Pathology of Immunologic Injury 2: the systemic autoimmune diseases Flashcards
1
Q
central tolerance happens
A
mostly before birth
2
Q
central tolerance T cells and b cells
A
Autoreactive T cells are killed
autoreactive B cells have their receptors modified
3
Q
The idea that autoimmunity may have to do with failure of ____ has some empirical support
A
central tolerance
4
Q
Autoimmune polyendocrinopathy type I is a fortunately uncommon autosomal ______ illness in which patients tend to suffer from
A
recessive
several different T cell mediated autoimmune diseases *as well as candidiasis and epidermal problems
- hypothyroidism, chronic hepatitis, vitiligo, pernicious anemia, type I diabetes
5
Q
Autoimmune polyendocirnopathy type one locus is ath
A
AIRE (autoimmune related), which is a key protein in deleting auto reactive T cells before birth
6
Q
after birth, auto reactive lymphocytes may be kept from causing trouble by several ________mechanisms
A
peripheral tolerance
7
Q
Peripheral tolerance: lymphocytes recognizing self antigen may be
A
rendered no responsive by the ways in which they are presented.
8
Q
mutations in CTLA-4 and PD-1 - immune response brakes are each linked to
A
risk for autoimmune disease
9
Q
Regulatory t cells are distinguished by
A
CD25/IL-2 a chain and foxp3/scurfin
10
Q
Regulatory t cell function
A
suppress immunity to self
11
Q
mutations in Treg cells (in either the CD25 or Foxp3) cause
A
a rare, grisly autoimmune disease that may require marrow transplantation
12
Q
When auto reactive T cells activate, they undergo
A
apoptosis.
13
Q
mice with defective fas or fasL get a ____ illness
A
lupus like
14
Q
Thinking about autoimmunity focuses on
A
polygenic inheritance with some environmental stimulus as well
15
Q
The most often mutated gene in autoimmuniity is
A
PTPN22, a tyrosine kinase involved in lymphocyte responses
16
Q
Other mutations in autoimmunity are
A
NOD2 (a microbe sensor)
CD25 (Treg)
IL-17 a chains
17
Q
actual triggers of autimmunity focus on
A
molecular mimicry by infections
18
Q
molecular mimicry
A
many known examples, the most famous is sensitization to strep cross-reacting with heart - rheumatic fever
19
Q
rheumatic fever
A
molecular mimicry
sensitization to strep cross reacting with the heart
20
Q
mutated lymphocytes
A
before birth, we destroy our auto reactive lymphocytes. are the lymphocytes of people with autoimmune disease mutants that form after birth?
21
Q
Microchimerism
A
everyone carries a few of their mother’s cells
all mothers keep a few of the cells of the children they have carried
rumored to be more abundant in those with autoimmune disease
22
Q
Antinuclear antibodies- rim pattern.
A
Think classic system lupus, anti ds-DNA
23
Q
Detect ANAs by
A
applying patient serum to normal cells then lighting up Abs that stick
24
Q
antinublear antibodies: homogenous pattern
A
think drug-lupus
25
antinuclear antibodies: speckled pattern
think anything
26
antinuclear antibodies: centromere pattern
think CREST
27
antinublear antibodies: nucleolar pattern
think Scleroderma
28
anti-dsDNA
sensitive and specific for systemic lupus.
| rim pattern on ANA
29
anti ss DNA
think of drug induced lupus
30
anti histone
think of drug induced lupus
31
anti-Sm (Smith)
only about 1/3 of systemic lupus patients have this autoantibodie, but it essentially makes the diagnosis
32
anti-Ro/SSA (Sjorgren's A)
Most Sjogren's patients, and many other folks. Much hated as the cause of neonatal lupus (heart block) when the mother has the antibody
33
anti-La/SSB (Sjogren's B)
most Sjogren's patients and many other folks
34
anti U1RNP (U1 ribonucleoprotein)
if this is your predominant autoantibody, you have mixed connective tissue disease
35
anti-Scl70 (anti topoisomerase)
common in patients with scleroderma, fairly specific
36
anti-RNA polymerase III:
common and fairly specific in scleroderma,
37
anti-centromere
the antibody for CREST, the "milder version of scleroderma"
38
Anti Jo (Jo, transfer RNA synthetase):
seen in many patients with polymyositis/dermatomyositis. Runs with severe disease, lung damage, arthritis, and mechanic's hand
39
Anti-Mi2 (against a helices that remodels nucleosomes)
seen in dermatomyositis, especially when the rash is prominent
40
Anti-SRP (signal recognizing polypeptide)
may define a sever polymyositis variant with severe necrotizing myopathy
41
anty P1-55 TIF1g and anti P140/MJ
juvenile and paraneoplastic dermatomysoitis
42
Lupus, scleroderma, Sjogrens, and polymyositis/ dermatomyositis may all be accompanied by a ______. unlike rheumatoid arthritis, there is usually no _____
synovitis
| major damage to the joints
43
Butterfly rash
lupus
| wolf-like.
44
systemic lupus erytematosus
susceptibility genes +external triggers
persistent high level antinuclear IgG antibody production
45
Lupus
is a systemic AI dz characterized primarily by autoantibodies, primarily against nuclear antigens
is a dz of exacerbations and remissions. UV light triggers flareups. XX and XXYs are much more likely to be affected than XYs and XOs. Identical twins are around 30% concordant; dizygotic twins only about 2%. People of european ancestry are at relatively less risk
46
Etiology of lupus
unknown. the linked genetic loci are involved with interferons and lymphocyte responses
47
who is immune to new onset SLE
no one
48
Models for lupus include several
drug reactions
(hydralazine and procainamide, and anti-aTNF)
genetic deficiencies in certain complement components
(perhaps these percent clearance of immune complexes; C1q is important in removing apoptotic bodies
49
the recent 30 new susceptibility loci for SLE are related to
interferons
50
Most of the tissue injury in SLE seems to be related to
deposition of immune complexes (typeIII).
| the destruction of RBC, neutrophils and/or platelets can be due to antibodies against these blood components (TypeII)
51
lupus anticoagulants
antibodies against phopholipid complexes produce lupus anticoagulants (they actually make the blood clot more in people, though less in the lab) and cause false positive syphilis screening tests
52
You need ___ of 11 criteron
4
53
Criterion for SLE, you need for of 11
malar rash
discoid rash
photosensitivity
oral ulcers
arthritis
serositis
Renal disorder (proteinuria or celluar casts)
Neuro disorder (seizures or psychosis)
Hematologic disorder (hemolysis, low WBC/lymphs/pl's)
Immune (anti-DNA/anti-Sm/antiphopholipid/false syph)
antinuclear antibodies
54
what triggers lupus
apoptoti bodies, alfalfa, much more
55
Hematoxylin bodies
stripped nuclei acted on by ANA's in lupus
56
LE cell
a stippped nucleus opsonized by anti nuclear antibodies and now being devoured by phacocytes
57
Similar homogenized nuclei produce
hematoxylin bodies
58
lupus in kidney
lupus glomerulopathy
59
lupus vasculitis
immune complex mediated
60
spleen in lupus
adventitial onion skinning in spleen
61
In the kidney with lupus, we see
lupus glomerular immune complex deposits
glomerulonephritis
segmental necrotizing lupus glomerulonephritis can happen
62
wire loop
a massive immune complex deposit in a glomerulus
63
interstitial nephritis in lupus
autoantibodies against tubules
64
if you were to biopsy the butterfly rash, you will find
hydropic change of the basal layer and vasculitis
65
lupus band test:
granular immunoglobulin and complement at the dermal -epidermal junction
66
mouth ulcers in lupus are
infarcts from vasculitis (so are the familiar canker sores that many of you have had)
67
Lupus pericarditis
fibrin on the heart surface
68
libman sacks endocarditis in lupus
sterile thrombi on the lines of closure
| all surfaces of leaflets
69
neonatal lupus
child has rash. more ominous is heart block caused by mom's autoantibodies, famously anti-Ro
70
Blood
polyclonal gammopahty (increased Igs of many kinds)
AI lysis of red cells (Ab against your own RBCS) "coombs positive hemolysis)
AI destruction of neutrophils
AI destruction of platelets
low total lymphocyte count (
71
______ kill many lupus patients
DVT/ pulmonary emboli
72
Brain
CNS involvement in its with SLE can produce physiological problems that include personality disorders and frank psychoses. Grand mal seizures may be seen, as well as strokes
73
behavioral changes in lupus
may range from mild to florid psychosis
74
Lupus patients feel _____ than they look
much worse
75
subacute cutaneous lupus
Anti-Ro is usually seen. many patients with this rash have lupus; others have Sjogren's or rheumatoid arthritis. (leave diagnosis to Derm. Stay out of sun, and treat with topical glucocorticoids)
76
Discoid lupus
the rash is familiar - patches with scales and lost hairs
"wolf bites?"
many its with systemic lupus have discoid lupus as well
just discoid=as common as systemic.
keep out of sun
77
can see patches of hyperkeratosis as plugs. hydropic change, lymphocytes in patches of
discoid lupus
78
Drug induced lupus
historically hydralazine, procainamide, and isoniazid.
| anti-histone antibodies and a homogenous pattern
79
Drug induced lupus - where do we see it
today 1 in 250 its receiving anti -a TNF rx will develop a rash and anti dsDNA antibodies
80
incomplete lupus
some ppl will seem to have lupus (feeling terrible most of the time) and have some of the symptoms/signs/labs, but not meet the official 4/11.
the prognosis is generally good
81
Sjoren's
the salivary and lacrimal glands fill with very angry lymphocytes
82
Sjorens syndrome
is a very poorly understood syndrome in which autoimmunity damages the salivary and lacrimal glands
HLA linkages are known, Viral syndromes (HIV, HTLV-1, Hep C) can mimic it, it tends to run with other systemic AI diseases (lupus, scleroderma, RA, PM.DM, MCTD) and most patients have a pari of autoantibodies (anti -SSA/Ro and anti SSB/La)
83
Sjogrens and teeth
having no saliva is bad for the teeth
84
Kerotoconjunctivitis sicca
sever dry eyes of sjorens
85
xerostomia
severe dry mouth (sjorens)
86
Mikulicz's syndrome
much enlarged salivary and lacrimal glands, usu in the setting of dry eyes/moutn (sjorens)
87
treatment of Sjogrens
symptomatic
88
Schirmer test
how far does the water go on the filter paper
| may be required to "prove the diagnosis of dry eyes" take a history instead.
89
Other organs that may be involved in Sjogren's
vasculitis with encephalopathy
lymphocytic pneumonitis
interstitial nephritis
pancreatic involvement with maldigestion may be missed easily.
90
most feared complication of Sjogrens
malignant lymphoma, much more frequent in Sjogren's pts
91
Scleroderma aka
systemic sclerosis
92
scleroderma
relatively common dread AI disease in which transient inflammation is followed by dense fibrosis, and the intimal layers of small blog vessel often undergo fibrous thickening
93
sclerodactyly
in which the hands come to resemble those of a mannequin in scleroderma
94
scleroderma almost always begins with
Raynaud's (although most Raynaud's its never get anything else)
95
Scleroderma mechainsm
early the involved areas become inflamed, with fibrosis following as the inflammation moves on. Biopsy would show abundant CD4 T cells at this stage
96
you can also see ____ deposits in scleroderma
calcium
97
telangiectasias at the nail bases. many vessel are gone, those that remain are dilated tufts
scleroderma
98
Face changes in scleroderma can include
telangiectasias on the face; thick skin
99
lungs in scleroderma
plumonary fibrosis. Death in scleroderma is often due to pulmonary fibrosis/ pulmonary vascualar narrowing "pulmonary ypertension:
100
gut involvemen in scleroderma
may include fibrosis of the esophagus (difficulty swallowing, strictures) and/or the small bowel (malabsorption)
not the hidebound crowding of the valvulae conniventes
101
skin in scleroderma
dense dermis, flattened dermal-epidermal junction. lost adnexal structures. adenoma gone except fro arrestor pili muscles. patches of lymphocytes
102
scleroderma in artery .
onionskining, lumen greatly narrowed (renal artery)
| intimal fibrosis in finger artery (hence reynauds)
103
limited scleroderma includes several entities that do not have the ________ and ________ of the diffuse dz.
rapid onset
| generalized distribution
104
CREST syndrome (anti centromere antibody disease) features
Calcinosis (calcium deposits in the skin)
Raynauds
Esophageal fibrosis
Sclerodactyly (and maybe involvement of the face)
Telangiectasias
105
morphea
scleroderma-like changes in a patch
the histopathology, with an initial CD4 lymphocyte rich inflammation, then fibrosis and vessel changes, is like slceroderma
106
en coup de sabre/ saber cut
localized linear scleroderma
107
Parry Romberg
scar contracts over 1/2 of face, the underlying skull is likely to become deformed. mystery illness
108
eosinophilic fasciitis
tight skin with many eosinophils in the subcutis and fascia
109
why should eosinophilic fasciitis not be called a scleroderma variant
there is no raynauds, little involvement of the skin, little else to suggest systemic illness, and non antinuclear or specific antibodies
110
Cause of eosinophilic fasciitis, and tx
cause - unknown
| glucocorticoid treatment--> remits
111
______ and _____ are a pair of dz.'s that are distinct but are usually discussed together
polymyositis and dermatomyositis
112
similarities of polymositis and dermatomyositis
| key difference?
clinical pictures are similar.
| key difference= only dermatomyositis has the characteristic rash
113
what is different between polymyositis and dermatomyositis
the muscle pathology and what we know of the immunopathology
114
presentation of polymyositis and dermatomyositis
usually present as gradual (weeks to months) onset of weakness in the proximal muscles, both are clearly systemic AI dz's
115
Findings in polymyositis and dermatomyositis
creatine kinase and aldolase levels are likely to be very high
muscle and skin can calcify
although mm dz is usually the most prominent feature, there may be inflammatory arthritis and/or lung damage (usu interstitial fibrosis)
involvement of the upper esophagus may make swallowing a problem and sometimes the heart muscle is involved and weakened
116
in polymyositis the distinctive lesion is
extensive infiltration of mm by Cd8 lymphocytes with obvious injury to the mm cells themselves
the lymphocytes are in endomysium around the mm cells
the vessels do not seem to be involved
117
damaged mm. lymphocyte infiltrate throughout , cd8 cells
polymyositis
118
polymyositis can cause
atrophy and calcification of the affected muscle
119
in dermatomyositis, the lymphocytic infiltrate is
within or near the perimysium and around the blood vessels
the infiltrate is a mix of Cd4 T cells, B cells, and plasma cells
MAC complex is often seen in vessel walls, unlike polymositis
120
most atropied muscle fibers in dermatomyositis
muscle fibers at the edges of the fascicles
121
Grotton's sign on the knuckles
marker for dermatomyositis
122
mechanic's hands
a poorly understood sign in polymyositis/ dermatomyositis/ anti-synthetase (Jo1) syndrome
123
new onset of polymyositis/dermatomyositis in an adult, especially ______ can warn of
dermatomyositis
| an occult cancer, usually one of the common ones
124
MCTD=
mixed connective tissue dz
125
MCTD is the best known of the overlap syndromes, combining
features of lupus, scleroderma, RA, and polymyositis.
| anti-U1-RNP is the high titer antibody
126
MCTD pathology
usually starts as synovits of the fingers plus Raynaud's. Sclerodactyly may occur as in scleroderma.
skin changes range from rash to calcification
epicardial fibrosis, muscle atrophy and fibrosis
fibrosis of the gut wall,
There's often a good response to glucocorticoids and the kidneys tend to be spared. - the only kidney lesion is vascular
127
if MCTD progresses
(if the dz proves aggressive), death is usu due to pulmonary vascular sclerosis (pulmonary hypertension)/ pulmonary fibrosis
128
IgG4-related disease is a newly recognized group of several previously mysterious _____ diseases
fibroinflammatory
whether this is AI disease, and best how to treat is still unanswered
129
IgG4 related diseases include
```
Riedel's fibrosing thyroiditis
AI pancreatitis
Retroperitoneal fibrosis/periaoritis
Fibrosis of the salivary and/or lacrimal glands
about a dozen others
```
130
The characteristic features of IgG4-related diseases are
fibrosis with a cartwheel pattern
plasma cells making IgG4 in the lesion(s)
Increased IgG4 in the blood (about 2/3 of patients)
