of >90% of glomeruli –> Corresponds to end stage renal disease
16
Q
Almost all SS patients exhibit
A
Raynaud
17
Q
ALPS is characterized by
A
Lymphadenopathy and multiple auto-antibodies, including anti-DNA
18
Q
Anti-CD20 Ab
A
Rituximab
19
Q
Anti-centromere Ab’s are MOST associated with
A
CREST syndrome
20
Q
Anti-histones indicates
A
SLE
21
Q
Anti-Jo 1 (histidyl tRNA ligase) Ab’s are associated with
A
Inflammatory myopathies
22
Q
Anti-RNP U1 Ab’s are associated with
A
Mixed CT Disease, SLE
23
Q
Anti-RNP U1 indicates
A
SLE, mixed CT disease
24
Q
Anti-Scl 70 (topo1) and Anticentromere Ab
A
2 ANA’s virtually unique to SS
25
Anti-Scl 70 Ab in SS indictaes
more aggressive disease with pulmonary fibrosis and peripheral vascular changes
26
Anti-Scl-70 Ab's are associated with
Systemic Sclerosis
27
Anti-Scl-70 indicates
Systemic Sclerosis
28
Anti-SS-A and -B are associated with
Sjogren Syndrome, SLE
29
Anti-SS-A, -B indicates
Sjogren, SLE
30
Anticentromere Ab in SS indicates
relatively benign course
31
Atherosclerosis in SLE
accelerated --> coronary artery disease
32
Auto-Ab's against phospholipids lead to
increased thrombosis --> recurrent spont abortions and thrombotic episodes
33
Autoamputaton
SS
34
Autoimmune disorder characterized by excessive fibrosis in multiple tissues, obliterative vascular disease, and multiple auto-Ab's
Systemic Sclerosis
35
B cells can become anergic if they encounter antigen in absence of
specific helpter T cells
36
B cells in Sjogren
Hyperactive, evidenced by ANA's and RF
37
Blood vessels in SLE
Acute necrotizing vasculitis --> Fibrinoid deposits withing vessel walls containing Ab, DNA, complement, and fibrinogen
38
Cardiac involvement in SLE
primarily endocarditis
39
Chronic GVHD develop skin lesions resembling
SS
40
Chronic rejection is dominated by
vascular changes (ateriosclerosis), interstitial fibrosis, loss of renal parenchyma
41
Chronic rejection is probably mediated by
T cell reaction and secretion of cytokines that induce proliferation of vascular SM cells
42
CNS disease in SLE is often ascribed to
Vascular lesions causing ischemia or multifocal cerebral microinfarcts
43
Concentric sclerosing intimal thickening of interlobar arteris
Onion skinning in SS
44
CREST presentation is seen in
Limited Scleroderma
45
CREST Syndrome
Scleroderma: Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangectasia
46
Cyclosporine and FK506 suppress
T cell mediated immunity by inhibiting IL-2 transcription
47
Diffuse Lupus Nephritis (IV) is distinguished from Focal Lupus Nephritis by
involvement of half or more glomeruli
48
Distinctive feature of SS
Striking cutaneous involvement
49
Does having a C1q, C2, or C4 deficiency predispose to Lupus?
Yes
50
Does having low leves of IFN-alpha predispose to getting lupus?
No, high levels do
51
Dominant T cells in Scleroderma
Th2
52
Dysfunction of LESphincter and Barret's Disease
SS
53
Esophageal involvement in SS leads to
Aspiration pneumonia
54
Extraglandular manifestations of Sjogren
Synovitis, Pulmonary Fibrosis, Peripheral Neuropathy
55
Fingers take on a tapered, clawlike appearance with limited motion
Late Scleroderma
56
Genetic deficiencies in classical complement pathway are seen in __ patients with SLE
10%
57
GI tract is affected in what percent of SS patients
90%
58
Having lymphocytes with __ predisposes to getting lupus
TLR7, 9
59
Histology of *cellular acute transplant rejection is marked by
Interstitial mononuclear cell infiltrate with edema and parenchymal injury
60
Histology of *humoral acute transplant rejection
Vasculitis
61
Histology of Hyperacute rejection
Acute arteritis, vessel thrombosis, and ischemic necrosis
62
Histopathological findings in skin of early SS
Edema and perivascular infiltrates containing CD4 T cells
63
Histopathological findings in skin of SLE
(1) Liquefactive degeneration of basal layer of epidermis; (2) Edema at dermoepidermal jxn; (3) Mononuclear inflitrates around blood vessels and skin appendages
64
HLA types predisposing to Lupus
HLA-DR2, HLA-DR3
65
How do Ab's mediate graft rejection
Bind to graft endothelium and cause vascular injury thru complement activation and recruitment of leukocytes
66
Hyperacute rejection is due to
Pre-formed anti-donor Ab's
67
IgG4-RD is characterized by
Tendency to form tumor-like lesions in severl organs
68
immune complex deposits are thought to cause tissue damage by
activating classical complement pathway
69
Immune complex is what type of hypersensitivity
Type 3
70
Immune responses in acute rejection
both cellular and humoral
71
In early SS, affeccted skin is somewhat
edematous and doughy in consistency
72
In hyperacute rejection, Ab's bind to graft endothelium and cause
Thrombosis, Ischemia, Rapid Graft failiure
73
In Scleroderma, activated T cells and mac's produce
cytokines that activated fibroblasts and stimulate collagen production
74
In Scleroderma, cytokines that activate fibroblasts include
TGF-Beta, IL-13, PDGF, others
75
In Scleroderma, TH2 cells and their cytokines induce
Alternative macrophage activation and collagen deposition
76
In Sjogren, there is a 40-fold increased risk for developing
non-Hodgkin b cell lymphoma
77
In SS, capillaries and small arteries may show
thickening of Basal Lamina, endothelial damage, and partial occlusion
78
In SS, in the absence of __ involvement, lifespan may be normal
Renal
79
In SS, repeated bouts of endothelial damage followed by platelet agg lead to
Endothelial proliferation and Intimal Fibrosis --> Narrow small vessels --> Ischemia injury
80
In SS, there is marked increase in __ in the dermis
compact collagen
81
Increasing number of patients with SLE show this cardiac pathology:
Coronary Artery Disease
82
INF-alpha in SLE
patients produce abnormally large amounts
83
Joint involvement in SLE
Swelling and nonspecific mononuclear cell infiltration of synovial membranes
84
Kidney transplant biopsy can also reveal
infections such as polyomavirus
85
LE/Hematoxylin Bodies
Nuclei of damaged cells react with ANAs, lose their chromatin pattern, and become homogenous
86
Limited Scleroderma is often confined to
Fingers and Face
87
Liver in SLE
Nonspecific inflammation of portal tracts
88
Lung involvement in SS
Pulmonary htn and/or interstitial fibrosis
89
Lung involvement in SS leads to
Interstitial fibrosis
90
Lungs in SLE
Interstitial fibrosis, Pleural inflammation
91
Lupus anticoagulants
Anti-phospholipid antibodies --> interfere with clotting tests
92
Major culprits contributing to direct recognition
DC's in the graft (many MHC's expressed)
93
Major target of Systemic Sclerosis
Skin
94
Membranous Lupus Nephritis is characterized by
widespread thickening of capillary wall due to deposition of subepithelial immune complexes
95
Mixed CT Disorder have high titers of
Anti-RNP U1
96
Mixed CT Disorder respond very well to
Corticosteroids
97
Most common associated disorders with Sjogren
RA first, SLE and others second
98
Most common causes of death from SLE are:
Renal Failure, Intercurrent Infections, Cardiovascular Disease
99
Most common glandular targets in Sjogrens
Lacrimal and Salivary glands
100
Most frequent pathologic CNS lesion in SLE
Small vessel angiopathy w/ noninflammatory intimal proliferation
101
Most important consequence of direct recognition
Activation of host CD8 T cells that recognize class I MHC (HLA-A and -B) in the graft
102
Most organ damage in SLE is caused by
Immune Complex Deposition
103
Most widely used method for detecting ANAs
Indirect immunofluorescence assay
104
Musculoskeletal changes in SS
Early: Synovial hyperplasia and inflammtion; Late: Fibrosis
105
Mutation in FAS gene
Autoimmune Lymphoproliferative Syndrome (ALPS)
106
Mutation in what causes ALPS
FAS
107
Mutation in what causes IPEX
Foxp3
108
Mutations in FOXP3 cause
IPEX --> Treg deficiency
109
Non-specific auto-Ab's for SLE
Anti-phospholipid, Anti-RNP U1, Anti-SSA A and B
110
Onion-Skin Lesions
Spleen of SLE --> Thickening and Perivascular fibrosis of Central penicillilary arteries
111
Organs affected in IgG4-RD
Almost every one
112
Pathogenesis of all forms of glomerulonephritis in SLE involves
deposition of anti-DNA immune complexes
113
Patients present with chronic rejection with progressive rise in
Serum Creatinine levels
114
Peak age incidence of SS
50-60
115
Percent of Sjogren patients that acquire extraglandular disease
25%
116
Percent of Sjogren patients with another accompanying autoimmune disorder
60%
117
Polyarteritis Nodosa belongs to a group of diseases characterized by
necrotizing inflammation of walls of blood vessels
118
Predominant cell type in acute transpant rejection
Depends on patient
119
Predominant cell type in IgG4-RD
T cells
120
Presentation of Sjogren
90% women between 35-45
121
Presenting manifestation of Systemic Sclerosis
Cutaneous involvement
122
Progressive rise of serum creatinine levels indicates
Chronic transplant rejection
123
Puffy fingers are often the first manifestation of
Systemic Sclerosis
124
Renal abnormalities are present in what percent of SS patients
two thirds
125
Renal lesions in Sjogren
Mild interstitial nephritis
126
Renal manifestation of SS
Thickening of vessel walls and interlobular arteries
127
Scleroderma is characterized by
(1) Excessive fibrosis in multiple tissues; (2) Obliterative vascular disease; (3) Multiple Auto-Ab's
128
Self-reactive B cells that are not deleted undergo
Receptor editing
129
Serosal manifestations of SLE
Inflammatory changes: Serous effusions, fibrinous exudates
130
Sjogren is autoimmune mediated by
CD4 T cells
131
SLE complement deficiencies may result in
defective clearance of immune complexes and apoptotic cells; failure of B cell tolerance
132
SLE patients have higher frequency of auto-reactive __ cells
B cells
133
SLE principally affects the
skin, kidneys, serosal membranes, joints, and heart
134
Specificity and Sensitivity of IFA for SLE
High Sensitivity, Limited Specificity
135
SS is most associated with Ab's against
DNA Topo 1 (Anti-Scl 70)
136
Systemic changes in SLE consist essentially of
acute vasculitis of small vessels, foci of mononuclear infiltrations, and fibrinoid deposits
137
T cells destroy graft parenchyma (and vessels) by cytotoxicyt and inflammatory reactions
Acute Cellular Rejection
138
T/F: Anti-RNP antigens SS-A and SS-B are dx for Sjogren
False, also present in SLE
139
T/F: People deficient in C1q are protected from SLE
FALSE
140
T/F: Sjogren has RF even in absence of RA
TRUE
141
The best-defined populations of Tregs express
CD25, one of the chains of the receptor for IL-2
142
Timeline of acute rejection of transplant
Days to months
143
Transplant patients can also have
infection
144
Tregs require __ for their generation and survival
IL-2
145
Vascular lesions in chronic rejection typically result in
compromised vascular perfusion --> Renal ischemia
146
Virtually are arteries in hyperacute rejection exhibit
characteristic acute fibrinoid necrosis of walls, with narrowing or complete occlusion of lumens
147
What causes ischemia injury in SS
Endotheial proliferation and Intimal Fibrosis --> Narrow small vessels --> Ischemic Injury
148
What causes wire loops
Circumferential thickening of capillary wall by extensive, subendothelial immune complexes
149
What clinical manifestation is present in 100% of patients with SLE
Hematologic
150
What has been implicated in neuropsychiatric complications of SLE
Auto-Ab's against CNS receptors for various NT's
151
What indicates B cell activation in SS
Hypergammaglobulinemia, ANAs
152
What indicates more aggressive SS
Anti-Scl 70
153
What indicates more benign SS
Anti-centromere Ab
154
What infiltrates affected glands in Sjogrens
Lymphocytes (CD4) and Plasma Cells
155
What is keratoconjunctivitis
Drying of corneal epithelium, inflammation, erosion, ucleration
156
What is used to detect antibody-mediated rejection of kidney allografts
Local deposition of complement breakdown products
157
Where is atrophy and fibrous replacement of GI most severe in SS
Esophagus
158
Which parts of glomerulus show proliferation in lupus nephritis
endothelium and mesangium
159
Wire loops are due to
subendothelial immune complex deposits
160
With advanced lung involvement in SS, what may develop
Secondary pulmonary htn --> Right sided heart failure
161
With progress of SS, edematous phase is replaced by
progressive fibrosis of dermis
162
Xerostomia
Inflammatory fissuring and ulceration of oral mucosa
