Immunopathology 2 Flashcards
1
Q
Autoimmunity can arise from these 3 factors?
A
Genetic
Environmental
Immunity
2
Q
Name 4 autoimmune disorders:
A
- SLE
- Rheumatoid arthritis
- Sjogren
- Scleroderma
- Dermatomyositis
3
Q
SLE damage is caused by what?
A
mostly due to deposition of immune complexes
4
Q
what is noticible in this picture?
A
SLE (Class IV): deposits thickening capillary walls and thrombi (blue arrows)
5
Q
SLE is what type of hypersensitivity?
A
Hypersensitivity type 3
6
Q
what disease is this?
what are the arrows pointing at?
A
Lupus nephritis (class 4 lupus)
arrows point at wire loop lesions
7
Q
what disease causes this?
A
SLE
8
Q
what is being shown here? (arrows)
what disease causes this?
A
Libman-Sacks endocarditis of the mitral valve in lupus erythematosus. The vegetations attached to the margin of the thickened valve leaflet are indicated by arrows. Non-bacterial verrucous
SLE causes this
9
Q
what disease is this?
what is the name for this symptom?
A
SLE
malar rash
10
Q
in what disease we see this?
what is being shown here?
A
SLE class 4
narrowing of glomerular capillaries by mesangial and endocapillary proliferation. Wire-loop deposits and hyaline thrombi are segmentally distributed
11
Q
what is the cell being shown by the arrow?
This characteristic appearace is found in what body parts or areas?
A
Pleural fluid. A neutrophil with an ingested large nucleus (nucleophagocytosis) (arrow) compressing the nucleus of the neutrophil (asterisk).
This appearance is characteristic of the L-E cell found in the blood, marrow, or serous effusions in patients with lupus erythematosus
12
Q
what disease causes this?
A
Rheumatoid arthritis
13
Q
In rheumatoid arthritis, what joint is usually spared? In what other disease is this joint not spared?
A
distal interphalangeal joint (DIP) unlike in osteoarthritis.
14
Q
what disease causes this?
what is going on in this picture?
A
Rheumatoid Arthritis
subsynovial tissue containing a dense lymphoid aggregate is seen
15
Q
what disease is this?
what is being seen in this picture?
A
Rheumatoid arthritis
Low magnification reveals marked synovial hypertrophy with formation of villi.
16
Q
what disease causes this?
What is being shown here?
A
Rheumatoid arthritis
A fibrinoid nodule = fibrinoid necrosis encapsulated by eptitheloid cells (granuloma formed)
17
Q
what is the clinical feature of rheumatoid arthritis?
A
- small joints of hands and feet
- early morning stiffness
- anything attached to the wrist will be affected
- ulnar deviation
- flexor tendon tendosynovitis (hallmark)
18
Q
what is this?
what disease?
A
swann neck deformity
rheumatoid arthritis
19
Q
what disease?
what is it?
A
rheumatoid arthritis
boutonnière deformity
20
Q
what disease causes this?
what is it?
A
rheumatoid arthritis
popliteal (Baker) cyst develops posteriorly and inferiorly to the knee as a distention of a local bursa
21
Q
what are the hematologic findings of rheumatoid arthritis?
A
Anemia of chronic disease (ACD)
22
Q
What will be the lab findings of rheumatoid arthritis?
A
- Rheumatoid Factor (RF): most common is IgM
- Normal to increased serum C3
- C3 levels are low in synovial fluid
- Synovial fluid analysis: presence of white cells
- RF can be detected in synovial fluid
- *antibodies to cyclic citrullinated peptides (anti-CCPs)
23
Q
what can be expected in radiological labs for rheumatoid arthritis?
A
Plain X-ray, USG, MRI
24
Q
what is Sjögren Syndrome?
A
chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration of exocrine glands
25
what are the main symptoms seen in Sjögren Syndrome?
xerostomia dry mouth
dry eyes (keratoconjunctivitis)
dental caries
26
why do you see decrease in tears and saliva (sicca syndrome)?
lymphocytic infiltrate and fibrosis of lacrimal and salivary gland
27
what cells are mostly predominate the inflammation?
CD4+ helper T-cells predominate the inflammation, along with B cells, and plasma cells
28
what other anti-bodies can be found in inflammation during Sjögren Syndrome? which are the most important?
also antinuclear antibodies such as rheumatoid factor , and other are present
most important:
SS-A (Ro)
SS-B (La)
29
Sjögren Syndrome is associated with what two HLA genes?
HLA association: HLA-B8, HLA-DR3
30
in Sjögren Syndrome, what do we find in the salivary glands?
periductal and perivascular lymphocytic infiltration
lymphoid follicles with germinal centers may appear
31
in Sjögren Syndrome, how do the ducts look? what does this lead to later?
ductal lining cells show hyperplasia, this leads to obstruction
later there is acinar atrophy, fibrosis, and hyalinization
32
where is this?
In what disease can we see this?
what is the left circle?
what is the right circle?
salivary gland
sjogren disease
gland
duct
33
what can we see in this picture?
in what disease can we expect this?
Note: dense lymphocytic inflammation, fibrosis
Sjogren syndrome
34
what can we find in the labs for sjogren syndrome?
antibodies in serum: SS-A(Ro), SS-B(La)
positive RF
35
patients with sjogren syndrome are at risk of what cancer?
lymphoma of marginal zone
36
what is Systemic Sclerosis (scleroderma)?
## Footnote
chronic inflammation (autoimmune),
2) widespread damage to small blood vessels, and
3) progressive interstitial and perivascular fibrosis in skin (hardening of skin (it stretches)) and multiple organs
37
in scleroderma, why is there autoimmunity?
CD4+ T cells responding to unknown antigen in skin
this activates inflammatory cells and fibroblasts
cytokines from T-cells (TGF-β, IL-13)
38
why is there vascular damage in scleroderma?
intimal proliferation, endothelial activation, and injury
39
why is there fibrosis in scleroderma?
due to activated macrophages,fibrogenic cytokines
40
in scleroderma, where does the sclerotic atrophy start? where does it go after?
begins with fingers and distal regions of upper extremities,
later involves neck and face
41
what will be seen in the histology of scleroderma?
* edema, perivascular infiltrates (CD4+ T cells)
* swelling and degeneration of collagen (eosinophilic staining)
* capillaries and small vessels show thickened basal lamina, endothelial damage, and partial occlusion
42
what are the clinical symptoms of scleroderma?
C: calcinosis cutis
R: Raynaud’s phenomenon
E: esophageal dysfuntion
S: sclerodactly (tapered fingers, claw-like)
T: telangiectasia
**CREST**
43
what changes do we see in the skin during scleroderma?
* increasing fibrosis of dermis, tightly bound to subcutaneous structures
* increase in compact collagen, and thinning of epidermis, loss of rete pegs
44
what disease is this?
what is being shown here?
scleroderma
## Footnote
Sclerodactyly with dermatogenous contractures
45
what disease is this?
what is being shown here?
scleroderma
## Footnote
Microstomia (radial furrowing around the mouth) with the typical frenulum sclerosis.
46
What disease causes this?
what is being shown here?
scleroderma
## Footnote
Skin hardening/thickening proximal of the metacarpophalangeal-joints
47
what disease causes this?
what is being shown here?
scleroderma
## Footnote
Scleroderma-typical facial physiognomy with hypermimia, microstomia, telangiectasias and a beaked nose
48
in what disease do we see this?
what is this?
scleroderma
Digital ulcerations at the fingertips
49
what disease causes this?
what is this?
scleroderma
## Footnote
Digital ulcerations and necrosis of the fingertips
50
what disease causes this?
what is seen here?
Scleroderma
Severe calcifications with deposition of subcutaneous masses.
51
what disease cause?
what is seen here?
scleroderma
## Footnote
Multiple ulcerations at bone protuberantes with inflammation in the surrounding sclerotic skin.
52
what do you see here?
In what disease do we see this?
perivascular mononuclear cell infiltrate at the early stages of disease. Perivascular changes are shown at high power in the left panel.
scleroderma
53
what disease is this?
what do we see here?
Later stage disease show skin sclerosis, a low density of blood vessels, and absence of inflammatory cells.
At this stage, there may be associated epidermal changes with thickening and loss of secondary skin structures, including hair follicles and sweat glands. Absence of the rete ridges is also characteristic at the later stages
54
What is Raynaud's phenomena?
what areas does it affect?
* type of systemic scleroderma
* episode of vasoconstriction in the fingers and toes that occurs in virtually every patient with scleroderma
• affect the tip of the nose and earlobes
55
in Raynaud's phenomena, what triggers the changes seen?
exposure to cold, a decrease in temperature, emotional stress, and vibration
56
what changes are seen in raynaud's phonemenon?
the 3 color changes reflect the pathogenesis are...
skin changes to pale, cyanotic and erythematous
## Footnote
vasoconstriction, ischemia, and reperfusion
57
what is this disease?
Raynauds phenomena
58
what changes do we see in scleroderma in the GI?
progressive atrophy
collagenous fibrous replacement of the muscularis may develop
\*at any level of the gut but are most severe in the esophagus
* lower two thirds of the esophagus often develops a rubber-hose–like inflexibility
* metaplasia can occur
* leads to GERD
59
What changes are seen in Scleroderma in the Musculoskeletal system?
* synovium show inflammation, hypertrophy & hyperplasia
* unlike Rheumatoid Arhtritis, no joint destruction
60
SLE immune complexes will target what areas of the body?
skin,
joints,
kidney,
serosal membrane
61
SLE incidence is higher in what sex?
women
62
what is the fundamental defect in SLE?
Inability to maintain self-tolerance
63
What is the genetic component found in SLE?
1. higher incidence among family members
2. higher incidence among monozygotic twins
3. HLA association
64
What locus in the HLA gene leads to SLE?
HLA-DQ
65
the HLA gene is associated with SLE because of what?
because it is responsible for the formation of autoantibodies:
1. anti-double stranded DNA (ds)
2. anti- Smith (Sm)
3. antiphospholipid antibodies
66
What does the immunological factor that is found in SLE do?
* leads to persistence and uncontrolled activation of self-reactive lymphocytes
67
what 2 reasons cause the immunological factor in SLE?
1. defective elimination of self-reactive B cells in bone marrow or defect in peripheral tolerance
2. CD4+ helper T cells specific for nucleosomal antigens also escape tolerance and contribute to production of auto antibodies
68
What environmental factor contributes to SLE?
1. UV ray exposure:
cells exposed to UV rays undergo apoptosis, which illicit an immune response, activate keratinocyte who release IL-1 and induce inflammation
1. Estrogen
stimulate B cells to produce antibodies directed against DNA
69
How do immune complexes cause damage in SLE?
* immune complexes formed initiates inflammatory response in organs/tissue and anti DNA complexes go to glomeruli & small blood vessels (in other words they get tagged)
* autoantibodies look for these tags and opsonize WBC/RBC/Platelets that are damaged (they expose the nucleus to antinuclear antibodies)
70
what is another name for LE cells?
What is a LE cell?
hematoxilin bodies
LE cell is any phagocytic leukocyte that has engulfed denatured nucleus of an injured cell
71
what can we see in blood vessels with SLE?
acute necrotizing vasculitis
• presence of fibrinoid necrosis
72
what can we see in the kidneys with SLE?
* deposition of immune complexes
* six (6) Classes are recognized.
73
What are the 6 classes of **kidney** SLE?
Class 1
* minimal mesangial lupus nephritis
Class 2
* mesangial proliferative lupus nephritis
Class 3
* focal lupus nephritis
Class 4
* diffuse lupus nephritis
Class 5
* membranous lupus nephritis
Class 6
* advanced sclerosing lupus nephritis
74
what can we see in the **skin** with SLE?
erythema: butterfly rash (malar) in 50%
* caused by sun exposure
75
what is the most common class of kidney SLE? and the least?
Class I
Class 4
76
What pericardial changes can we expect to see with SLE?
Libman-Sacks endocarditis
**Libman-Sacks endocarditis** = Non-bacterial verrucous endocarditis (fibrinous)
77
In a quick summary, how do we detect a diagnosis of SLE using symptoms only?
* malar rash (butterfly rash)
* photosensitivity
* recurrent spontaneous abortions
78
how do we confirma a diagnosis of SLE?
* + for Anti-nuclear antibodies
* high titer of IgG to dsDNA
* antibodies agains Sm
* + LE cell
* proteinuria
79
how do you confirm a diagnosis of scleroderma with labs?
* + anti-Scl 70
* anti-centromere antibody
80
what is dermatomyositis?
genetically determined autoimmune disorder that target the skeletal muscle or the skin
81
what is the general pathogenesis of dermatomyositis?
1. damage to small blood vessels
2. muscle injury
3. telangiectasia (dilated capillary loops)
82
what body structures do we find affected by dermatomyositis?
nail folds, eyelids, and gums
83
In dermatomyositis, if a biopsy is done of the affected structures (muscle of skin), what will we find?
deposits of complement: C5b-9
84
what are the antibodies are associated with the gottron papules seen in dermatomyositis?
anti-Mi2
85
what are the antibodies are associated with the interstitial lung disease, non-erosive arthritis, skin rash seen in dermatomyositis?
Anti-Jo1 antibodies
86
what are the antibodies are associated with the paraneoplastic & juvenile cases of dermatomyositis?
Anti-P155/P140 antibodies
87
what type of atrophy will be expected in a muscle with dermatomyositis?
if a immunohistochemistry is done of this biopsy, what is expected to be seen?
perifasicular atrophy of muscle
inflammatory cells stain positive for CD4+ T-helper cells, and deposition of C5b-9 in capillary vessels
88
in what disease can we expect to see this?
what is happening here?
dermatomyositis
**gottron** sign (violaceous erythema, over the mcp/icp joints of the hand and fingers.
89
what is happening in the outlined area?
perifascicular atrophy
90
what are the clinical signs we need to see in order to diagnose dermatomyositis?
* muscle weakness
* lilac colored discoloration of upper eyelids
* Gottron papules = scaling erythematous eruption or dusky red patches over knuckles/elbows/knee
91
what sign of dermatomyositis can be found in a lab report?
elevated Creatine kinase
92
what is Mixed connective tissue disorder?
disease with clinical features that are a mixture of the features of SLE, systemic sclerosis, and polymyositis
93
what is characteristic of mixed connective tissue disorder?
characterized serologically by high titers of antibodies to **ribonucleoprotein particle-containing U1 ribonucleoprotein**
94
what is the clinical presentation of mixed connective tissue disorder?
* synovitis of the fingers,
* Raynaud phenomenon
* mild myositis,
